Sample records for delayed biological effects

  1. Effects of Ion Irradiation on Seedlings Growth Monitored by Ultraweak Delayed Luminescence

    PubMed Central

    Abe, Tomoko; Cirrone, Giuseppe A. P.; Cuttone, Giacomo; Gulino, Marisa; Musumeci, Francesco; Romano, Francesco; Ryuto, Hiromichi; Scordino, Agata

    2016-01-01

    The optical technique based on the measurement of delayed luminescence emitted from the biological samples has demonstrated its ability to provide valid and predictive information on the functional status of various biological systems. We want to extend this technique to study the effect of ionizing radiation on biological systems. In particular we are interested in the action of ion beams, used for therapeutic purposes or to increase the biological diversity. In general, the assessment of the damage that radiation produces both in the target objects and in the surrounding tissues, requires considerable time because is based on biochemical analysis or on the examination of the evolution of the irradiated systems. The delayed luminescence technique could help to simplify this investigation. We have so started our studies performing irradiations of some relatively simple vegetable models. In this paper we report results obtained from mung bean (Vigna radiata) seeds submitted to a 12C ion beam at the energy of 62 MeV/nucleon. The dry seeds were irradiated at doses from 50 to 7000 Gy. The photoinduced delayed luminescence of each seed before and after ion irradiation was measured. The growth of seedlings after irradiation was compared with that of untreated seeds. A growth reduction on increasing the dose was registered. The results show strong correlations between the ion irradiation dose, seeds growth and delayed luminescence intensity. In particular, the delayed luminescence intensity is correlated by a logistic function to the seedlings elongation and, after performing a suitable measurement campaign based on blind tests, it could become a tool able to predict the growth of seeds after ion irradiation. Moreover these results demonstrate that measurements of delayed luminescence could be used as a fast and non-invasive technique to check the effects of ion beams on relatively simple biological systems. PMID:27936220

  2. Uncertainties in biological responses that influence hazard and risk approaches to the regulation of endocrine active substances

    EPA Science Inventory

    Endocrine Disrupting Substances (EDSs) may have certain biological effects including delayed effects, multigenerational effects, and non-monotonic dose response relationships (NMDRs) that require careful consideration when determining environmental hazards. The case studies evalu...

  3. SETAC: Uncertainties in biological responses that influence hazard or risk approaches to the regulation of endocrine active substances

    EPA Science Inventory

    Endocrine Disrupting Substances (EDSs) may have certain biological effects including delayed effects, multigenerational effects, and non-monotonic dose response relationships (NMDRs) that require careful consideration when determining environmental hazards. The case studies evalu...

  4. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    A long-standing dogma in the radiation sciences is that energy from radiation must be deposited in the cell nucleus to elicit a biological effect. A number of non-targeted, delayed effects of ionizing radiation have been described that challenge this dogma and pose new challenges to evaluating potential hazards associated with radiation exposure. These effects include induced genomic instability and non-targeted bystander effects. The in vitro evidence for non-targeted effects in radiation biology will be reviewed, but the question as to how one extrapolates from these in vitro observations to the risk of radiation-induced adverse health effects such as cancer remains open.

  5. Extracting rate changes in transcriptional regulation from MEDLINE abstracts.

    PubMed

    Liu, Wenting; Miao, Kui; Li, Guangxia; Chang, Kuiyu; Zheng, Jie; Rajapakse, Jagath C

    2014-01-01

    Time delays are important factors that are often neglected in gene regulatory network (GRN) inference models. Validating time delays from knowledge bases is a challenge since the vast majority of biological databases do not record temporal information of gene regulations. Biological knowledge and facts on gene regulations are typically extracted from bio-literature with specialized methods that depend on the regulation task. In this paper, we mine evidences for time delays related to the transcriptional regulation of yeast from the PubMed abstracts. Since the vast majority of abstracts lack quantitative time information, we can only collect qualitative evidences of time delays. Specifically, the speed-up or delay in transcriptional regulation rate can provide evidences for time delays (shorter or longer) in GRN. Thus, we focus on deriving events related to rate changes in transcriptional regulation. A corpus of yeast regulation related abstracts was manually labeled with such events. In order to capture these events automatically, we create an ontology of sub-processes that are likely to result in transcription rate changes by combining textual patterns and biological knowledge. We also propose effective feature extraction methods based on the created ontology to identify the direct evidences with specific details of these events. Our ontologies outperform existing state-of-the-art gene regulation ontologies in the automatic rule learning method applied to our corpus. The proposed deterministic ontology rule-based method can achieve comparable performance to the automatic rule learning method based on decision trees. This demonstrates the effectiveness of our ontology in identifying rate-changing events. We also tested the effectiveness of the proposed feature mining methods on detecting direct evidence of events. Experimental results show that the machine learning method on these features achieves an F1-score of 71.43%. The manually labeled corpus of events relating to rate changes in transcriptional regulation for yeast is available in https://sites.google.com/site/wentingntu/data. The created ontologies summarized both biological causes of rate changes in transcriptional regulation and corresponding positive and negative textual patterns from the corpus. They are demonstrated to be effective in identifying rate-changing events, which shows the benefits of combining textual patterns and biological knowledge on extracting complex biological events.

  6. Spread of hatch and delayed feed access affect post hatch performance of female broiler chicks up to day 5.

    PubMed

    Wang, Y; Li, Y; Willems, E; Willemsen, H; Franssens, L; Koppenol, A; Guo, X; Tona, K; Decuypere, E; Buyse, J; Everaert, N

    2014-04-01

    It is not rare that newly hatched chicks remain without feed for about 24 to 48 h before they are placed on farms due to a series of logistic operations. Furthermore, the spread in hatching time can also mount up to 30 to 48 h for late v. early hatchers. In other words, the practice is a complex combination of spread of hatch and delayed feed access. The present study was aimed to investigate the combined effects of hatching time with a delay in feed access of 48 h, starting from their hatch-time (biological age). When chicks had access to feed immediately after hatch, late hatchers had a higher feed intake and relative growth rate up to day 5 compared with their early hatched counterparts. Feed deprivation during the first 48 h resulted in retarded early growth rate, which was further aggravated by an impaired feed intake after refeeding. In addition, the differential effects of hatching time on relative growth rate and feed intake observed in immediately fed chicks were eliminated by the 48 h feed delay. The yolk utilization after hatch was faster for the late hatchers up to biological day 2 regardless of the feeding treatments. Hatching muscle glycogen content was higher in the late hatchers compared with that of their early counterparts at hatch and at biological day 2 independent of feeding treatment. Moreover, the liver glycogen content of the late hatchers was also higher at hatch. For the immediately fed chicks, the proportional breast muscle weight of the late hatchers was higher at biological day 2 and 5. For the starved chicks, on the other hand, this effect was only observed after they had access to feed (biological day 5). The different plasma T3 levels at hatch may have contributed to the different post hatch performance. It is concluded that the spread of hatch influenced post hatch performance, especially appetite and growth at least until day 5. Moreover, the delay in feed access interacted with the hatching time and caused adverse effects on the post hatch performance.

  7. Effects of Phytoplankton Growth Phase on Delayed Settling Behavior of Marine Snow Aggregates at Sharp Density Transitions

    NASA Astrophysics Data System (ADS)

    Proctor, K. W.; Montgomery, Q. W.; Prairie, J. C.

    2016-02-01

    Marine snow aggregates play a fundamental role in the marine carbon cycle. Since marine snow aggregates are larger and thus sink faster than individual phytoplankton, aggregates often dominate carbon flux. Previous studies have shown that marine snow aggregates will significantly decrease their settling velocity when passing through sharp density transitions within the ocean, a phenomenon defined as delayed settling. Given the importance of aggregate settling to carbon export, these small-scale changes in aggregate settling dynamics may have significant impacts on the efficiency of the biological pump. However, there is still a lack of knowledge about how different physical properties of aggregates can affect this delayed settling. In this study, we investigated the effect of phytoplankton growth phase on delayed settling behavior. Using phytoplankton cultures stopped at four different growth phases, we formed marine snow aggregates in the laboratory in rotating cylindrical tanks. We then observed individual aggregates as they settled through a stratified tank. We will present data which illustrates that aggregates experience greatly reduced settling rates when passing through sharp density gradients and that the growth phase of the phytoplankton used to form these aggregates has a significant effect on this delayed settling behavior. A thorough understanding of the impact of phytoplankton growth phase on the delayed settling behavior of marine snow will offer insight into the way phytoplankton growth phase may influence the efficiency of the biological pump, carbon flux, and the carbon cycle as a whole.

  8. Modeling migratory energetics of Connecticut River American shad (Alosa sapidissima): implications for the conservation of an iteroparous anadromous fish

    USGS Publications Warehouse

    Castro-Santos, Theodore; Letcher, Benjamin H.

    2010-01-01

    We present a simulation model in which individual adult migrant American shad (Alosa sapidissima) ascend the Connecticut River and spawn, and survivors return to the marine environment. Our approach synthesizes bioenergetics, reproductive biology, and behavior to estimate the effects of migratory distance and delays incurred at dams on spawning success and survival. We quantified both the magnitude of effects and the consequences of uncertainty in the estimates of input variables. Behavior, physiology, and energetics strongly affected both the distribution of spawning effort and survival to the marine environment. Delays to both upstream and downstream movements had dramatic effects on spawning success, determining total fecundity and spatial extent of spawning. Delays, combined with cues for migratory reversal, also determined the likelihood of survival. Spawning was concentrated in the immediate vicinity of dams and increased with greater migratory distance and delays to downstream migration. More research is needed on reproductive biology, behavior, energetics, and barrier effects to adequately understand the interplay of the various components of this model; it does provide a framework, however, that suggests that provision of upstream passage at dams in the absence of expeditious downstream passage may increase spawning success — but at the expense of reduced iteroparity. 

  9. Language Delay in Severely Neglected Children: A Cumulative or Specific Effect of Risk Factors?

    ERIC Educational Resources Information Center

    Sylvestre, Audette; Merette, Chantal

    2010-01-01

    Objectives: This research sought to determine if the language delay (LD) of severely neglected children under 3 years old was better explained by a cumulative risk model or by the specificity of risk factors. The objective was also to identify the risk factors with the strongest impact on LD among various biological, psychological, and…

  10. Intra-articular Implantation of Mesenchymal Stem Cells, Part 1

    PubMed Central

    Kraeutler, Matthew J.; Mitchell, Justin J.; Chahla, Jorge; McCarty, Eric C.; Pascual-Garrido, Cecilia

    2017-01-01

    Osteoarthritis (OA) after a partial or total meniscectomy procedure is a common pathology. Because of the high incidence of meniscectomy in the general population, as well as the significant burden of knee OA, there is increasing interest in determining methods for delaying postmeniscectomy OA. Biological therapies, including mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), have been proposed as possible therapies that could delay OA in this and other settings. Several studies in various animal models have evaluated the effect of injecting MSCs into the knee joints of animals with OA induced either by meniscal excision with or without anterior cruciate ligament transection. When compared with control groups receiving injections without progenitor cells, short-term benefits in the experimental groups have been reported. In human subjects, there are limited data to determine the effect of biological therapies for use in delaying or preventing the onset of OA after a meniscectomy procedure. The purpose of this review is to highlight the findings in the presently available literature on the use of intra-articular implantation of MSCs postmeniscectomy and to offer suggestions for future research with the goal of delaying or treating early OA postmeniscectomy with MSCs. PMID:28203597

  11. Effects of delayed mating on the reproductive biology of the vine mealybug, Planococcus ficus (Hemiptera: Pseudococcidae).

    PubMed

    Lentini, A; Mura, A; Muscas, E; Nuvoli, M T; Cocco, A

    2018-04-01

    The effect of increasing mating delay on the reproductive performance and population growth rates of the vine mealybug, Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae), was investigated under laboratory conditions. Virgin females were mated at 1, 3, 5, 7, 14, 21 and 28 days after emergence and reproductive and life table parameters were estimated. The pre-oviposition period (number of days between mating and the onset of oviposition) significantly decreased in females mated within 7 days, whereas females mated at older ages showed equivalent pre-oviposition periods (7 days, as shorter delays in mating did not reduce the population growth rates.

  12. Conduction Delay Learning Model for Unsupervised and Supervised Classification of Spatio-Temporal Spike Patterns

    PubMed Central

    Matsubara, Takashi

    2017-01-01

    Precise spike timing is considered to play a fundamental role in communications and signal processing in biological neural networks. Understanding the mechanism of spike timing adjustment would deepen our understanding of biological systems and enable advanced engineering applications such as efficient computational architectures. However, the biological mechanisms that adjust and maintain spike timing remain unclear. Existing algorithms adopt a supervised approach, which adjusts the axonal conduction delay and synaptic efficacy until the spike timings approximate the desired timings. This study proposes a spike timing-dependent learning model that adjusts the axonal conduction delay and synaptic efficacy in both unsupervised and supervised manners. The proposed learning algorithm approximates the Expectation-Maximization algorithm, and classifies the input data encoded into spatio-temporal spike patterns. Even in the supervised classification, the algorithm requires no external spikes indicating the desired spike timings unlike existing algorithms. Furthermore, because the algorithm is consistent with biological models and hypotheses found in existing biological studies, it could capture the mechanism underlying biological delay learning. PMID:29209191

  13. Conduction Delay Learning Model for Unsupervised and Supervised Classification of Spatio-Temporal Spike Patterns.

    PubMed

    Matsubara, Takashi

    2017-01-01

    Precise spike timing is considered to play a fundamental role in communications and signal processing in biological neural networks. Understanding the mechanism of spike timing adjustment would deepen our understanding of biological systems and enable advanced engineering applications such as efficient computational architectures. However, the biological mechanisms that adjust and maintain spike timing remain unclear. Existing algorithms adopt a supervised approach, which adjusts the axonal conduction delay and synaptic efficacy until the spike timings approximate the desired timings. This study proposes a spike timing-dependent learning model that adjusts the axonal conduction delay and synaptic efficacy in both unsupervised and supervised manners. The proposed learning algorithm approximates the Expectation-Maximization algorithm, and classifies the input data encoded into spatio-temporal spike patterns. Even in the supervised classification, the algorithm requires no external spikes indicating the desired spike timings unlike existing algorithms. Furthermore, because the algorithm is consistent with biological models and hypotheses found in existing biological studies, it could capture the mechanism underlying biological delay learning.

  14. Derivation and computation of discrete-delay and continuous-delay SDEs in mathematical biology.

    PubMed

    Allen, Edward J

    2014-06-01

    Stochastic versions of several discrete-delay and continuous-delay differential equations, useful in mathematical biology, are derived from basic principles carefully taking into account the demographic, environmental, or physiological randomness in the dynamic processes. In particular, stochastic delay differential equation (SDDE) models are derived and studied for Nicholson's blowflies equation, Hutchinson's equation, an SIS epidemic model with delay, bacteria/phage dynamics, and glucose/insulin levels. Computational methods for approximating the SDDE models are described. Comparisons between computational solutions of the SDDEs and independently formulated Monte Carlo calculations support the accuracy of the derivations and of the computational methods.

  15. Simultaneous learning of instantaneous and time-delayed genetic interactions using novel information theoretic scoring technique

    PubMed Central

    2012-01-01

    Background Understanding gene interactions is a fundamental question in systems biology. Currently, modeling of gene regulations using the Bayesian Network (BN) formalism assumes that genes interact either instantaneously or with a certain amount of time delay. However in reality, biological regulations, both instantaneous and time-delayed, occur simultaneously. A framework that can detect and model both these two types of interactions simultaneously would represent gene regulatory networks more accurately. Results In this paper, we introduce a framework based on the Bayesian Network (BN) formalism that can represent both instantaneous and time-delayed interactions between genes simultaneously. A novel scoring metric having firm mathematical underpinnings is also proposed that, unlike other recent methods, can score both interactions concurrently and takes into account the reality that multiple regulators can regulate a gene jointly, rather than in an isolated pair-wise manner. Further, a gene regulatory network (GRN) inference method employing an evolutionary search that makes use of the framework and the scoring metric is also presented. Conclusion By taking into consideration the biological fact that both instantaneous and time-delayed regulations can occur among genes, our approach models gene interactions with greater accuracy. The proposed framework is efficient and can be used to infer gene networks having multiple orders of instantaneous and time-delayed regulations simultaneously. Experiments are carried out using three different synthetic networks (with three different mechanisms for generating synthetic data) as well as real life networks of Saccharomyces cerevisiae, E. coli and cyanobacteria gene expression data. The results show the effectiveness of our approach. PMID:22691450

  16. Proliferation of Weapons of Mass Destruction: Assessing and Risks

    DTIC Science & Technology

    1993-10-01

    Disarmament Studies Matthew S. Meselson Leonard S. Spector Department of Biochemistry Senior Associate Thomas R. Fox and Molecular Biology Carnegie...Nuclear radiation (immediate) Flash burns, blinding, burning or suffocation from building fires Nuclear radiation (delayed effects and fallout effects

  17. [Effects of biologically active pectin-containing dietary supplement on gastroduodenal motility in patients with a functional dyspepsia].

    PubMed

    Loranskaia, T I; Kabanova, I N; Klykova, E V

    2002-01-01

    For 21 patients with a functional dyspepsia the influencing biologically active additives to nutrition "Pekcecom" on dynamics of clinical symptoms and parameters gastroduodenal motility under the data gastroduodenoscintigraphy was studied. The usage of biologically active additives during 4 weeks was accompanied by deboosting of accelerated gastric emptying for want of statistically significant influencing on a normal and delayed gastric emptying and parameters of duodenal transit.

  18. Behavioral characteristics of very-low-birth-weight infants of varying biologic risk at 6, 15, and 24 months of age.

    PubMed

    Oehler, J M; Thompson, R J; Goldstein, R F; Gustafson, K E; Brazy, J E

    1996-01-01

    To explore the relationship between developmental outcome and behavior of very-low-birth-weight (VLBW) infants (< or = 1500 g) at high and low biologic risk. Descriptive, ex post facto. Clinic for follow-up of infants at high risk. A convenience sample of 102 VLBW infants, free of major congenital anomalies, who completed 6-, 15-, and 24-month developmental testing and who were part of a larger study of 274 VLBW infants. Bayley Scales of Infant Development. Infants at high biologic risk, versus infants at low biologic risk, were less attentive and active through age 15 months and were less adept in gross and fine motor skills through age 24 months (p < or = 0.05-0.001). Infants with continuous delay were less attentive than infants with no delay or late delay through age 24 months, less active through age 15 months (p < or = 0.001-0.001), and less skilled in motor behaviors through age 24 months (p < or = 0.05-0.001). Infants at high biologic risk and infants with developmental delays are less attentive, less active, and less skilled in motor tasks during the first 15-24 months of life, suggesting an association between biologic risk and behavior and developmental delay and behavior.

  19. Hindrance of conservation biology by delays in the submission of manuscripts.

    PubMed

    O'Donnell, Ryan P; Supp, Sarah R; Cobbold, Stephanie M

    2010-04-01

    Timely dissemination of scientific findings depends not only on rapid publication of submitted manuscripts, a topic which has received much discussion, but also on rapid submission of research after the research is completed. We measured submission delay (time from the last date of data collection to the submission of a manuscript) for every paper from 14 journals in 2007 and compared these submission delays among four fields of biology (conservation, taxonomy, behavior, and evolution). Manuscripts published in leading journals in the field of conservation biology have the longest delays in publication of accepted manuscripts and the longest intervals between completion of research and submission of the manuscript. Delay in manuscript submission accounts for more than half of the total time from last date of data collection to publication. Across fields, the number of authors was significantly negatively correlated with submission delay, but conservation journals had the second highest number of authors and the greatest submission delay, so submission of conservation manuscripts was not hindered by a shortage of collaboration relative to other fields. Rejection rates were greater in conservation journals than in behavior and evolution, but rejection times were faster; thus, there were no obvious net differences among fields in the time papers spent waiting to be rejected. Publication delay has been reduced significantly in the last 7 years, but was still greater in conservation journals than in any of the other three fields we studied. Thus, the urgent field of conservation biology is hindered in both preparation and publication of manuscripts.

  20. Introduction to Focus Issue: Time-delay dynamics

    NASA Astrophysics Data System (ADS)

    Erneux, Thomas; Javaloyes, Julien; Wolfrum, Matthias; Yanchuk, Serhiy

    2017-11-01

    The field of dynamical systems with time delay is an active research area that connects practically all scientific disciplines including mathematics, physics, engineering, biology, neuroscience, physiology, economics, and many others. This Focus Issue brings together contributions from both experimental and theoretical groups and emphasizes a large variety of applications. In particular, lasers and optoelectronic oscillators subject to time-delayed feedbacks have been explored by several authors for their specific dynamical output, but also because they are ideal test-beds for experimental studies of delay induced phenomena. Topics include the control of cavity solitons, as light spots in spatially extended systems, new devices for chaos communication or random number generation, higher order locking phenomena between delay and laser oscillation period, and systematic bifurcation studies of mode-locked laser systems. Moreover, two original theoretical approaches are explored for the so-called Low Frequency Fluctuations, a particular chaotical regime in laser output which has attracted a lot of interest for more than 30 years. Current hot problems such as the synchronization properties of networks of delay-coupled units, novel stabilization techniques, and the large delay limit of a delay differential equation are also addressed in this special issue. In addition, analytical and numerical tools for bifurcation problems with or without noise and two reviews on concrete questions are proposed. The first review deals with the rich dynamics of simple delay climate models for El Nino Southern Oscillations, and the second review concentrates on neuromorphic photonic circuits where optical elements are used to emulate spiking neurons. Finally, two interesting biological problems are considered in this Focus Issue, namely, multi-strain epidemic models and the interaction of glucose and insulin for more effective treatment.

  1. Oscillatory dynamics of an intravenous glucose tolerance test model with delay interval

    NASA Astrophysics Data System (ADS)

    Shi, Xiangyun; Kuang, Yang; Makroglou, Athena; Mokshagundam, Sriprakash; Li, Jiaxu

    2017-11-01

    Type 2 diabetes mellitus (T2DM) has become prevalent pandemic disease in view of the modern life style. Both diabetic population and health expenses grow rapidly according to American Diabetes Association. Detecting the potential onset of T2DM is an essential focal point in the research of diabetes mellitus. The intravenous glucose tolerance test (IVGTT) is an effective protocol to determine the insulin sensitivity, glucose effectiveness, and pancreatic β-cell functionality, through the analysis and parameter estimation of a proper differential equation model. Delay differential equations have been used to study the complex physiological phenomena including the glucose and insulin regulations. In this paper, we propose a novel approach to model the time delay in IVGTT modeling. This novel approach uses two parameters to simulate not only both discrete time delay and distributed time delay in the past interval, but also the time delay distributed in a past sub-interval. Normally, larger time delay, either a discrete or a distributed delay, will destabilize the system. However, we find that time delay over a sub-interval might not. We present analytically some basic model properties, which are desirable biologically and mathematically. We show that this relatively simple model provides good fit to fluctuating patient data sets and reveals some intriguing dynamics. Moreover, our numerical simulation results indicate that our model may remove the defect in well known Minimal Model, which often overestimates the glucose effectiveness index.

  2. Parturition dysfunction in obesity: time to target the pathobiology.

    PubMed

    Carlson, Nicole S; Hernandez, Teri L; Hurt, K Joseph

    2015-12-18

    Over a third of women of childbearing age in the United States are obese, and during pregnancy they are at increased risk for delayed labor onset and slow labor progress that often results in unplanned cesarean delivery. The biology behind this dysfunctional parturition is not well understood. Studies of obesity-induced changes in parturition physiology may facilitate approaches to optimize labor in obese women. In this review, we summarize known and proposed biologic effects of obesity on labor preparation, contraction/synchronization, and endurance, drawing on both clinical observation and experimental data. We present evidence from human and animal studies of interactions between obesity and parturition signaling in all elements of the birth process, including: delayed cervical ripening, prostaglandin insensitivity, amniotic membrane strengthening, decreased myometrial oxytocin receptor expression, decreased myocyte action potential initiation and contractility, decreased myocyte gap junction formation, and impaired myocyte neutralization of reactive oxygen species. We found convincing clinical data on the effect of obesity on labor initiation and successful delivery, but few studies on the underlying pathobiology. We suggest research opportunities and therapeutic interventions based on plausible biologic mechanisms.

  3. Aging Biology and Novel Targets for Drug Discovery

    PubMed Central

    McLachlan, Andrew J.; Quinn, Ronald J.; Simpson, Stephen J.; de Cabo, Rafael

    2012-01-01

    Despite remarkable technological advances in genetics and drug screening, the discovery of new pharmacotherapies has slowed and new approaches to drug development are needed. Research into the biology of aging is generating many novel targets for drug development that may delay all age-related diseases and be used long term by the entire population. Drugs that successfully delay the aging process will clearly become “blockbusters.” To date, the most promising leads have come from studies of the cellular pathways mediating the longevity effects of caloric restriction (CR), particularly target of rapamycin and the sirtuins. Similar research into pathways governing other hormetic responses that influence aging is likely to yield even more targets. As aging becomes a more attractive target for drug development, there will be increasing demand to develop biomarkers of aging as surrogate outcomes for the testing of the effects of new agents on the aging process. PMID:21693687

  4. Sensitivity analysis of dynamic biological systems with time-delays.

    PubMed

    Wu, Wu Hsiung; Wang, Feng Sheng; Chang, Maw Shang

    2010-10-15

    Mathematical modeling has been applied to the study and analysis of complex biological systems for a long time. Some processes in biological systems, such as the gene expression and feedback control in signal transduction networks, involve a time delay. These systems are represented as delay differential equation (DDE) models. Numerical sensitivity analysis of a DDE model by the direct method requires the solutions of model and sensitivity equations with time-delays. The major effort is the computation of Jacobian matrix when computing the solution of sensitivity equations. The computation of partial derivatives of complex equations either by the analytic method or by symbolic manipulation is time consuming, inconvenient, and prone to introduce human errors. To address this problem, an automatic approach to obtain the derivatives of complex functions efficiently and accurately is necessary. We have proposed an efficient algorithm with an adaptive step size control to compute the solution and dynamic sensitivities of biological systems described by ordinal differential equations (ODEs). The adaptive direct-decoupled algorithm is extended to solve the solution and dynamic sensitivities of time-delay systems describing by DDEs. To save the human effort and avoid the human errors in the computation of partial derivatives, an automatic differentiation technique is embedded in the extended algorithm to evaluate the Jacobian matrix. The extended algorithm is implemented and applied to two realistic models with time-delays: the cardiovascular control system and the TNF-α signal transduction network. The results show that the extended algorithm is a good tool for dynamic sensitivity analysis on DDE models with less user intervention. By comparing with direct-coupled methods in theory, the extended algorithm is efficient, accurate, and easy to use for end users without programming background to do dynamic sensitivity analysis on complex biological systems with time-delays.

  5. [BIOLOGICAL EFFECTIVENESS OF FISSION SPECTRUM NEUTRONS AND PROTONS WITH ENERGIES OF 60-126 MEV DURING ACUTE AND PROLONGED IRRADIATION].

    PubMed

    Shafirkin, A V

    2015-01-01

    Neutrons of the fission spectrum are characterized by relatively high values of linear energy transfer (LET). Data about their effects on biological objects are used to evaluate the risk of delayed effects of accelerated ions within the same LET range that serve as an experimental model of the nuclei component of galactic cosmic rays (GCR). Additionally, risks of delayed consequences to cosmonaut's health and average lifetime from certain GCR fluxes and secondary neutrons can be also prognosticated. The article deals with comparative analysis of the literature on reduction of average lifespan (ALS) of animals exposed to neutron reactor spectrum, 60-126 MeV protons, and X- and γ-rays in a broad range of radiation intensity and duration. It was shown that a minimal lifespan reduction by 5% occurs due to a brief exposure to neutrons with the absorbed dose of 5 cGy, whereas same lifespan reduction due to hard X- and γ-radiation occurs after absorption of a minimal dose of 100 cGy. Therefore, according to the estimated minimal ALS reduction in mice, neutron effectiveness is 20-fold higher. Biological effectiveness of protons as regards ALS reduction is virtually equal to that of standard types of radiation. Exposure to X- and γ-radiation with decreasing daily doses, and increasing number of fractions and duration gives rise to an apparent trend toward a less dramatic ALS reduction in mice; on the contrary, exposure to neutrons of varying duration had no effect on threshold doses for the specified ALS reductions. Factors of relative biological effectiveness of neutrons reached 40.

  6. Epidemic spreading and global stability of an SIS model with an infective vector on complex networks

    NASA Astrophysics Data System (ADS)

    Kang, Huiyan; Fu, Xinchu

    2015-10-01

    In this paper, we present a new SIS model with delay on scale-free networks. The model is suitable to describe some epidemics which are not only transmitted by a vector but also spread between individuals by direct contacts. In view of the biological relevance and real spreading process, we introduce a delay to denote average incubation period of disease in a vector. By mathematical analysis, we obtain the epidemic threshold and prove the global stability of equilibria. The simulation shows the delay will effect the epidemic spreading. Finally, we investigate and compare two major immunization strategies, uniform immunization and targeted immunization.

  7. Breastfeeding and developmental delay: findings from the millennium cohort study.

    PubMed

    Sacker, Amanda; Quigley, Maria A; Kelly, Yvonne J

    2006-09-01

    We investigated whether the duration and exclusivity of breastfeeding affects the likelihood of gross and fine motor delay in infants and examined the effect of factors that might explain any observed differences. The study sample included all term singleton infants who weighed > 2500 g at birth and were not placed in a special care infant unit and whose mothers participated in the first survey of the Millennium Cohort Study. Missing data reduced the sample to 14660 (94%) with complete data. Almost half (47%) of the infants initially were exclusively breastfed, but only 3.5% of these infants were still being fed exclusively on breast milk after 4 months of age, and 34% of infants were not breastfed at all; 9% of the infants were identified with delays in gross motor coordination and 6% with fine motor coordination delays at age 9 months. The proportion of infants who mastered the developmental milestones increased with duration and exclusivity of breastfeeding. Infants who had never been breastfed were 50% more likely to have gross motor coordination delays than infants who had been breastfed exclusively for at least 4 months (10.7% vs 7.3%). Any breast milk also was positively related to development: infants who had never been breastfed were 30% more likely to have gross motor delays than infants who were given some breast milk for up to 2 months (10.7% vs 8.4%). The odds ratios for gross motor delay were not attenuated after adjustment for biological, socioeconomic, or psychosocial factors. Infants who were never breastfed had at least a 40% greater likelihood of fine motor delay than infants who were given breast milk for a prolonged period. Our results suggest that the protective effect of breastfeeding on the attainment of gross motor milestones is attributable to some component(s) of breast milk or feature of breastfeeding and is not simply a product of advantaged social position, education, or parenting style, because control for these factors did not explain any of the observed association. In contrast, the association between breastfeeding and fine motor delay was explained by biological, socioeconomic, and psychosocial factors.

  8. Stability and Hopf Bifurcation in a Reaction-Diffusion Model with Chemotaxis and Nonlocal Delay Effect

    NASA Astrophysics Data System (ADS)

    Li, Dong; Guo, Shangjiang

    Chemotaxis is an observed phenomenon in which a biological individual moves preferentially toward a relatively high concentration, which is contrary to the process of natural diffusion. In this paper, we study a reaction-diffusion model with chemotaxis and nonlocal delay effect under Dirichlet boundary condition by using Lyapunov-Schmidt reduction and the implicit function theorem. The existence, multiplicity, stability and Hopf bifurcation of spatially nonhomogeneous steady state solutions are investigated. Moreover, our results are illustrated by an application to the model with a logistic source, homogeneous kernel and one-dimensional spatial domain.

  9. Maturation delay for the predators can enhance stable coexistence for a class of prey-predator models.

    PubMed

    Banerjee, Malay; Takeuchi, Yasuhiro

    2017-01-07

    Maturation time delay for the predators is introduced in prey-predator models to implicitly model the stage-structure of predators. Most of the prey-predator models with maturation delay are known to exhibit destabilization of coexistence steady-state. Discrete time delay induced destabilization is a common finding, however, this is due to the introduction of time delay with lack of ecological justification. The main objective of the present work is to show the stabilizing role of maturation delay for a class of delayed prey-predator model. To be specific, we consider prey-predator models with strong and weak Allee effects in prey growth and Michaelis-Menten type functional response. We provide ecological justification for the introduction of maturation delay parameter in predator's growth equation. We obtain the conditions for stable and oscillatory coexistence of prey and their specialist predator in case of strong as well as weak Allee effect for non-delayed and delayed models. Apart from the analytical results for the models under consideration, we perform extensive numerical simulations to construct the relevant bifurcation diagrams. Our analytical and supportive numerical findings reveal that delay is not always a destabilizing factor rather the stable coexistence in the presence of time delay depends upon the formulation of the delayed model. The biological implications of the current investigation are provided in the conclusion section. We also explain the validity of obtained results for other types of prey-predator models with a specialist predator. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. DL-ReSuMe: A Delay Learning-Based Remote Supervised Method for Spiking Neurons.

    PubMed

    Taherkhani, Aboozar; Belatreche, Ammar; Li, Yuhua; Maguire, Liam P

    2015-12-01

    Recent research has shown the potential capability of spiking neural networks (SNNs) to model complex information processing in the brain. There is biological evidence to prove the use of the precise timing of spikes for information coding. However, the exact learning mechanism in which the neuron is trained to fire at precise times remains an open problem. The majority of the existing learning methods for SNNs are based on weight adjustment. However, there is also biological evidence that the synaptic delay is not constant. In this paper, a learning method for spiking neurons, called delay learning remote supervised method (DL-ReSuMe), is proposed to merge the delay shift approach and ReSuMe-based weight adjustment to enhance the learning performance. DL-ReSuMe uses more biologically plausible properties, such as delay learning, and needs less weight adjustment than ReSuMe. Simulation results have shown that the proposed DL-ReSuMe approach achieves learning accuracy and learning speed improvements compared with ReSuMe.

  11. Why wait? Three mechanisms selecting for environment-dependent developmental delays.

    PubMed

    Scott, M F; Otto, S P

    2014-10-01

    Many species delay development unless particular environments or rare disturbance events occur. How can such a strategy be favoured over continued development? Typically, it is assumed that continued development (e.g. germination) is not advantageous in environments that have low juvenile/seedling survival (mechanism 1), either due to abiotic or competitive effects. However, it has not previously been shown how low early survival must be in order to favour environment-specific developmental delays for long-lived species. Using seed dormancy as an example of developmental delays, we identify a threshold level of seedling survival in 'bad' environments below which selection can favour germination that is limited to 'good' environments. This can be used to evaluate whether observed differences in seedling survival are sufficient to favour conditional germination. We also present mathematical models that demonstrate two other, often overlooked, mechanisms that can favour conditional germination in the absence of differences in seedling survival. Specifically, physiological trade-offs can make it difficult to have germination rates that are equally high in all environments (mechanism 2). We show that such trade-offs can either favour conditional germination or intermediate (mixed) strategies, depending on the trade-off shape. Finally, germination in every year increases the likelihood that some individuals are killed in population-scale disturbances before reproducing; it can thus be favourable to only germinate immediately after a disturbance (mechanism 3). We demonstrate how demographic data can be used to evaluate these selection pressures. By presenting these three mechanisms and the conditions that favour conditional germination in each case, we provide three hypotheses that can be tested as explanations for the evolution of environment-dependent developmental delays. © 2014 European Society for Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  12. Reliability of biologic indicators in a mail-return sterilization-monitoring service: a review of 3 years.

    PubMed

    Andrés, M T; Tejerina, J M; Fierro, J F

    1995-12-01

    Most mail-return sterilization-monitoring services use spore strips to test sterilizers in dental clinics, but factors such as delay caused by mailing to the laboratory could cause false negatives. The aims of this study were to determine the influence of poststerilization time and temperature on the biologic indicator recovery system and to evaluate sterilization failure and its possible causes in dental clinics subscribing to a mail-return sterilization-monitoring service. Spore strips used in independent tests revealed the poststerilization time and temperature after a 7-day delay to have no significant influence. Sixty-six dental clinics that received quarterly biologic indicators to evaluate the effectiveness of their sterilizers had sterilization failure rates of 28.7% in 1992, 18.1% in 1993, and 9.1% in 1994, a statistically significant decrease in sterilization failure during the 3-year period. The usual causes of failure were operator error in wrapping of instruments, loading, operating temperature, or exposure time.

  13. Global analysis of an impulsive delayed Lotka-Volterra competition system

    NASA Astrophysics Data System (ADS)

    Xia, Yonghui

    2011-03-01

    In this paper, a retarded impulsive n-species Lotka-Volterra competition system with feedback controls is studied. Some sufficient conditions are obtained to guarantee the global exponential stability and global asymptotic stability of a unique equilibrium for such a high-dimensional biological system. The problem considered in this paper is in many aspects more general and incorporates as special cases various problems which have been extensively studied in the literature. Moreover, applying the obtained results to some special cases, I derive some new criteria which generalize and greatly improve some well known results. A method is proposed to investigate biological systems subjected to the effect of both impulses and delays. The method is based on Banach fixed point theory and matrix's spectral theory as well as Lyapunov function. Moreover, some novel analytic techniques are employed to study GAS and GES. It is believed that the method can be extended to other high-dimensional biological systems and complex neural networks. Finally, two examples show the feasibility of the results.

  14. Food reinforcement and delay discounting in zBMI-discordant siblings.

    PubMed

    Feda, Denise M; Roemmich, James N; Roberts, April; Epstein, Leonard H

    2015-02-01

    The interaction of food reinforcement and the inability to delay gratification are related to adult energy intake and obesity. This study was designed to test the association of sibling pair differences in relative reinforcing efficacy of food and delay discounting on sibling pair differences in zBMI scores of same-gender zBMI-discordant siblings. We tested main and interactive relationships between delay discounting and relative reinforcing efficacy of food on zBMI discordance in 14 zBMI-discordant biological sibling pairs (6 female pairs) using a discordant sibling study design. Sibling pair differences in relative reinforcing efficacy of food were associated with sibling pair differences in zBMI (p= 0.046); this effect was moderated by delay discounting (p <0.002). Sibling pairs with greater differences in relative reinforcing efficacy and delay discounting had greater differences in zBMI. The combination of greater sibling pair differences in delay discounting and relative reinforcing efficacy is associated with greater discordance in zBMI in adolescent sibling pairs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Food reinforcement and delay discounting in zBMI-discordant siblings ☆

    PubMed Central

    Feda, Denise M.; Roemmich, James N.; Roberts, April; Epstein, Leonard H.

    2014-01-01

    Objective The interaction of food reinforcement and the inability to delay gratification are related to adult energy intake and obesity. This study was designed to test the association of sibling pair differences in relative reinforcing efficacy of food and delay discounting on sibling pair differences in zBMI scores of same-gender zBMI-discordant siblings. Design and methods We tested main and interactive relationships between delay discounting and relative reinforcing efficacy of food on zBMI discordance in 14 zBMI-discordant biological sibling pairs (6 female pairs) using a discordant sibling study design. Results Sibling pair differences in relative reinforcing efficacy of food were associated with sibling pair differences in zBMI (p = 0.046); this effect was moderated by delay discounting (p < 0.002). Sibling pairs with greater differences in relative reinforcing efficacy and delay discounting had greater differences in zBMI. Conclusions The combination of greater sibling pair differences in delay discounting and relative reinforcing efficacy is associated with greater discordance in zBMI in adolescent sibling pairs. PMID:25464024

  16. Apparatus for eliminating background interference in fluorescence measurements

    DOEpatents

    Martin, J.C.; Jett, J.H.

    1984-01-06

    The disclosure is directed to an apparatus for eliminating background interference during fluorescence measurements in a multiple laser flow cytometer. A biological particle stained with fluorescent dyes is excited by a laser. A fluorescence detector detects the fluorescence. The particle scatters light and a gate signal is generated and delayed until the biological particle reaches the next laser. The delayed signal turns on this next laser which excites a different stained component of the same biological particle.

  17. Apparatus for eliminating background interference in fluorescence measurements

    DOEpatents

    Martin, John C.; Jett, James H.

    1986-01-01

    The disclosure is directed to an apparatus for eliminating background interference during fluorescence measurements in a multiple laser flow cytometer. A biological particle stained with fluorescent dyes is excited by a laser. A fluorescence detector detects the fluorescence. The particle scatters light and a gate signal is generated and delayed until the biological particle reaches the next laser. The delayed signal turns on this next laser, which excites a different stained component of the same biological particle.

  18. Apparatus for eliminating background interference in fluorescence measurements

    DOEpatents

    Martin, J.C.; Jett, J.H.

    1986-03-04

    The disclosure is directed to an apparatus for eliminating background interference during fluorescence measurements in a multiple laser flow cytometer. A biological particle stained with fluorescent dyes is excited by a laser. A fluorescence detector detects the fluorescence. The particle scatters light and a gate signal is generated and delayed until the biological particle reaches the next laser. The delayed signal turns on this next laser, which excites a different stained component of the same biological particle. 8 figs.

  19. Application of Time-Delay Absorber to Suppress Vibration of a Dynamical System to Tuned Excitation.

    PubMed

    El-Ganaini, W A A; El-Gohary, H A

    2014-08-01

    In this work, we present a comprehensive investigation of the time delay absorber effects on the control of a dynamical system represented by a cantilever beam subjected to tuned excitation forces. Cantilever beam is one of the most widely used system in too many engineering applications, such as mechanical and civil engineering. The main aim of this work is to control the vibration of the beam at simultaneous internal and combined resonance condition, as it is the worst resonance case. Control is conducted via time delay absorber to suppress chaotic vibrations. Time delays often appear in many control systems in the state, in the control input, or in the measurements. Time delay commonly exists in various engineering, biological, and economical systems because of the finite speed of the information processing. It is a source of performance degradation and instability. Multiple time scale perturbation method is applied to obtain a first order approximation for the nonlinear differential equations describing the system behavior. The different resonance cases are reported and studied numerically. The stability of the steady-state solution at the selected worst resonance case is investigated applying Runge-Kutta fourth order method and frequency response equations via Matlab 7.0 and Maple11. Time delay absorber is effective, but within a specified range of time delay. It is the critical factor in selecting such absorber. Time delay absorber is better than the ordinary one as from the effectiveness point of view. The effects of the different absorber parameters on the system behavior and stability are studied numerically. A comparison with the available published work showed a close agreement with some previously published work.

  20. A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings.

    PubMed

    Sonuga-Barke, Edmund J S; Kumsta, Robert; Schlotz, Wolff; Lasky-Su, Jessica; Marco, Rafaela; Miranda, Ana; Mulas, Fernando; Oades, Robert D; Banaschewski, Tobias; Mueller, Ueli; Andreou, Penny; Christiansen, Hanna; Gabriels, Isabel; Uebel, Henrik; Kuntsi, Jonna; Franke, Barbara; Buitelaar, Jan; Ebstein, Richard; Gill, Michael; Anney, Richard; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Steinhausen, Hans Christoph; Asherson, Philip; Faraone, Stephen V

    2011-08-01

    Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes. Impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3'-untranslated region of the gene. There was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms. The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Effects of additional food in a delayed predator-prey model.

    PubMed

    Sahoo, Banshidhar; Poria, Swarup

    2015-03-01

    We examine the effects of supplying additional food to predator in a gestation delay induced predator-prey system with habitat complexity. Additional food works in favor of predator growth in our model. Presence of additional food reduces the predatory attack rate to prey in the model. Supplying additional food we can control predator population. Taking time delay as bifurcation parameter the stability of the coexisting equilibrium point is analyzed. Hopf bifurcation analysis is done with respect to time delay in presence of additional food. The direction of Hopf bifurcations and the stability of bifurcated periodic solutions are determined by applying the normal form theory and the center manifold theorem. The qualitative dynamical behavior of the model is simulated using experimental parameter values. It is observed that fluctuations of the population size can be controlled either by supplying additional food suitably or by increasing the degree of habitat complexity. It is pointed out that Hopf bifurcation occurs in the system when the delay crosses some critical value. This critical value of delay strongly depends on quality and quantity of supplied additional food. Therefore, the variation of predator population significantly effects the dynamics of the model. Model results are compared with experimental results and biological implications of the analytical findings are discussed in the conclusion section. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Uncertainties in biological responses that influence hazard or risk approaches to the regulation of endocrine active substances

    EPA Science Inventory

    Endocrine Disrupting Chemicals (EDCs) may have delayed or transgenerational effects and display non-monotonic dose response relationships (NMDRs) that require careful consideration when determining environmental hazards. The case studies evaluated for the SETAC Pellston Workshop&...

  3. Long-Term Phenological Shifts in Raptor Migration and Climate

    PubMed Central

    Jaffré, Mikaël; Beaugrand, Grégory; Goberville, Éric; Jiguet, Frédéric; Kjellén, Nils; Troost, Gerard; Dubois, Philippe J.; Leprêtre, Alain; Luczak, Christophe

    2013-01-01

    Climate change is having a discernible effect on many biological and ecological processes. Among observed changes, modifications in bird phenology have been widely documented. However, most studies have interpreted phenological shifts as gradual biological adjustments in response to the alteration of the thermal regime. Here we analysed a long-term dataset (1980-2010) of short-distance migratory raptors in five European regions. We revealed that the responses of these birds to climate-induced changes in autumn temperatures are abrupt and synchronous at a continental scale. We found that when the temperatures increased, birds delayed their mean passage date of autumn migration. Such delay, in addition to an earlier spring migration, suggests that a significant warming may induce an extension of the breeding-area residence time of migratory raptors, which may eventually lead to residency. PMID:24223888

  4. Clinical efficacy of dim light melatonin onset testing in diagnosing delayed sleep phase syndrome.

    PubMed

    Rahman, Shadab A; Kayumov, Leonid; Tchmoutina, Ekaterina A; Shapiro, Colin M

    2009-05-01

    Delayed Sleep Phase Syndrome (DSPS) arises from biological clock desynchrony and accounts for 10% of chronic insomnia patients. Currently DSPS is diagnosed based on sleep/wake cycle disruptions rather than examining the underlying biological clock alterations. The objective of the study was to determine the sensitivity and specificity of the Dim Light Melatonin Onset (DLMO) Test in diagnosing DSPS in a clinical setting. Fifty-six patients (mean age 28 years) symptomatic of DSPS participated in the study. Following an initial assessment of DSPS using sleep diaries, participants underwent two consecutive nights of polysomnography (PSG), with an imposed sleep period on the second night to demonstrate the delay in the timing of habitual sleep period and to thereby confirm DSPS. Circadian phase delays were also measured using melatonin secretion profiles, and the efficacy of diagnosing DSPS using DLMO was compared to using sleep diaries and PSG. Melatonin secretion was assayed for each individual by ELISA using saliva samples. Main outcome measures included the time of melatonin secretion onset, clinical sensitivity and specificity of the DLMO test. The time of melatonin secretion onset was significantly delayed in DSPS patients. Clinical sensitivity and specificity of the DLMO test in diagnosing DSPS were 90.3% and 84.0%, respectively. The DLMO test is an accurate tool for differentiating between sleep disorder patients with or without underlying circadian rhythm disruption. It is effective for phase typing DSPS patients in a clinical setting.

  5. Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates

    PubMed Central

    Messaoudi, Ilhem; Warner, Jessica; Fischer, Miranda; Park, Buyng; Hill, Brenna; Mattison, Julie; Lane, Mark A.; Roth, George S.; Ingram, Donald K.; Picker, Louis J.; Douek, Daniel C.; Mori, Motomi; Nikolich-Žugich, Janko

    2006-01-01

    Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decreases mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. In rodents, CR was reported to delay the aging of the immune system (immune senescence), which is believed to be largely responsible for a dramatic increase in age-related susceptibility to infectious diseases. However, it is unclear whether CR can exert similar effects in long-lived organisms. Previous studies involving 2- to 4-year CR treatment of long-lived primates failed to find a CR effect or reported effects on the immune system opposite to those seen in CR-treated rodents. Here we show that long-term CR delays the adverse effects of aging on nonhuman primate T cells. CR effected a marked improvement in the maintenance and/or production of naïve T cells and the consequent preservation of T cell receptor repertoire diversity. Furthermore, CR also improved T cell function and reduced production of inflammatory cytokines by memory T cells. Our results provide evidence that CR can delay immune senescence in nonhuman primates, potentially contributing to an extended lifespan by reducing susceptibility to infectious disease. PMID:17159149

  6. Delay decomposition approach to [Formula: see text] filtering analysis of genetic oscillator networks with time-varying delays.

    PubMed

    Revathi, V M; Balasubramaniam, P

    2016-04-01

    In this paper, the [Formula: see text] filtering problem is treated for N coupled genetic oscillator networks with time-varying delays and extrinsic molecular noises. Each individual genetic oscillator is a complex dynamical network that represents the genetic oscillations in terms of complicated biological functions with inner or outer couplings denote the biochemical interactions of mRNAs, proteins and other small molecules. Throughout the paper, first, by constructing appropriate delay decomposition dependent Lyapunov-Krasovskii functional combined with reciprocal convex approach, improved delay-dependent sufficient conditions are obtained to ensure the asymptotic stability of the filtering error system with a prescribed [Formula: see text] performance. Second, based on the above analysis, the existence of the designed [Formula: see text] filters are established in terms of linear matrix inequalities with Kronecker product. Finally, numerical examples including a coupled Goodwin oscillator model are inferred to illustrate the effectiveness and less conservatism of the proposed techniques.

  7. Investigation of stability in a two-delay model of the ultradian oscillations in glucose-insulin regulation

    NASA Astrophysics Data System (ADS)

    Huard, B.; Easton, J. F.; Angelova, M.

    2015-09-01

    In this paper, a two-delay model for the ultradian oscillatory behaviour of the glucose-insulin regulation system is studied. Hill functions are introduced to model nonlinear physiological interactions within this system and ranges on parameters reproducing biological oscillations are determined on the basis of analytical and numerical considerations. Local and global stability are investigated and delay-dependent conditions are obtained through the construction of Lyapunov-Krasovskii functionals. The effect of Hill parameters on these conditions, as well as the boundary of the stability region in the delay domain, are established for the first time. Numerical simulations demonstrate that the model with Hill functions represents well the oscillatory behaviour of the system with the advantage of incorporating new meaningful parameters. The influence of the time delays on the period of oscillations and the sensitivity of the latter to model parameters, in particular glucose infusion, are investigated. The model can contribute to the better understanding and treatment of diabetes.

  8. The sensitivity of Turing self-organization to biological feedback delays: 2D models of fish pigmentation.

    PubMed

    Gaffney, E A; Lee, S Seirin

    2015-03-01

    Turing morphogen models have been extensively explored in the context of large-scale self-organization in multicellular biological systems. However, reconciling the detailed biology of morphogen dynamics, while accounting for time delays associated with gene expression, reveals aberrant behaviours that are not consistent with early developmental self-organization, especially the requirement for exquisite temporal control. Attempts to reconcile the interpretation of Turing's ideas with an increasing understanding of the mechanisms driving zebrafish pigmentation suggests that one should reconsider Turing's model in terms of pigment cells rather than morphogens (Nakamasu et al., 2009, PNAS, 106: , 8429-8434; Yamaguchi et al., 2007, PNAS, 104: , 4790-4793). Here the dynamics of pigment cells is subject to response delays implicit in the cell cycle and apoptosis. Hence we explore simulations of fish skin patterning, focussing on the dynamical influence of gene expression delays in morphogen-based Turing models and response delays for cell-based Turing models. We find that reconciling the mechanisms driving the behaviour of Turing systems with observations of fish skin patterning remains a fundamental challenge. © The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  9. On determining firing delay time of transitions for Petri net based signaling pathways by introducing stochastic decision rules.

    PubMed

    Miwa, Yoshimasa; Li, Chen; Ge, Qi-Wei; Matsuno, Hiroshi; Miyano, Satoru

    2010-01-01

    Parameter determination is important in modeling and simulating biological pathways including signaling pathways. Parameters are determined according to biological facts obtained from biological experiments and scientific publications. However, such reliable data describing detailed reactions are not reported in most cases. This prompted us to develop a general methodology of determining the parameters of a model in the case of that no information of the underlying biological facts is provided. In this study, we use the Petri net approach for modeling signaling pathways, and propose a method to determine firing delay times of transitions for Petri net models of signaling pathways by introducing stochastic decision rules. Petri net technology provides a powerful approach to modeling and simulating various concurrent systems, and recently have been widely accepted as a description method for biological pathways. Our method enables to determine the range of firing delay time which realizes smooth token flows in the Petri net model of a signaling pathway. The availability of this method has been confirmed by the results of an application to the interleukin-1 induced signaling pathway.

  10. On determining firing delay time of transitions for petri net based signaling pathways by introducing stochastic decision rules.

    PubMed

    Miwa, Yoshimasa; Li, Chen; Ge, Qi-Wei; Matsuno, Hiroshi; Miyano, Satoru

    2011-01-01

    Parameter determination is important in modeling and simulating biological pathways including signaling pathways. Parameters are determined according to biological facts obtained from biological experiments and scientific publications. However, such reliable data describing detailed reactions are not reported in most cases. This prompted us to develop a general methodology of determining the parameters of a model in the case of that no information of the underlying biological facts is provided. In this study, we use the Petri net approach for modeling signaling pathways, and propose a method to determine firing delay times of transitions for Petri net models of signaling pathways by introducing stochastic decision rules. Petri net technology provides a powerful approach to modeling and simulating various concurrent systems, and recently have been widely accepted as a description method for biological pathways. Our method enables to determine the range of firing delay time which realizes smooth token flows in the Petri net model of a signaling pathway. The availability of this method has been confirmed by the results of an application to the interleukin-1 induced signaling pathway.

  11. Effect of longer health service provider delays on stage at diagnosis and mortality in symptomatic breast cancer.

    PubMed

    Murchie, P; Raja, E A; Lee, A J; Brewster, D H; Campbell, N C; Gray, N M; Ritchie, L D; Robertson, R; Samuel, L

    2015-06-01

    This study explored whether longer provider delays (between first presentation and treatment) were associated with later stage and poorer survival in women with symptomatic breast cancer. Data from 850 women with symptomatic breast cancer were linked with the Scottish Cancer Registry; Death Registry; and hospital discharge dataset. Logistic regression and Cox survival analyses with restricted cubic splines explored relationships between provider delays, stage and survival, with sequential adjustment for patient and tumour factors. Although confidence intervals were wide in both adjusted analyses, those with the shortest provider delays had more advanced breast cancer at diagnosis. Beyond approximately 20 weeks, the trend suggests longer delays are associated with more advanced stage, but is not statistically significant. Those with symptomatic breast cancer and the shortest presentation to treatment time (within 4 weeks) had the poorest survival. Longer time to treatment was not significantly associated with worsening mortality. Poor prognosis patients with breast cancer are being triaged for rapid treatment with limited effect on outcome. Prolonged time to treatment does not appear to be strongly associated with poorer outcomes for patients with breast cancer, but the power of this study to assess the effect of very long delays (>25 weeks) was limited. Efforts to reduce waiting times are important from a quality of life perspective, but tumour biology may often be a more important determinant of stage at diagnosis and survival outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Economic benefits of optimizing anchor therapy for rheumatoid arthritis.

    PubMed

    Fautrel, Bruno

    2012-06-01

    The total cost of RA is substantial, particularly in patients with high levels of disability. There are considerable differences in cost between countries, driven in part by differences in the use of biologic therapies. Economic evaluations are needed to assess the extra cost of using these treatments and the benefits obtained, to ensure appropriate allocation of limited health care resources. The BeSt trial, evaluating four treatment strategies, found comparable medium-term efficacy but substantially higher costs with early biologic therapy. A systematic review of such cost-effectiveness analyses concluded that biologic therapy should be used after therapy has failed with less costly alternatives such as synthetic DMARDs and glucocorticoids. Optimizing such relatively low-cost therapy to improve outcomes may delay the need for biologic therapy, thereby saving costs. A simple model has confirmed the value of this approach. The addition of modified-release prednisone 5 mg/day to existing synthetic DMARD therapy in patients with active disease resulted in improvement in DAS-28 to below the threshold level for initiation of reimbursed biologic therapy in 28-34% of patients. On a conservative estimate (i.e. assuming no further benefits beyond the 12 weeks of the study and a 12-week wait-and-see approach to starting biologic therapy), cost savings amounted to nearly € 400 per patient. While treatment decisions should never be based only on cost considerations, prolonging disease control by optimizing the use of non-biologic treatments may bring benefits to patients and also economic benefits by delaying the need for biologic treatments.

  13. Biological effects of the 1997/98 ENSO in Cook Inlet, Alaska

    USGS Publications Warehouse

    Piatt, John F.; Drew, Gary S.; van Pelt, Thomas I.; Abookire, Alisa A.; Nielsen, April; Shultz, Michael T.; Kitaysky, Alexander S.

    1999-01-01

    We have been conducting detailed studies of the biology of seabirds in relation to oceanography and forage fish ecology in lower Cook Inlet, Alaska, since 1995. This fortuitously allowed us to document biological effects of the 1997/98 ENSO in this region. Anomalously warm sea surface temperatures (SSTs) were observed in the Gulf of Alaska (GOA) beginning in June of 1997, but not in Cook Inlet until September, 1997. Warm temperature anomalies at the surface and at depth persisted until May of 1998, when temperatures returned to average in the GOA and Cook Inlet. Thus, temperature anomalies occurred outside the core window of productivity (June–August) for forage fish and seabirds in both 1997 and 1998. Abundance or production of phytoplankton, zooplankton, fish, and seabirds in lower Cook Inlet varied among years, and overall appeared to be depressed in 1998. We observed a few biological anomalies that might be attributed to ENSO effects: (1) a significant die-off of Common Murres occurred in March–May of 1998, (2) murres and Black-legged Kittiwakes were physiologically stressed during the 1998 breeding season, (3) murres failed to reproduce at one colony in 1998, (4) kittiwake breeding success was lower than usual at colonies in 1998, and (5) phenology of breeding was later in 1998 for both murres and kittiwakes. We presume that seabird die-offs, reduced productivity and delayed phenology were linked to a reduction or delay in food availability, but the mechanism by which anomalously warm water temperatures in winter reduce forage fish availability during the summer breeding season for seabirds is not known.

  14. Delayed bet-hedging resilience strategies under environmental fluctuations

    NASA Astrophysics Data System (ADS)

    Ogura, Masaki; Wakaiki, Masashi; Rubin, Harvey; Preciado, Victor M.

    2017-05-01

    Many biological populations, such as bacterial colonies, have developed through evolution a protection mechanism, called bet hedging, to increase their probability of survival under stressful environmental fluctuation. In this context, the concept of preadaptation refers to a common type of bet-hedging protection strategy in which a relatively small number of individuals in a population stochastically switch their phenotypes to a dormant metabolic state in which they increase their probability of survival against potential environmental shocks. Hence, if an environmental shock took place at some point in time, preadapted organisms would be better adapted to survive and proliferate once the shock is over. In many biological populations, the mechanisms of preadaptation and proliferation present delays whose influence in the fitness of the population are not well understood. In this paper, we propose a rigorous mathematical framework to analyze the role of delays in both preadaptation and proliferation mechanisms in the survival of biological populations, with an emphasis on bacterial colonies. Our theoretical framework allows us to analytically quantify the average growth rate of a bet-hedging bacterial colony with stochastically delayed reactions with arbitrary precision. We verify the accuracy of the proposed method by numerical simulations and conclude that the growth rate of a bet-hedging population shows a nontrivial dependency on their preadaptation and proliferation delays. Contrary to the current belief, our results show that faster reactions do not, in general, increase the overall fitness of a biological population.

  15. Effects of precommercial thinning in naturally regenerated loblolly-shortleaf pine stands in the upper west gulf coastal plain: results after two growing seasons

    Treesearch

    James M. Guldin; Michael G. Shelton

    2010-01-01

    The benefits of precommercial thinning in naturally regenerated stands of southern pines have been well documented, but questions remain about how long precommercial thinning can be delayed and still be biologically and economically effective. In 2004, a precommercial thinning demonstration study was installed in naturally regenerated loblolly-shortleaf pine (...

  16. Delayed plumage maturation and delayed reproductive investment in birds.

    PubMed

    Hawkins, Gerard L; Hill, Geoffrey E; Mercadante, Austin

    2012-05-01

    Delayed plumage maturation is the delayed acquisition of a definitive colour and pattern of plumage until after the first potential breeding period in birds. Here we provide a comprehensive overview of the numerous studies of delayed plumage maturation and a revised theoretical framework for understanding the function of delayed plumage maturation in all birds. We first distinguish between hypotheses that delayed plumage maturation is attributable to a moult constraint with no adaptive function and hypotheses that propose that delayed plumage maturation is a component of an adaptive life-history strategy associated with delayed reproductive investment. We then recognize three potential benefits of delayed plumage maturation: crypsis, mimicry and status signaling. Evidence suggests that delayed plumage maturation is not a consequence of developmental constraints and instead represents a strategy to maximize reproductive success in circumstances where young adults cannot effectively compete with older adults for limited resources, particularly breeding opportunities. A multi-factorial explanation that takes into account lifespan and the degree of competition for limited breeding resources and that combines the benefits of an inconspicuous appearance with the benefits of honest signaling of reduced competitiveness provides a general explanation for the function of delayed plumage maturation in most bird species. Delayed plumage maturation should be viewed as a component of alternative reproductive strategies that can include delay in both plumage and sexual development. Such strategies are frequently facultative, with individuals breeding prior to the acquisition of definitive plumages when conditions are favourable. Presumably, the benefits of delayed plumage maturation ultimately enhance lifetime reproductive success, and studying delayed plumage maturation within the context of lifetime reproductive success should be a goal of future studies. © 2011 The Authors. Biological Reviews © 2011 Cambridge Philosophical Society.

  17. Introducing time delay in the evolution of new technology: the case study of nanotechnology

    NASA Astrophysics Data System (ADS)

    Georgalis, Evangelos E.; Aifantis, Elias C.

    2013-12-01

    Starting with Feynman's "There's Plenty of Room at the Bottom" prophetic lecture at Caltech in the 1960s, the term "nanotechnology" was first coined in the scientific literature in the 1980s. This was followed by the unprecedented growth in the corresponding scientific field in 2000 due to the financial incentive provided by President Clinton in the US, followed up by similar efforts in Europe, Japan, China and Russia. Today, nanotechnology has become a driving force for economic development, with applications in all fields of engineering, information technology, transport and energy, as well as biology and medicine. Thus, it is important to forecast its future growth and evolution on the basis of two different criteria: (1) the government and private capital invested in related activities, and (2) the number of scientific publications and popular articles dedicated to this field. This article aims to extract forecasts on the evolution of nanotechnology, using the standard logistic equation that result in familiar sigmoid curves, as well as to explore the effect of time delay on its evolution. Time delay is commonly known from previous biological and ecological models, in which time lag is either already known or can be experimentally measured. In contrast, in the case of a new technology, we must first define the method for determining time delay and then interpret its existence and role. Then we describe the implications that time delay may have on the stability of the sigmoidal behavior of nanotechnology evolution and on the related oscillations that may appear.

  18. Retarded ejaculation in men: an overview of psychological and neurobiological insights.

    PubMed

    Waldinger, Marcel D; Schweitzer, Dave H

    2005-06-01

    Disorders of orgasm and ejaculation are erroneously mixed up in the DSM-IV classification system. Male Orgasmic Disorder to denote "delayed ejaculation" is inadequate as orgasm and ejaculation represent clinical expressions of different neurobiological phenomena. Unfortunately, the DSM-IV criteria for delayed ejaculation were accepted regardless of any research with appropriate methodology and design. The psychological approach and associated psychotherapy to solve this problem is rather disappointing. The neurobiological approach, which started with animal studies, has demonstrated various neurotransmitters with the potency to inhibit ejaculation. Indeed, several experimental drugs have been tested in rats, showing the successful acceleration of ejaculation. We propose that human research should start with the development of an operational definition of delayed ejaculation. To achieve this goal, we propose unselected epidemiological stopwatch studies which also provide information on the prevalence and incidence of delayed ejaculation in men. Currently, no effective and safe drugs are available to accelerate ejaculation time in men. The best way to treat lifelong delayed ejaculation is, thus far, to inform the patients about biological and psychological inhibiting factors which they need to avoid, and to remain critical about unrealistic expectations from psychotherapy. Psychotherapy may be useful in subgroups, particularly in the absence of effective and safe drugs.

  19. Computer-aided design, synthesis and biological assay of p-methylsulfonamido phenylethylamine analogues.

    PubMed

    Liu, H; Ji, M; Jiang, H; Liu, L; Hua, W; Chen, K; Ji, R

    2000-10-02

    Class III antiarrhythmic agents selectively delay the effective refractory period (ERP) and increase the transmembrance action potential duration (APD). Based on our previous studies, a set of 17 methylsulfonamido phenylethylamine analogues were investigated by 3D-QSAR techniques of CoMFA and CoMSIA. The 3D-QSAR models proved a good predictive ability, and could describe the steric, electrostatic and hydrophobic requirements for recognition forces of the receptor site. According to the clues provided by this 3D-QSAR analysis, we designed and synthesized a series of new analogues of methanesulfonamido phenylethylamine (VIa-i). Pharmacological assay indicated that the effective concentrations of delaying the functional refractory period (FRP) 10ms of these new compounds have a good correlation with the 3D-QSAR predicted values. It is remarkable that the maximal percent change of delaying FRP in microM of compound VIc is much higher than that of dofetilide. The results showed that the 3D-QSAR models are reliable.

  20. [Bio-objects and biological methods of space radiation effects evaluation].

    PubMed

    Kaminskaia, E V; Nevzgodina, L V; Platova, N G

    2009-01-01

    The unique conditions of space experiments place austere requirements to bio-objects and biological methods of radiation effects evaluation. The paper discusses suitability of a number of bio-objects varying in stage of evolution and metabolism for space researches aimed to state common patterns of the radiation damage caused by heavy ions (HI), and character of HI-cell interaction. Physical detectors in space experiments of the BIOBLOCK series make it possible to identify bio-objects hit by space HI and to set correlation between HI track topography and biological effect. The paper provides an all-round description of the bio-objects chosen for two BIOBLOCK experiments (population of hydrophyte Wolffia arrhiza (fam. duckweed) and Lactuca sativa seeds) and the method of evaluating effects from single space radiation HI. Direct effects of heavy ions on cells can be determined by the criteria of chromosomal aberrations and delayed morphologic abnormalities. The evaluation results are compared with the data about human blood lymphocytes. Consideration is being given to the procedures of test-objects' treatment and investigation.

  1. Delayed Luminescence and Biophotons from Biological Materials

    NASA Astrophysics Data System (ADS)

    Knoesel, Ernst; Hann, Patrick; Garzon, Maria; Pfeiffer, Erik; Lofland, Samuel

    2008-03-01

    There has recently been increased interest in the field of biophotonics, since it is a non-invasive technique. Many biological systems, such as yeast, bacteria, leaves, seeds, and algae display the unusual phenomenon of a weak, delayed luminescence on the timescale of seconds to minutes after transient illumination. It is also observed that the time decay of the biophotonic emission is not exponential, even after the delay, and that there can be oscillations in intensity with time, which depend on the duration of the illumination. Results from two types of yeast, i.e. bread yeast, and saccharomyces, as well as those from several types of algae are presented. Possible mechanisms for the source of the ultraweak photon emission are discussed.

  2. Mental and physical activities delay cognitive decline in older persons with dementia.

    PubMed

    Cheng, Sheung-Tak; Chow, Pizza K; Song, You-Qiang; Yu, Edwin C S; Chan, Alfred C M; Lee, Tatia M C; Lam, John H M

    2014-01-01

    To examine the effects of cognitive stimulation (mahjong) and physical exercise (tai chi [TC]) on cognitive performance in persons with dementia. Cluster-randomized open-label controlled design. Nursing homes. One hundred ten residents, most of whom were cholinesterase-inhibitor naive. Inclusion criteria were Mini-Mental State Examination (MMSE) = 10-24 and suffering from at least very mild dementia (Clinical Dementia Rating ≥ 0.5). Exclusion criteria were being bedbound, audio/visual impairment, regular activity participation before study, or contraindications for physical or group activities. Homes were randomized into three conditions (mahjong, TC, and simple handicrafts [control]). Activities were conducted three times weekly for 12 weeks. Primary outcome was MMSE. Secondary outcomes were immediate/delayed recall, categorical fluency, and digit span. Various biological risk factors, including apolipoprotein E ε4 allele, were included as covariates. Measures were collected at 0 (baseline), 3 (posttreatment), 6, and 9 months. Intent-to-treat analyses were performed using mixed-effects regression. Mahjong's effect varied by time for MMSE, delayed recall, and forward digit span. TC had similar effects but not for delayed recall. The typical pattern was that control participants deteriorated while mahjong and TC participants maintained their abilities over time, leading to enlarged treatment effects as time progressed. By 9 months, mahjong and TC differed from control by 4.5 points (95% confidence interval: 2.0-6.9; d = 0.48) and 3.7 points (95% confidence interval: 1.4-6.0; d = 0.40), respectively, on MMSE. No treatment effects were observed for immediate recall and backward digit span. Mahjong and TC can preserve functioning or delay decline in certain cognitive domains, even in those with significant cognitive impairment. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Calculation of energy-deposition distributions and microdosimetric estimation of the biological effect of a 9C beam.

    PubMed

    Mancusi, Davide; Sihver, Lembit; Niita, Koji; Li, Qiang; Sato, Tatsuhiko; Iwase, Hiroshi; Iwamoto, Yosuke; Matsuda, Norihiro; Sakamoto, Yukio; Nakashima, Hiroshi

    2009-04-01

    Among the alternative beams being recently considered for external cancer radiotherapy, (9)C has received some attention because it is expected that its biological effectiveness could be boosted by the beta-delayed emission of two alpha particles and a proton that takes place at the ion-stopping site. Experiments have been performed to characterise this exotic beam physically and models have been developed to estimate quantitatively its biological effect. Here, the particle and heavy-ion transport code system ( PHITS ) is used to calculate energy-deposition and linear energy transfer distributions for a (9)C beam in water and the results are compared with published data. Although PHITS fails to reproduce some of the features of the distributions, it suggests that the decay of (9)C contributes negligibly to the energy-deposition distributions, thus contradicting the previous interpretation of the measured data. We have also performed a microdosimetric calculation to estimate the biological effect of the decay, which was found to be negligible; previous microdosimetric Monte-Carlo calculations were found to be incorrect. An analytical argument, of geometrical nature, confirms this conclusion and gives a theoretical upper bound on the additional biological effectiveness of the decay. However, no explanation can be offered at present for the observed difference in the biological effectiveness between (9)C and (12)C; the reproducibility of this surprising result will be verified in coming experiments.

  4. Clinical trials with rasagiline: evidence for short-term and long-term effects.

    PubMed

    Siderowf, Andrew; Stern, Matthew

    2006-05-23

    Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

  5. Time-resolved photoacoustic measurement for evaluation of viscoelastic properties of biological tissues

    NASA Astrophysics Data System (ADS)

    Zhao, Yue; Chen, Conggui; Liu, Hongwei; Yang, Sihua; Xing, Da

    2016-11-01

    In this letter, we proposed a method for viscoelastic characterization of biological tissues based on time-resolved photoacoustic measurement. The theoretical and experimental study was performed on the influence of viscoelasticity effects on photoacoustic generation. Taking the time delay between the photoacoustic signal and the exciting laser, the viscoelasticity distribution of biological tissues can be mapped. To validate our method, gelatin phantoms with different densities were measured. We also applied this method in discrimination between fat and liver to confirm the usefulness of the viscoelastic evaluation. Furthermore, pilot experiments were performed on atherosclerosis artery from an apolipoprotein E-knockout mouse to show the viscoelastic characterization of atherosclerotic plaque. Our results demonstrate that this technique has the potential for visualizing the biomechanical properties and lesions of biological tissues.

  6. Effective protection of biological membranes against photo-oxidative damage: Polymeric antioxidant forming a protecting shield over the membrane.

    PubMed

    Mertins, Omar; Mathews, Patrick D; Gomide, Andreza B; Baptista, Mauricio S; Itri, Rosangela

    2015-10-01

    We have prepared a chitosan polymer modified with gallic acid in order to develop an efficient protection strategy biological membranes against photodamage. Lipid bilayers were challenged with photoinduced damage by photosensitization with methylene blue, which usually causes formation of hydroperoxides, increasing area per lipid, and afterwards allowing leakage of internal materials. The damage was delayed by a solution of gallic acid in a concentration dependent manner, but further suppressed by the polymer at very low concentrations. The membrane of giant unilamellar vesicles was covered with this modified macromolecule leading to a powerful shield against singlet oxygen and thus effectively protecting the lipid membrane from oxidative stress. The results have proven the discovery of a promising strategy for photo protection of biological membranes. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Theoretical foundations for traditional and generalized sensitivity functions for nonlinear delay differential equations.

    PubMed

    Banks, H Thomas; Robbins, Danielle; Sutton, Karyn L

    2013-01-01

    In this paper we present new results for differentiability of delay systems with respect to initial conditions and delays. After motivating our results with a wide range of delay examples arising in biology applications, we further note the need for sensitivity functions (both traditional and generalized sensitivity functions), especially in control and estimation problems. We summarize general existence and uniqueness results before turning to our main results on differentiation with respect to delays, etc. Finally we discuss use of our results in the context of estimation problems.

  8. Time‐of‐flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions

    PubMed Central

    Vanbellingen, Quentin P.; Elie, Nicolas; Eller, Michael J.; Della‐Negra, Serge; Touboul, David

    2015-01-01

    Rationale In Time‐of‐Flight Secondary Ion Mass Spectrometry (TOF‐SIMS), pulsed and focused primary ion beams enable mass spectrometry imaging, a method which is particularly useful to map various small molecules such as lipids at the surface of biological samples. When using TOF‐SIMS instruments, the focusing modes of the primary ion beam delivered by liquid metal ion guns can provide either a mass resolution of several thousand or a sub‐µm lateral resolution, but the combination of both is generally not possible. Methods With a TOF‐SIMS setup, a delayed extraction applied to secondary ions has been studied extensively on rat cerebellum sections in order to compensate for the effect of long primary ion bunches. Results The use of a delayed extraction has been proven to be an efficient solution leading to unique features, i.e. a mass resolution up to 10000 at m/z 385.4 combined with a lateral resolution of about 400 nm. Simulations of ion trajectories confirm the experimental determination of optimal delayed extraction and allow understanding of the behavior of ions as a function of their mass‐to‐charge ratio. Conclusions Although the use of a delayed extraction has been well known for many years and is very popular in MALDI, it is much less used in TOF‐SIMS. Its full characterization now enables secondary ion images to be recorded in a single run with a submicron spatial resolution and with a mass resolution of several thousand. This improvement is very useful when analyzing lipids on tissue sections, or rare, precious, or very small size samples. © 2015 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd. PMID:26395603

  9. Association between delayed bedtime and sleep-related problems among community-dwelling 2-year-old children in Japan.

    PubMed

    Kitamura, Shingo; Enomoto, Minori; Kamei, Yuichi; Inada, Naoko; Moriwaki, Aiko; Kamio, Yoko; Mishima, Kazuo

    2015-03-13

    Although delayed sleep timing causes many socio-psycho-biological problems such as sleep loss, excessive daytime sleepiness, obesity, and impaired daytime neurocognitive performance in adults, there are insufficient data showing the clinical significance of a 'night owl lifestyle' in early life. This study examined the association between habitual delayed bedtime and sleep-related problems among community-dwelling 2-year-old children in Japan. Parents/caregivers of 708 community-dwelling 2-year-old children in Nishitokyo City, Tokyo, participated in the study. The participants answered a questionnaire to evaluate their child's sleep habits and sleep-related problems for the past 1 month. Of the 425 children for whom complete data were collected, 90 (21.2%) went to bed at 22:00 or later. Children with delayed bedtime showed significantly more irregular bedtime, delayed wake time, shorter total sleep time, and difficulty in initiating and terminating sleep. Although this relationship indicated the presence of sleep debt in children with delayed bedtime, sleep onset latency did not differ between children with earlier bedtime and those with delayed bedtime. Rather, delayed bedtime was significantly associated with bedtime resistance and problems in the morning even when adjusting for nighttime and daytime sleep time. Even in 2-year-old children, delayed bedtime was associated with various sleep-related problems. The causal factors may include diminished homeostatic sleep drive due to prolonged daytime nap as well as diurnal preference (morning or night type) regulated by the biological clock.

  10. Persistent Memory in Single Node Delay-Coupled Reservoir Computing.

    PubMed

    Kovac, André David; Koall, Maximilian; Pipa, Gordon; Toutounji, Hazem

    2016-01-01

    Delays are ubiquitous in biological systems, ranging from genetic regulatory networks and synaptic conductances, to predator/pray population interactions. The evidence is mounting, not only to the presence of delays as physical constraints in signal propagation speed, but also to their functional role in providing dynamical diversity to the systems that comprise them. The latter observation in biological systems inspired the recent development of a computational architecture that harnesses this dynamical diversity, by delay-coupling a single nonlinear element to itself. This architecture is a particular realization of Reservoir Computing, where stimuli are injected into the system in time rather than in space as is the case with classical recurrent neural network realizations. This architecture also exhibits an internal memory which fades in time, an important prerequisite to the functioning of any reservoir computing device. However, fading memory is also a limitation to any computation that requires persistent storage. In order to overcome this limitation, the current work introduces an extended version to the single node Delay-Coupled Reservoir, that is based on trained linear feedback. We show by numerical simulations that adding task-specific linear feedback to the single node Delay-Coupled Reservoir extends the class of solvable tasks to those that require nonfading memory. We demonstrate, through several case studies, the ability of the extended system to carry out complex nonlinear computations that depend on past information, whereas the computational power of the system with fading memory alone quickly deteriorates. Our findings provide the theoretical basis for future physical realizations of a biologically-inspired ultrafast computing device with extended functionality.

  11. Persistent Memory in Single Node Delay-Coupled Reservoir Computing

    PubMed Central

    Pipa, Gordon; Toutounji, Hazem

    2016-01-01

    Delays are ubiquitous in biological systems, ranging from genetic regulatory networks and synaptic conductances, to predator/pray population interactions. The evidence is mounting, not only to the presence of delays as physical constraints in signal propagation speed, but also to their functional role in providing dynamical diversity to the systems that comprise them. The latter observation in biological systems inspired the recent development of a computational architecture that harnesses this dynamical diversity, by delay-coupling a single nonlinear element to itself. This architecture is a particular realization of Reservoir Computing, where stimuli are injected into the system in time rather than in space as is the case with classical recurrent neural network realizations. This architecture also exhibits an internal memory which fades in time, an important prerequisite to the functioning of any reservoir computing device. However, fading memory is also a limitation to any computation that requires persistent storage. In order to overcome this limitation, the current work introduces an extended version to the single node Delay-Coupled Reservoir, that is based on trained linear feedback. We show by numerical simulations that adding task-specific linear feedback to the single node Delay-Coupled Reservoir extends the class of solvable tasks to those that require nonfading memory. We demonstrate, through several case studies, the ability of the extended system to carry out complex nonlinear computations that depend on past information, whereas the computational power of the system with fading memory alone quickly deteriorates. Our findings provide the theoretical basis for future physical realizations of a biologically-inspired ultrafast computing device with extended functionality. PMID:27783690

  12. Comparative analysis of biological effect of corannulene and graphene on developmental and sleep/wake profile of zebrafish larvae.

    PubMed

    Li, Xiang; Zhang, Yuan; Li, Xu; Feng, DaoFu; Zhang, ShuHui; Zhao, Xin; Chen, DongYan; Zhang, ZhiXiang; Feng, XiZeng

    2017-06-01

    Little is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. In this study, we compared the effect of corannulene (non-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviors of larval zebrafish. First, the toxicity of graded doses of corannulene (1, 10, and 50μg/mL) was tested in developing zebrafish embryos. Corannulene showed minimal developmental toxicity only induced an epiboly delay. Further, a significant decrease in locomotion/increase in sleep was observed in larvae treated with the highest dose (50μg/mL) of corannulene while no significant locomotion alterations were induced by graphene. Finally, the effect of corannulene or graphene on the hypocretin (hcrt) system and sleep/wake regulators such as hcrt, hcrt G-protein coupled receptor (hcrtr), and arylalkylamine N-acetyltransferase-2 (aanat2) was evaluated. Corannulene increased sleep and reduced locomotor activity and the expression of hcrt and hcrtr mRNA while graphene did not obviously disturb the sleep behavior and gene expression patterns. These results suggest that the corannulene has the potential to cause hypnosis-like behavior in larvae and provides a fundamental comparative understanding of the effects of corannulene and graphene on biology systems. Little is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. Here, we compare the effect of corannulene (no-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviors of larval zebrafish. And we aim to investigate the effect of curvature on biological system. First, toxicity of corannulene over the range of doses (1μg/mL, 10μg/mL and 50μg/mL) was tested in developing zebrafish embryos. Corannulene has minimal developmental toxicity, only incurred epiboly delay. Subsequently, a significant decrease in locomotion/increase in sleep at the highest dose (50μg/mL) was detected in corannulene treated larvae while no significant locomotion alterations was induced by graphene. Finally, the impact of corannulene or graphene on hypocretin system and sleep/wake regulator such as hcrt, hcrtr and aanat2 was evaluated. Corannulene increased sleep, reduced locomotor activity and the expression of hcrt and hcrtr mRNA while graphene did not obviously disturb the sleep behaviors and gene expression patterns. This result may indicate the potential effect of corannulene to cause hypnosia-like behavior in larvae and provide the fundamental understanding for the biological effect of curvature on biology system. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Good things come to those who wait: attenuated discounting of delayed rewards in aged Fischer 344 rats

    PubMed Central

    Simon, Nicholas W.; LaSarge, Candi L.; Montgomery, Karienn S.; Williams, Matthew T.; Mendez, Ian A.; Setlow, Barry; Bizon, Jennifer

    2010-01-01

    The ability to make advantageous choices among outcomes that differ in magnitude, probability, and delay until their arrival is critical for optimal survival and well-being across the lifespan. Aged individuals are often characterized as less impulsive in their choices than their young adult counterparts, demonstrating an increased ability to forgo immediate in favor of delayed (and often more beneficial) rewards. Such “wisdom” is usually characterized as a consequence of learning and life experience. However, aging is also associated with prefrontal cortical dysfunction and concomitant impairments in advantageous choice behavior. Animal models afford the opportunity to isolate the effects of biological aging on decision making from experiential factors. To model one critical component of decision making, young adult and aged Fischer 344 rats were trained on a two-choice delay discounting task in which one choice provided immediate delivery of a small reward and the other provided a large reward delivered after a variable delay period. Whereas young adult rats showed a characteristic pattern of choice behavior (choosing the large reward at short delays and shifting preference to the small reward as delays increased), aged rats maintained a preference for the large reward at all delays (i.e. – attenuated “discounting” of delayed rewards). This increased preference for the large reward in aged rats was not due to perceptual, motor, or motivational factors. The data strongly suggest that, independent of life experience, there are underlying neurobiological factors that contribute to age-related changes in decision making, and particularly the ability to delay gratification. PMID:18657883

  14. Does infrared or ultraviolet light damage the lens?

    PubMed Central

    Söderberg, P G; Talebizadeh, N; Yu, Z; Galichanin, K

    2016-01-01

    In daylight, the human eye is exposed to long wavelength ultraviolet radiation (UVR), visible radiation and short wavelength infrared radiation (IRR). Almost all the UVR and a fraction of the IRR waveband, respectively, left over after attenuation in the cornea, is absorbed in the lens. The time delay between exposure and onset of biological response in the lens varies from immediate-to-short-to-late. After exposure to sunlight or artificial sources, generating irradiances of the same order of magnitude or slightly higher, biological damage may occur photochemically or thermally. Epidemiological studies suggest a dose-dependent association between short wavelength UVR and cortical cataract. Experimental data infer that repeated daily in vivo exposures to short wavelength UVR generate photochemically induced damage in the lens, and that short delay onset cataract after UVR exposure is photochemically induced. Epidemiology suggests that daily high-intensity short wavelength IRR exposure of workers, is associated with a higher prevalence of age-related cataract. It cannot be excluded that this effect is owing to a thermally induced higher denaturation rate. Recent experimental data rule out a photochemical effect of 1090 nm in the lens but other wavelengths in the near IRR should be investigated. PMID:26768915

  15. Predator interference effects on biological control: The "paradox" of the generalist predator revisited

    NASA Astrophysics Data System (ADS)

    Parshad, Rana D.; Bhowmick, Suman; Quansah, Emmanuel; Basheer, Aladeen; Upadhyay, Ranjit Kumar

    2016-10-01

    An interesting conundrum in biological control questions the efficiency of generalist predators as biological control agents. Theory suggests, generalist predators are poor agents for biological control, primarily due to mutual interference. However field evidence shows they are actually quite effective in regulating pest densities. In this work we provide a plausible answer to this paradox. We analyze a three species model, where a generalist top predator is introduced into an ecosystem as a biological control, to check the population of a middle predator, that in turn is depredating on a prey species. We show that the inclusion of predator interference alone, can cause the solution of the top predator equation to blow-up in finite time, while there is global existence in the no interference case. This result shows that interference could actually cause a population explosion of the top predator, enabling it to control the target species, thus corroborating recent field evidence. Our results might also partially explain the population explosion of certain species, introduced originally for biological control purposes, such as the cane toad (Bufo marinus) in Australia, which now functions as a generalist top predator. We also show both Turing instability and spatio-temporal chaos in the model. Lastly we investigate time delay effects.

  16. Mitochondrial pharmacology: electron transport chain bypass as strategies to treat mitochondrial dysfunction.

    PubMed

    Atamna, Hani; Mackey, Jeanette; Dhahbi, Joseph M

    2012-01-01

    Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential (-0.1 V; 0.1 V) improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. This is different from redox agents with strong negative (-0.4 V; -0.2 V) or positive (0.2 V; 0.4 V) redox potentials who alter the redox status of redox-centers (i.e., become permanently reduced or oxidized). This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB, redox potential ≅10 mV) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  17. In Vitro Studies on Space Radiation-Induced Delayed Genetic Responses: Shielding Effects

    NASA Technical Reports Server (NTRS)

    Kadhim, Munira A.; Green, Lora M.; Gridley, Daila S.; Murray, Deborah K.; Tran, Da Thao; Andres, Melba; Pocock, Debbie; Macdonald, Denise; Goodhead, Dudley T.; Moyers, Michael F.

    2003-01-01

    Understanding the radiation risks involved in spaceflight is of considerable importance, especially with the long-term occupation of ISS and the planned crewed exploration missions. Several independent causes may contribute to the overall risk to astronauts exposed to the complex space environment, such as exposure to GCR as well as SPES. Protons and high-Z energetic particles comprise the GCR spectrum and may exert considerable biological effects even at low fluence. There are also considerable uncertainties associated with secondary particle effects (e.g. HZE fragments, neutrons etc.). The interaction of protons and high-LET particles with biological materials at all levels of biological organization needs to be investigated fully in order to establish a scientific basis for risk assessment. The results of these types of investigation will foster the development of appropriately directed countermeasures. In this study, we compared the biological responses to proton irradiation presented to the target cells as a monoenergetic beam of particles of complex composition delivered to cells outside or inside a tissue phantom head placed in the United States EVA space suit helmet. Measurements of chromosome aberrations, apoptosis, and the induction of key proteins were made in bone marrow from CBA/CaJ and C57BL/6 mice at early and late times post exposure to radiation at 0, 0.5, 1 and 2 Gy while inside or outside of the helmet. The data showed that proton irradiation induced transmissible chromosomal/genomic instability in haematopoietic stem cells in both strains of mice under both irradiation conditions and especially at low doses. Although differences were noted between the mouse strains in the degree and kinetics of transforming growth factor-beta 1 and tumor necrosis factor-alpha secretion, there were no significant differences observed in the level of the induced instability under either radiation condition, or for both strains of mice. Consequently, when normalized to physical dose, the monoenergetic proton field present inside the helmet-protected phantom produced equivalent biological responses, when compared to unshielded cells, as measured by the induction of delayed genetic effects in murine haematopoietic stem cells.

  18. TOXIC ACTIVITY AND DELAYED EFFECTS OF FIVE BOTANICAL OILS ON THE FOLLOWING GENERATIONS OF AGROTIS IPSILON (HUFNAGEL) (INSECTA: LEPIDOPTERA: NOCTUIDAE) AFTER PARENTS TREATMENT.

    PubMed

    Mesbah, H A; El-Sayed, N A; El-Kady, M B; Mourad, A K; Kordy, A M; Henaidy, Z M

    2014-01-01

    The present study is carried out to evaluate the toxic efficiency and delayed effects of five botanical oils on the greasy cut worm Agrotis ipsilon (Lepidoptera: Noctuidae), as a trial for the attainment of a possible use of an alternative safe and effective phytochemicals against the insect-pest. So as to minimize or prevent the repeated usage of conventional insecticides, then reduce the environmental pollution as well as the occurring hazards to man and domestic animal due to the use of the pesticides alone. Four tested concentrations (0.5, 1.0, 1.5 and 2.5% v/v) from each of camphor, red basil, menthol, rose and anise oils, were bioassayed by treating the offered castor oil bean leaves, to the 4th instar larvae along 48h, under the laboratory higrothermic conditions of 25±2 °C and 65±5% R.H. The obtained results showed that the five tested oils were found to have more or less toxic activity and drastic effects on the inspected parameters of fitness components of the treated parent generation of the insect, in particular, pupae, emerged adult moths and laid eggs/female. In this respect camphor and red basil oils were highly effective, followed by menthol oil, anise oil and the least effective one was rose oil. Moreover, the assessed unprofitable delayed effects on the going on of the biological performance within the treated insects showed the adverse effects on the fitness components of the consequent generations (fs) post (p) one treatment with each of the bioassyed oils. The prevalence of adverse effects and disturbance in the going on biological performance through the period of (p) generation; which is followed by the distinct failure of insect development in (f1) generation were recorded for each of the tested menthol oil at 0.5 and 1.5% (v/v); camphor oil at 1.5 and 2.5% and red basil oil at 2.5% (v/v). While anise and rose oils were somewhat less efficient causing the distinct failure of the following generations up to the 3rd and/or the 6th ones. That observed distinct failure of the insect development could be attributed to the rapid or/and slow cumulative effect of the induced recessive lethal genes in both influenced sexes along the interval of the following developed generations (fs) after (p) one treatment, causing apparent adverse disturbance of the normal biological performance, which finally appears at the beginning of the failed generation.

  19. Temporal discounting and heart rate reactivity to stress.

    PubMed

    Diller, James W; Patros, Connor H G; Prentice, Paula R

    2011-07-01

    Temporal discounting is the reduction of the value of a reinforcer as a function of increasing delay to its presentation. Impulsive individuals discount delayed consequences more rapidly than self-controlled individuals, and impulsivity has been related to substance abuse, gambling, and other problem behaviors. A growing body of literature has identified biological correlates of impulsivity, though little research to date has examined relations between delay discounting and markers of poor health (e.g., cardiovascular reactivity to stress). We evaluated the relation between one aspect of impulsivity, measured using a computerized temporal discounting task, and heart rate reactivity, measured as a change in heart rate from rest during a serial subtraction task. A linear regression showed that individuals who were more reactive to stress responded more impulsively (i.e., discounted delayed reinforcers more rapidly). When results were stratified by gender, the effect was observed for females, but not for males. This finding supports previous research on gender differences in cardiovascular reactivity and suggests that this type of reactivity may be an important correlate of impulsive behavior. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. A biologically inspired approach to modeling unmanned vehicle teams

    NASA Astrophysics Data System (ADS)

    Cortesi, Roger S.; Galloway, Kevin S.; Justh, Eric W.

    2008-04-01

    Cooperative motion control of teams of agile unmanned vehicles presents modeling challenges at several levels. The "microscopic equations" describing individual vehicle dynamics and their interaction with the environment may be known fairly precisely, but are generally too complicated to yield qualitative insights at the level of multi-vehicle trajectory coordination. Interacting particle models are suitable for coordinating trajectories, but require care to ensure that individual vehicles are not driven in a "costly" manner. From the point of view of the cooperative motion controller, the individual vehicle autopilots serve to "shape" the microscopic equations, and we have been exploring the interplay between autopilots and cooperative motion controllers using a multivehicle hardware-in-the-loop simulator. Specifically, we seek refinements to interacting particle models in order to better describe observed behavior, without sacrificing qualitative understanding. A recent analogous example from biology involves introducing a fixed delay into a curvature-control-based feedback law for prey capture by an echolocating bat. This delay captures both neural processing time and the flight-dynamic response of the bat as it uses sensor-driven feedback. We propose a comparable approach for unmanned vehicle modeling; however, in contrast to the bat, with unmanned vehicles we have an additional freedom to modify the autopilot. Simulation results demonstrate the effectiveness of this biologically guided modeling approach.

  1. Analytical approximate solutions for a general class of nonlinear delay differential equations.

    PubMed

    Căruntu, Bogdan; Bota, Constantin

    2014-01-01

    We use the polynomial least squares method (PLSM), which allows us to compute analytical approximate polynomial solutions for a very general class of strongly nonlinear delay differential equations. The method is tested by computing approximate solutions for several applications including the pantograph equations and a nonlinear time-delay model from biology. The accuracy of the method is illustrated by a comparison with approximate solutions previously computed using other methods.

  2. Time-Delayed Two-Step Selective Laser Photodamage of Dye-Biomolecule Complexes

    NASA Astrophysics Data System (ADS)

    Andreoni, A.; Cubeddu, R.; de Silvestri, S.; Laporta, P.; Svelto, O.

    1980-08-01

    A scheme is proposed for laser-selective photodamage of biological molecules, based on time-delayed two-step photoionization of a dye molecule bound to the biomolecule. The validity of the scheme is experimentally demonstrated in the case of the dye Proflavine, bound to synthetic polynucleotides.

  3. Microscopic time-resolved imaging of singlet oxygen by delayed fluorescence in living cells.

    PubMed

    Scholz, Marek; Dědic, Roman; Hála, Jan

    2017-11-08

    Singlet oxygen is a highly reactive species which is involved in a number of processes, including photodynamic therapy of cancer. Its very weak near-infrared emission makes imaging of singlet oxygen in biological systems a long-term challenge. We address this challenge by introducing Singlet Oxygen Feedback Delayed Fluorescence (SOFDF) as a novel modality for semi-direct microscopic time-resolved wide-field imaging of singlet oxygen in biological systems. SOFDF has been investigated in individual fibroblast cells incubated with a well-known photosensitizer aluminium phthalocyanine tetrasulfonate. The SOFDF emission from the cells is several orders of magnitude stronger and much more readily detectable than the very weak near-infrared phosphorescence of singlet oxygen. Moreover, the analysis of SOFDF kinetics enables us to estimate the lifetimes of the involved excited states. Real-time SOFDF images with micrometer spatial resolution and submicrosecond temporal-resolution have been recorded. Interestingly, a steep decrease in the SOFDF intensity after the photodynamically induced release of a photosensitizer from lysosomes has been demonstrated. This effect could be potentially employed as a valuable diagnostic tool for monitoring and dosimetry in photodynamic therapy.

  4. Intrinsic modulation of pulse-coupled integrate-and-fire neurons

    NASA Astrophysics Data System (ADS)

    Coombes, S.; Lord, G. J.

    1997-11-01

    Intrinsic neuromodulation is observed in sensory and neuromuscular circuits and in biological central pattern generators. We model a simple neuronal circuit with a system of two pulse-coupled integrate-and-fire neurons and explore the parameter regimes for periodic firing behavior. The inclusion of biologically realistic features shows that the speed and onset of neuronal response plays a crucial role in determining the firing phase for periodic rhythms. We explore the neurophysiological function of distributed delays arising from both the synaptic transmission process and dendritic structure as well as discrete delays associated with axonal communication delays. Bifurcation and stability diagrams are constructed with a mixture of simple analysis, numerical continuation and the Kuramoto phase-reduction technique. Moreover, we show that, for asynchronous behavior, the strength of electrical synapses can control the firing rate of the system.

  5. Robust optimization for nonlinear time-delay dynamical system of dha regulon with cost sensitivity constraint in batch culture

    NASA Astrophysics Data System (ADS)

    Yuan, Jinlong; Zhang, Xu; Liu, Chongyang; Chang, Liang; Xie, Jun; Feng, Enmin; Yin, Hongchao; Xiu, Zhilong

    2016-09-01

    Time-delay dynamical systems, which depend on both the current state of the system and the state at delayed times, have been an active area of research in many real-world applications. In this paper, we consider a nonlinear time-delay dynamical system of dha-regulonwith unknown time-delays in batch culture of glycerol bioconversion to 1,3-propanediol induced by Klebsiella pneumonia. Some important properties and strong positive invariance are discussed. Because of the difficulty in accurately measuring the concentrations of intracellular substances and the absence of equilibrium points for the time-delay system, a quantitative biological robustness for the concentrations of intracellular substances is defined by penalizing a weighted sum of the expectation and variance of the relative deviation between system outputs before and after the time-delays are perturbed. Our goal is to determine optimal values of the time-delays. To this end, we formulate an optimization problem in which the time delays are decision variables and the cost function is to minimize the biological robustness. This optimization problem is subject to the time-delay system, parameter constraints, continuous state inequality constraints for ensuring that the concentrations of extracellular and intracellular substances lie within specified limits, a quality constraint to reflect operational requirements and a cost sensitivity constraint for ensuring that an acceptable level of the system performance is achieved. It is approximated as a sequence of nonlinear programming sub-problems through the application of constraint transcription and local smoothing approximation techniques. Due to the highly complex nature of this optimization problem, the computational cost is high. Thus, a parallel algorithm is proposed to solve these nonlinear programming sub-problems based on the filled function method. Finally, it is observed that the obtained optimal estimates for the time-delays are highly satisfactory via numerical simulations.

  6. Genetic basis of delay discounting in frequent gamblers: examination of a priori candidates and exploration of a panel of dopamine-related loci

    PubMed Central

    Gray, Joshua C; MacKillop, James

    2014-01-01

    Introduction Delay discounting is a behavioral economic index of impulsivity that reflects preferences for small immediate rewards relative to larger delayed rewards. It has been consistently linked to pathological gambling and other forms of addictive behavior, and has been proposed to be a behavioral characteristic that may link genetic variation and risk of developing addictive disorders (i.e., an endophenotype). Studies to date have revealed significant associations with polymorphisms associated with dopamine neurotransmission. The current study examined associations between delay discounting and both previously linked variants and a novel panel of dopamine-related variants in a sample of frequent gamblers. Methods Participants were 175 weekly gamblers of European ancestry who completed the Monetary Choice Questionnaire to assess delay discounting preferences and provided a DNA via saliva. Results In a priori tests, two loci previously associated with delayed reward discounting (rs1800497 and rs4680) were not replicated, however, the long form of DRD4 VNTR was significantly associated with lower discounting of delayed rewards. Exploratory analysis of the dopamine-related panel revealed 11 additional significant associations in genes associated with dopamine synthesis, breakdown, reuptake, and receptor function (DRD3, SLC6A3, DDC, DBH, and SLC18A2). An aggregate genetic risk score from the nominally significant loci accounted for 17% of the variance in discounting. Mediational analyses largely supported the presence of indirect effects between the associated loci, delay discounting, and pathological gambling severity. Conclusions These findings do not replicate previously reported associations but identify several novel candidates and provide preliminary support for a systems biology approach to understand the genetic basis of delay discounting. PMID:25365808

  7. Stability switches, Hopf bifurcation and chaos of a neuron model with delay-dependent parameters

    NASA Astrophysics Data System (ADS)

    Xu, X.; Hu, H. Y.; Wang, H. L.

    2006-05-01

    It is very common that neural network systems usually involve time delays since the transmission of information between neurons is not instantaneous. Because memory intensity of the biological neuron usually depends on time history, some of the parameters may be delay dependent. Yet, little attention has been paid to the dynamics of such systems. In this Letter, a detailed analysis on the stability switches, Hopf bifurcation and chaos of a neuron model with delay-dependent parameters is given. Moreover, the direction and the stability of the bifurcating periodic solutions are obtained by the normal form theory and the center manifold theorem. It shows that the dynamics of the neuron model with delay-dependent parameters is quite different from that of systems with delay-independent parameters only.

  8. Oral magnetite nanoparticles disturb the development of Drosophila melanogaster from oogenesis to adult emergence.

    PubMed

    Chen, Hanqing; Wang, Bing; Feng, Weiyue; Du, Wei; Ouyang, Hong; Chai, Zhifang; Bi, Xiaolin

    2015-05-01

    The potential impacts of nanomaterials (NMs) on fetal development have attracted great concerns because of the increased potential exposure to NMs during pregnancy. Drosophila melanogaster oogenesis and developmental transitions may provide an attractive system to study the biological and environmental effects of NMs on the embryonic development. In this study, the effects of three types of magnetite (Fe3O4) nanoparticles (MNPs): UN-MNPs (pristine), CA-MNPs (citric acid modified) and APTS-MNPs (3-aminopropyltriethoxylsilane coated) on the development of Drosophila at 300 and 600 μg/g dosage were studied. The uptake of MNPs by female and male flies caused obvious reduction in the female fecundity, and the developmental delay at the egg-pupae and pupae-adult transitions, especially in those treated by the positive APTS-MNPs. Further investigation demonstrates that the parental uptake of MNPs disturbs the oogenesis period, induces ovarian defect, reduces the length of eggs, decreases the number of nurse cells and delays egg chamber development, which may contribute to the decrease of fecundity of female Drosophila and the development delay of their offspring. Using the synchrotron radiation-based micro-X-ray fluorescence (SR-μXRF), the dyshomeostasis of trace elements such as Fe, Ca and Cu along the anterior-posterior axis of the fertilized eggs was found, which may be an important reason for the development delay of Drosophila.

  9. Utilizing a Rat Delayed Implantation Model to Teach Integrative Endocrinology and Reproductive Biology

    ERIC Educational Resources Information Center

    Geisert, Rodney D.; Smith, Michael F.; Schmelzle, Amanda L.; Green, Jonathan A.

    2018-01-01

    In this teaching laboratory, the students are directed in an exercise that involves designing and performing an experiment to determine estrogen's role in regulating delayed implantation (diapause) in female rats. To encourage active participation by the students, a discussion question is provided before the laboratory exercise in which each…

  10. EVALUATION OF FERTILIZATION FOLLOWING OVULATORY DELAY WITH THIRAM IN THE LONG-EVANS HOODED RAT

    EPA Science Inventory

    Evaluation of fertilization following ovulatory delay with thiram in the Long-Evans Hooded Rat

    1TE Stoker, 1* S Jeffay, and 1 SD Perreault.

    1Gamete and Early Embryogenesis Biology Branch and 2 Endocrinology Branch, Reproductive Toxicology Division, NHEERL, US EPA, R...

  11. Women's Health and Mindfulness (WHAM): A Randomized Intervention Among Older Lesbian/Bisexual Women.

    PubMed

    Ingraham, Natalie; Harbatkin, Dawn; Lorvick, Jennifer; Plumb, Marj; Minnis, Alexandra M

    2017-05-01

    Lesbian and bisexual (LB) women have higher body weight than heterosexual women. Interventions focused on health and well-being versus weight loss may be more likely to succeed among LB women. This article describes effects of Women's Health and Mindfulness, a 12-week pilot intervention addressing mindfulness, healthy eating, and physical activity, on outcomes associated with chronic disease risk among overweight and obese LB women older than 40 years. Eighty women were randomized, using a stepped-wedge design, to either an immediate- or a delayed-start intervention group; the delayed-start group served as the control. Eligible participants were aged 40 years or older, identified as LB, and had a body mass index of 27 or greater. We compared differences in biological markers of chronic disease, mindfulness, nutrition, and physical activity between immediate- and delayed-start intervention groups. We observed clinically significant improvements in low-density lipoprotein cholesterol but no change in hemoglobin A1c. We found evidence of intervention effects on improved mindfulness and mindful eating scores and on nutrition (improved vegetable intake). The Women's Health and Mindfulness pilot intervention appears to have initiated positive behavioral and physical health changes in this population. Refinements to the intervention model, such as extended intervention duration, and longer term follow-up are warranted to determine sustained effects.

  12. Butyrate Infusions in the Ovine Fetus Delay the Biologic Clock for Globin Gene Switching

    NASA Astrophysics Data System (ADS)

    Perrine, Susan P.; Rudolph, Abraham; Faller, Douglas V.; Roman, Christine; Cohen, Ruth A.; Chen, Shao-Jing; Kan, Yuet Wai

    1988-11-01

    The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus. Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal β -globin genes. Butyric acid, which is found in increased plasma concentrations in infants of diabetic mothers who have delayed globin gene switching, was infused into catheterized fetal lambs in utero during the time of the normal globin gene switch period. The globin gene switch was significantly delayed in three of four butyrate-treated fetuses compared with controls and was entirely prevented in one fetus in whom the infusion was begun before the globin switch was under way. These data provide a model for investigating and arresting the biologic clock of hemoglobin switching.

  13. [Environmental and biological determinants of neuropsychomotor development in a sample of children in Canoas/RS].

    PubMed

    Pilz, Elsa Maria Luz; Schermann, Lígia Braun

    2007-01-01

    The object of this study is to determine the prevalence of potential delays in neuropsychomotor development and their possible association with, on one hand, environmental and biological factors, and maternal competence on the other, in a sample of children up to six years old living in Canoas, in Rio Grande do Sul state. A questionnaire was submitted to mothers including questions on social, economic and reproduction factors; child's conditions at birth; child's pathologies; family structure; child care and elements on maternal competence. The potential for neuropsychomotor development delay was assessed by the Denver II Test. Forty clusters were visited in Canoas, a city in Rio Grande do Sul state, in accordance with the cluster probabilistic sampling process. From 197 children assessed by this analytical cross-section study, there was a 27% (n=53) prevalence of potential delay in neuropsychomotor development. The multivariate analysis showed that factors associated with potential development delays were: low income (or = 9,3); mothers with less than 18-month intervals between pregnancies (or=3,9) ; and lack of support from child's father (or=7,0). These results support the importance of implementing income generating programs, health education, and family planning in order to prevent child development delays.

  14. Effects of outside air temperature on the preparation of antineoplastic drug solutions in biological safety cabinets.

    PubMed

    Umemura, Masayuki; Itoh, Akio; Ando, Yuichi; Yamada, Kiyofumi; Wakiya, Yoshifumi; Nabeshima, Toshitaka

    2015-08-01

    In Japan, biological safety cabinets are commonly used by medical staff to prepare antineoplastic agents. At the Division of Chemotherapy for Outpatients, Nagoya University Hospital, a class II B2 biological safety cabinet is used. The temperature inside this biological safety cabinet decreases in winter. In this study, we investigated the effect of low outside air temperature on the biological safety cabinet temperature, time required to admix antineoplastic agents, and accuracy of epirubicin weight measurement. Studies were conducted from 1 January to 31 March 2008 (winter). The outside air temperature near the biological safety cabinet intake nozzle was compared with the biological safety cabinet temperature. The correlation between the outside air temperature and the biological safety cabinet temperature, time for cyclophosphamide and gemcitabine solubilization, and accuracy of epirubicin weight measurement were investigated at low and high biological safety cabinet temperatures. The biological safety cabinet temperature correlated with the outside air temperature of 5-20℃ (p < 0.0001). Compared to cyclophosphamide and gemcitabine solubilization in the biological safety cabinet at 25℃, solubilization at 10℃ was significantly delayed (p < 0.01 and p < 0.0001, respectively). Measurement of epirubicin weight by using a syringe lacked accuracy because of epirubicin's high viscosity at low temperatures (p < 0.01). These results suggest that the biological safety cabinet temperature decreases when cool winter air is drawn into the biological safety cabinet, affecting the solubilization of antineoplastic agents. We suggest that a decrease in biological safety cabinet temperature may increase the time required to admix antineoplastic agents, thereby increasing the time for which outpatients must wait for chemotherapy. © The Author(s) 2014.

  15. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

    NASA Technical Reports Server (NTRS)

    Zeitzer, J. M.; Dijk, D. J.; Kronauer, R.; Brown, E.; Czeisler, C.

    2000-01-01

    Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

  16. Human evolution, life history theory, and the end of biological reproduction.

    PubMed

    Last, Cadell

    2014-01-01

    Throughout primate history there have been three major life history transitions towards increasingly delayed sexual maturation and biological reproduction, as well as towards extended life expectancy. Monkeys reproduce later and live longer than do prosimians, apes reproduce later and live longer than do monkeys, and humans reproduce later and live longer than do apes. These life history transitions are connected to increased encephalization. During the last life history transition from apes to humans, increased encephalization co-evolved with increased dependence on cultural knowledge for energy acquisition. This led to a dramatic pressure for more energy investment in growth over current biological reproduction. Since the industrial revolution socioeconomic development has led to even more energy being devoted to growth over current biological reproduction. I propose that this is the beginning of an ongoing fourth major primate life history transition towards completely delayed biological reproduction and an extension of the evolved human life expectancy. I argue that the only fundamental difference between this primate life history transition and previous life history transitions is that this transition is being driven solely by cultural evolution, which may suggest some deeper evolutionary transition away from biological evolution is already in the process of occurring.

  17. Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study.

    PubMed

    Gross, Wibke; Linden, Ulrike; Ostermann, Thomas

    2010-07-21

    Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for children with delayed speech development. Further studies should be conducted to investigate the mechanisms of these interactions in greater depth. The trial is registered in the German clinical trials register; Trial-No.: DRKS00000343.

  18. Rapid Long-Range Disynaptic Inhibition Explains the Formation of Cortical Orientation Maps

    PubMed Central

    Antolík, Ján

    2017-01-01

    Competitive interactions are believed to underlie many types of cortical processing, ranging from memory formation, attention and development of cortical functional organization (e.g., development of orientation maps in primary visual cortex). In the latter case, the competitive interactions happen along the cortical surface, with local populations of neurons reinforcing each other, while competing with those displaced more distally. This specific configuration of lateral interactions is however in stark contrast with the known properties of the anatomical substrate, i.e., excitatory connections (mediating reinforcement) having longer reach than inhibitory ones (mediating competition). No satisfactory biologically plausible resolution of this conflict between anatomical measures, and assumed cortical function has been proposed. Recently a specific pattern of delays between different types of neurons in cat cortex has been discovered, where direct mono-synaptic excitation has approximately the same delay, as the combined delays of the disynaptic inhibitory interactions between excitatory neurons (i.e., the sum of delays from excitatory to inhibitory and from inhibitory to excitatory neurons). Here we show that this specific pattern of delays represents a biologically plausible explanation for how short-range inhibition can support competitive interactions that underlie the development of orientation maps in primary visual cortex. We demonstrate this statement analytically under simplifying conditions, and subsequently show using network simulations that development of orientation maps is preserved when long-range excitation, direct inhibitory to inhibitory interactions, and moderate inequality in the delays between excitatory and inhibitory pathways is added. PMID:28408869

  19. Theoretical substantiation of biological efficacy enhancement for β-delayed particle decay {sup 9}C beam: A Monte Carlo study in combination with analysis with the local effect model approach

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

    Tian, Liheng; Yan, Yuanlin; Ma, Yuanyuan

    Purpose: To improve the efficacy of heavy ion therapy, β-delayed particle decay {sup 9}C beam as a double irradiation source for cancer therapy has been proposed. The authors’ previous experiment showed that relative biological effectiveness (RBE) values at the depths around the Bragg peak of a {sup 9}C beam were enhanced and compared to its stable counterpart {sup 12}C beam. The purpose of this study was to explore the nature of the biological efficacy enhancement theoretically. Methods: A Monte Carlo simulation study was conducted in this study. First a simplified cell model was established so as to form a tumormore » tissue. Subsequently, the tumor tissue was imported into the Monte Carlo simulation software package GATE and then the tumor cells were virtually irradiated with comparable {sup 9}C and {sup 12}C beams, respectively, in the simulations. The transportation and particle deposition data of the {sup 9}C and {sup 12}C beams, derived from the GATE simulations, were analyzed with the authors’ local effect model implementation so as to deduce cell survival fractions. Results: The particles emitted from the decay process of deposited {sup 9}C particles around a cell nucleus increased the dose delivered to the nucleus and elicited clustered damages around the secondary particles’ trajectories. Therefore, compared to the {sup 12}C beam, the RBE value of the {sup 9}C beam increased at the depths around their Bragg peaks. Conclusions: Collectively, the increased local doses and clustered damages due to the decayed particles emitted from deposited {sup 9}C particles led to the RBE enhancement in contrast with the {sup 12}C beam. Thus, the enhanced RBE effect of a {sup 9}C beam for a simplified tumor model was shown theoretically in this study.« less

  20. Soybean fruit development and set at the node level under combined photoperiod and radiation conditions.

    PubMed

    Nico, Magalí; Mantese, Anita I; Miralles, Daniel J; Kantolic, Adriana G

    2016-01-01

    In soybean, long days during post-flowering increase seed number. This positive photoperiodic effect on seed number has been previously associated with increments in the amount of radiation accumulated during the crop cycle because long days extend the duration of the crop cycle. However, evidence of intra-nodal processes independent of the availability of assimilates suggests that photoperiodic effects at the node level might also contribute to pod set. This work aims to identify the main mechanisms responsible for the increase in pod number per node in response to long days; including the dynamics of flowering, pod development, growth and set at the node level. Long days increased pods per node on the main stems, by increasing pods on lateral racemes (usually dominated positions) at some main stem nodes. Long days lengthened the flowering period and thereby increased the number of opened flowers on lateral racemes. The flowering period was prolonged under long days because effective seed filling was delayed on primary racemes (dominant positions). Long days also delayed the development of flowers into pods with filling seeds, delaying the initiation of pod elongation without modifying pod elongation rate. The embryo development matched the external pod length irrespective of the pod's chronological age. These results suggest that long days during post-flowering enhance pod number per node through a relief of the competition between pods of different hierarchy within the node. The photoperiodic effect on the development of dominant pods, delaying their elongation and therefore postponing their active growth, extends flowering and allows pod set at positions that are usually dominated. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. Intergovernmental Unity of Effort in Support of Biological Threat Prevention

    DTIC Science & Technology

    2013-09-01

    jurisdictional barriers (such as time delays in developing decisions and implementing large scale action) are tangible. Connecting the “dots” of awareness...groups are developing the capability and the intention to deliver biological weapons of mass destruction. Four coalitions of governments were studied...Intelligence sources from around the globe report that terrorist groups are developing the capability and the intention to deliver biological weapons

  2. Load-sensitive impairment of working memory for biological motion in schizophrenia.

    PubMed

    Lee, Hannah; Kim, Jejoong

    2017-01-01

    Impaired working memory (WM) is a core cognitive deficit in schizophrenia. Nevertheless, past studies have reported that patients may also benefit from increasing salience of memory stimuli. Such efficient encoding largely depends upon precise perception. Thus an investigation on the relationship between perceptual processing and WM would be worthwhile. Here, we used biological motion (BM), a socially relevant stimulus that schizophrenics have difficulty discriminating from similar meaningless motions, in a delayed-response task. Non-BM stimuli and static polygons were also used for comparison. In each trial, one of the three types of stimuli was presented followed by two probes, with a short delay in between. Participants were asked to indicate whether one of them was identical to the memory item or both were novel. The number of memory items was one or two. Healthy controls were more accurate in recognizing BM than non-BM regardless of memory loads. Patients with schizophrenia exhibited similar accuracy patterns to those of controls in the Load 1 condition only. These results suggest that information contained in BM could facilitate WM encoding in general, but the effect is vulnerable to the increase of cognitive load in schizophrenia, implying inefficient encoding driven by imprecise perception.

  3. Brazilian infant motor and cognitive development: Longitudinal influence of risk factors.

    PubMed

    Pereira, Keila Rg; Valentini, Nadia C; Saccani, Raquel

    2016-12-01

    Infant developmental delays have been associated with several risk factors, such as familial environmental, individual and demographic characteristics. The goal of this study was to longitudinally investigate the effects of maternal knowledge and practices, home environment and biological factors on infant motor and cognitive outcomes. This was a prospective cohort study with a sample of 49 infants from Southern Brazil. The infants were assessed three times over 4 months using the Alberta Infant Motor Scale and the Bayley Scale of Infant Development (Mental Development Scale). Parents completed the Daily Activities Scale of Infants, the Affordances in The Home Environment for Motor Development - Infant Scale, the Knowledge of Infant Development Inventory and a demographic questionnaire. Generalized estimating equation with Bonferroni method as the follow-up test and Spearman correlation and multivariate linear backward regression were used. Cognitive and motor scores were strongly associated longitudinally and increased over time. Associations between the home affordances, parental practices and knowledge, and motor and cognitive development over time were observed. This relationship explained more variability in motor and cognitive scores compared with biological factors. Variability in motor and cognitive development is better explained by environment and parental knowledge and practice. The investigation of factors associated with infant development allows the identification of infants at risk and the implementation of educational programs and parental training to minimize the effects of developmental delay. © 2016 Japan Pediatric Society.

  4. Predictive modeling of nanomaterial exposure effects in biological systems

    PubMed Central

    Liu, Xiong; Tang, Kaizhi; Harper, Stacey; Harper, Bryan; Steevens, Jeffery A; Xu, Roger

    2013-01-01

    Background Predictive modeling of the biological effects of nanomaterials is critical for industry and policymakers to assess the potential hazards resulting from the application of engineered nanomaterials. Methods We generated an experimental dataset on the toxic effects experienced by embryonic zebrafish due to exposure to nanomaterials. Several nanomaterials were studied, such as metal nanoparticles, dendrimer, metal oxide, and polymeric materials. The embryonic zebrafish metric (EZ Metric) was used as a screening-level measurement representative of adverse effects. Using the dataset, we developed a data mining approach to model the toxic endpoints and the overall biological impact of nanomaterials. Data mining techniques, such as numerical prediction, can assist analysts in developing risk assessment models for nanomaterials. Results We found several important attributes that contribute to the 24 hours post-fertilization (hpf) mortality, such as dosage concentration, shell composition, and surface charge. These findings concur with previous studies on nanomaterial toxicity using embryonic zebrafish. We conducted case studies on modeling the overall effect/impact of nanomaterials and the specific toxic endpoints such as mortality, delayed development, and morphological malformations. The results show that we can achieve high prediction accuracy for certain biological effects, such as 24 hpf mortality, 120 hpf mortality, and 120 hpf heart malformation. The results also show that the weighting scheme for individual biological effects has a significant influence on modeling the overall impact of nanomaterials. Sample prediction models can be found at http://neiminer.i-a-i.com/nei_models. Conclusion The EZ Metric-based data mining approach has been shown to have predictive power. The results provide valuable insights into the modeling and understanding of nanomaterial exposure effects. PMID:24098077

  5. Psychophysiology of Delayed Extinction and Reconsolidation in Humans

    DTIC Science & Technology

    2014-02-01

    M., & Soeter, M. (2013). Reconsolidation in a human fear conditioning study: a test of extinction as updating mechanism. Biological Psychology , 92(1...relative strengths of various pharmacological and behavioral, reconsolidation-blocking interventions can be tested . Thus far, we have completed data... test the relative strengths of various reconsolidation-blocking (or memory updating) interventions. In other words, if propranolol or delayed

  6. Cellular changes in microgravity and the design of space radiation experiments

    NASA Technical Reports Server (NTRS)

    Morrison, D. R.

    1994-01-01

    Cell metabolism, secretion and cell-cell interactions can be altered during space flight. Early radiobiology experiments have demonstrated synergistic effects of radiation and microgravity as indicated by increased mutagenesis, increased chromosome aberrations, inhibited development, and retarded growth. Microgravity-induced changes in immune cell functions include reduced blastogenesis and cell-mediated, delayed-type hypersensitivity responses, increased cytokine secretions, but inhibited cytotoxic effects an macrophage differentiation. These effects are important because of the high radiosensitivity of immune cells. It is difficult to compare ground studies with space radiation biology experiments because of the complexity of the space radiation environment, types of radiation damage and repair mechanisms. Altered intracellular functions and molecular mechanisms must be considered in the design and interpretation of space radiation experiments. Critical steps in radiocarcinogenesis could be affected. New cell systems and hardware are needed to determine the biological effectiveness of the low dose rate, isotropic, multispectral space radiation and the potential usefulness of radioprotectants during space flight.

  7. Analysis of an age structured model for tick populations subject to seasonal effects

    NASA Astrophysics Data System (ADS)

    Liu, Kaihui; Lou, Yijun; Wu, Jianhong

    2017-08-01

    We investigate an age-structured hyperbolic equation model by allowing the birth and death functions to be density dependent and periodic in time with the consideration of seasonal effects. By studying the integral form solution of this general hyperbolic equation obtained through the method of integration along characteristics, we give a detailed proof of the uniqueness and existence of the solution in light of the contraction mapping theorem. With additional biologically natural assumptions, using the tick population growth as a motivating example, we derive an age-structured model with time-dependent periodic maturation delays, which is quite different from the existing population models with time-independent maturation delays. For this periodic differential system with seasonal delays, the basic reproduction number R0 is defined as the spectral radius of the next generation operator. Then, we show the tick population tends to die out when R0 < 1 while remains persistent if R0 > 1. When there is no intra-specific competition among immature individuals due to the sufficient availability of immature tick hosts, the global stability of the positive periodic state for the whole model system of four delay differential equations can be obtained with the observation that a scalar subsystem for the adult stage size can be decoupled. The challenge for the proof of such a global stability result can be overcome by introducing a new phase space, based on which, a periodic solution semiflow can be defined which is eventually strongly monotone and strictly subhomogeneous.

  8. Model of two infectious diseases in nettle caterpillar population

    NASA Astrophysics Data System (ADS)

    Firdausi, F. Z.; Nuraini, N.

    2016-04-01

    Palm oil is a vital commodity to the economy of Indonesia. The area of oil palm plantations in Indonesia has increased from year to year. However, the effectiveness of palm oil production is reduced by pest infestation. One of the pest which often infests oil palm plantations is nettle caterpillar. The pest control used in this study is biological control, viz. biological agents given to oil palm trees. This paper describes a mathematical model of two infectious diseases in nettle caterpillar population. The two infectious diseases arise due to two biological agents, namely Bacillus thuringiensis bacterium and parasite which usually attack nettle caterpillars. The derivation of the model constructed in this paper is obtained from ordinary differential equations without time delay. The equilibrium points are analyzed. Two of three equilibrium points are stable if the Routh-Hurwitz criteria are fulfilled. In addition, this paper also presents the numerical simulation of the model which has been constructed.

  9. Comparison of ballistic impact effects between biological tissue and gelatin.

    PubMed

    Jin, Yongxi; Mai, Ruimin; Wu, Cheng; Han, Ruiguo; Li, Bingcang

    2018-02-01

    Gelatin is commonly used in ballistic testing as substitute for biological tissue. Comparison of ballistic impact effects produced in the gelatin and living tissue is lacking. The work in this paper was aimed to compare the typical ballistic impact effects (penetration trajectory, energy transfer, temporary cavity) caused by 4.8mm steel ball penetrating the 60kg porcine hind limbs and 10wt% gelatin. The impact event in the biological tissue was recorded by high speed flash X-ray machine at different delay time, while the event in the gelatin continuously recorded by high speed video was compared to that in the biological tissue. The collected results clearly displayed that the ballistic impact effects in the muscle and gelatin were similar for the steel ball test; as for instance, the projectile trajectory in the two targets was basically similar, the process of energy transfer was highly coincident, and the expansion of temporary cavity followed the same pattern. This study fully demonstrated that choosing gelatin as muscle simulant was reasonable. However, the maximum temporary cavity diameter in the gelatin was a little larger than that in the muscle, and the expansion period of temporary cavity was longer in the gelatin. Additionally, the temporary cavity collapse process in the two targets followed different patterns, and the collapse period in the gelatin was two times as long as that in the muscle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Behavioral modeling of human choices reveals dissociable effects of physical effort and temporal delay on reward devaluation.

    PubMed

    Klein-Flügge, Miriam C; Kennerley, Steven W; Saraiva, Ana C; Penny, Will D; Bestmann, Sven

    2015-03-01

    There has been considerable interest from the fields of biology, economics, psychology, and ecology about how decision costs decrease the value of rewarding outcomes. For example, formal descriptions of how reward value changes with increasing temporal delays allow for quantifying individual decision preferences, as in animal species populating different habitats, or normal and clinical human populations. Strikingly, it remains largely unclear how humans evaluate rewards when these are tied to energetic costs, despite the surge of interest in the neural basis of effort-guided decision-making and the prevalence of disorders showing a diminished willingness to exert effort (e.g., depression). One common assumption is that effort discounts reward in a similar way to delay. Here we challenge this assumption by formally comparing competing hypotheses about effort and delay discounting. We used a design specifically optimized to compare discounting behavior for both effort and delay over a wide range of decision costs (Experiment 1). We then additionally characterized the profile of effort discounting free of model assumptions (Experiment 2). Contrary to previous reports, in both experiments effort costs devalued reward in a manner opposite to delay, with small devaluations for lower efforts, and progressively larger devaluations for higher effort-levels (concave shape). Bayesian model comparison confirmed that delay-choices were best predicted by a hyperbolic model, with the largest reward devaluations occurring at shorter delays. In contrast, an altogether different relationship was observed for effort-choices, which were best described by a model of inverse sigmoidal shape that is initially concave. Our results provide a novel characterization of human effort discounting behavior and its first dissociation from delay discounting. This enables accurate modelling of cost-benefit decisions, a prerequisite for the investigation of the neural underpinnings of effort-guided choice and for understanding the deficits in clinical disorders characterized by behavioral inactivity.

  11. Behavioral Modeling of Human Choices Reveals Dissociable Effects of Physical Effort and Temporal Delay on Reward Devaluation

    PubMed Central

    Klein-Flügge, Miriam C.; Kennerley, Steven W.; Saraiva, Ana C.; Penny, Will D.; Bestmann, Sven

    2015-01-01

    There has been considerable interest from the fields of biology, economics, psychology, and ecology about how decision costs decrease the value of rewarding outcomes. For example, formal descriptions of how reward value changes with increasing temporal delays allow for quantifying individual decision preferences, as in animal species populating different habitats, or normal and clinical human populations. Strikingly, it remains largely unclear how humans evaluate rewards when these are tied to energetic costs, despite the surge of interest in the neural basis of effort-guided decision-making and the prevalence of disorders showing a diminished willingness to exert effort (e.g., depression). One common assumption is that effort discounts reward in a similar way to delay. Here we challenge this assumption by formally comparing competing hypotheses about effort and delay discounting. We used a design specifically optimized to compare discounting behavior for both effort and delay over a wide range of decision costs (Experiment 1). We then additionally characterized the profile of effort discounting free of model assumptions (Experiment 2). Contrary to previous reports, in both experiments effort costs devalued reward in a manner opposite to delay, with small devaluations for lower efforts, and progressively larger devaluations for higher effort-levels (concave shape). Bayesian model comparison confirmed that delay-choices were best predicted by a hyperbolic model, with the largest reward devaluations occurring at shorter delays. In contrast, an altogether different relationship was observed for effort-choices, which were best described by a model of inverse sigmoidal shape that is initially concave. Our results provide a novel characterization of human effort discounting behavior and its first dissociation from delay discounting. This enables accurate modelling of cost-benefit decisions, a prerequisite for the investigation of the neural underpinnings of effort-guided choice and for understanding the deficits in clinical disorders characterized by behavioral inactivity. PMID:25816114

  12. Staphylococcus aureus-Induced G2/M Phase Transition Delay in Host Epithelial Cells Increases Bacterial Infective Efficiency

    PubMed Central

    Almeida, Sintia; Legembre, Patrick; Edmond, Valérie; Azevedo, Vasco; Miyoshi, Anderson; Even, Sergine; Taieb, Frédéric; Arlot-Bonnemains, Yannick; Le Loir, Yves; Berkova, Nadia

    2013-01-01

    Staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. The epithelial surface is its principal site of colonization and infection. In this work, we investigated the cytopathic effect of S. aureus strains from human and animal origins and their ability to affect the host cell cycle in human HeLa and bovine MAC-T epithelial cell lines. S. aureus invasion slowed down cell proliferation and induced a cytopathic effect, resulting in the enlargement of host cells. A dramatic decrease in the number of mitotic cells was observed in the infected cultures. Flow cytometry analysis revealed an S. aureus-induced delay in the G2/M phase transition in synchronous HeLa cells. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. The results of Western blot experiments showed that the G2/M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a reduction of the mitotic cell number. Analysis of S. aureus proliferation in asynchronous, G1- and G2-phase-enriched HeLa cells showed that the G2 phase was preferential for bacterial infective efficiency, suggesting that the G2 phase delay may be used by S. aureus for propagation within the host. Taken together, our results divulge the potential of S. aureus in the subversion of key cellular processes such as cell cycle progression, and shed light on the biological significance of S. aureus-induced host cell cycle alteration. PMID:23717407

  13. Dimensionality of brain networks linked to life-long individual differences in self-control.

    PubMed

    Berman, Marc G; Yourganov, Grigori; Askren, Mary K; Ayduk, Ozlem; Casey, B J; Gotlib, Ian H; Kross, Ethan; McIntosh, Anthony R; Strother, Stephen; Wilson, Nicole L; Zayas, Vivian; Mischel, Walter; Shoda, Yuichi; Jonides, John

    2013-01-01

    The ability to delay gratification in childhood has been linked to positive outcomes in adolescence and adulthood. Here we examine a subsample of participants from a seminal longitudinal study of self-control throughout a subject's life span. Self-control, first studied in children at age 4 years, is now re-examined 40 years later, on a task that required control over the contents of working memory. We examine whether patterns of brain activation on this task can reliably distinguish participants with consistently low and high self-control abilities (low versus high delayers). We find that low delayers recruit significantly higher-dimensional neural networks when performing the task compared with high delayers. High delayers are also more homogeneous as a group in their neural patterns compared with low delayers. From these brain patterns, we can predict with 71% accuracy, whether a participant is a high or low delayer. The present results suggest that dimensionality of neural networks is a biological predictor of self-control abilities.

  14. Stochastic modelling for biodosimetry: Predicting the chromosomal response to radiation at different time points after exposure

    NASA Astrophysics Data System (ADS)

    Deperas-Standylo, Joanna; Gudowska-Nowak, Ewa; Ritter, Sylvia

    2014-07-01

    Cytogenetic data accumulated from the experiments with peripheral blood lymphocytes exposed to densely ionizing radiation clearly demonstrate that for particles with linear energy transfer (LET) >100 keV/ μm the derived relative biological effectiveness (RBE) will strongly depend on the time point chosen for the analysis. A reasonable prediction of radiation-induced chromosome damage and its distribution among cells can be achieved by exploiting Monte Carlo methodology along with the information about the radius of the penetrating ion-track and the LET of the ion beam. In order to examine the relationship between the track structure and the distribution of aberrations induced in human lymphocytes and to clarify the correlation between delays in the cell cycle progression and the aberration burden visible at the first post-irradiation mitosis, we have analyzed chromosome aberrations in lymphocytes exposed to Fe-ions with LET values of 335 keV/ μm and formulated a Monte Carlo model which reflects time-delay in mitosis of aberrant cells. Within the model the frequency distributions of aberrations among cells follow the pattern of local energy distribution and are well approximated by a time-dependent compound Poisson statistics. The cell-division cycle of undamaged and aberrant cells and chromosome aberrations are modelled as a renewal process represented by a random sum of (independent and identically distributed) random elements S N = ∑ N i=0 X i . Here N stands for the number of particle traversals of cell nucleus, each leading to a statistically independent formation of X i aberrations. The parameter N is itself a random variable and reflects the cell cycle delay of heavily damaged cells. The probability distribution of S N follows a general law for which the moment generating function satisfies the relation Φ S N = Φ N ( Φ X i ). Formulation of the Monte Carlo model which allows to predict expected fluxes of aberrant and non-aberrant cells has been based on several input information: (i) experimentally measured mitotic index in the population of irradiated cells; (ii) scored fraction of cells in first cell cycle; (iii) estimated average number of particle traversals per cell nucleus. By reconstructing the local dose distribution in the biological target, the relevant amount of lesions induced by ions is estimated from the biological effect induced by photons at the same dose level. Moreover, the total amount of aberrations induced within the entire population has been determined. For each subgroup of intact (non-hit) and aberrant cells the cell-division cycle has been analyzed reproducing correctly an expected correlation between mitotic delay and the number of aberrations carried by a cell. This observation is of particular importance for the proper estimation of the biological efficiency of ions and for the estimation of health risks associated with radiation exposure.

  15. Effects of polychlorinated biphenyls on metamorphosis of a marine fish Japanese flounder (Paralichthys olivaceus) in relation to thyroid disruption.

    PubMed

    Dong, Yifei; Zhang, Xiaona; Tian, Hua; Li, Xiang; Wang, Wei; Ru, Shaoguo

    2017-06-15

    This study examined the influence of environmental concentrations of Aroclor 1254 (10, 100, and 1000ng/L) on metamorphosis of Paralichthys olivaceus, and analyzed the mechanisms in relation to thyroid disruption. Results showed that 100 and 1000ng/L Aroclor 1254 delayed metamorphosis and that 1000ng/L Aroclor 1254 caused abnormal morphology. Thyroxine and triiodothyronine levels in the control group were significantly elevated at metamorphic climax, but treatment with 100 and 1000ng/L delayed the increase in thyroid hormones (THs) and retarded metamorphic processes. In larvae exposed to 1000ng/L Aroclor 1254, TH levels at metamorphic climax were significantly lower than those of the control group at the same metamorphic stage. We suggest that the effects of Aroclor 1254 on larval metamorphosis can be explained by disruption of thyroid homeostasis. These findings provide a new perspective and biological model for thyroid-disrupting chemicals (TDCs) screening and investigating interference of thyroid function by TDCs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. DELAY OF CLEAVAGE OF THE ARBACIA EGG BY ULTRAVIOLET RADIATION

    PubMed Central

    Blum, Harold F.; Price, Judith P.

    1950-01-01

    While our data do not permit us to state the exact locus or mode of action of ultraviolet radiation in the Arbacia egg, certain general conclusions may be reached. The amount of delay of cleavage of these eggs is determined by two principal factors: (1) The extent of an effect, resulting from photochemical action induced by ultraviolet radiation, which is reversible in a biological sense, the reversibility not being directly dependent upon the process of cell division. (2) The sensitivity of the cell division process to the effects of the ultraviolet-induced photochemical reaction. This factor varies with the stage of cell division, the cell being insensitive during a period corresponding to most of mitosis. It seems likely that these findings may apply to cell division in general, but, since the quantitative relationships observed must, in this case, reflect the integration of two semi-independent factors, the over-all picture may appear quite different for different kinds of cells. PMID:15410486

  17. Natural Variation in Banana Varieties Highlights the Role of Melatonin in Postharvest Ripening and Quality.

    PubMed

    Hu, Wei; Yang, Hai; Tie, Weiwei; Yan, Yan; Ding, Zehong; Liu, Yang; Wu, Chunlai; Wang, Jiashui; Reiter, Russel J; Tan, Dun-Xian; Shi, Haitao; Xu, Biyu; Jin, Zhiqiang

    2017-11-22

    This study aimed to investigate the role of melatonin in postharvest ripening and quality in various banana varieties with contrasting ripening periods. During the postharvest life, endogenous melatonin showed similar performance with ethylene in connection to ripening. In comparison to ethylene, melatonin was more correlated with postharvest banana ripening. Exogenous application of melatonin resulted in a delay of postharvest banana ripening. Moreover, this effect is concentration-dependent, with 200 and 500 μM treatments more effective than the 50 μM treatment. Exogenous melatonin also led to elevated endogenous melatonin content, reduced ethylene production through regulation of the expression of MaACO1 and MaACS1, and delayed sharp changes of quality indices. Taken together, this study highlights that melatonin is an indicator for banana fruit ripening in various varieties, and the repression of ethylene biosynthesis and postharvest ripening by melatonin can be used for biological control of postharvest fruit ripening and quality.

  18. The Evaluation and Treatment of Delayed Ejaculation.

    PubMed

    Shin, Daniel H; Spitz, Aaron

    2014-10-01

    Delayed ejaculation is a small but important subsection of ejaculatory dysfunction, with prevalence estimated at 1-4%. It is most commonly defined by DSM-IV-TR criteria, as "a persistent delay in, or absence of, orgasm in a male following a normal sexual excitement phase during sexual activity that the clinician, taking into account the person's age, judges to be adequate in focus, intensity, and duration." The pathophysiology of delayed ejaculation is related to disruptions in ejaculatory apparatus, nervous transmission, hormonal or neurochemical ejaculatory control, or psychosocial factors. To update the clinician on the evaluation and treatment of delayed ejaculation. The keywords "delayed ejaculation" and "retarded ejaculation" were utilized to search Pubmed for relevant publications. 319 results were generated from the search, and those publications judged relevant to the pathophysiology, epidemiology, evaluation, and treatment of delayed ejaculation were included in the review. 110 articles were ultimately selected for inclusion in this review. The evaluation of this condition requires a focused history and physical, which includes a detailed sexual history, examination of the genitalia, and inquiry into the status of the partner. Laboratory tests are aimed at the detection of abnormalities in the blood count, glucose level, hormone levels, or kidney function. If a correctable etiology is discovered, treatment is directed towards the reversal of this condition. In some cases, the delayed ejaculation may be a lifelong problem. Also, in some cases the etiology of the delayed ejaculation may be irreversible, such as in the case of age-related sensation loss or diabetes-related neuropathy. In these instances treatment may require a combination of behavioral modification, sexual therapy, or perhaps pharmaceutical drugs. Participation of the partner in therapy may sometimes be necessary. Future investigations will continue to elucidate the complex biological and psychosocial factors which contribute to delayed ejaculation, leading to more effective treatments. Shin DH and Spitz A. The evaluation and treatment of delayed ejaculation. Sex Med Rev 2014;2:121-133. Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  19. Capacity to delay reward differentiates obsessive-compulsive disorder and obsessive-compulsive personality disorder.

    PubMed

    Pinto, Anthony; Steinglass, Joanna E; Greene, Ashley L; Weber, Elke U; Simpson, H Blair

    2014-04-15

    Although the relationship between obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD) has long been debated, clinical samples of OCD (without OCPD) and OCPD (without OCD) have never been systematically compared. We studied whether individuals with OCD, OCPD, or both conditions differ on symptomatology, functioning, and a measure of self-control: the capacity to delay reward. Twenty-five OCD, 25 OCPD, 25 comorbid OCD + OCPD, and 25 healthy control subjects completed clinical assessments and a validated intertemporal choice task that measures capacity to forego small immediate rewards for larger delayed rewards. OCD and OCPD subjects both showed impairment in psychosocial functioning and quality of life, as well as compulsive behavior, but only subjects with OCD reported obsessions. Individuals with OCPD, with or without comorbid OCD, discounted the value of delayed monetary rewards significantly less than OCD and healthy control subjects. This excessive capacity to delay reward discriminates OCPD from OCD and is associated with perfectionism and rigidity. OCD and OCPD are both impairing disorders marked by compulsive behaviors, but they can be differentiated by the presence of obsessions in OCD and by excessive capacity to delay reward in OCPD. That individuals with OCPD show less temporal discounting (suggestive of excessive self-control), whereas prior studies have shown that individuals with substance use disorders show greater discounting (suggestive of impulsivity), supports the premise that this component of self-control lies on a continuum in which both extremes (impulsivity and overcontrol) contribute to psychopathology. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  20. Detection of silver nanoparticles in parsley by solid sampling high-resolution-continuum source atomic absorption spectrometry.

    PubMed

    Feichtmeier, Nadine S; Leopold, Kerstin

    2014-06-01

    In this work, we present a fast and simple approach for detection of silver nanoparticles (AgNPs) in biological material (parsley) by solid sampling high-resolution-continuum source atomic absorption spectrometry (HR-CS AAS). A novel evaluation strategy was developed in order to distinguish AgNPs from ionic silver and for sizing of AgNPs. For this purpose, atomisation delay was introduced as significant indication of AgNPs, whereas atomisation rates allow distinction of 20-, 60-, and 80-nm AgNPs. Atomisation delays were found to be higher for samples containing silver ions than for samples containing silver nanoparticles. A maximum difference in atomisation delay normalised by the sample weight of 6.27 ± 0.96 s mg(-1) was obtained after optimisation of the furnace program of the AAS. For this purpose, a multivariate experimental design was used varying atomisation temperature, atomisation heating rate and pyrolysis temperature. Atomisation rates were calculated as the slope of the first inflection point of the absorbance signals and correlated with the size of the AgNPs in the biological sample. Hence, solid sampling HR-CS AAS was proved to be a promising tool for identifying and distinguishing silver nanoparticles from ionic silver directly in solid biological samples.

  1. [Using delayed auditory feedback in the treatment of stuttering: evidence to consider].

    PubMed

    Van Borsel, John; Sierens, Sarah; Pereira, Mônica Medeiros de Britto

    2007-01-01

    There is some indication that the use of delayed auditory feedback (DAF) is a potentially helpful technique in the treatment of stuttering. Several devices for DAF are also commercially. However, not all individuals who stutter experience a positive effect on speech fluency when speaking under DAF. And those who do show a positive effect, may differ considerably as to the degree and the conditions in which the effect is seen. Therefore, the decision whether or not to attempt the use of DAF in an given client is usually not straightforward. Starting from a literature review, the present paper discusses and illustrates factors to take into account when considering the use of RAA in an individual client. Four types of factors are distinguished: factors inherent to the client such as gender, age, stuttering severity, dysfluency pattern, origin of stuttering, and biological subtype; factors outside the client including delay time, intensity, manner of delivery, speech mode, and speech situation; possible side-effects like a reduction in speech rate, an increase of speaking fundamental frequency and vocal intensity, lengthening of vowels, and a possible effect on speech naturalness; others namely cosmetics, finances, and the long-term effect. The review shows that most likely multiple factors play a role, but with the currently available data it is very hard to predict whether a given individual will or will not benefit from the use of DAF. Overall, the evidence for the influence of the different factors is still meager. Moreover, some studies present data of a quality that can hardly be considered "evidence".

  2. Diaphyseal long bone nonunions - types, aetiology, economics, and treatment recommendations.

    PubMed

    Rupp, Markus; Biehl, Christoph; Budak, Matthäus; Thormann, Ulrich; Heiss, Christian; Alt, Volker

    2018-02-01

    The intention of the current article is to review the epidemiology with related socioeconomic costs, pathophysiology, and treatment options for diaphyseal long bone delayed unions and nonunions. Diaphyseal nonunions in the tibia and in the femur are estimated to occur 4.6-8% after modern intramedullary nailing of closed fractures with an even much higher risk in open fractures. There is a high socioeconomic burden for long bone nonunions mainly driven by indirect costs, such as productivity losses due to long treatment duration. The classic classification of Weber and Cech of the 1970s is based on the underlying biological aspect of the nonunion differentiating between "vital" (hypertrophic) and "avital" (hypo-/atrophic) nonunions, and can still be considered to represent the basis for basic evaluation of nonunions. The "diamond concept" units biomechanical and biological aspects and provides the pre-requisites for successful bone healing in nonunions. For humeral diaphyseal shaft nonunions, excellent results for augmentation plating were reported. In atrophic humeral shaft nonunions, compression plating with stimulation of bone healing by bone grafting or BMPs seem to be the best option. For femoral and tibial diaphyseal shaft fractures, dynamization of the nail is an atraumatic, effective, and cheap surgical possibility to achieve bony consolidation, particularly in delayed nonunions before 24 weeks after initial surgery. In established hypertrophic nonunions in the tibia and femur, biomechanical stability should be addressed by augmentation plating or exchange nailing. Hypotrophic or atrophic nonunions require additional biological stimulation of bone healing for augmentation plating.

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

    Andres, B.A.

    Black oystercatchers (Haematopus bachmani) were studied in central Prince William Sound, Alaska, to determine the effects that the Exxon Valdez oil spill had on their population, reproductive biology, and behavioral ecology. Estimates of direct mortality of black oystercatchers varied widely among the methods used to assess losses and ranged from 4% to 57% of the population inhabitating the spill zone; mortality probably did not exceed 20% of the population. Although the black oystercatcher population appears to be recovering in some areas of the Sound, delayed reproduction in the species precludes determination of the total effect of the spill on themore » population until at least 1994.« less

  4. Focused tandem shock waves in water and their potential application in cancer treatment

    NASA Astrophysics Data System (ADS)

    Lukes, P.; Sunka, P.; Hoffer, P.; Stelmashuk, V.; Pouckova, P.; Zadinova, M.; Zeman, J.; Dibdiak, L.; Kolarova, H.; Tomankova, K.; Binder, S.; Benes, J.

    2014-01-01

    The generator of two focused successive (tandem) shock waves (FTSW) in water produced by underwater multichannel electrical discharges at two composite electrodes, with a time delay between the first and second shock waves of 10 s, was developed. It produces, at the focus, a strong shock wave with a peak positive pressure of up to 80 MPa, followed by a tensile wave with a peak negative pressure of up to MPa, thus generating at the focus a large amount of cavitation. Biological effects of FTSW were demonstrated in vitro on hemolysis of erythrocytes and cell viability of human acute lymphoblastic leukemia cells as well as on tumor growth delay ex vivo and in vivo experiments performed with B16 melanoma, T-lymphoma, and R5-28 sarcoma cell lines. It was demonstrated in vivo that FTSW can enhance antitumor effects of chemotherapeutic drugs, such as cisplatin, most likely due to increased permeability of the membrane of cancer cells induced by FTSW. Synergetic cytotoxicity of FTSW with sonosensitive porphyrin-based drug Photosan on tumor growth was observed, possibly due to the cavitation-induced sonodynamic effect of FTSW.

  5. Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

    PubMed Central

    Samson, Eugenie; Arlia-Ciommo, Anthony; Dakik, Pamela; Cortes, Berly; Feldman, Rachel; Mohtashami, Sadaf; McAuley, Mélissa; Chancharoen, Marisa; Rukundo, Belise; Simard, Éric; Titorenko, Vladimir I.

    2016-01-01

    We discovered six plant extracts that increase yeast chronological lifespan to a significantly greater extent than any of the presently known longevity-extending chemical compounds. One of these extracts is the most potent longevity-extending pharmacological intervention yet described. We show that each of the six plant extracts is a geroprotector which delays the onset and decreases the rate of yeast chronological aging by eliciting a hormetic stress response. We also show that each of these extracts has different effects on cellular processes that define longevity in organisms across phyla. These effects include the following: 1) increased mitochondrial respiration and membrane potential; 2) augmented or reduced concentrations of reactive oxygen species; 3) decreased oxidative damage to cellular proteins, membrane lipids, and mitochondrial and nuclear genomes; 4) enhanced cell resistance to oxidative and thermal stresses; and 5) accelerated degradation of neutral lipids deposited in lipid droplets. Our findings provide new insights into mechanisms through which chemicals extracted from certain plants can slow biological aging. PMID:26918729

  6. Additional effects of taurine on the benefits of BCAA intake for the delayed-onset muscle soreness and muscle damage induced by high-intensity eccentric exercise.

    PubMed

    Ra, Song-Gyu; Miyazaki, Teruo; Ishikura, Keisuke; Nagayama, Hisashi; Suzuki, Takafumi; Maeda, Seiji; Ito, Masaharu; Matsuzaki, Yasushi; Ohmori, Hajime

    2013-01-01

    Taurine (TAU) has a lot of the biological, physiological, and pharmocological functions including anti-inflammatory and anti-oxidative stress. Although previous studies have appreciated the effectiveness of branched-chain amino acids (BCAA) on the delayed-onset muscle soreness (DOMS), consistent finding has not still convinced. The aim of this study was to examine the additional effect of TAU with BCAA on the DOMS and muscle damages after eccentric exercise. Thirty-six untrained male volunteers were equally divided into four groups, and ingested a combination with 2.0 g TAU (or placebo) and 3.2 g BCAA (or placebo), thrice a day, 2 weeks prior to and 4 days after elbow flexion eccentric exercise. Following the period after eccentric exercise, the physiological and blood biochemical markers for DOMS and muscle damage showed improvement in the combination of TAU and BCAA supplementation rather than in the single or placebo supplementations. In conclusion, additional supplement of TAU with BCAA would be a useful way to attenuate DOMS and muscle damages induced by high-intensity exercise.

  7. Judgement on "hit or non-hit" of CHO cells exposed to accelerated heavy-ions (Fe- or Ar-ions) using division delay and CR-39 plastics as an indicator.

    PubMed

    Mehnati, P; Yatagai, F; Tsuzuki, T; Hanaoka, F; Sasaki, H

    2001-03-01

    The cell killing effect of ionizing radiation depends on the degree of linear energy transfer (LET). The relative biological effectiveness (RBE) reaches a maximum at LET of around 100-200 keV/micron and decreases at higher levels. The ion clusters produced by high-LET radiation are not uniformly distributed. The incidence of non-hit cell events is higher in high LET irradiation than in the cases of low-LET irradiation. This fact could explain the decrease in the cell killing effect at higher levels of LET irradiation. Since the cell killing effect may be related to the nuclear traversal of heavy-ions, it is necessary to establish methods to distinguish the hit cells from the non-hit cells, especially in case with high LET irradiation. Using time-lapse photography, we first examined the hit events by observing the division delay in the cells caused by high-LET irradiation. In addition, we explored the use of CR-39 plastics to detect the exact position of heavy-ion traversal on the surface of a flask where cells were growing. When Chinese hamster ovary (CHO-K1) cells were exposed to 4 Gy of accelerated Fe-ions (2000 keV/micron) or Ar (1640 keV/micron)-ions, the surviving fraction decreased to about 30% in both cases of irradiation. Eighty percent of the irradiated cells, suffered a division delay in contrast to the remaining 20% of the cells which showed a normal division time (12-13 hrs). The later 20% of the cells is considered to be a population of cells which were not actually traversed by heavy-ions. The difference between the higher values of the surviving fraction (approximately 30%) and the non-hit cell population (20%) indicates that some hit cells can grow even after being hit by heavy-ions. The fraction of recovered cells determined by the time-lapse photography method was 10%, and this value closely correlated with the difference between the surviving fraction and the non-hit cells. We used the Poisson distribution of the hit-events by heavy-ions among the cell population in order to calculate the fraction of cells receiving at least a single-hit in the cell nucleus (130 micron 2 in average size). From this calculation we determined that 80% of the cells had a single hit to their nuclei by a heavy-ion which induced such early cellular responses as division delay. Our finding in the experiments using CR-39 plastics as a detector for hit-sites further supported the idea that the hit lethality of a cell is related to heavy-ion traversal through its nucleus. This study indicates the possible usefulness of both the division delay and CR-39 plastic methods for evaluating the biological effects of heavy-ions, especially when these two methods are combined.

  8. Predation and fragmentation portrayed in the statistical structure of prey time series

    PubMed Central

    Hendrichsen, Ditte K; Topping, Chris J; Forchhammer, Mads C

    2009-01-01

    Background Statistical autoregressive analyses of direct and delayed density dependence are widespread in ecological research. The models suggest that changes in ecological factors affecting density dependence, like predation and landscape heterogeneity are directly portrayed in the first and second order autoregressive parameters, and the models are therefore used to decipher complex biological patterns. However, independent tests of model predictions are complicated by the inherent variability of natural populations, where differences in landscape structure, climate or species composition prevent controlled repeated analyses. To circumvent this problem, we applied second-order autoregressive time series analyses to data generated by a realistic agent-based computer model. The model simulated life history decisions of individual field voles under controlled variations in predator pressure and landscape fragmentation. Analyses were made on three levels: comparisons between predated and non-predated populations, between populations exposed to different types of predators and between populations experiencing different degrees of habitat fragmentation. Results The results are unambiguous: Changes in landscape fragmentation and the numerical response of predators are clearly portrayed in the statistical time series structure as predicted by the autoregressive model. Populations without predators displayed significantly stronger negative direct density dependence than did those exposed to predators, where direct density dependence was only moderately negative. The effects of predation versus no predation had an even stronger effect on the delayed density dependence of the simulated prey populations. In non-predated prey populations, the coefficients of delayed density dependence were distinctly positive, whereas they were negative in predated populations. Similarly, increasing the degree of fragmentation of optimal habitat available to the prey was accompanied with a shift in the delayed density dependence, from strongly negative to gradually becoming less negative. Conclusion We conclude that statistical second-order autoregressive time series analyses are capable of deciphering interactions within and across trophic levels and their effect on direct and delayed density dependence. PMID:19419539

  9. Cosmos 1887 - Science overview

    NASA Technical Reports Server (NTRS)

    Grindeland, R. E.

    1990-01-01

    Twenty two groups of U.S. investigators participated in joint studies of ten male rats flown on the Cosmos 1887 biosatellite. A summary of these studies embracing skeletal muscle, bone, endocrine, neural, intestinal, metabolic, immunology, cardiac, and gonadal investigations is presented. Three general objectives of the rat experiments are outlined - verification of previous observations of the biological responses to microgravity; clarification of the effects of microgravity on both the tissues investigated and the measurements performed; and relation of biological responses to flight duration. It is concluded that the first objective is met fully and the second with a varying degree of success. The confounding effects of overshooting the designated landing site and delayed recovery of the animals largely precluded meeting the last objective. It is also noted that investigations were performed for the first time on brain and spinal cord enzymes, a neurotransmitter, transmitter receptors, hypothalamic regulatory factors, pineal metabolites, atrial granules, liver histology, and jejunal mitotic rate in spaceflight animals.

  10. Quantitative assessment of image motion blur in diffraction images of moving biological cells

    NASA Astrophysics Data System (ADS)

    Wang, He; Jin, Changrong; Feng, Yuanming; Qi, Dandan; Sa, Yu; Hu, Xin-Hua

    2016-02-01

    Motion blur (MB) presents a significant challenge for obtaining high-contrast image data from biological cells with a polarization diffraction imaging flow cytometry (p-DIFC) method. A new p-DIFC experimental system has been developed to evaluate the MB and its effect on image analysis using a time-delay-integration (TDI) CCD camera. Diffraction images of MCF-7 and K562 cells have been acquired with different speed-mismatch ratios and compared to characterize MB quantitatively. Frequency analysis of the diffraction images shows that the degree of MB can be quantified by bandwidth variations of the diffraction images along the motion direction. The analytical results were confirmed by the p-DIFC image data acquired at different speed-mismatch ratios and used to validate a method of numerical simulation of MB on blur-free diffraction images, which provides a useful tool to examine the blurring effect on diffraction images acquired from the same cell. These results provide insights on the dependence of diffraction image on MB and allow significant improvement on rapid biological cell assay with the p-DIFC method.

  11. The Corticostriatal Adenosine A2A Receptor Controls Maintenance and Retrieval of Spatial Working Memory.

    PubMed

    Li, Zhihui; Chen, Xingjun; Wang, Tao; Gao, Ying; Li, Fei; Chen, Long; Xue, Jin; He, Yan; Li, Yan; Guo, Wei; Zheng, Wu; Zhang, Liping; Ye, Fenfen; Ren, Xiangpeng; Feng, Yue; Chan, Piu; Chen, Jiang-Fan

    2018-03-15

    Working memory (WM) taps into multiple executive processes including encoding, maintenance, and retrieval of information, but the molecular and circuit modulation of these WM processes remains undefined due to the lack of methods to control G protein-coupled receptor signaling with temporal resolution of seconds. By coupling optogenetic control of the adenosine A 2A receptor (A 2A R) signaling, the Cre-loxP-mediated focal A 2A R knockdown with a delayed non-match-to-place (DNMTP) task, we investigated the effect of optogenetic activation and focal knockdown of A 2A Rs in the dorsomedial striatum (n = 8 to 14 per group) and medial prefrontal cortex (n = 16 to 22 per group) on distinct executive processes of spatial WM. We also evaluated the therapeutic effect of the A 2A R antagonist KW6002 on delayed match-to-sample/place tasks in 6 normal and 6 MPTP-treated cynomolgus monkeys. Optogenetic activation of striatopallidal A 2A Rs in the dorsomedial striatum selectively at the delay and choice (not sample) phases impaired DNMTP performance. Optogenetic activation of A 2A Rs in the medial prefrontal cortex selectively at the delay (not sample or choice) phase improved DNMTP performance. The corticostriatal A 2A R control of spatial WM was specific for a novel but not well-trained DNMTP task. Focal dorsomedial striatum A 2A R knockdown or KW6002 improved DNMTP performance in mice. Last, KW6002 improved spatial WM in delayed match-to-sample and delayed match-to-place tasks of normal and dopamine-depleted cynomolgus monkeys. The A 2A Rs in striatopallidal and medial prefrontal cortex neurons exert distinctive control of WM maintenance and retrieval to achieve cognitive stability and flexibility. The procognitive effect of KW6002 in nonhuman primates provides the preclinical data to translate A 2A R antagonists for improving cognitive impairments in Parkinson's disease. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Point process analysis of noise in early invertebrate vision

    PubMed Central

    Vinnicombe, Glenn

    2017-01-01

    Noise is a prevalent and sometimes even dominant aspect of many biological processes. While many natural systems have adapted to attenuate or even usefully integrate noise, the variability it introduces often still delimits the achievable precision across biological functions. This is particularly so for visual phototransduction, the process responsible for converting photons of light into usable electrical signals (quantum bumps). Here, randomness of both the photon inputs (regarded as extrinsic noise) and the conversion process (intrinsic noise) are seen as two distinct, independent and significant limitations on visual reliability. Past research has attempted to quantify the relative effects of these noise sources by using approximate methods that do not fully account for the discrete, point process and time ordered nature of the problem. As a result the conclusions drawn from these different approaches have led to inconsistent expositions of phototransduction noise performance. This paper provides a fresh and complete analysis of the relative impact of intrinsic and extrinsic noise in invertebrate phototransduction using minimum mean squared error reconstruction techniques based on Bayesian point process (Snyder) filters. An integrate-fire based algorithm is developed to reliably estimate photon times from quantum bumps and Snyder filters are then used to causally estimate random light intensities both at the front and back end of the phototransduction cascade. Comparison of these estimates reveals that the dominant noise source transitions from extrinsic to intrinsic as light intensity increases. By extending the filtering techniques to account for delays, it is further found that among the intrinsic noise components, which include bump latency (mean delay and jitter) and shape (amplitude and width) variance, it is the mean delay that is critical to noise performance. As the timeliness of visual information is important for real-time action, this delay could potentially limit the speed at which invertebrates can respond to stimuli. Consequently, if one wants to increase visual fidelity, reducing the photoconversion lag is much more important than improving the regularity of the electrical signal. PMID:29077703

  13. Miniature Telerobots in Space Applications

    NASA Technical Reports Server (NTRS)

    Venema, S. C.; Hannaford, B.

    1995-01-01

    Ground controlled telerobots can be used to reduce astronaut workload while retaining much of the human capabilities of planning, execution, and error recovery for specific tasks. Miniature robots can be used for delicate and time consuming tasks such as biological experiment servicing without incurring the significant mass and power penalties associated with larger robot systems. However, questions remain regarding the technical and economic effectiveness of such mini-telerobotic systems. This paper address some of these open issues and the details of two projects which will provide some of the needed answers. The Microtrex project is a joint University of Washington/NASA project which plans on flying a miniature robot as a Space Shuttle experiment to evaluate the effects of microgravity on ground-controlled manipulation while subject to variable time-delay communications. A related project involving the University of Washington and Boeing Defense and Space will evaluate the effectiveness f using a minirobot to service biological experiments in a space station experiment 'glove-box' rack mock-up, again while subject to realistic communications constraints.

  14. Cytotoxic effects of ultra-diluted remedies on breast cancer cells.

    PubMed

    Frenkel, Moshe; Mishra, Bal Mukund; Sen, Subrata; Yang, Peiying; Pawlus, Alison; Vence, Luis; Leblanc, Aimee; Cohen, Lorenzo; Banerji, Pratip; Banerji, Prasanta

    2010-02-01

    The use of ultra-diluted natural products in the management of disease and treatment of cancer has generated a lot of interest and controversy. We conducted an in vitro study to determine if products prescribed by a clinic in India have any effect on breast cancer cell lines. We studied four ultra-diluted remedies (Carcinosin, Phytolacca, Conium and Thuja) against two human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) and a cell line derived from immortalized normal human mammary epithelial cells (HMLE). The remedies exerted preferential cytotoxic effects against the two breast cancer cell lines, causing cell cycle delay/arrest and apoptosis. These effects were accompanied by altered expression of the cell cycle regulatory proteins, including downregulation of phosphorylated Rb and upregulation of the CDK inhibitor p27, which were likely responsible for the cell cycle delay/arrest as well as induction of the apoptotic cascade that manifested in the activation of caspase 7 and cleavage of PARP in the treated cells. The findings demonstrate biological activity of these natural products when presented at ultra-diluted doses. Further in-depth studies with additional cell lines and animal models are warranted to explore the clinical applicability of these agents.

  15. Collective motion patterns of swarms with delay coupling: Theory and experiment.

    PubMed

    Szwaykowska, Klementyna; Schwartz, Ira B; Mier-Y-Teran Romero, Luis; Heckman, Christoffer R; Mox, Dan; Hsieh, M Ani

    2016-03-01

    The formation of coherent patterns in swarms of interacting self-propelled autonomous agents is a subject of great interest in a wide range of application areas, ranging from engineering and physics to biology. In this paper, we model and experimentally realize a mixed-reality large-scale swarm of delay-coupled agents. The coupling term is modeled as a delayed communication relay of position. Our analyses, assuming agents communicating over an Erdös-Renyi network, demonstrate the existence of stable coherent patterns that can be achieved only with delay coupling and that are robust to decreasing network connectivity and heterogeneity in agent dynamics. We also show how the bifurcation structure for emergence of different patterns changes with heterogeneity in agent acceleration capabilities and limited connectivity in the network as a function of coupling strength and delay. Our results are verified through simulation as well as preliminary experimental results of delay-induced pattern formation in a mixed-reality swarm.

  16. Collective motion patterns of swarms with delay coupling: Theory and experiment

    NASA Astrophysics Data System (ADS)

    Szwaykowska, Klementyna; Schwartz, Ira B.; Mier-y-Teran Romero, Luis; Heckman, Christoffer R.; Mox, Dan; Hsieh, M. Ani

    2016-03-01

    The formation of coherent patterns in swarms of interacting self-propelled autonomous agents is a subject of great interest in a wide range of application areas, ranging from engineering and physics to biology. In this paper, we model and experimentally realize a mixed-reality large-scale swarm of delay-coupled agents. The coupling term is modeled as a delayed communication relay of position. Our analyses, assuming agents communicating over an Erdös-Renyi network, demonstrate the existence of stable coherent patterns that can be achieved only with delay coupling and that are robust to decreasing network connectivity and heterogeneity in agent dynamics. We also show how the bifurcation structure for emergence of different patterns changes with heterogeneity in agent acceleration capabilities and limited connectivity in the network as a function of coupling strength and delay. Our results are verified through simulation as well as preliminary experimental results of delay-induced pattern formation in a mixed-reality swarm.

  17. Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study

    PubMed Central

    2010-01-01

    Background Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. Methods A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Results Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. Conclusions This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for children with delayed speech development. Further studies should be conducted to investigate the mechanisms of these interactions in greater depth. Trial registration The trial is registered in the German clinical trials register; Trial-No.: DRKS00000343 PMID:20663139

  18. miR-378 attenuates muscle regeneration by delaying satellite cell activation and differentiation in mice.

    PubMed

    Zeng, Ping; Han, Wanhong; Li, Changyin; Li, Hu; Zhu, Dahai; Zhang, Yong; Liu, Xiaohong

    2016-09-01

    Skeletal muscle mass and homeostasis during postnatal muscle development and regeneration largely depend on adult muscle stem cells (satellite cells). We recently showed that global overexpression of miR-378 significantly reduced skeletal muscle mass in mice. In the current study, we used miR-378 transgenic (Tg) mice to assess the in vivo functional effects of miR-378 on skeletal muscle growth and regeneration. Cross-sectional analysis of skeletal muscle tissues showed that the number and size of myofibers were significantly lower in miR-378 Tg mice than in wild-type mice. Attenuated cardiotoxin-induced muscle regeneration in miR-378 Tg mice was found to be associated with delayed satellite cell activation and differentiation. Mechanistically, miR-378 was found to directly target Igf1r in muscle cells both in vitro and in vivo These miR-378 Tg mice may provide a model for investigating the physiological and pathological roles of skeletal muscle in muscle-associated diseases in humans, particularly in sarcopenia. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Small head size and delayed body weight growth in wild Japanese monkey fetuses after the Fukushima Daiichi nuclear disaster.

    PubMed

    Hayama, Shin-Ichi; Tsuchiya, Moe; Ochiai, Kazuhiko; Nakiri, Sachie; Nakanishi, Setsuko; Ishii, Naomi; Kato, Takuya; Tanaka, Aki; Konno, Fumiharu; Kawamoto, Yoshi; Omi, Toshinori

    2017-06-14

    To evaluate the biological effect of the Fukushima Daiichi nuclear disaster, relative differences in the growth of wild Japanese monkeys (Macaca fuscata) were measured before and after the disaster of 2011 in Fukushima City, which is approximately 70 km from the nuclear power plant, by performing external measurements on fetuses collected from 2008 to 2016. Comparing the relative growth of 31 fetuses conceived prior to the disaster and 31 fetuses conceived after the disaster in terms of body weight and head size (product of the occipital frontal diameter and biparietal diameter) to crown-rump length ratio revealed that body weight growth rate and proportional head size were significantly lower in fetuses conceived after the disaster. No significant difference was observed in nutritional indicators for the fetuses' mothers. Accordingly, radiation exposure could be one factor contributed to the observed growth delay in this study.

  20. Healthy aging: The ultimate preventative medicine.

    PubMed

    Kaeberlein, Matt; Rabinovitch, Peter S; Martin, George M

    2015-12-04

    Age is the greatest risk factor for nearly every major cause of mortality in developed nations. Despite this, most biomedical research focuses on individual disease processes without much consideration for the relationships between aging and disease. Recent discoveries in the field of geroscience, which aims to explain biological mechanisms of aging, have provided insights into molecular processes that underlie biological aging and, perhaps more importantly, potential interventions to delay aging and promote healthy longevity. Here we describe some of these advances, along with efforts to move geroscience from the bench to the clinic. We also propose that greater emphasis should be placed on research into basic aging processes, because interventions that slow aging will have a greater effect on quality of life compared with disease-specific approaches. Copyright © 2015, American Association for the Advancement of Science.

  1. A continuous time delay-difference type model (CTDDM) applied to stock assessment of the southern Atlantic albacore Thunnus alalunga

    NASA Astrophysics Data System (ADS)

    Liao, Baochao; Liu, Qun; Zhang, Kui; Baset, Abdul; Memon, Aamir Mahmood; Memon, Khadim Hussain; Han, Yanan

    2016-09-01

    A continuous time delay-diff erence model (CTDDM) has been established that considers continuous time delays of biological processes. The southern Atlantic albacore ( Thunnus alalunga) stock is the one of the commercially important tuna population in the marine world. The age structured production model (ASPM) and the surplus production model (SPM) have already been used to assess the albacore stock. However, the ASPM requires detailed biological information and the SPM lacks the biological realism. In this study, we focus on applying a CTDDM to the southern Atlantic albacore ( T. alalunga) species, which provides an alternative method to assess this fishery. It is the first time that CTDDM has been provided for assessing the Atlantic albacore ( T. alalunga) fishery. CTDDM obtained the 80% confidence interval of MSY (maximum sustainable yield) of (21 510 t, 23 118t). The catch in 2011 (24 100 t) is higher than the MSY values and the relative fishing mortality ratio ( F 2011/ F MSY) is higher than 1.0. The results of CTDDM were analyzed to verify the proposed methodology and provide reference information for the sustainable management of the southern Atlantic albacore stock. The CTDDM treats the recruitment, the growth, and the mortality rates as all varying continuously over time and fills gaps between ASPM and SPM in this stock assessment.

  2. Effects of high-energy shock waves combined with biological response modifiers or Adriamycin on a human kidney cancer xenograft.

    PubMed

    Oosterhof, G O; Smiths, G A; deRuyter, J E; Schalken, J A; Debruyne, F M

    1990-01-01

    We have studied the effect of high-energy shock waves (HESW) alone or in combination with biological response modifiers (BRMs) or Adriamycin on the growth of the NU-1 human kidney cancer xenograft. When HESW are administered repeatedly (four sessions of 800 shock waves on days 0, 2, 4 and 6) a prolonged delay in tumor growth was found compared with that following a single administration. This effect was temporary, and several days after stopping the HESW administration the tumor regained its original growth potential (same doubling time). Tumor growth was suppressed for a longer period by the combination of 4 sessions of HESW and a single administration of Adriamycin, 5 mg/kg. Combination of HESW treatment with interferon alpha (5.0 ng/g body weight, three times/week) and tumor necrosis factor alpha (500 ng/g body weight, 5 days/week) s.c. around the tumor resulted in a complete cessation of tumor growth. While Adriamycin had an additive effect on HESW treatment, the combination with BRMs was highly synergistic.

  3. Efficient rejection-based simulation of biochemical reactions with stochastic noise and delays

    NASA Astrophysics Data System (ADS)

    Thanh, Vo Hong; Priami, Corrado; Zunino, Roberto

    2014-10-01

    We propose a new exact stochastic rejection-based simulation algorithm for biochemical reactions and extend it to systems with delays. Our algorithm accelerates the simulation by pre-computing reaction propensity bounds to select the next reaction to perform. Exploiting such bounds, we are able to avoid recomputing propensities every time a (delayed) reaction is initiated or finished, as is typically necessary in standard approaches. Propensity updates in our approach are still performed, but only infrequently and limited for a small number of reactions, saving computation time and without sacrificing exactness. We evaluate the performance improvement of our algorithm by experimenting with concrete biological models.

  4. Contamination delays the release of Laricobius osakensis for biological control of hemlock woolly adelgid: cryptic diversity in Japanese Laricobius spp

    Treesearch

    Melissa J. Fischer; Nathan P. Havill; Carrie S. Jubb; Sean W. Prosser; Brent D. Opell; Scott M. Salom; Loke T. Kok

    2014-01-01

    Laricobius osakensis (Coleoptera: Derodontidae) was imported from Japan to the United States in 2006 for study in quarantine facilities as a potential biological control of Hemlock Woolly Adelgid. Laricobius osakensis was released from quarantine in 2010, but it was soon discovered that the colony also contained a cryptic species...

  5. Evidence for auditory-visual processing specific to biological motion.

    PubMed

    Wuerger, Sophie M; Crocker-Buque, Alexander; Meyer, Georg F

    2012-01-01

    Biological motion is usually associated with highly correlated sensory signals from more than one modality: an approaching human walker will not only have a visual representation, namely an increase in the retinal size of the walker's image, but also a synchronous auditory signal since the walker's footsteps will grow louder. We investigated whether the multisensorial processing of biological motion is subject to different constraints than ecologically invalid motion. Observers were presented with a visual point-light walker and/or synchronised auditory footsteps; the walker was either approaching the observer (looming motion) or walking away (receding motion). A scrambled point-light walker served as a control. Observers were asked to detect the walker's motion as quickly and as accurately as possible. In Experiment 1 we tested whether the reaction time advantage due to redundant information in the auditory and visual modality is specific for biological motion. We found no evidence for such an effect: the reaction time reduction was accounted for by statistical facilitation for both biological and scrambled motion. In Experiment 2, we dissociated the auditory and visual information and tested whether inconsistent motion directions across the auditory and visual modality yield longer reaction times in comparison to consistent motion directions. Here we find an effect specific to biological motion: motion incongruency leads to longer reaction times only when the visual walker is intact and recognisable as a human figure. If the figure of the walker is abolished by scrambling, motion incongruency has no effect on the speed of the observers' judgments. In conjunction with Experiment 1 this suggests that conflicting auditory-visual motion information of an intact human walker leads to interference and thereby delaying the response.

  6. The rise of oxygen in Earth's early ocean and atmosphere.

    PubMed

    Lyons, Timothy W; Reinhard, Christopher T; Planavsky, Noah J

    2014-02-20

    The rapid increase of carbon dioxide concentration in Earth's modern atmosphere is a matter of major concern. But for the atmosphere of roughly two-and-half billion years ago, interest centres on a different gas: free oxygen (O2) spawned by early biological production. The initial increase of O2 in the atmosphere, its delayed build-up in the ocean, its increase to near-modern levels in the sea and air two billion years later, and its cause-and-effect relationship with life are among the most compelling stories in Earth's history.

  7. Action potential propagation: ion current or intramembrane electric field?

    PubMed

    Martí, Albert; Pérez, Juan J; Madrenas, Jordi

    2018-01-01

    The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

  8. A Cross-Correlated Delay Shift Supervised Learning Method for Spiking Neurons with Application to Interictal Spike Detection in Epilepsy.

    PubMed

    Guo, Lilin; Wang, Zhenzhong; Cabrerizo, Mercedes; Adjouadi, Malek

    2017-05-01

    This study introduces a novel learning algorithm for spiking neurons, called CCDS, which is able to learn and reproduce arbitrary spike patterns in a supervised fashion allowing the processing of spatiotemporal information encoded in the precise timing of spikes. Unlike the Remote Supervised Method (ReSuMe), synapse delays and axonal delays in CCDS are variants which are modulated together with weights during learning. The CCDS rule is both biologically plausible and computationally efficient. The properties of this learning rule are investigated extensively through experimental evaluations in terms of reliability, adaptive learning performance, generality to different neuron models, learning in the presence of noise, effects of its learning parameters and classification performance. Results presented show that the CCDS learning method achieves learning accuracy and learning speed comparable with ReSuMe, but improves classification accuracy when compared to both the Spike Pattern Association Neuron (SPAN) learning rule and the Tempotron learning rule. The merit of CCDS rule is further validated on a practical example involving the automated detection of interictal spikes in EEG records of patients with epilepsy. Results again show that with proper encoding, the CCDS rule achieves good recognition performance.

  9. Elucidating dynamic responses of North Pacific fish populations to climatic forcing: Influence of life-history strategy

    NASA Astrophysics Data System (ADS)

    Yatsu, A.; Aydin, K. Y.; King, J. R.; McFarlane, G. A.; Chiba, S.; Tadokoro, K.; Kaeriyama, M.; Watanabe, Y.

    2008-05-01

    In order to explore mechanistic linkages between low-frequency ocean/climate variability, and fish population responses, we undertook comparative studies of time-series of recruitment-related productivity and the biomass levels of fish stocks representing five life-history strategies in the northern North Pacific between the 1950s and the present. We selected seven species: Japanese sardine ( Sardinopus melanostictus) and California sardine ( Sardinopus sagax) (opportunistic strategists), walleye pollock ( Theragra chalcogramma, intermediate strategist), pink salmon ( Oncorhynchus gorbuscha, salmonic strategist), sablefish ( Anoplopoma fimbria) and Pacific halibut ( Hippoglossus stenolepis) (periodic strategists) and spiny dogfish ( Squalus acanthias, equilibrium strategist). The responses in terms of productivity of sardine, pink salmon, sablefish and halibut to climatic regime shifts were generally immediate, delayed, or no substantial responses depending on the particular regime shift year and fish stock (population). In walleye pollock, there were some periods of high productivity and low productivity, but not coincidental to climatic regime shifts, likely due to indirect climate forcing impacts on both bottom-up and top-down processes. Biomass of zooplankton and all fish stocks examined, except for spiny dogfish whose data were limited, indicated a decadal pattern with the most gradual changes in periodic strategists and most intensive and rapid changes in opportunistic strategists. Responses of sardine productivity to regime shifts were the most intense, probably due to the absence of density-dependent effects and the availability of refuges from predators when sardine biomass was extremely low. Spiny dogfish were least affected by environmental variability. Conversely, spiny dogfish are likely to withstand only modest harvest rates due to their very low intrinsic rate of increase. Thus, each life-history strategy type had a unique response to climatic forcing, owing to their inherent biological traits such as mode, frequency and intensity of reproduction, early life style, age of maturity and longevity. On the other hand, responses of different stocks within a species to climatic regime shifts were unique to each local region, because large-scale climatic forcings are modulated by local physical, chemical and biological processes. The observed response time or absence of response in recruitment-related fish productivity to climatic regime shifts may be influenced by (1) local environmental conditions (immediate, with a delay or no effects), (2) phenological shifts in zooplankton life-history (immediate or with a delay), and (3) stochastic episodic events in both top-down and bottom-up processes (immediate, with a delay or no effects).

  10. Global asymptotic stability for HIV-1 dynamics with two distributed delays.

    PubMed

    Wang, Jinliang; Huang, Gang; Takeuchi, Yasuhiro

    2012-09-01

    Based on the drugs treatment to control HIV-1 infection and viral replication, we express the intracellular eclipse phase of virions in host cell as distributed delays because of pharmacological actions. In present paper, we investigate a class of HIV-1 infection dynamical model with two distributed delays. One of them describes the period between the time that HIV virion enters (infects) target cell and the time that the infected cell starts to produce new viral particles. The other describes the time for the virion maturation process. They are both allowed to tend to be infinite because of drugs resistent strains. By the Lyapunov direct method of and utilizing the technology of constructing Lyapunov functionals, we identify the basic reproduction number R(0) as a threshold quantity for the stability of equilibria. More precisely, if R(0) ≤ 1, the infection-free equilibrium is globally asymptotically stable; on the contrary, if R(0) > 1, then an infected equilibrium appears which is globally asymptotically stable. The dynamical results indicate that time delays have effect on the global stability of two equilibria through threshold value R(0), which is a decreasing function of delays. The biological meanings imply that any drugs that can prolong the time of viral reproduction through slowing down the reverse transcription of HIV in host and virus maturation process may also help control the HIV-1 infection and virus loads. Another way to increase the efficacy of the protease inhibitor and the reverse transcriptase inhibitor (i.e. increasing n(p) and n(rt)) is also desirable treatment strategies.

  11. Hybrid modeling in biochemical systems theory by means of functional petri nets.

    PubMed

    Wu, Jialiang; Voit, Eberhard

    2009-02-01

    Many biological systems are genuinely hybrids consisting of interacting discrete and continuous components and processes that often operate at different time scales. It is therefore desirable to create modeling frameworks capable of combining differently structured processes and permitting their analysis over multiple time horizons. During the past 40 years, Biochemical Systems Theory (BST) has been a very successful approach to elucidating metabolic, gene regulatory, and signaling systems. However, its foundation in ordinary differential equations has precluded BST from directly addressing problems containing switches, delays, and stochastic effects. In this study, we extend BST to hybrid modeling within the framework of Hybrid Functional Petri Nets (HFPN). First, we show how the canonical GMA and S-system models in BST can be directly implemented in a standard Petri Net framework. In a second step we demonstrate how to account for different types of time delays as well as for discrete, stochastic, and switching effects. Using representative test cases, we validate the hybrid modeling approach through comparative analyses and simulations with other approaches and highlight the feasibility, quality, and efficiency of the hybrid method.

  12. Determinants of relative skeletal maturity in South African children.

    PubMed

    Hawley, Nicola L; Rousham, Emily K; Johnson, William; Norris, Shane A; Pettifor, John M; Cameron, Noël

    2012-01-01

    The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex-specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (p<0.01) and heavier at 2 years (p<0.01) predicted less delay in RSM at age 9/10 years, independent of current size and body composition. In females, both height at 2 years and conditional weight at 2 years predicted less delay in RSM at 9/10 years (p<0.05) but this effect was mediated by current body composition. Having greater lean mass at 9/10 years was associated with less delayed RSM in females (p<0.01) as was pubertal status at the time of skeletal maturity assessment (p<0.01). This study identifies several predictors of skeletal maturation at 9/10 years, indicating a role for early life exposures in determining the rate of skeletal maturation during childhood independently of current stature. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Curcumin Alleviates the Functional Gastrointestinal Disorders of Mice In Vivo.

    PubMed

    Yu, Jing; Xu, Wen-Hua; Sun, Wei; Sun, Yi; Guo, Zhi-Li; Yu, Xiao-Ling

    2017-12-01

    Curcumin is a natural polyphenol extracted from the turmeric rhizome, which has a wide range of biological activities, but until now the effects of curcumin on the gastrointestinal peristalsis have not been fully understood. In vivo study, we observed the effects of curcumin on gastric emptying and intestinal propulsion rates of mice in normal state and in delayed state by atropine (ATR) or nitric oxide precursor L-arginine (L-Arg). An in vitro study explored the direct effects of curcumin on the intestinal contractility, but were studied through measuring spontaneous contraction of isolated jejunum of mice. Our results showed that intragastric administration of curcumin (200 mg/kg/day) for 10-20 days significantly improved gastric emptying and intestinal propulsion rates of mice delayed by ATR. Moreover, intragastric administration of curcumin (200 mg/kg/day) for 15 days also significantly improved mice gastric emptying and intestinal propulsion rates delayed by L-Arg. There was no significant effect on normal gastrointestinal propulsion of mice after intragastric administration of curcumin (200 mg/kg/day) for 1-20 days. When normal isolated jejunum of mice were incubated with curcumin in vitro, the amplitude of the spontaneous contractile waves of jejunum was reduced in a concentration-dependent manner. Moreover, curcumin reduced the amplitude of the contractile waves of jejunum in both contracted and relaxed state induced by acetylcholine or ATR individually. Taken together, our results suggest that curcumin has quite different effects on gastrointestinal peristalsis in vivo and in vitro. Moderate dose of curcumin by intragastric administration for more than 10 days can alleviate the functional gastrointestinal disorders of mice, but cannot affect normal gastrointestinal propulsion.

  14. Gerontology Nurses: Are They Needed in the Air Force?

    DTIC Science & Technology

    1985-04-01

    post-World War II "baby boom" and advances in technology. The death rates from heart disease and cerebrovascular accidents have steeply declined in the...people, the elderly also react differently to illnesses.j Some symptoms may be masked or absent causing a delay in seeking medical attention. This delay...biological factors. 4. The unusual or atypical response of the elderly to illness 5. The different forms of disease that appear in the elderly 6

  15. Biological control of the Pulse beetle, Callosobruchus maculatus in stored grains using the entomopathogenic bacteria, Bacillus thuringiensis.

    PubMed

    Malaikozhundan, Balasubramanian; Vinodhini, Jayaraj

    2018-01-01

    In the present study, we reported the biological control of stored product insect pest, Callosobruchus maculatus using the entomopathogenic bacteria, Bacillus thuringiensis. A significant delay in the larval, pupal and total development period of C. maculatus was observed after treatment with B. thuringiensis at 4 × 10 8  cells/mL. Furthermore, B. thuringiensis are highly effective in the control of C. maculatus and produced 100% mortality at 4 × 10 8  cells/mL. The LC 50 value was estimated to be 3 × 10 7  cells/mL. In addition, a significant decrease in the activity of mid-gut α-amylase, cysteine protease, α & β-glucosidases, lipase, glutathione S-transferase (GST) and lactate dehydrogenase (LDH) was observed after treatment with B. thuringiensis at 4 × 10 8  cells/mL. This study concludes that B. thuringiensis are more effective against C. maculatus and could be used as a potential biological control agent in the management of stored product insect pests in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Microgravity Effects on the Early Events of Biological Nitrogen Fixation in Medicago Truncatula: Results from the SyNRGE Experiment

    NASA Astrophysics Data System (ADS)

    Stutte, Gary W.; Roberts, Michael S.

    2013-02-01

    SyNRGE (Symbiotic Nodulation in a Reduced Gravity Environment) was a sortie mission on STS-135 in the Biological Research in Canisters (BRIC) hardware to study the effect of μg on a plant-microbe symbiosis resulting in biological nitrogen fixation. Medicago truncatula, a model species for the legume family, was inoculated with its bacterial symbiont, Sinorhizobium meliloti, to observe early biomolecular events associated with infection and nodulation in Petri Dish Fixation Units (PDFU’s). Two sets of experiments were conducted in orbit and in 24-hour delayed ground controls. Experiments were designed to determine if S. meliloti would infect M. truncatula and initiate biomolecular changes associated with nodule formation and if the μg environment altered the host plant and/or bacteria to induce nodule formation upon return to 1g. Initial analysis results demonstrate that the legumes and bacteria cultivated in μg have potential to develop a symbiotic interaction, but suggest that μg alters their ability to form nodules upon return to 1g. (Research supported by NASA ESMD/ Advance Capabilities Division grant NNX10AR09A)

  17. Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

    PubMed Central

    Goodman, S. B.; Gibon, E.; Pajarinen, J.; Lin, T.-H.; Keeney, M.; Ren, P.-G.; Nich, C.; Yao, Z.; Egashira, K.; Yang, F.; Konttinen, Y. T.

    2014-01-01

    Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 (pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-κB) by delivery of an NF-κB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants. PMID:24478281

  18. Homeostatic plasticity for single node delay-coupled reservoir computing.

    PubMed

    Toutounji, Hazem; Schumacher, Johannes; Pipa, Gordon

    2015-06-01

    Supplementing a differential equation with delays results in an infinite-dimensional dynamical system. This property provides the basis for a reservoir computing architecture, where the recurrent neural network is replaced by a single nonlinear node, delay-coupled to itself. Instead of the spatial topology of a network, subunits in the delay-coupled reservoir are multiplexed in time along one delay span of the system. The computational power of the reservoir is contingent on this temporal multiplexing. Here, we learn optimal temporal multiplexing by means of a biologically inspired homeostatic plasticity mechanism. Plasticity acts locally and changes the distances between the subunits along the delay, depending on how responsive these subunits are to the input. After analytically deriving the learning mechanism, we illustrate its role in improving the reservoir's computational power. To this end, we investigate, first, the increase of the reservoir's memory capacity. Second, we predict a NARMA-10 time series, showing that plasticity reduces the normalized root-mean-square error by more than 20%. Third, we discuss plasticity's influence on the reservoir's input-information capacity, the coupling strength between subunits, and the distribution of the readout coefficients.

  19. The amount effect and marginal value.

    PubMed

    Rachlin, Howard; Arfer, Kodi B; Safin, Vasiliy; Yen, Ming

    2015-07-01

    The amount effect of delay discounting (by which the value of larger reward amounts is discounted by delay at a lower rate than that of smaller amounts) strictly implies that value functions (value as a function of amount) are steeper at greater delays than they are at lesser delays. That is, the amount effect and the difference in value functions at different delays are actually a single empirical finding. Amount effects of delay discounting are typically found with choice experiments. Value functions for immediate rewards have been empirically obtained by direct judgment. (Value functions for delayed rewards have not been previously obtained.) The present experiment obtained value functions for both immediate and delayed rewards by direct judgment and found them to be steeper when the rewards were delayed--hence, finding an amount effect with delay discounting. © Society for the Experimental Analysis of Behavior.

  20. Influence of shieldings or antioxidants on DNA damage and early and delyed cell death induced in human fibroblasts by accelerated 595 MeV/u Fe ions

    NASA Astrophysics Data System (ADS)

    Antonelli, Francesca; Esposito, Giuseppe; Dini, Valentina; Belli, Mauro; Campa, Alessandro; Sorrentino, Eugenio; Antonella Tabocchini, Maria; Lobascio, Cesare; Berra, Bruno

    HZE particles from space radiation raise an important protection concern during long-term astronauts' travels. As high charge, high energy particles interact with a shield, both projec-tile and target fragmentation may occurs, so that the biological properties of the emerging radiation field depend on the nature and energy of the incident particles, and on the nature and thickness of the shield. We have studied the influence of PMMA and Kevlar shielding as well as the antioxidant compounds Rosmarinic acid or Resveratrol on DNA damage induction and processing (as evaluated by the g-H2AX phosphorylation assay) and on early and delayed cell death in AG01522 human fibroblasts irradiated with Fe ions of 595 MeV/u at the NASA Space Radiation Laboratory (NSRL), Brookhaven National Laboratory (BNL, Upton, USA). Insertion of PMMA or Kevlar shields (10 g/cm2 thick) gave no substantial change in the bio-logical effect per unit dose on the sample for all the end points studied. When irradiation was performed in the presence of 300 mM Rosmarinic acid or Resveratrol no difference were found for both early and delayed cell death, while a slight protective effect was observed for the initial and residual DNA damage. For both early and delayed cell death, Fe-ions are more effective than g-rays. The number of Fe-ion induced g-H2AX foci is instead lower than that induced by g-rays, due to the presence of multiple DSB within a single focus induced by Fe-ions. From a comparison of the g-H2AX data with the results on DNA fragmentation obtained with 414 MeV/u Fe ions at the Heavy Ions Medical Accelerator (HIMAC, Chiba, Japan) and with 1 GeV/u Fe ions at BNL, in the absence or in the presence of PMMA shields (Esposito et al, Advance in Space Research 2004) we speculate that the overall effect of the shield is a balance between the contributions due to the slowing down of the primary particles and that due to the nuclear fragmentation. Acknowledgment: Financial support from ASI project "From Molecules to Man: Space Re-search Applied to the improvement of the Quality of Life of the Ageing Population on Earth (MoMa)"

  1. A COMPARISON OF THE EFFECTS OF BRIEF RULES, A TIMER, AND PREFERRED TOYS ON SELF-CONTROL

    PubMed Central

    Newquist, Matthew H; Dozier, Claudia L; Neidert, Pamela L

    2012-01-01

    Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining delay fading with a countdown timer are effective for increasing self-control (i.e., choosing the large but delayed reinforcer over the small but immediate reinforcer). The purpose of the current study was to compare the effects of various interventions in the absence of delay fading (i.e., providing brief rules, providing a countdown timer during the delay, or providing preferred toys during the delay) on self-control. Results suggested that providing brief rules or a countdown timer during the delay was ineffective for enhancing self-control. However, providing preferred toys during the delay effectively enhanced self-control. PMID:23060664

  2. A comparison of the effects of brief rules, a timer, and preferred toys on self-control.

    PubMed

    Newquist, Matthew H; Dozier, Claudia L; Neidert, Pamela L

    2012-01-01

    Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining delay fading with a countdown timer are effective for increasing self-control (i.e., choosing the large but delayed reinforcer over the small but immediate reinforcer). The purpose of the current study was to compare the effects of various interventions in the absence of delay fading (i.e., providing brief rules, providing a countdown timer during the delay, or providing preferred toys during the delay) on self-control. Results suggested that providing brief rules or a countdown timer during the delay was ineffective for enhancing self-control. However, providing preferred toys during the delay effectively enhanced self-control.

  3. Detection of time delays and directional interactions based on time series from complex dynamical systems

    NASA Astrophysics Data System (ADS)

    Ma, Huanfei; Leng, Siyang; Tao, Chenyang; Ying, Xiong; Kurths, Jürgen; Lai, Ying-Cheng; Lin, Wei

    2017-07-01

    Data-based and model-free accurate identification of intrinsic time delays and directional interactions is an extremely challenging problem in complex dynamical systems and their networks reconstruction. A model-free method with new scores is proposed to be generally capable of detecting single, multiple, and distributed time delays. The method is applicable not only to mutually interacting dynamical variables but also to self-interacting variables in a time-delayed feedback loop. Validation of the method is carried out using physical, biological, and ecological models and real data sets. Especially, applying the method to air pollution data and hospital admission records of cardiovascular diseases in Hong Kong reveals the major air pollutants as a cause of the diseases and, more importantly, it uncovers a hidden time delay (about 30-40 days) in the causal influence that previous studies failed to detect. The proposed method is expected to be universally applicable to ascertaining and quantifying subtle interactions (e.g., causation) in complex systems arising from a broad range of disciplines.

  4. The Impact of Competing Time Delays in Stochastic Coordination Problems

    NASA Astrophysics Data System (ADS)

    Korniss, G.; Hunt, D.; Szymanski, B. K.

    2011-03-01

    Coordinating, distributing, and balancing resources in coupled systems is a complex task as these operations are very sensitive to time delays. Delays are present in most real communication and information systems, including info-social and neuro-biological networks, and can be attributed to both non-zero transmission times between different units of the system and to non-zero times it takes to process the information and execute the desired action at the individual units. Here, we investigate the importance and impact of these two types of delays in a simple coordination (synchronization) problem in a noisy environment. We establish the scaling theory for the phase boundary of synchronization and for the steady-state fluctuations in the synchronizable regime. Further, we provide the asymptotic behavior near the boundary of the synchronizable regime. Our results also imply the potential for optimization and trade-offs in stochastic synchronization and coordination problems with time delays. Supported in part by DTRA, ARL, and ONR.

  5. Efficient rejection-based simulation of biochemical reactions with stochastic noise and delays

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

    Thanh, Vo Hong, E-mail: vo@cosbi.eu; Priami, Corrado, E-mail: priami@cosbi.eu; Department of Mathematics, University of Trento

    2014-10-07

    We propose a new exact stochastic rejection-based simulation algorithm for biochemical reactions and extend it to systems with delays. Our algorithm accelerates the simulation by pre-computing reaction propensity bounds to select the next reaction to perform. Exploiting such bounds, we are able to avoid recomputing propensities every time a (delayed) reaction is initiated or finished, as is typically necessary in standard approaches. Propensity updates in our approach are still performed, but only infrequently and limited for a small number of reactions, saving computation time and without sacrificing exactness. We evaluate the performance improvement of our algorithm by experimenting with concretemore » biological models.« less

  6. The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers.

    PubMed

    Hindocha, C; Freeman, T P; Grabski, M; Crudgington, H; Davies, A C; Stroud, J B; Das, R K; Lawn, W; Morgan, C J A; Curran, H V

    2018-05-15

    Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.

  7. Autonomic reactivity and hypothalamic pituitary adrenal axis dysregulation in spouses of Oklahoma City bombing survivors 7 years after the attack

    PubMed Central

    Pfefferbaum, Betty; Tucker, Phebe; North, Carol S.; Jeon-Slaughter, Haekyung

    2012-01-01

    Objective The objective of this exploratory pilot study was to examine autonomic reactivity and hypothalamic pituitary adrenal axis dysregulation in spouses of highly exposed survivors of the 1995 Oklahoma City bombing. Methods This study compared psychiatric diagnoses and biological stress markers (physiological reactivity and cortisol measures) in spouses of bombing survivors and matched community participants. Spouses were recruited through bombing survivors who participated in prior studies. Individuals with medical illnesses and those taking psychotropic medications that would confound biological stress measures were excluded. The final sample included 15 spouses and 15 community participants. The primary outcome measures were psychiatric diagnoses assessed with the Diagnostic Interview Schedule for DSM-IV (DIS-IV). Biological stress markers were physiological reactivity and recovery in heart rate and blood pressure responses to a trauma interview and cortisol (morning, afternoon, and diurnal variation). Results Compared to the community participants, spouses evidenced greater reactivity in heart rate, systolic blood pressure, and diastolic blood pressure; delayed recovery in systolic blood pressure; and higher afternoon salivary cortisol. Conclusions The results support the need for further research in this area to clarify post-disaster effects on biological stress measures in the spouses of survivors and the potential significance of these effects and to address the needs of this important population which may be overlooked in recovery efforts. PMID:22520087

  8. Autonomic reactivity and hypothalamic pituitary adrenal axis dysregulation in spouses of Oklahoma City bombing survivors 7 years after the attack.

    PubMed

    Pfefferbaum, Betty; Tucker, Phebe; North, Carol S; Jeon-Slaughter, Haekyung

    2012-10-01

    The objective of this exploratory pilot study was to examine autonomic reactivity and hypothalamic pituitary adrenal axis dysregulation in spouses of highly exposed survivors of the 1995 Oklahoma City bombing. This study compared psychiatric diagnoses and biological stress markers (physiological reactivity and cortisol measures) in spouses of bombing survivors and matched community participants. Spouses were recruited through bombing survivors who participated in prior studies. Individuals with medical illnesses and those taking psychotropic medications that would confound biological stress measures were excluded. The final sample included 15 spouses and 15 community participants. The primary outcome measures were psychiatric diagnoses assessed with the Diagnostic Interview Schedule for DSM-IV (DIS-IV). Biological stress markers were physiological reactivity and recovery in heart rate and blood pressure responses to a trauma interview and cortisol (morning, afternoon, and diurnal variation). Compared to the community participants, spouses evidenced greater reactivity in heart rate, systolic blood pressure, and diastolic blood pressure; delayed recovery in systolic blood pressure; and higher afternoon salivary cortisol. The results support the need for further research in this area to clarify post-disaster effects on biological stress measures in the spouses of survivors and the potential significance of these effects and to address the needs of this important population which may be overlooked in recovery efforts. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells.

    PubMed

    Kim, Dae Seong; Ko, Young Jong; Lee, Myoung Woo; Park, Hyun Jin; Park, Yoo Jin; Kim, Dong-Ik; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2016-11-01

    Culture of mesenchymal stem cells (MSCs) under ambient conditions does not replicate the low oxygen environment of normal physiological or pathological states and can result in cellular impairment during culture. To overcome these limitations, we explored the effect of hypoxia (1 % O 2 ) on the biological characteristics of MSCs over the course of different culture periods. The following biological characteristics were examined in human bone marrow-derived MSCs cultured under hypoxia for 8 weeks: proliferation rate, morphology, cell size, senescence, immunophenotypic characteristics, and the expression levels of stemness-associated factors and cytokine and chemokine genes. MSCs cultured under hypoxia for approximately 2 weeks showed increased proliferation and viability. During long-term culture, hypoxia delayed phenotypic changes in MSCs, such as increased cell volume, altered morphology, and the expression of senescence-associated-β-gal, without altering their characteristic immunophenotypic characteristics. Furthermore, hypoxia increased the expression of stemness and chemokine-related genes, including OCT4 and CXCR7, and did not decrease the expression of KLF4, C-MYC, CCL2, CXCL9, CXCL10, and CXCR4 compared with levels in cells cultured under normoxia. In conclusion, low oxygen tension improved the biological characteristics of MSCs during ex vivo expansion. These data suggest that hypoxic culture could be a useful method for increasing the efficacy of MSC cell therapies.

  10. Arctigenin, a potential anti-arrhythmic agent, inhibits aconitine-induced arrhythmia by regulating multi-ion channels.

    PubMed

    Zhao, Zhenying; Yin, Yongqiang; Wu, Hong; Jiang, Min; Lou, Jianshi; Bai, Gang; Luo, Guo'an

    2013-01-01

    Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I(Na)), L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to)) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of arctigenin, leading to its antiarrhythmic effect. © 2013 S. Karger AG, Basel.

  11. Impacts of the phenylpyrazole insecticide fipronil on larval fish: time-series gene transcription responses in fathead minnow (Pimephales promelas) following short-term exposure.

    PubMed

    Beggel, Sebastian; Werner, Inge; Connon, Richard E; Geist, Juergen P

    2012-06-01

    The utilization of molecular endpoints in ecotoxicology can provide rapid and valuable information on immediate organismal responses to chemical stressors and is increasingly used for mechanistic interpretation of effects at higher levels of biological organization. This study contributes knowledge on the sublethal effects of a commonly used insecticide, the phenylpyrazole fipronil, on larval fathead minnow (Pimephales promelas), utilizing a quantitative transcriptomic approach. Immediately after 24h of exposure to fipronil concentrations of ≥31 μg.L(-1), highly significant changes in gene transcription were observed for aspartoacylase, metallothionein, glucocorticoid receptor, cytochrome P450 3A126 and vitellogenin. Different mechanisms of toxicity were apparent over the course of the experiment, with short-term responses indicating neurotoxic effects. After 6 days of recovery, endocrine effects were observed with vitellogenin being up-regulated 90-fold at 61 μg.L(-1) fipronil. Principal component analysis demonstrated a significant increase in gene transcription changes over time and during the recovery period. In conclusion, multiple mechanisms of action were observed in response to fipronil exposure, and unknown delayed effects would have been missed if transcriptomic responses had only been measured at a single time-point. These challenges can be overcome by the inclusion of multiple endpoints and delayed effects in experimental designs. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry

    PubMed Central

    Choudhury, Niloy; Chen, Fangyi; Wang, Ruikang K.; Jacques, Steven L.; Nuttall, Alfred L.

    2013-01-01

    Abstract. We present an optical vibrometer based on delay-encoded, dual-beamlet phase-sensitive Fourier domain interferometric system to provide depth-resolved subnanometer scale vibration information from scattering biological specimens. System characterization, calibration, and preliminary vibrometry with biological specimens were performed. The proposed system has the potential to provide both amplitude and direction of vibration of tissue microstructures on a single two-dimensional plane. PMID:23455961

  13. Mechanisms of neuroblastoma regression

    PubMed Central

    Brodeur, Garrett M.; Bagatell, Rochelle

    2014-01-01

    Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches. PMID:25331179

  14. Adaptive developmental delay in Chagas disease vectors: an evolutionary ecology approach.

    PubMed

    Menu, Frédéric; Ginoux, Marine; Rajon, Etienne; Lazzari, Claudio R; Rabinovich, Jorge E

    2010-05-25

    The developmental time of vector insects is important in population dynamics, evolutionary biology, epidemiology and in their responses to global climatic change. In the triatomines (Triatominae, Reduviidae), vectors of Chagas disease, evolutionary ecology concepts, which may allow for a better understanding of their biology, have not been applied. Despite delay in the molting in some individuals observed in triatomines, no effort was made to explain this variability. We applied four methods: (1) an e-mail survey sent to 30 researchers with experience in triatomines, (2) a statistical description of the developmental time of eleven triatomine species, (3) a relationship between development time pattern and climatic inter-annual variability, (4) a mathematical optimization model of evolution of developmental delay (diapause). 85.6% of responses informed on prolonged developmental times in 5(th) instar nymphs, with 20 species identified with remarkable developmental delays. The developmental time analysis showed some degree of bi-modal pattern of the development time of the 5(th) instars in nine out of eleven species but no trend between development time pattern and climatic inter-annual variability was observed. Our optimization model predicts that the developmental delays could be due to an adaptive risk-spreading diapause strategy, only if survival throughout the diapause period and the probability of random occurrence of "bad" environmental conditions are sufficiently high. Developmental delay may not be a simple non-adaptive phenotypic plasticity in development time, and could be a form of adaptive diapause associated to a physiological mechanism related to the postponement of the initiation of reproduction, as an adaptation to environmental stochasticity through a spreading of risk (bet-hedging) strategy. We identify a series of parameters that can be measured in the field and laboratory to test this hypothesis. The importance of these findings is discussed in terms of global climatic change and epidemiological consequences.

  15. Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

    PubMed Central

    Li, Xia; Rao, Shaoqi; Jiang, Wei; Li, Chuanxing; Xiao, Yun; Guo, Zheng; Zhang, Qingpu; Wang, Lihong; Du, Lei; Li, Jing; Li, Li; Zhang, Tianwen; Wang, Qing K

    2006-01-01

    Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network) to address the underlying regulations of genes that can span any unit(s) of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex gene regulations related to the development, aging and progressive pathogenesis of a complex disease where potential dependences between different experiment units might occurs. PMID:16420705

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

    D'Huys, Otti, E-mail: otti.dhuys@phy.duke.edu; Haynes, Nicholas D.; Lohmann, Johannes

    Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays. We observe transients that last millions to billions of characteristic time scales and scale exponentially with the amount of time delaysmore » between nodes, a phenomenon known as super-transient scaling. We develop a hybrid model that includes time delays along network links and allows for stochastic variation in the delays. Using this model, we explain the observed super-transient scaling of both motifs and recreate the experimentally measured transient distributions.« less

  17. Biological consequences of earlier snowmelt from desert dust deposition in alpine landscapes.

    PubMed

    Steltzer, Heidi; Landry, Chris; Painter, Thomas H; Anderson, Justin; Ayres, Edward

    2009-07-14

    Dust deposition to mountain snow cover, which has increased since the late 19(th) century, accelerates the rate of snowmelt by increasing the solar radiation absorbed by the snowpack. Snowmelt occurs earlier, but is decoupled from seasonal warming. Climate warming advances the timing of snowmelt and early season phenological events (e.g., the onset of greening and flowering); however, earlier snowmelt without warmer temperatures may have a different effect on phenology. Here, we report the results of a set of snowmelt manipulations in which radiation-absorbing fabric and the addition and removal of dust from the surface of the snowpack advanced or delayed snowmelt in the alpine tundra. These changes in the timing of snowmelt were superimposed on a system where the timing of snowmelt varies with topography and has been affected by increased dust loading. At the community level, phenology exhibited a threshold response to the timing of snowmelt. Greening and flowering were delayed before seasonal warming, after which there was a linear relationship between the date of snowmelt and the timing of phenological events. Consequently, the effects of earlier snowmelt on phenology differed in relation to topography, which resulted in increasing synchronicity in phenology across the alpine landscape with increasingly earlier snowmelt. The consequences of earlier snowmelt from increased dust deposition differ from climate warming and include delayed phenology, leading to synchronized growth and flowering across the landscape and the opportunity for altered species interactions, landscape-scale gene flow via pollination, and nutrient cycling.

  18. Thinking of biology: asteroid impacts, microbes, and the cooling of the atmosphere

    NASA Technical Reports Server (NTRS)

    Oberbeck, V. R.; Mancinelli, R. L.

    1994-01-01

    The authors examine the cooling of the Earth's surface from 3.75 to 1 billion years ago. Three effects of the bombardment of Earth by asteroids and comets that may have delayed surface cooling include time to form continents, volatilization of carbonate rocks which released carbon dioxide into the atmosphere, and inability of microbes to inhabit land masses during large impact events. Continental microbes may have helped reduce high temperatures from 3.75 to 3.5 billion years ago. If so, the evolutionary sequence of microbes is proposed to be anaerobic heterotrophs, chemoautotrophs, and then photoautotrophs.

  19. History of Science as an Instructional Context: Student Learning in Genetics and Nature of Science

    NASA Astrophysics Data System (ADS)

    Kim, Sun Young; Irving, Karen E.

    2010-02-01

    This study (1) explores the effectiveness of the contextualized history of science on student learning of nature of science (NOS) and genetics content knowledge (GCK), especially interrelationships among various genetics concepts, in high school biology classrooms; (2) provides an exemplar for teachers on how to utilize history of science in genetics instruction; and (3) suggests a modified concept mapping assessment tool for both NOS and GCK. A quasi-experimental control group research design was utilized with pretests, posttests, and delayed posttests, combining qualitative data and quantitative data. The experimental group was taught with historical curricular lessons, while the control group was taught with non-historical curricular lessons. The results indicated that students in the experimental group developed better understanding in targeted aspects of NOS immediately after the intervention and retained their learning 2 months after the intervention. Both groups developed similar genetics knowledge in the posttest, and revealed a slight decay in their understanding in the delayed posttest.

  20. Collective signaling behavior in a networked-oscillator model

    NASA Astrophysics Data System (ADS)

    Liu, Z.-H.; Hui, P. M.

    2007-09-01

    We propose and study the collective behavior of a model of networked signaling objects that incorporates several ingredients of real-life systems. These ingredients include spatial inhomogeneity with grouping of signaling objects, signal attenuation with distance, and delayed and impulsive coupling between non-identical signaling objects. Depending on the coupling strength and/or time-delay effect, the model exhibits completely, partially, and locally collective signaling behavior. In particular, a correlated signaling (CS) behavior is observed in which there exist time durations when nearly a constant fraction of oscillators in the system are in the signaling state. These time durations are much longer than the duration of a spike when a single oscillator signals, and they are separated by regular intervals in which nearly all oscillators are silent. Such CS behavior is similar to that observed in biological systems such as fireflies, cicadas, crickets, and frogs. The robustness of the CS behavior against noise is also studied. It is found that properly adjusting the coupling strength and noise level could enhance the correlated behavior.

  1. Single-photon imager based on a superconducting nanowire delay line

    NASA Astrophysics Data System (ADS)

    Zhao, Qing-Yuan; Zhu, Di; Calandri, Niccolò; Dane, Andrew E.; McCaughan, Adam N.; Bellei, Francesco; Wang, Hao-Zhu; Santavicca, Daniel F.; Berggren, Karl K.

    2017-03-01

    Detecting spatial and temporal information of individual photons is critical to applications in spectroscopy, communication, biological imaging, astronomical observation and quantum-information processing. Here we demonstrate a scalable single-photon imager using a single continuous superconducting nanowire that is not only a single-photon detector but also functions as an efficient microwave delay line. In this context, photon-detection pulses are guided in the nanowire and enable the readout of the position and time of photon-absorption events from the arrival times of the detection pulses at the nanowire's two ends. Experimentally, we slowed down the velocity of pulse propagation to ∼2% of the speed of light in free space. In a 19.7 mm long nanowire that meandered across an area of 286 × 193 μm2, we were able to resolve ∼590 effective pixels with a temporal resolution of 50 ps (full width at half maximum). The nanowire imager presents a scalable approach for high-resolution photon imaging in space and time.

  2. Antimalarial drug resistance: a review of the biology and strategies to delay emergence and spread.

    PubMed

    Klein, E Y

    2013-04-01

    The emergence of resistance to former first-line antimalarial drugs has been an unmitigated disaster. In recent years, artemisinin class drugs have become standard and they are considered an essential tool for helping to eradicate the disease. However, their ability to reduce morbidity and mortality and to slow transmission requires the maintenance of effectiveness. Recently, an artemisinin delayed-clearance phenotype was described. This is believed to be the precursor to resistance and threatens local elimination and global eradication plans. Understanding how resistance emerges and spreads is important for developing strategies to contain its spread. Resistance is the result of two processes: (i) drug selection of resistant parasites; and (ii) the spread of resistance. In this review, we examine the factors that lead to both drug selection and the spread of resistance. We then examine strategies for controlling the spread of resistance, pointing out the complexities and deficiencies in predicting how resistance will spread. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  3. A supervised learning rule for classification of spatiotemporal spike patterns.

    PubMed

    Lilin Guo; Zhenzhong Wang; Adjouadi, Malek

    2016-08-01

    This study introduces a novel supervised algorithm for spiking neurons that take into consideration synapse delays and axonal delays associated with weights. It can be utilized for both classification and association and uses several biologically influenced properties, such as axonal and synaptic delays. This algorithm also takes into consideration spike-timing-dependent plasticity as in Remote Supervised Method (ReSuMe). This paper focuses on the classification aspect alone. Spiked neurons trained according to this proposed learning rule are capable of classifying different categories by the associated sequences of precisely timed spikes. Simulation results have shown that the proposed learning method greatly improves classification accuracy when compared to the Spike Pattern Association Neuron (SPAN) and the Tempotron learning rule.

  4. Facilitating a More Efficient Commercial Review Process for Pediatric Drugs and Biologics

    PubMed Central

    Rykhus, Ryan D.; Shepard, Zachary V.; Young, Alix; Frisby, Hadley; Calder, Kailee A.; Coon, Collin M.; Falk, Justin A.; McAndrews, Sydney R.; Turner, Aspen; Chang, Christina; Michelsohn, Johanna; Petch, Raegan; Dieker, Sarah M.; Markworth, Benjamin H.; Alamo-Perez, Kevin; Hosack, Aaron J.; Berg, Jacob M.; Schmidt, Christian; Storsberg, Joachim; Brown, Mark A.

    Over the past two decades, the biopharmaceutical industry has seen unprecedented expansion and innovation in concert with significant technological advancements. While the industry has experienced marked growth, the regulatory system in the United States still operates at a capacity much lower than the influx of new drug and biologic candidates. As a result, it has become standard for months or even years of waiting for commercial approval by the U.S. Food and Drug Administration. These regulatory delays have generated a system that stifles growth and innovation due to the exorbitant costs associated with awaiting approval from the nation’s sole regulatory agency. The recent re-emergence of diseases that impact pediatric demographics represents one particularly acute reason for developing a regulatory system that facilitates a more efficient commercial review process. Herein, we present a range of initiatives that could represent early steps toward alleviating the delays in approving life-saving therapeutics. PMID:29271878

  5. Bone healing in 2016

    PubMed Central

    Buza, John A.; Einhorn, Thomas

    2016-01-01

    Summary Delayed fracture healing and nonunion occurs in up to 5–10% of all fractures, and can present a challenging clinical scenario for the treating physician. Methods for the enhancement of skeletal repair may benefit patients that are at risk of, or have experienced, delayed healing or nonunion. These methods can be categorized into either physical stimulation therapies or biological therapies. Physical stimulation therapies include electrical stimulation, low-intensity pulsed ultrasonography, or extracorporeal shock wave therapy. Biological therapies can be further classified into local or systemic therapy based on the method of delivery. Local methods include autologous bone marrow, autologous bone graft, fibroblast growth factor-2, platelet-rich plasma, platelet-derived growth factor, and bone morphogenetic proteins. Systemic therapies include parathyroid hormone and bisphosphonates. This article reviews the current applications and supporting evidence for the use of these therapies in the enhancement of fracture healing. PMID:27920804

  6. Effect of electromagnetic fields on some biomechanical and biochemical properties of rat’s blood

    NASA Astrophysics Data System (ADS)

    Mohaseb, M. A.; Shahin, F. A.; Ali, F. M.; Baieth, H. A.

    2017-06-01

    In order to study the effect of electromagnetic fields (0.3 mT, 50 Hz) on some biomechanical and biochemical properties of rats’ blood, healthy thirty male albino rats of 150 ± 10 g were divided into three equal groups namely A, B1, B2. Group A used as a control group, group B1 was continuously exposed to a magnetic field of (0.3 mT, 50 Hz) for a period of 21 days for direct effect studies. Group B2 was continuously exposed to the same magnetic field for the same period of time, then was housed away from the magnetic field for a period of 45 days for delayed effects studies. After examination, the results indicated that the apparent viscosity and the consistency index increased significantly and very high significantly for groub B1 and B2 compared to control at P<0.05. Red blood cell counts (RBCs) membrane elasticity had significantly and very high significantly decreased for groups B1 and B2. Moreover, delayed effects studies indicated that there is deterioration in the bone marrow functions. These results are supported by the blood film image, where irregularities and deformations in the RBCs membranes had been occurred. We conclude that the cell membrane properties are highly affected by the extremely low frequency (ELF) magnetic fields, which proved to be biologically toxic.

  7. Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death.

    PubMed

    Iwasa, Kensuke; Yamamoto, Shinji; Yagishita, Sosuke; Maruyama, Kei; Yoshikawa, Keisuke

    2017-04-01

    Excitotoxicity is the pivotal mechanism of neuronal death. Prostaglandins (PGs) produced during excitotoxicity play important roles in neurodegenerative conditions. Previously, we demonstrated that initial burst productions of PGD 2 , PGE 2 , and PGF 2α are produced by cyclooxygenase-2 (COX-2) in the hippocampus following a single systemic kainic acid (KA) administration. In addition, we showed that blocking of all PG productions ameliorated hippocampal delayed neuronal death at 30 days after KA administration. To investigate the role of individual PGs in the delayed neuronal death, we performed intracerebroventricular injection of PGD 2 , PGE 2 , or PGF 2α in rats whose hippocampal PG productions were entirely blocked by pretreatment of NS398, a COX-2 selective inhibitor. Administration of PGD 2 and PGF 2α had a latent contribution to the delayed neuronal death, sustained over 30 days after a single KA treatment. Furthermore, PGD 2 enhanced microglial activation, which may be involved in the delayed neuronal death in the hippocampus. These findings suggest that excitotoxic delayed neuronal death is mediated through microglia activated by PGD 2 . Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  8. Simulation analysis of the effect of initial delay on flight delay diffusion

    NASA Astrophysics Data System (ADS)

    Que, Zufu; Yao, Hongguang; Yue, Wei

    2018-01-01

    The initial delay of the flight is an important factor affecting the spread of flight delays, so clarifying their relationship conduces to control flight delays in the aeronautical network. Through establishing a model of the chain aviation network and making simulation analysis of the effects of initial delay on the delay longitudinal diffusion, it’s found that the number of delayed airports in the air network, the total delay time and the average delay time of the delayed airport are generally positively correlated with the initial delay. This indicates that the occurrence of the initial delay should be avoided or reduced as much as possible to improve the punctuality of the flight.

  9. Effect of Time Delay on Recognition Memory for Pictures: The Modulatory Role of Emotion

    PubMed Central

    Wang, Bo

    2014-01-01

    This study investigated the modulatory role of emotion in the effect of time delay on recognition memory for pictures. Participants viewed neutral, positive and negative pictures, and took a recognition memory test 5 minutes, 24 hours, or 1 week after learning. The findings are: 1) For neutral, positive and negative pictures, overall recognition accuracy in the 5-min delay did not significantly differ from that in the 24-h delay. For neutral and positive pictures, overall recognition accuracy in the 1-week delay was lower than in the 24-h delay; for negative pictures, overall recognition in the 24-h and 1-week delay did not significantly differ. Therefore negative emotion modulates the effect of time delay on recognition memory, maintaining retention of overall recognition accuracy only within a certain frame of time. 2) For the three types of pictures, recollection and familiarity in the 5-min delay did not significantly differ from that in the 24-h and the 1-week delay. Thus emotion does not appear to modulate the effect of time delay on recollection and familiarity. However, recollection in the 24-h delay was higher than in the 1-week delay, whereas familiarity in the 24-h delay was lower than in the 1-week delay. PMID:24971457

  10. Using delay differential equations to induce alternans in a model of cardiac electrophysiology.

    PubMed

    Eastman, Justin; Sass, Julian; Gomes, Johnny M; Dos Santos, Rodrigo Weber; Cherry, Elizabeth M

    2016-09-07

    Cardiac electrical alternans is a period-2 dynamical behavior with alternating long and short action potential durations (APD) that often precedes dangerous arrhythmias associated with cardiac arrest. Despite the importance of alternans, many current ordinary differential equations models of cardiac electrophysiology do not produce alternans, thereby limiting the use of these models for studying the mechanisms that underlie this condition. Because delay differential equations (DDEs) commonly induce complex dynamics in other biological systems, we investigate whether incorporating DDEs can lead to alternans development in cardiac models by studying the Fox et al. canine ventricular action potential model. After suppressing the alternans in the original model, we show that alternans can be obtained by introducing DDEs in the model gating variables, and we quantitatively compare the DDE-induced alternans with the alternans present in the original model. We analyze the behavior of the voltage, currents, and gating variables of the model to study the effects of the delays and to determine how alternans develops in that setting, and we discuss the mathematical and physiological implications of our findings. In future work, we aim to apply our approach to induce alternans in models that do not naturally exhibit such dynamics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Suppression of Cocaine Self-Administration in Monkeys: Effects of Delayed Punishment

    PubMed Central

    Woolverton, William L.; Freeman, Kevin B.; Myerson, Joel; Green, Leonard

    2014-01-01

    Rationale Delaying presentation of a drug can decrease its effectiveness as a reinforcer, but the effect of delaying punishment of drug self-administration is unknown. Objective This study examined whether a histamine injection could punish cocaine self-administration in a drug-drug choice, whether delaying histamine would decrease its effectiveness, and whether the effects of delay could be described within a delay discounting framework. Methods Monkeys were implanted with double-lumen catheters to allow separate injection of cocaine and histamine. In discrete trials, subjects first chose between cocaine (50 or 100 μg/kg/inj) alone and an injection of the same dose of cocaine followed immediately by an injection of histamine (0.37–50 μg/kg). Next, they chose between cocaine followed immediately by histamine and cocaine followed by an equal but delayed dose of histamine. Results When choosing between cocaine alone and cocaine followed immediately by histamine, preference increased with histamine dose from indifference to > 80% choice of cocaine alone. When choosing between cocaine followed by immediate histamine and cocaine followed by delayed histamine, monkeys showed strong position preferences. When delayed histamine was associated with the non-preferred position, preference for that option increased with delay from ≤ 30% to > 85%. The corresponding decrease in choice of the preferred position was well described by a hyperboloid discounting function. Conclusions Histamine can function as a punisher in the choice between injections of cocaine and delay can decrease its effectiveness as a punisher. The effects of delaying punishment of drug self-administration can be conceptualized within the delay discounting framework. PMID:21956240

  12. Suppression of cocaine self-administration in monkeys: effects of delayed punishment.

    PubMed

    Woolverton, William L; Freeman, Kevin B; Myerson, Joel; Green, Leonard

    2012-04-01

    Delaying presentation of a drug can decrease its effectiveness as a reinforcer, but the effect of delaying punishment of drug self-administration is unknown. This study examined whether a histamine injection could punish cocaine self-administration in a drug-drug choice, whether delaying histamine would decrease its effectiveness, and whether the effects of delay could be described within a delay discounting framework. Monkeys were implanted with double-lumen catheters to allow separate injection of cocaine and histamine. In discrete trials, subjects first chose between cocaine (50 or 100 μg/kg/inj) alone and an injection of the same dose of cocaine followed immediately by an injection of histamine (0.37-50 μg/kg). Next, they chose between cocaine followed immediately by histamine and cocaine followed by an equal but delayed dose of histamine. When choosing between cocaine alone and cocaine followed immediately by histamine, preference increased with histamine dose from indifference to >80% choice of cocaine alone. When choosing between cocaine followed by immediate histamine and cocaine followed by delayed histamine, monkeys showed strong position preferences. When delayed histamine was associated with the nonpreferred position, preference for that option increased with delay from ≤30% to >85%. The corresponding decrease in choice of the preferred position was well described by a hyperboloid discounting function. Histamine can function as a punisher in the choice between injections of cocaine and delay can decrease its effectiveness as a punisher. The effects of delaying punishment of drug self-administration can be conceptualized within the delay discounting framework.

  13. Effects of amphetamine on delay discounting in rats depend upon the manner in which delay is varied

    PubMed Central

    Maguire, David R; Henson, Cedric; France, Charles P

    2014-01-01

    Whether stimulant drugs like amphetamine increase or decrease choice of larger delayed reinforcers over smaller immediately available reinforcers under delay discounting procedures can depend on several factors, including the order in which delay is presented. This study examined whether the order of delay presentation impacts drug effects on discounting in rats (n=8) trained and tested under an ascending order, a descending order, as well as under a fixed delay condition. Responses on one lever delivered 1 food pellet immediately and responses on the other lever delivered 3 food pellets immediately or after a delay (4–32 s). In Experiment 1, the delay to the larger reinforcer varied within session and the order of delay presentation (ascending or descending) varied across conditions. In Experiment 2, the same delay value was presented in all blocks of the session (i.e., delay was fixed), and delay varied across phases. Under the ascending order of delay, amphetamine (0.32–1.78 mg/kg) increased choice of the larger reinforcer in some rats and decreased choice in others. In the same rats responding under the descending and fixed delay conditions, amphetamine markedly decreased choice of the larger reinforcer even in the component associated with no delay. In some subjects, the effects of amphetamine differed depending on the manner in which delay was presented, indicating that drug-induced changes in performance were due, in part, to mechanisms other than altered sensitivity to reinforcer delay. These results also suggest that a history of responding under both orders of delay presentation can modulate drug effects. PMID:24780379

  14. Effects of Acute and Chronic Cocaine Administration on Titrating-Delay Matching-to-Sample Performance

    ERIC Educational Resources Information Center

    Kangas, Brian D.; Branch, Marc N.

    2012-01-01

    The effects of cocaine were examined under a titrating-delay matching-to-sample procedure. In this procedure, the delay between sample stimulus offset and comparison stimuli onset adjusts as a function of the subject's performance. Specifically, matches increase the delay and mismatches decrease the delay. Titrated delay values served as the…

  15. Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

    PubMed Central

    Das, Rina; Hammamieh, Rasha; Neill, Roger; Ludwig, George V; Eker, Steven; Lincoln, Patrick; Ramamoorthy, Preveen; Dhokalia, Apsara; Mani, Sachin; Mendis, Chanaka; Cummings, Christiano; Kearney, Brian; Royaee, Atabak; Huang, Xiao-Zhe; Paranavitana, Chrysanthi; Smith, Leonard; Peel, Sheila; Kanesa-Thasan, Niranjan; Hoover, David; Lindler, Luther E; Yang, David; Henchal, Erik; Jett, Marti

    2008-01-01

    Background Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs. Methods To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays. Results We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin. Conclusion Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents. PMID:18667072

  16. Viral Vectors for Gene Delivery to the Central Nervous System

    PubMed Central

    Lentz, Thomas B.; Gray, Steven J.; Samulski, R. Jude

    2011-01-01

    The potential benefits of gene therapy for neurological diseases such as Parkinson’s, Amyotrophic Lateral Sclerosis (ALS), Epilepsy, and Alzheimer’s are enormous. Even a delay in the onset of severe symptoms would be invaluable to patients suffering from these and other diseases. Significant effort has been placed in developing vectors capable of delivering therapeutic genes to the CNS in order to treat neurological disorders. At the forefront of potential vectors, viral systems have evolved to efficiently deliver their genetic material to a cell. The biology of different viruses offers unique solutions to the challenges of gene therapy, such as cell targeting, transgene expression and vector production. It is important to consider the natural biology of a vector when deciding whether it will be the most effective for a specific therapeutic function. In this review, we outline desired features of the ideal vector for gene delivery to the CNS and discuss how well available viral vectors compare to this model. Adeno-associated virus, retrovirus, adenovirus and herpesvirus vectors are covered. Focus is placed on features of the natural biology that have made these viruses effective tools for gene delivery with emphasis on their application in the CNS. Our goal is to provide insight into features of the optimal vector and which viral vectors can provide these features. PMID:22001604

  17. Neural Processing of Target Distance by Echolocating Bats: Functional Roles of the Auditory Midbrain

    PubMed Central

    Wenstrup, Jeffrey J.; Portfors, Christine V.

    2011-01-01

    Using their biological sonar, bats estimate distance to avoid obstacles and capture moving prey. The primary distance cue is the delay between the bat's emitted echolocation pulse and the return of an echo. The mustached bat's auditory midbrain (inferior colliculus, IC) is crucial to the analysis of pulse-echo delay. IC neurons are selective for certain delays between frequency modulated (FM) elements of the pulse and echo. One role of the IC is to create these “delay-tuned”, “FM-FM” response properties through a series of spectro-temporal integrative interactions. A second major role of the midbrain is to project target distance information to many parts of the brain. Pathways through auditory thalamus undergo radical reorganization to create highly ordered maps of pulse-echo delay in auditory cortex, likely contributing to perceptual features of target distance analysis. FM-FM neurons in IC also project strongly to pre-motor centers including the pretectum and the pontine nuclei. These pathways may contribute to rapid adjustments in flight, body position, and sonar vocalizations that occur as a bat closes in on a target. PMID:21238485

  18. Transition of Care from Childhood to Adulthood: Congenital Hypogonadotropic Hypogonadism.

    PubMed

    Dwyer, Andrew A; Pitteloud, Nelly

    2018-01-01

    Passage from childhood to adult life involves biological changes culminating in full reproductive capacity as well as psychosocial development. For patients with congenital hypogonadotropic hypogonadism (CHH), this can be an emotionally challenging time as their pubertal failure results in striking physical differences from their peers. CHH is difficult to differentiate from common disorders of puberty such as constitutional delay of growth and puberty. As such, delays in diagnosis are frequent, and it is a common source of stress and frustration for these adolescents. While effective treatments are available for inducing puberty and attaining fertility is possible in most cases, patients may find it difficult to cope with living with CHH. A critical issue for adolescents with CHH is the risk for being lost to follow-up during the transition from pediatric-centered care to adult care. This article will review the state of the art in diagnosis and treatment of patients with CHH with a particular focus on supporting an effective transition from pediatric-centered care to adult-oriented endocrine services. A synthesis of best practices is offered to help guide clinicians in supporting patients and families during this challenging period of care. © 2018 S. Karger AG, Basel.

  19. Early developmental characteristics and features of major depressive disorder among child psychiatric patients in Hungary.

    PubMed

    Kapornai, Krisztina; Gentzler, Amy L; Tepper, Ping; Kiss, Eniko; Mayer, László; Tamás, Zsuzsanna; Kovacs, Maria; Vetró, Agnes

    2007-06-01

    We investigate the relations of early atypical characteristics (perinatal problems, developmental delay, and difficult temperament) and onset-age (as well as severity of) first major depressive disorder (MDD) and first internalizing disorder in a clinical sample of depressed children in Hungary. Participants were 371 children (ages 7-14) with MDD, and their biological mothers, recruited through multiple clinical sites. Diagnoses (via DSM-IV criteria) and onset dates of disorders were finalized "best estimate" psychiatrists, and based on multiple information sources. Mothers provided developmental data in a structured interview. Difficult temperament predicted earlier onset of MDD and first internalizing disorder, but its effect was ameliorated if the family was intact during early childhood. Further, the importance of difficult temperament decreased as a function of time. Perinatal problems and developmental delay did not impact onset ages of disorders, and none of the early childhood characteristics associated with MDD episode severity. Children with MDD may have added disadvantage of earlier onset if they had a difficult temperament in infancy. Because early temperament mirrors physiological reactivity and regulatory capacity, it can affect various areas of functioning related to psychopathology. Early caregiver stability may attenuate some adverse effects of difficult infant temperament.

  20. Qualitative analysis of a stochastic epidemic model with specific functional response and temporary immunity

    NASA Astrophysics Data System (ADS)

    Hattaf, Khalid; Mahrouf, Marouane; Adnani, Jihad; Yousfi, Noura

    2018-01-01

    In this paper, we propose a stochastic delayed epidemic model with specific functional response. The time delay represents temporary immunity period, i.e., time from recovery to becoming susceptible again. We first show that the proposed model is mathematically and biologically well-posed. Moreover, the extinction of the disease and the persistence in the mean are established in the terms of a threshold value R0S which is smaller than the basic reproduction number R0 of the corresponding deterministic system.

  1. Delay time and Hartman effect in strain engineered graphene

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

    Chen, Xi, E-mail: xchen@shu.edu.cn; Deng, Zhi-Yong; Ban, Yue, E-mail: yban@shu.edu.cn

    2014-05-07

    Tunneling times, including group delay and dwell time, are studied for massless Dirac electrons transmitting through a one-dimensional barrier in strain-engineered graphene. The Hartman effect, the independence of group delay on barrier length, is induced by the strain effect, and associated with the transmission gap and the evanescent mode. The influence of barrier height/length and strain modulus/direction on the group delay is also discussed, which provides the flexibility to control the group delay with applications in graphene-based devices. The relationship between group delay and dwell time is finally derived to clarify the nature of the Hartman effect.

  2. Isolating behavioral mechanisms of intertemporal choice: nicotine effects on delay discounting and amount sensitivity.

    PubMed

    Locey, Matthew L; Dallery, Jesse

    2009-03-01

    Many drugs of abuse produce changes in impulsive choice, that is, choice for a smaller-sooner reinforcer over a larger-later reinforcer. Because the alternatives differ in both delay and amount, it is not clear whether these drug effects are due to the differences in reinforcer delay or amount. To isolate the effects of delay, we used a titrating delay procedure. In phase 1, 9 rats made discrete choices between variable delays (1 or 19 s, equal probability of each) and a delay to a single food pellet. The computer titrated the delay to a single food pellet until the rats were indifferent between the two options. This indifference delay was used as the starting value for the titrating delay for all future sessions. We next evaluated the acute effects of nicotine (subcutaneous 1.0, 0.3, 0.1, and 0.03 mg/kg) on choice. If nicotine increases delay discounting, it should have increased preference for the variable delay. Instead, nicotine had very little effect on choice. In a second phase, the titrated delay alternative produced three food pellets instead of one, which was again produced by the variable delay (1 s or 19 s) alternative. Under this procedure, nicotine increased preference for the one pellet alternative. Nicotine-induced changes in impulsive choice are therefore likely due to differences in reinforcer amount rather than differences in reinforcer delay. In addition, it may be necessary to include an amount sensitivity parameter in any mathematical model of choice when the alternatives differ in reinforcer amount.

  3. Development of biosimilars in an era of oncologic drug shortages

    PubMed Central

    Li, Edward; Subramanian, Janakiraman; Anderson, Scott; Thomas, Dolca; McKinley, Jason; Jacobs, Ira A

    2015-01-01

    Acute and chronic shortages of various pharmaceuticals and particularly of sterile injectable products are being reported on a global scale, prompting evaluation of more effective strategies to manage current shortages and development of new, high-quality pharmaceutical products to mitigate the risk of potential future shortages. Oncology drugs such as liposomal doxorubicin and 5-fluorouracil represent examples of first-choice drugs critically affected by shortages. Survey results indicate that the majority of hospitals and practicing oncologists have experienced drug shortages, which may have compromised patient safety and clinical outcomes, and increased health care costs, due to delays or changes in treatment regimens. Clinical trials evaluating novel agents in combination with standard-of-care drugs are also being affected by drug shortages. Clinical and ethical considerations on treatment objectives, drug indication, and availability of alternative options may help in prioritizing cancer patients involved in active drug shortages. The United States Food and Drug Administration and the European Medicines Agency have identified manufacturing problems, delays in supply, and lack of available active ingredients as the most frequent causes of recent or ongoing drug shortages, and have released specific guidance to monitor, manage, and reduce the risk of shortages. The upcoming loss of exclusivity for a number of anticancer biologics, together with the introduction of an abbreviated approval pathway for biosimilars, raises the question of whether these products will be vulnerable to shortages. Future supply by reliable manufacturers of well characterized biosimilar monoclonal antibodies, developed in compliance with regulatory and manufacturing guidelines and with substantial investments, may contribute to prevent future biologics shortages and ensure access to effective and safe treatment options for patients with cancer. Preclinical and clinical characterization is ongoing for potential biosimilars of trastuzumab, rituximab, and bevacizumab, with promising results. PMID:26150698

  4. Effects of open-air temperature on air temperature inside biological safety cabinet.

    PubMed

    Umemura, Masayuki; Shigeno, Katsuro; Yamamura, Keiko; Osada, Takashi; Soda, Midori; Yamada, Kiyofumi; Ando, Yuichi; Wakiya, Yoshifumi

    2011-02-14

    In Japan, biological safety cabinets (BSCs) are normally used by medical staff while handling antineoplastic agents. We have also set up a class II B2 BSC at the Division of Chemotherapy for Outpatients. The air temperature inside this BSC, however, decreases in winter. We assumed that this decrease is caused by the intake of open-air. Therefore, we investigated the effects of low open-air temperature on the BSC temperature and the time of admixtures of antineoplastic agents. The studies were conducted from January 1 to March 31, 2008. The outdoor air temperature was measured in the shade near the intake nozzle of the BSC and was compared with the BSC temperature. The correlation between the outdoor air temperature and the BSC temperature, the dissolution time of cyclophosphamide (CPA) and gemcitabine (GEM), and accurate weight measurement of epirubicin (EPI) solution were investigated for low and normal BSC temperatures. The BSC temperature was correlated with the open-air temperature for open-air temperatures of 5-20°C (p < 0.0001). The dissolution of CPA and GEM at these temperatures was significantly delayed as compared to that at 25°C (p < 0.01 and p < 0.0001, respectively). The weight measurement of EPI solution using a syringe method lacks accuracy because of its high coefficient of viscosity at low temperatures (p < 0.01). These results suggest that the BSC temperature decreases below room temperature in winter when air is drawn from outdoors. We showed that the BSC temperature affects the dissolution rate of antineoplastic agents. Further, we suggested that the BSC temperature drop might delay the affair of the admixtures of antineoplastic agents and increase the waiting time of outpatients for chemotherapy.

  5. International Retrospective Chart Review of Treatment Patterns in Severe Familial Mediterranean Fever, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome, and Mevalonate Kinase Deficiency/Hyperimmunoglobulinemia D Syndrome.

    PubMed

    Ozen, Seza; Kuemmerle-Deschner, Jasmin B; Cimaz, Rolando; Livneh, Avi; Quartier, Pierre; Kone-Paut, Isabelle; Zeft, Andrew; Spalding, Steve; Gul, Ahmet; Hentgen, Veronique; Savic, Sinisa; Foeldvari, Ivan; Frenkel, Joost; Cantarini, Luca; Patel, Dony; Weiss, Jeffrey; Marinsek, Nina; Degun, Ravi; Lomax, Kathleen G; Lachmann, Helen J

    2017-04-01

    Periodic fever syndrome (PFS) conditions are characterized by recurrent attacks of fever and localized inflammation. This study examined the diagnostic pathway and treatments at tertiary centers for familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD)/hyperimmunoglobulinemia D syndrome (HIDS). PFS specialists at medical centers in the US, the European Union, and the eastern Mediterranean participated in a retrospective chart review, providing de-identified data in an electronic case report form. Patients were treated between 2008 and 2012, with at least 1 year of followup; all had clinical and/or genetically proven disease and were on/eligible for biologic treatment. A total of 134 patients were analyzed: FMF (n = 49), TRAPS (n = 47), and MKD/HIDS (n = 38). Fever was commonly reported as severe across all indications. Other frequently reported severe symptoms were serositis for FMF patients and elevated acute-phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 and 7.1 years, respectively) compared to a 1.8-year delay in FMF patients. An equal proportion of TRAPS patients first received anti-interleukin-1 (anti-IL-1) and anti-tumor necrosis factor (anti-TNF) biologic agents, whereas IL-1 blockade was the main choice for FMF patients resistant to colchicine and MKD/HIDS patients. For TRAPS patients, treatment with anakinra versus anti-TNF treatments as first biologic agent resulted in significantly higher clinical and biochemical responses (P = 0.03 and P < 0.01, respectively). No significant differences in responses were observed between biologic agents among other cohorts. Referral patterns and diagnostic delays highlight the need for greater awareness and improved diagnostics for PFS. This real-world treatment assessment supports the need for further refinement of treatment practices. © 2016, American College of Rheumatology.

  6. The spacing effect in immediate and delayed free recall.

    PubMed

    Godbole, Namrata R; Delaney, Peter F; Verkoeijen, Peter P J L

    2014-01-01

    Spacing repetitions improves learning relative to massing repetitions (the spacing effect). While most studies have examined the spacing effect at short retention intervals, there are contradictory claims about its fate at a delay. Certain empirical findings suggest that the spacing effect persists at a delay. However, a recent theoretical account proposes that in free recall the spacing effect should disappear at a delay. The few studies that have examined the spacing effect at a delay are sub-optimally designed, preventing an unbiased conclusion. The current study used incidental learning and controlled recency and encoding strategy in order to examine the effect of delay on the recall of spaced items within a free recall paradigm. The results demonstrated that the spacing effect persists after a delay. The results point to an important dissociation between intentional forgetting and context-change designs (which produce more forgetting of spaced than massed items) and the passage of time (which produces similar forgetting of spaced and massed items).

  7. Passiflora cincinnata Extract Delays the Development of Motor Signs and Prevents Dopaminergic Loss in a Mice Model of Parkinson's Disease

    PubMed Central

    Brandão, Luiz Eduardo Mateus; Nôga, Diana Aline Morais Ferreira; Dierschnabel, Aline Lima; Meurer, Ywlliane da Silva Rodrigues; Lima, Ramón Hypolito; Cavalcante, Jeferson Souza; Lima, Clésio Andrade; Marchioro, Murilo; Estevam, Charles dos Santos; Santos, José Ronaldo

    2017-01-01

    Passiflora cincinnata Masters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects of P. cincinnata extracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of the P. cincinnata ethanolic extract (PAS) on mice submitted to a progressive model of Parkinson's disease (PD) induced by reserpine. Male (6-month-old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus-maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine-induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in the substantia nigra pars compacta (SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD. PMID:28835767

  8. PSI:Biology-Materials Repository: A Biologist’s Resource for Protein Expression Plasmids

    PubMed Central

    Cormier, Catherine Y.; Park, Jin G.; Fiacco, Michael; Steel, Jason; Hunter, Preston; Kramer, Jason; Singla, Rajeev; LaBaer, Joshua

    2011-01-01

    The Protein Structure Initiative:Biology-Materials Repository (PSI:Biology-MR; MR; http://psimr.asu.edu) sequence-verifies, annotates, stores, and distributes the protein expression plasmids and vectors created by the Protein Structure Initiative (PSI). The MR has developed an informatics and sample processing pipeline that manages this process for thousands of samples per month from nearly a dozen PSI centers. DNASU (http://dnasu.asu.edu), a freely searchable database, stores the plasmid annotations, which include the full-length sequence, vector information, and associated publications for over 130,000 plasmids created by our laboratory, by the PSI and other consortia, and by individual laboratories for distribution to researchers worldwide. Each plasmid links to external resources, including the PSI Structural Biology Knowledgebase (http://sbkb.org), which facilitates cross-referencing of a particular plasmid to additional protein annotations and experimental data. To expedite and simplify plasmid requests, the MR uses an expedited material transfer agreement (EP-MTA) network, where researchers from network institutions can order and receive PSI plasmids without institutional delays. Currently over 39,000 protein expression plasmids and 78 empty vectors from the PSI are available upon request from DNASU. Overall, the MR’s repository of expression-ready plasmids, its automated pipeline, and the rapid process for receiving and distributing these plasmids more effectively allows the research community to dissect the biological function of proteins whose structures have been studied by the PSI. PMID:21360289

  9. Bistability and delay-induced stability switches in a cancer network with the regulation of microRNA

    NASA Astrophysics Data System (ADS)

    Song, Yongli; Cao, Xin; Zhang, Tonghua

    2018-01-01

    In this paper, we are concerned with a cancer network including a protein module and a corresponding microRNA cluster that inhibits the synthesis of proteins. The existence of multiple steady states and their stability depending on the parameters are firstly determined. Bistability and dependency on the parameters, Hopf bifurcations and the corresponding properties like direction and stability of Hopf bifurcations are determined by computing the normal form on the center manifold. Then, the role of the delay in the process of synthesis of the protein is investigated. We show that the delay can stabilize the unstable equilibrium and destabilize the stable equilibrium. Some simulations are carried out to numerically illustrate the obtained theoretical results. Finally, the biological interpretation of the theoretical results is discussed.

  10. Pharmacological evaluation of a novel cyclic phosphatidic acid derivative 3-S-cyclic phosphatidic acid (3-S-cPA).

    PubMed

    Nozaki, Emi; Gotoh, Mari; Tanaka, Ryo; Kato, Masaru; Suzuki, Takahiro; Nakazaki, Atsuo; Hotta, Harumi; Kobayashi, Susumu; Murakami-Murofushi, Kimiko

    2012-05-15

    Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator possessing cyclic phosphate ring, which is necessary for its specific biological activities. To stabilize cyclic phosphate ring of cPA, we synthesized a series of cPA derivatives. We have shown that racemic 3-S-cPA, with a phosphate oxygen atom replaced with a sulfur atom at the sn-3, was a more effective autotaxin (ATX) inhibitor than cPA. In this study, we showed that racemic 3-S-cPA also had potent biological activities such as inhibition of cancer cell migration, suppression of the nociceptive reflex, and attenuation of ischemia-induced delayed neuronal cell death in the hippocampal CA1. Moreover, we synthesized both enantiomers of palmitoleoyl derivative of 3-S-cPA, and found that the chirality of 3-S-cPA is not involved in ATX inhibition. Based on these findings, racemic 3-S-cPA is suggested as an effective therapeutic compound like cPA. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Xu, Zhe; Wu, Chaochao; Xie, Fang

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective andmore » robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.« less

  12. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

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

    Xu, Zhe; Wu, Chaochao; Xie, Fang

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective andmore » robust analytical platform for comprehensive analyses of tissue peptidomes, and which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Additionally, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. In conclusion, peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.« less

  13. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    DOE PAGES

    Xu, Zhe; Wu, Chaochao; Xie, Fang; ...

    2014-10-28

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective andmore » robust analytical platform for comprehensive analyses of tissue peptidomes, and which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Additionally, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. In conclusion, peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.« less

  14. Heat shock protein 27 overexpression in CHO cells modulates apoptosis pathways and delays activation of caspases to improve recombinant monoclonal antibody titre in fed-batch bioreactors.

    PubMed

    Tan, Janice G L; Lee, Yih Yean; Wang, Tianhua; Yap, Miranda G S; Tan, Tin Wee; Ng, Say Kong

    2015-05-01

    CHO cells are major production hosts for recombinant biologics including the rapidly expanding recombinant monoclonal antibodies (mAbs). Heat shock protein 27 (HSP27) expression was observed to be down-regulated towards the late-exponential and stationary phase of CHO fed-batch bioreactor cultures, whereas HSP27 was found to be highly expressed in human pathological cells and reported to have anti-apoptotic functions. These phenotypes suggest that overexpression of HSP27 is a potential cell line engineering strategy for improving robustness of CHO cells. In this work, HSP27 was stably overexpressed in CHO cells producing recombinant mAb and the effects of HSP27 on cell growth, volumetric production titer and product quality were assessed. Concomitantly, HSP27 anti-apoptosis functions in CHO cells were investigated. Stably transfected clones cultured in fed-batch bioreactors displayed 2.2-fold higher peak viable cell density, delayed loss of culture viability by two days and 2.3-fold increase in mAb titer without affecting the N-glycosylation profile, as compared to clones stably transfected with the vector backbone. Co-immunoprecipitation studies revealed HSP27 interactions with Akt, pro-caspase 3 and Daxx and caspase activity profiling showed delayed increase in caspase 2, 3, 8 and 9 activities. These results suggest that HSP27 modulates apoptosis signaling pathways and delays caspase activities to improve performance of CHO fed-batch bioreactor cultures. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Photoionization of water molecules by a train of attosecond pulses assisted by a near-infrared laser: delay and polarization control

    NASA Astrophysics Data System (ADS)

    Martini, Lara; Boll, Diego I. R.; Fojón, Omar A.

    2017-08-01

    Basic reactions involving water molecules are essential to understand the interaction between radiation and the biological tissue because living cells are composed mostly by water. Therefore, the knowledge of ionization of the latter is crucial in many domains of Biology and Physics. So, we study theoretically the photoionization of water molecules by extreme ultraviolet attopulse trains assisted by lasers in the near-infrared range. We use a separable Coulomb-Volkov model in which the temporal evolution of the system can be divided into three stages allowing spatial and temporal separation for the Coulomb and Volkov final state wavefunctions. First, we analyze photoelectron angular distributions for different delays between the attopulse train and the assistant laser field. We compare our results for water and Ne atoms as they belong to the same isoelectronic series. Moreover, we contrast our calculations with previous theoretical and experimental work for Ar atoms due to the similarities of the orbitals involved in the reaction. Second, we study the effect of varying the relative orientations of the attopulse and laser field polarizations and we compare our predictions with other theories and experiments. We expect these studies contribute to the improvement of polarization experiments and the development of the attopulse trains and assistant laser fields technologies. Finally, we hope our work promote progress on the control of the chemical reactivity of water molecules since this could be useful in different fields such as radiobiology and medical physics.

  16. Microgravity simulation by diamagnetic levitation: effects of a strong gradient magnetic field on the transcriptional profile of Drosophila melanogaster.

    PubMed

    Herranz, Raul; Larkin, Oliver J; Dijkstra, Camelia E; Hill, Richard J A; Anthony, Paul; Davey, Michael R; Eaves, Laurence; van Loon, Jack J W A; Medina, F Javier; Marco, Roberto

    2012-02-01

    Many biological systems respond to the presence or absence of gravity. Since experiments performed in space are expensive and can only be undertaken infrequently, Earth-based simulation techniques are used to investigate the biological response to weightlessness. A high gradient magnetic field can be used to levitate a biological organism so that its net weight is zero. We have used a superconducting magnet to assess the effect of diamagnetic levitation on the fruit fly D. melanogaster in levitation experiments that proceeded for up to 22 consecutive days. We have compared the results with those of similar experiments performed in another paradigm for microgravity simulation, the Random Positioning Machine (RPM). We observed a delay in the development of the fruit flies from embryo to adult. Microarray analysis indicated changes in overall gene expression of imagoes that developed from larvae under diamagnetic levitation, and also under simulated hypergravity conditions. Significant changes were observed in the expression of immune-, stress-, and temperature-response genes. For example, several heat shock proteins were affected. We also found that a strong magnetic field, of 16.5 Tesla, had a significant effect on the expression of these genes, independent of the effects associated with magnetically-induced levitation and hypergravity. Diamagnetic levitation can be used to simulate an altered effective gravity environment in which gene expression is tuned differentially in diverse Drosophila melanogaster populations including those of different age and gender. Exposure to the magnetic field per se induced similar, but weaker, changes in gene expression.

  17. Microgravity simulation by diamagnetic levitation: effects of a strong gradient magnetic field on the transcriptional profile of Drosophila melanogaster

    PubMed Central

    2012-01-01

    Background Many biological systems respond to the presence or absence of gravity. Since experiments performed in space are expensive and can only be undertaken infrequently, Earth-based simulation techniques are used to investigate the biological response to weightlessness. A high gradient magnetic field can be used to levitate a biological organism so that its net weight is zero. Results We have used a superconducting magnet to assess the effect of diamagnetic levitation on the fruit fly D. melanogaster in levitation experiments that proceeded for up to 22 consecutive days. We have compared the results with those of similar experiments performed in another paradigm for microgravity simulation, the Random Positioning Machine (RPM). We observed a delay in the development of the fruit flies from embryo to adult. Microarray analysis indicated changes in overall gene expression of imagoes that developed from larvae under diamagnetic levitation, and also under simulated hypergravity conditions. Significant changes were observed in the expression of immune-, stress-, and temperature-response genes. For example, several heat shock proteins were affected. We also found that a strong magnetic field, of 16.5 Tesla, had a significant effect on the expression of these genes, independent of the effects associated with magnetically-induced levitation and hypergravity. Conclusions Diamagnetic levitation can be used to simulate an altered effective gravity environment in which gene expression is tuned differentially in diverse Drosophila melanogaster populations including those of different age and gender. Exposure to the magnetic field per se induced similar, but weaker, changes in gene expression. PMID:22296880

  18. Base drive circuit

    DOEpatents

    Lange, A.C.

    1995-04-04

    An improved base drive circuit having a level shifter for providing bistable input signals to a pair of non-linear delays. The non-linear delays provide gate control to a corresponding pair of field effect transistors through a corresponding pair of buffer components. The non-linear delays provide delayed turn-on for each of the field effect transistors while an associated pair of transistors shunt the non-linear delays during turn-off of the associated field effect transistor. 2 figures.

  19. Cannibalistic Predator-Prey Model with Disease in Predator — A Delay Model

    NASA Astrophysics Data System (ADS)

    Biswas, Santosh; Samanta, Sudip; Chattopadhyay, Joydev

    In this paper, we propose and analyze a cannibalistic predator-prey model with a transmissible disease in the predator population. The disease can be transmitted through contacts with infected individuals as well as the cannibalism of an infected predator. We also consider incubation delay in disease transmission, where the incubation period represents the time in which the infectious agent develops in the host. Local stability analysis of the system around the biologically feasible equilibria is studied. Bifurcation analysis of the system around interior equilibrium is also studied. Applying the normal form theory and central manifold theorem, the direction of Hopf bifurcation, the stability and the period of bifurcating periodic solutions are derived. Under appropriate conditions, the permanence of the system with time delay is proved. Our results suggest that incubation delay destabilizes the system and can produce chaos. We also observe that cannibalism can control disease and population oscillations. Extensive numerical simulations are performed to support our analytical results.

  20. Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae.

    PubMed

    Di Paolo, Carolina; Groh, Ksenia J; Zennegg, Markus; Vermeirssen, Etiënne L M; Murk, Albertinka J; Eggen, Rik I L; Hollert, Henner; Werner, Inge; Schirmer, Kristin

    2015-12-01

    The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. The methane production of poultry slaughtering residues and effects of pre-treatments on the methane production of poultry feather.

    PubMed

    Salminen, E; Einola, J; Rintala, J

    2003-09-01

    The biological methane production rate and yield of different poultry slaughtering residues were studied. Poultry offal, blood, and bonemeal were rich in proteins and lipids and showed high methane yields, 0.7-0.9, 0.5, and 0.6-0.7 m3 kg(-1) volatile solids(added), respectively (270-340, 100, and 150-170 m3 ton(-1) wet weight). Blood and bonemeal produced methane rapidly, whereas the methane production of offal was more delayed probably due to long-chain fatty acid inhibition. The length of delay depended on the source and concentration of inoculum and incubation temperature, sewage sludge at 35 degrees C having the shortest delay of a few days, while granular sludge did not produce methane within 94 days of incubation. Feather showed a somewhat lower methane yield, 0.21 m3 kg(-1) volatile solids(added) (50 m3 ton(-1) wet weight). Combined thermal (120 degrees C, 5 min) and enzymatic (commercial alkaline endopeptidase, 2-10 g l(-1)) pre-treatments increased its methane yield by 37 to 51%. Thermal (70-120 degrees C, 5-60 min), chemical (NaOH 2-10 g l(-1), 2-24 h), and enzymatic pre-treatments were less effective, with methane yield increasing by 5 to 32%. Based on the present results, anaerobic digestion of the studied poultry slaughtering residues appears a promising possibility because of the high methane yield and nitrogen content of these residues (8 to 14% N of total solids), whereas pre-treatments were shown to improve the methane production of feather.

  2. Chemical event chain model of coupled genetic oscillators.

    PubMed

    Jörg, David J; Morelli, Luis G; Jülicher, Frank

    2018-03-01

    We introduce a stochastic model of coupled genetic oscillators in which chains of chemical events involved in gene regulation and expression are represented as sequences of Poisson processes. We characterize steady states by their frequency, their quality factor, and their synchrony by the oscillator cross correlation. The steady state is determined by coupling and exhibits stochastic transitions between different modes. The interplay of stochasticity and nonlinearity leads to isolated regions in parameter space in which the coupled system works best as a biological pacemaker. Key features of the stochastic oscillations can be captured by an effective model for phase oscillators that are coupled by signals with distributed delays.

  3. Chemical event chain model of coupled genetic oscillators

    NASA Astrophysics Data System (ADS)

    Jörg, David J.; Morelli, Luis G.; Jülicher, Frank

    2018-03-01

    We introduce a stochastic model of coupled genetic oscillators in which chains of chemical events involved in gene regulation and expression are represented as sequences of Poisson processes. We characterize steady states by their frequency, their quality factor, and their synchrony by the oscillator cross correlation. The steady state is determined by coupling and exhibits stochastic transitions between different modes. The interplay of stochasticity and nonlinearity leads to isolated regions in parameter space in which the coupled system works best as a biological pacemaker. Key features of the stochastic oscillations can be captured by an effective model for phase oscillators that are coupled by signals with distributed delays.

  4. Cognitive person variables in the delay of gratification of older children at risk.

    PubMed

    Rodriguez, M L; Mischel, W; Shoda, Y

    1989-08-01

    The components of self-regulation were analyzed, extending the self-imposed delay of gratification paradigm to older children with social adjustment problems. Delay behavior was related to a network of conceptually relevant cognitive person variables, consisting of attention deployment strategies during delay, knowledge of delay rules, and intelligence. A positive relationship was demonstrated between concurrent indexes of intelligence, attention deployment, and actual delay time. Moreover, attention deployment, measured as an individual differences variable during the delay process, had a direct, positive effect on delay behavior. Specifically, as the duration of delay and the frustration of the situation increased, children who spent a higher proportion of the time distracting themselves from the tempting elements of the delay situation were able to delay longer. The effect of attention deployment on delay behavior was significant even when age, intelligence, and delay rule knowledge were controlled. Likewise, delay rule knowledge significantly predicted delay time, even when age, attention deployment, and intelligence were controlled.

  5. Language delay in severely neglected children: a cumulative or specific effect of risk factors?

    PubMed

    Sylvestre, Audette; Mérette, Chantal

    2010-06-01

    This research sought to determine if the language delay (LD) of severely neglected children under 3 years old was better explained by a cumulative risk model or by the specificity of risk factors. The objective was also to identify the risk factors with the strongest impact on LD among various biological, psychological, and environmental factors. Sixty-eight severely neglected children and their mothers participated in this cross-sectional study. Children were between 2 and 36 months of age. Data included information about the child's language development and biological, psychological, and environmental risk factors. Prevalence of LD is significantly higher in this subgroup of children than in the population as a whole. Although we observed that the risk of LD significantly increased with an increase in the cumulative count of the presence of the child's biological-psychological risk factors, the one-by-one analysis of the individual factors revealed that the cumulative effect mainly reflected the specific impact of the child's cognitive development. When we considered also the environmental risk factors, multivariate logistic regression established that cognitive development, the mother's own physical and emotional abuse experience as a child, and the mother's low acceptability level towards her child are linked to LD in severely neglected children. Language development is the result of a complex interaction between risk factors. LD in severely neglected children is better explained by the specificity of risk factors than by the cumulative risk model. Most prevention and early intervention programs promote and target an increase in the quantity and quality of language stimulation offered to the child. Our results suggest that particular attention should be given to other environmental factors, specifically the mother's psychological availability and her sensitivity towards the child. It is essential to suggest interventions targeting various ecological dimensions of neglectful mothers to help break the intergenerational neglect transmission cycle. It is also important to develop government policies and ensure that efforts among the various response networks are concerted since in-depth changes to neglect situations can only come about when all interested parties become involved. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Tunable delay time and Hartman effect in graphene magnetic barriers

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

    Ban, Yue; Wang, Lin-Jun; Chen, Xi, E-mail: xchen@shu.edu.cn

    2015-04-28

    Tunable group delay and Hartman effect have been investigated for massless Dirac electrons in graphene magnetic barriers. In the presence of magnetic field, dwell time is found to be equal to net group delay plus the group delay contributing from the lateral shifts. The group delay times are discussed in both cases of normal and oblique incidence, to clarify the nature of Hartman effect. In addition, the group delay in transmission can be modulated from subluminality to superluminality by adjusting the magnetic field, which may also lead to potential applications in graphene-based microelectronics.

  7. Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine.

    PubMed

    Schwager, Andrea L; Haack, Andrew K; Taha, Sharif A

    2014-10-01

    Stress-induced disruption of decision making has been hypothesized to contribute to drug-seeking behaviors and addiction. Noradrenergic signaling plays a central role in mediating stress responses. However, the effects of acute stress on decision making, and the role of noradrenergic signaling in regulating these effects, have not been well characterized. To characterize changes in decision making caused by acute pharmacological stress, the effects of yohimbine (an α2-adrenergic antagonist) were examined in a delay discounting task. Noradrenergic contributions to decision making were further characterized by examining the effects of propranolol (a β antagonist), prazosin (an α1 antagonist), and guanfacine (an α2 agonist). Sprague-Dawley rats were administered drugs prior to performance on a delay discounting task, in which the delay preceding the large reward increased within each session (ascending delays). To dissociate drug-induced changes in delay sensitivity from behavioral inflexibility, drug effects were subsequently tested in a modified version of the discounting task, in which the delay preceding the large reward decreased within each session (descending delays). Yohimbine increased choice of the large reward when tested with ascending delays but decreased choice of the same large reward when tested with descending delays, suggesting that drug effects could be attributed to perseverative choice of the lever preferred at the beginning of the session. Propranolol increased choice of the large reward when tested with ascending delays. Prazosin and guanfacine had no effect on reward choice. The stress-like effects of yohimbine administration may impair decision making by causing inflexible, perseverative behavior.

  8. Biodemography of human ageing

    PubMed Central

    Vaupel, James W.

    2014-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival — and healthy survival — to even greater ages. PMID:20336136

  9. Effect of Multiple Delays in an Eco-Epidemiological Model with Strong Allee Effect

    NASA Astrophysics Data System (ADS)

    Ghosh, Kakali; Biswas, Santanu; Samanta, Sudip; Tiwari, Pankaj Kumar; Alshomrani, Ali Saleh; Chattopadhyay, Joydev

    In the present article, we make an attempt to investigate the effect of two time delays, logistic delay and gestation delay, on an eco-epidemiological model. In the proposed model, strong Allee effect is considered in the growth term of the prey population. We incorporate two time lags and inspect elementary mathematical characteristic of the proposed model such as boundedness, uniform persistence, stability and Hopf-bifurcation for all possible combinations of both delays at the interior equilibrium point of the system. We observe that increase in gestation delay leads to chaotic solutions through the limit cycle. We also observe that the Allee effect play a major role in controlling the chaos. We execute several numerical simulations to illustrate the proposed mathematical model and our analytical findings.

  10. Casualty Evacuation Delay and Outcomes

    DTIC Science & Technology

    2003-01-01

    consequences of delay in therapy on wounded individuals. The contractor was charged with studying the effect of delay on evacuation on outcome of...process. 3 There are a remarkably small proportion of patient diagnoses and states in which time has an effect on outcome . This is because the vast...emphasis on estimating the effect of delayed evacuation on injury outcome and means to mitigating such effects . Since some of the Specific Aims were

  11. The effect of space radiation on the induction of chromosome damage

    NASA Technical Reports Server (NTRS)

    George, K.; Wu, H.; Willingham, V.; Cucinotta, F. A.

    2001-01-01

    To obtain information on the cytogenetic damage caused by space radiation, chromosome exchanges in lymphocytes from crewmembers of long-term Mir missions, and a shorter duration shuttle mission, were examined using fluorescence in situ hybridization. A significant increase in chromosomal aberrations was observed after the long duration flights. The ratio of aberrations identified as complex was higher post-flight for some crewmembers, which is thought to be an indication of exposure to high-LET radiation. Ground-based studies have shown that the frequency of aberrations measured post-flight could be influenced by a mitotic delay in cells damaged by high-LET radiation and this effect could lower biological dose estimates. To counteract this effect, prematurely condensed chromosome (PCC) spreads were collected. Frequencies of aberrations in PCC were compared with those in metaphase spreads.

  12. Delayed response and biosonar perception explain movement coordination in trawling bats.

    PubMed

    Giuggioli, Luca; McKetterick, Thomas J; Holderied, Marc

    2015-03-01

    Animal coordinated movement interactions are commonly explained by assuming unspecified social forces of attraction, repulsion and alignment with parameters drawn from observed movement data. Here we propose and test a biologically realistic and quantifiable biosonar movement interaction mechanism for echolocating bats based on spatial perceptual bias, i.e. actual sound field, a reaction delay, and observed motor constraints in speed and acceleration. We found that foraging pairs of bats flying over a water surface swapped leader-follower roles and performed chases or coordinated manoeuvres by copying the heading a nearby individual has had up to 500 ms earlier. Our proposed mechanism based on the interplay between sensory-motor constraints and delayed alignment was able to recreate the observed spatial actor-reactor patterns. Remarkably, when we varied model parameters (response delay, hearing threshold and echolocation directionality) beyond those observed in nature, the spatio-temporal interaction patterns created by the model only recreated the observed interactions, i.e. chases, and best matched the observed spatial patterns for just those response delays, hearing thresholds and echolocation directionalities found to be used by bats. This supports the validity of our sensory ecology approach of movement coordination, where interacting bats localise each other by active echolocation rather than eavesdropping.

  13. Photoemission and photoionization time delays and rates

    PubMed Central

    Gallmann, L.; Jordan, I.; Wörner, H. J.; Castiglioni, L.; Hengsberger, M.; Osterwalder, J.; Arrell, C. A.; Chergui, M.; Liberatore, E.; Rothlisberger, U.; Keller, U.

    2017-01-01

    Ionization and, in particular, ionization through the interaction with light play an important role in fundamental processes in physics, chemistry, and biology. In recent years, we have seen tremendous advances in our ability to measure the dynamics of photo-induced ionization in various systems in the gas, liquid, or solid phase. In this review, we will define the parameters used for quantifying these dynamics. We give a brief overview of some of the most important ionization processes and how to resolve the associated time delays and rates. With regard to time delays, we ask the question: how long does it take to remove an electron from an atom, molecule, or solid? With regard to rates, we ask the question: how many electrons are emitted in a given unit of time? We present state-of-the-art results on ionization and photoemission time delays and rates. Our review starts with the simplest physical systems: the attosecond dynamics of single-photon and tunnel ionization of atoms in the gas phase. We then extend the discussion to molecular gases and ionization of liquid targets. Finally, we present the measurements of ionization delays in femto- and attosecond photoemission from the solid–vacuum interface. PMID:29308414

  14. Pattern reverberation in networks of excitable systems with connection delays

    NASA Astrophysics Data System (ADS)

    Lücken, Leonhard; Rosin, David P.; Worlitzer, Vasco M.; Yanchuk, Serhiy

    2017-01-01

    We consider the recurrent pulse-coupled networks of excitable elements with delayed connections, which are inspired by the biological neural networks. If the delays are tuned appropriately, the network can either stay in the steady resting state, or alternatively, exhibit a desired spiking pattern. It is shown that such a network can be used as a pattern-recognition system. More specifically, the application of the correct pattern as an external input to the network leads to a self-sustained reverberation of the encoded pattern. In terms of the coupling structure, the tolerance and the refractory time of the individual systems, we determine the conditions for the uniqueness of the sustained activity, i.e., for the functionality of the network as an unambiguous pattern detector. We point out the relation of the considered systems with cyclic polychronous groups and show how the assumed delay configurations may arise in a self-organized manner when a spike-time dependent plasticity of the connection delays is assumed. As excitable elements, we employ the simplistic coincidence detector models as well as the Hodgkin-Huxley neuron models. Moreover, the system is implemented experimentally on a Field-Programmable Gate Array.

  15. An efficient approach to ARMA modeling of biological systems with multiple inputs and delays

    NASA Technical Reports Server (NTRS)

    Perrott, M. H.; Cohen, R. J.

    1996-01-01

    This paper presents a new approach to AutoRegressive Moving Average (ARMA or ARX) modeling which automatically seeks the best model order to represent investigated linear, time invariant systems using their input/output data. The algorithm seeks the ARMA parameterization which accounts for variability in the output of the system due to input activity and contains the fewest number of parameters required to do so. The unique characteristics of the proposed system identification algorithm are its simplicity and efficiency in handling systems with delays and multiple inputs. We present results of applying the algorithm to simulated data and experimental biological data In addition, a technique for assessing the error associated with the impulse responses calculated from estimated ARMA parameterizations is presented. The mapping from ARMA coefficients to impulse response estimates is nonlinear, which complicates any effort to construct confidence bounds for the obtained impulse responses. Here a method for obtaining a linearization of this mapping is derived, which leads to a simple procedure to approximate the confidence bounds.

  16. Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model.

    PubMed

    Castillo-Montiel, E; Chimal-Eguía, J C; Tello, J Ignacio; Piñon-Zaráte, G; Herrera-Enríquez, M; Castell-Rodríguez, A E

    2015-06-09

    The immunotherapy using dendritic cells (DCs) against different varieties of cancer is an approach that has been previously explored which induces a specific immune response. This work presents a mathematical model of DCs immunotherapy for melanoma in mice based on work by Experimental Immunotherapy Laboratory of the Medicine Faculty in the Universidad Autonoma de Mexico (UNAM). The model is a five delay differential equation (DDEs) which represents a simplified view of the immunotherapy mechanisms. The mathematical model takes into account the interactions between tumor cells, dendritic cells, naive cytotoxic T lymphocytes cells (inactivated cytotoxic cells), effector cells (cytotoxic T activated cytotoxic cells) and transforming growth factor β cytokine (T G F-β). The model is validated comparing the computer simulation results with biological trial results of the immunotherapy developed by the research group of UNAM. The results of the growth of tumor cells obtained by the control immunotherapy simulation show a similar amount of tumor cell population than the biological data of the control immunotherapy. Moreover, comparing the increase of tumor cells obtained from the immunotherapy simulation and the biological data of the immunotherapy applied by the UNAM researchers obtained errors of approximately 10 %. This allowed us to use the model as a framework to test hypothetical treatments. The numerical simulations suggest that by using more doses of DCs and changing the infusion time, the tumor growth decays compared with the current immunotherapy. In addition, a local sensitivity analysis is performed; the results show that the delay in time " τ", the maximal growth rate of tumor "r" and the maximal efficiency of tumor cytotoxic cells rate "aT" are the most sensitive model parameters. By using this mathematical model it is possible to simulate the growth of the tumor cells with or without immunotherapy using the infusion protocol of the UNAM researchers, to obtain a good approximation of the biological trials data. It is worth mentioning that by manipulating the different parameters of the model the effectiveness of the immunotherapy may increase. This last suggests that different protocols could be implemented by the Immunotherapy Laboratory of UNAM in order to improve their results.

  17. Combined effects of THC and caffeine on working memory in rats

    PubMed Central

    Panlilio, Leigh V; Ferré, Sergi; Yasar, Sevil; Thorndike, Eric B; Schindler, Charles W; Goldberg, Steven R

    2012-01-01

    BACKGROUND AND PURPOSE Cannabis and caffeine are two of the most widely used psychoactive substances. Δ9-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. EXPERIMENTAL APPROACH Rats were given THC (0, 1 and 3 mg·kg−1, i.p.) along with caffeine (0, 1, 3 and 10 mg·kg−1, i.p.), the selective adenosine A1-receptor antagonist CPT (0, 3 and 10 mg·kg−1) or the selective adenosine A2A-receptor antagonist SCH58261 (0 and 5 mg·kg−1) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. KEY RESULTS THC alone produced memory deficits at 3 mg·kg−1. The initial exposure to caffeine (10 mg·kg−1) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg−1) was combined with caffeine (10 mg·kg−1) or CPT (10 mg·kg−1), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. CONCLUSION AND IMPLICATIONS Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A1 receptors modulate cannabinoid signalling in the hippocampus. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21699509

  18. Angular dependence of EWS time delay for photoionization of @Xe

    NASA Astrophysics Data System (ADS)

    Mandal, Ankur; Deshmukh, Pranawa; Kheifets, Anatoli; Dolmatov, Valeriy; Manson, Steven

    2017-04-01

    Interference between photoionization channels leads to angular dependence in photoionization time delay. Angular dependence is found to be a common effect for two-photon absorption experiments very recently. The effect of confinement on the time delay where each partial wave contributions to the ionization are studied. In this work we report angular dependence and confinement effects on Eisenbud-Wigner-Smith (EWS) time delay in atomic photoionization. Using and we computed the EWS time delay for free and confined Xe atom for photoionization from inner 4d3/2 and 4d5/2 and outer 5p1/2 and 5p3/2 subshells at various angles. The calculated EWS time delay is few tens to few hundreds of attoseconds (10-18 second). The photoionization time delay for @Xe follows that in the free Xe atom on which the confinement oscillations are built. The present work reveals the effect of confinement on the photoionization time delay at different angles between photoelectron ejection and the photon polarization.

  19. Fitted Fourier-pseudospectral methods for solving a delayed reaction-diffusion partial differential equation in biology

    NASA Astrophysics Data System (ADS)

    Adam, A. M. A.; Bashier, E. B. M.; Hashim, M. H. A.; Patidar, K. C.

    2017-07-01

    In this work, we design and analyze a fitted numerical method to solve a reaction-diffusion model with time delay, namely, a delayed version of a population model which is an extension of the logistic growth (LG) equation for a food-limited population proposed by Smith [F.E. Smith, Population dynamics in Daphnia magna and a new model for population growth, Ecology 44 (1963) 651-663]. Seeing that the analytical solution (in closed form) is hard to obtain, we seek for a robust numerical method. The method consists of a Fourier-pseudospectral semi-discretization in space and a fitted operator implicit-explicit scheme in temporal direction. The proposed method is analyzed for convergence and we found that it is unconditionally stable. Illustrative numerical results will be presented at the conference.

  20. Mathematical properties and parameter estimation for transit compartment pharmacodynamic models.

    PubMed

    Yates, James W T

    2008-07-03

    One feature of recent research in pharmacodynamic modelling has been the move towards more mechanistically based model structures. However, in all of these models there are common sub-systems, such as feedback loops and time-delays, whose properties and contribution to the model behaviour merit some mathematical analysis. In this paper a common pharmacodynamic model sub-structure is considered: the linear transit compartment. These models have a number of interesting properties as the length of the cascade chain is increased. In the limiting case a pure time-delay is achieved [Milsum, J.H., 1966. Biological Control Systems Analysis. McGraw-Hill Book Company, New York] and the initial behaviour becoming increasingly sensitive to parameter value perturbation. It is also shown that the modelled drug effect is attenuated, though the duration of action is longer. Through this analysis the range of behaviours that such models are capable of reproducing are characterised. The properties of these models and the experimental requirements are discussed in order to highlight how mathematical analysis prior to experimentation can enhance the utility of mathematical modelling.

  1. Detecting and modelling delayed density-dependence in abundance time series of a small mammal (Didelphis aurita)

    NASA Astrophysics Data System (ADS)

    Brigatti, E.; Vieira, M. V.; Kajin, M.; Almeida, P. J. A. L.; de Menezes, M. A.; Cerqueira, R.

    2016-02-01

    We study the population size time series of a Neotropical small mammal with the intent of detecting and modelling population regulation processes generated by density-dependent factors and their possible delayed effects. The application of analysis tools based on principles of statistical generality are nowadays a common practice for describing these phenomena, but, in general, they are more capable of generating clear diagnosis rather than granting valuable modelling. For this reason, in our approach, we detect the principal temporal structures on the bases of different correlation measures, and from these results we build an ad-hoc minimalist autoregressive model that incorporates the main drivers of the dynamics. Surprisingly our model is capable of reproducing very well the time patterns of the empirical series and, for the first time, clearly outlines the importance of the time of attaining sexual maturity as a central temporal scale for the dynamics of this species. In fact, an important advantage of this analysis scheme is that all the model parameters are directly biologically interpretable and potentially measurable, allowing a consistency check between model outputs and independent measurements.

  2. EFFICIENCY OF PREPARED BAITS OF LONE OR/AND ADMIXED FOUR BOTANICAL OILS ON THE VIABILITY OF SUCCESSIVE RAISED GENERATIONS OF AGROTIS IPSILON (HUFNAGEL) (INSECTA: LEPIDOPTERA: NOCTUIDAE) AFTER TREATING THE PARENT ONES.

    PubMed

    Mesbah, H A; El-Sayed, Nagda A; El-Kady, Magda B; Tayeb, E H; Mourad, A K; Kordy, A M; Henaidy, Zeinab M

    2014-01-01

    The present study is initiated to determine the toxic and delayed effects of four botanical oils on the greasy cutworm A. ipsilon, aiming to attain an alternative environmentally safe and effective phytochemicals against the insect-pest. Four botanical oils (camphor, red basil, menthol and rose oil) were added at rates of 0.5 and 1.0% (v/w). The tested oils were added alone, and/or admixed at proportional rate of 1:1 in the prepared baits against the exposed 4th instar till the 6th instar larvae of the insect. The study was run under the laboratory higrothermic conditions of 25±2°C and 65±5% R.H. The results showed that the tested baits of camphor, red basil and menthol oils at concentration rates of 0.5 and 1.0% (v/w) adversely affected the inspected parameters of fitness components of the treated individuals of parent (p) generation. They gave more or less fewer numbers of weak unviable adult-moths, which were either sterile or they laid few numbers of infertile eggs and died before the induction of (F1) progeny. That failure could be elucidated by the rapid occurrence of drastic effects on the biological performance of both the influenced sexes of adult-moths along the period of parent's development. Finally it ended by the inhibited induction of (F1) progeny. A delayed effect of the prepared baits of rose oil at 0.5 and 1.0% (v/w), was assessed on the following raised F1, F2, F3 and F4 generations after parent's treatment. The delayed effect was detected as less efficient latent effect on each of these consequently raised generations; characterized by the gradual decrease of the number of alive immatures and adult-moths. The effect was recorded as gradual increase of dead and malformed individuals and adult-moths. In addition to the gradual decrease of deposited and/or hatched eggs up to the 4th generation, which ended by the complete failure of the development. That failure could be also attributed to the cumulated effects of the induced recessive lethal genes in both the influenced sexes during the periods of raised F1, F2 and F3 generations. The recessive lethal genes caused drastic unprofitable effects that appeared at the beginning of the 4th generation that failed. Also, the tested baits (0.5 and 1.0%, v/w) of each of admixed camphor, red basil and menthol oil with rose oil (1:1), greatly affected the developmental parameters of the treated insects. The highest efficient toxicity and an adverse biological performance of the admixed camphor and/or red basil oils with rose oil at 0.5 and 1.0 (v/w), and menthol/rose oil at 0.5% (v/w) on the treated parent generation were detected. The previous treatment gave unviable sterile adults, which died before the induction of (F1) progeny. That recorded failure of (F1) proves the fastest toxic efficiency and a drastic biological performance which were entirely unable to induce (F1) progeny. The tested bait of mixed menthol/rose oils (1.0%, v/w), showed significant reduction in all studied parameters of F1 and F2 fitness components. The tested bait raised sterile unviable adult-moths of (F2) generation which furtherly ended by the distinct failure of (F2) development. This effect may be caused by the cumulative effects of the induced recessive lethal genes in both of the affected sexes through the developmental period of (F1) generation after (P) one treatment, inducing apparent drastic effects, which were revealed at the beginning of (F2) generation. Remarkably, the inspected faster or slower occurred toxicity and drastic biological performance of these admixed botanical oils, may be referred to the synergistic action for most of the evaluated mixtures or/and the additive one for menthol/rose oil (1.0%), which needs further investigation.

  3. Isolating Behavioral Mechanisms of Inter-Temporal Choice: Nicotine Effects on Delay Discounting and Amount Sensitivity

    ERIC Educational Resources Information Center

    Locey, Matthew L.; Dallery, Jesse

    2009-01-01

    Many drugs of abuse produce changes in impulsive choice, that is, choice for a smaller-sooner reinforcer over a larger-later reinforcer. Because the alternatives differ in both delay and amount, it is not clear whether these drug effects are due to the differences in reinforcer delay or amount. To isolate the effects of delay, we used a titrating…

  4. Streamlining the Design-to-Build Transition with Build-Optimization Software Tools.

    PubMed

    Oberortner, Ernst; Cheng, Jan-Fang; Hillson, Nathan J; Deutsch, Samuel

    2017-03-17

    Scaling-up capabilities for the design, build, and test of synthetic biology constructs holds great promise for the development of new applications in fuels, chemical production, or cellular-behavior engineering. Construct design is an essential component in this process; however, not every designed DNA sequence can be readily manufactured, even using state-of-the-art DNA synthesis methods. Current biological computer-aided design and manufacture tools (bioCAD/CAM) do not adequately consider the limitations of DNA synthesis technologies when generating their outputs. Designed sequences that violate DNA synthesis constraints may require substantial sequence redesign or lead to price-premiums and temporal delays, which adversely impact the efficiency of the DNA manufacturing process. We have developed a suite of build-optimization software tools (BOOST) to streamline the design-build transition in synthetic biology engineering workflows. BOOST incorporates knowledge of DNA synthesis success determinants into the design process to output ready-to-build sequences, preempting the need for sequence redesign. The BOOST web application is available at https://boost.jgi.doe.gov and its Application Program Interfaces (API) enable integration into automated, customized DNA design processes. The herein presented results highlight the effectiveness of BOOST in reducing DNA synthesis costs and timelines.

  5. Biological response modifiers: their possibilities for cancer treatment.

    PubMed

    Franz, G

    1989-01-01

    Immunotherapy with the so-called 'Biological Response Modifiers' is based on the concept that the immune system can be activated to control neoplastic growth. Immunotherapy gained popularity as a treatment in the 1960's because of data from experimental tumor models. This indicated that mainly nonspecific stimulation with products of bacterial or fungal origine could prevent recurrence of, or delay growth of experimentally transplanted tumors. Since immunotherapy was most effective against relatively small tumors, clinical investigators began to view it mainly as a post-surgical treatment for a inhibition of micrometastasis. Mainly the activation of the non specific killer cells, macrophages and lymphocytes seems very promising to target an immune stimulant in the tumor site with a relatively high specificity. In the present study a whole series of biological polymers were tested in view of their capacity to enhance the immune system. However, the relatively small number of such compounds which can be applied therapeutically demonstrates that the ability of a compound to stimulate the immune systems is dependent on several conditions, such as the molecular dimension, the structure type and the solubility criteria. It will be shown that specific fungal glucans are very promising candidates for a successful cancer treatment.

  6. The Effects of Financial Education on Impulsive Decision Making

    PubMed Central

    DeHart, William B.; Friedel, Jonathan E.; Lown, Jean M.; Odum, Amy L.

    2016-01-01

    Delay discounting, as a behavioral measure of impulsive choice, is strongly related to substance abuse and other risky behaviors. Therefore, effective techniques that alter delay discounting are of great interest. We explored the ability of a semester long financial education course to change delay discounting. Participants were recruited from a financial education course (n = 237) and an abnormal psychology course (n = 80). Both groups completed a delay-discounting task for $100 during the first two weeks (Time 1) of the semester as well as during the last two weeks (Time 2) of the semester. Participants also completed a personality inventory and financial risk tolerance scale both times and a delay-discounting task for $1,000 during Time 2. Delay discounting decreased in the financial education group at the end of the semester whereas there was no change in delay discounting in the abnormal psychology group. Financial education may be an effective method for reducing delay discounting. PMID:27442237

  7. The Effects of Financial Education on Impulsive Decision Making.

    PubMed

    DeHart, William B; Friedel, Jonathan E; Lown, Jean M; Odum, Amy L

    2016-01-01

    Delay discounting, as a behavioral measure of impulsive choice, is strongly related to substance abuse and other risky behaviors. Therefore, effective techniques that alter delay discounting are of great interest. We explored the ability of a semester long financial education course to change delay discounting. Participants were recruited from a financial education course (n = 237) and an abnormal psychology course (n = 80). Both groups completed a delay-discounting task for $100 during the first two weeks (Time 1) of the semester as well as during the last two weeks (Time 2) of the semester. Participants also completed a personality inventory and financial risk tolerance scale both times and a delay-discounting task for $1,000 during Time 2. Delay discounting decreased in the financial education group at the end of the semester whereas there was no change in delay discounting in the abnormal psychology group. Financial education may be an effective method for reducing delay discounting.

  8. Down Syndrome = Sindrome de Down.

    ERIC Educational Resources Information Center

    Pueschel, S. M.; Glasgow, R. E.

    Presented both in English and Spanish, the brochure is primarily concerned with biological and developmental characteristics of the person with Down's syndrome. An emphasis is on the valuable humanizing influence these individuals have on society. Brief sections in the document discuss the delayed developmental aspects of Down's syndrome; the…

  9. Cytokinin delays dark-induced senescence in rice by maintaining the chlorophyll cycle and photosynthetic complexes.

    PubMed

    Talla, Sai Krishna; Panigrahy, Madhusmita; Kappara, Saivishnupriya; Nirosha, P; Neelamraju, Sarla; Ramanan, Rajeshwari

    2016-03-01

    The phytohormone cytokinin (CK) is known to delay senescence in plants. We studied the effect of a CK analog, 6-benzyl adenine (BA), on rice leaves to understand the possible mechanism by which CK delays senescence in a drought- and heat-tolerant rice cultivar Nagina22 (N22) using dark-induced senescence (DIS) as a surrogate for natural senescence of leaves. Leaves of N22-H-dgl162, a stay-green mutant of N22, and BA-treated N22 showed retention of chlorophyll (Chl) pigments, maintenance of the Chl a/b ratio, and delay in reduction of both photochemical efficiency and rate of oxygen evolution during DIS. HPLC analysis showed accumulation of 7-hydroxymethyl chlorophyll (HmChl) during DIS, and the kinetics of its accumulation correlated with progression of senescence. Transcriptome analysis revealed that several plastid-localized genes, specifically those associated with photosystem II (PSII), showed higher transcript levels in BA-treated N22 and the stay-green mutant leaves compared with naturally senescing N22 leaves. Real-time PCR analyses showed that genes coding for enzymes associated with Chl a/b interconversion and proteins associated with light-harvesting complexes maintained higher transcript levels up to 72h of DIS following BA treatment. The pigment-protein complexes analyzed by green gel remained intact in both N22-H-dgl162 and BA-treated N22 leaves even after 96h of DIS. Thus, CK delays senescence by accumulation of HmChl and up-regulating genes in the Chl cycle, thereby maintaining the Chl a/b ratio. Also, CK treatment retains higher transcript levels of PSII-related genes, resulting in the stability of photosynthetic pigment complexes and functional stay-greenness in rice. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  10. The effects of delay duration on visual working memory for orientation.

    PubMed

    Shin, Hongsup; Zou, Qijia; Ma, Wei Ji

    2017-12-01

    We used a delayed-estimation paradigm to characterize the joint effects of set size (one, two, four, or six) and delay duration (1, 2, 3, or 6 s) on visual working memory for orientation. We conducted two experiments: one with delay durations blocked, another with delay durations interleaved. As dependent variables, we examined four model-free metrics of dispersion as well as precision estimates in four simple models. We tested for effects of delay time using analyses of variance, linear regressions, and nested model comparisons. We found significant effects of set size and delay duration on both model-free and model-based measures of dispersion. However, the effect of delay duration was much weaker than that of set size, dependent on the analysis method, and apparent in only a minority of subjects. The highest forgetting slope found in either experiment at any set size was a modest 1.14°/s. As secondary results, we found a low rate of nontarget reports, and significant estimation biases towards oblique orientations (but no dependence of their magnitude on either set size or delay duration). Relative stability of working memory even at higher set sizes is consistent with earlier results for motion direction and spatial frequency. We compare with a recent study that performed a very similar experiment.

  11. A systematic approach to designing reliable VV optimization methodology: assessment of internal validity of echocardiographic, electrocardiographic and haemodynamic optimization of cardiac resynchronization therapy.

    PubMed

    Kyriacou, Andreas; Li Kam Wa, Matthew E; Pabari, Punam A; Unsworth, Beth; Baruah, Resham; Willson, Keith; Peters, Nicholas S; Kanagaratnam, Prapa; Hughes, Alun D; Mayet, Jamil; Whinnett, Zachary I; Francis, Darrel P

    2013-08-10

    In atrial fibrillation (AF), VV optimization of biventricular pacemakers can be examined in isolation. We used this approach to evaluate internal validity of three VV optimization methods by three criteria. Twenty patients (16 men, age 75 ± 7) in AF were optimized, at two paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG (minimizing QRS duration). Each optimization method was evaluated for: singularity (unique peak of function), reproducibility of optimum, and biological plausibility of the distribution of optima. The reproducibility (standard deviation of the difference, SDD) of the optimal VV delay was 10 ms for pressure, versus 8 ms (p=ns) for QRS and 34 ms (p<0.01) for flow. Singularity of optimum was 85% for pressure, 63% for ECG and 45% for flow (Chi(2)=10.9, p<0.005). The distribution of pressure optima was biologically plausible, with 80% LV pre-excited (p=0.007). The distributions of ECG (55% LV pre-excitation) and flow (45% LV pre-excitation) optima were no different to random (p=ns). The pressure-derived optimal VV delay is unaffected by the paced rate: SDD between slow and fast heart rate is 9 ms, no different from the reproducibility SDD at both heart rates. Using non-invasive arterial pressure, VV delay optimization by parabolic fitting is achievable with good precision, satisfying all 3 criteria of internal validity. VV optimum is unaffected by heart rate. Neither QRS minimization nor LVOT VTI satisfy all validity criteria, and therefore seem weaker candidate modalities for VV optimization. AF, unlinking interventricular from atrioventricular delay, uniquely exposes resynchronization concepts to experimental scrutiny. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Efficient reinforcement learning of a reservoir network model of parametric working memory achieved with a cluster population winner-take-all readout mechanism.

    PubMed

    Cheng, Zhenbo; Deng, Zhidong; Hu, Xiaolin; Zhang, Bo; Yang, Tianming

    2015-12-01

    The brain often has to make decisions based on information stored in working memory, but the neural circuitry underlying working memory is not fully understood. Many theoretical efforts have been focused on modeling the persistent delay period activity in the prefrontal areas that is believed to represent working memory. Recent experiments reveal that the delay period activity in the prefrontal cortex is neither static nor homogeneous as previously assumed. Models based on reservoir networks have been proposed to model such a dynamical activity pattern. The connections between neurons within a reservoir are random and do not require explicit tuning. Information storage does not depend on the stable states of the network. However, it is not clear how the encoded information can be retrieved for decision making with a biologically realistic algorithm. We therefore built a reservoir-based neural network to model the neuronal responses of the prefrontal cortex in a somatosensory delayed discrimination task. We first illustrate that the neurons in the reservoir exhibit a heterogeneous and dynamical delay period activity observed in previous experiments. Then we show that a cluster population circuit decodes the information from the reservoir with a winner-take-all mechanism and contributes to the decision making. Finally, we show that the model achieves a good performance rapidly by shaping only the readout with reinforcement learning. Our model reproduces important features of previous behavior and neurophysiology data. We illustrate for the first time how task-specific information stored in a reservoir network can be retrieved with a biologically plausible reinforcement learning training scheme. Copyright © 2015 the American Physiological Society.

  13. Base drive circuit

    DOEpatents

    Lange, Arnold C.

    1995-01-01

    An improved base drive circuit (10) having a level shifter (24) for providing bistable input signals to a pair of non-linear delays (30, 32). The non-linear delays (30, 32) provide gate control to a corresponding pair of field effect transistors (100, 106) through a corresponding pair of buffer components (88, 94). The non-linear delays (30, 32) provide delayed turn-on for each of the field effect transistors (100, 106) while an associated pair of transistors (72, 80) shunt the non-linear delays (30, 32) during turn-off of the associated field effect transistor (100, 106).

  14. Facilitation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor transmission in the suprachiasmatic nucleus by aniracetam enhances photic responses of the biological clock in rodents.

    PubMed

    Moriya, Takahiro; Ikeda, Masayuki; Teshima, Koji; Hara, Reiko; Kuriyama, Koji; Yoshioka, Tohru; Allen, Charles N; Shibata, Shigenobu

    2003-05-01

    This study was designed to test whether the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-facilitating drug, aniracetam, could potentiate photic responses of the biological clock in the suprachiasmatic nucleus (SCN) of rodents. Using the whole-cell patch technique, we first demonstrated that AMPA currents elicited by either local AMPA application or optic chiasm stimulation were augmented by aniracetam in the neurons of the SCN. The AMPA application-elicited increase of intracellular Ca2+ concentration in SCN slices was also enhanced by aniracetam treatment. The systemic injection of aniracetam dose-dependently (10-100 mg/kg) potentiated the phase delay in behavioral rhythm induced by brief light exposure of low intensity (3 lux) but not high intensity (10 or 60 lux) during early subjective night. Under the blockade of NMDA receptors by (+) MK801, aniracetam failed to potentiate a light (3 lux)-induced phase delay in behavioral rhythm. Aniracetam increased the photic induction of c-Fos protein in the SCN that was elicited by low intensity light exposure (3 lux). These results suggest that AMPA receptor-mediated responses facilitated by aniracetam can explain enhanced photic responses of the biological clock in the SCN of rodents.

  15. The effects of storage and sterilization on de-cellularized and re-cellularized whole lung.

    PubMed

    Bonenfant, Nicholas R; Sokocevic, Dino; Wagner, Darcy E; Borg, Zachary D; Lathrop, Melissa J; Lam, Ying Wai; Deng, Bin; Desarno, Michael J; Ashikaga, Taka; Loi, Roberto; Weiss, Daniel J

    2013-04-01

    Despite growing interest on the potential use of de-cellularized whole lungs as 3-dimensional scaffolds for ex vivo lung tissue generation, optimal processing including sterilization and storage conditions, are not well defined. Further, it is unclear whether lungs need to be obtained immediately or may be usable even if harvested several days post-mortem, a situation mimicking potential procurement of human lungs from autopsy. We therefore assessed effects of delayed necropsy, prolonged storage (3 and 6 months), and of two commonly utilized sterilization approaches: irradiation or final rinse with peracetic acid, on architecture and extracellular matrix (ECM) protein characteristics of de-cellularized mouse lungs. These different approaches resulted in significant differences in both histologic appearance and in retention of ECM and intracellular proteins as assessed by immunohistochemistry and mass spectrometry. Despite these differences, binding and proliferation of bone marrow-derived mesenchymal stromal cells (MSCs) over a one month period following intratracheal inoculation was similar between experimental conditions. In contrast, significant differences occurred with C10 mouse lung epithelial cells between the different conditions. Therefore, delayed necropsy, duration of scaffold storage, sterilization approach, and cell type used for re-cellularization may significantly impact the usefulness of this biological scaffold-based model of ex vivo lung tissue regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

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

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis, however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-inducedmore » mutations, double-strand breaks, or changes in mRNA levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesize that epigenetics may be the missing link in understanding the mechanism behind RIGI.« less

  17. Homeostatic effect of laughter on diabetic cardiovascular complications: The myth turned to fact.

    PubMed

    Noureldein, Mohamed H; Eid, Assaad A

    2018-01-01

    Laughter has been used for centuries to alleviate pain in morbid conditions. It was not until 1976 that scientists thought about laughter as a form of therapy that can modulate hormonal and immunological parameters that affect the outcome of many serious diseases. Moreover, laughter therapy was shown to be beneficial in type 2 diabetes mellitus (T2DM) by delaying the onset of many diabetic complications. Laughter is also described to influence the cardiovascular and endothelial functions and thus may protect against diabetic cardiovascular complications. In this review, we outline the different biochemical, physiological and immunological mechanisms by which laughter may influence the overall state of wellbeing and enhance disease prognosis. We also focus on the biological link between laughter therapy and diabetic cardiovascular complications as well as the underlying mechanisms involved in T2DM. Reviewing all the essential databases for "laughter" and "type 2 diabetes mellitus". Although laughter therapy is still poorly investigated, recent studies show that laughter may retard the onset of diabetic complications, enhance cardiovascular functions and rectify homeostatic abnormalities associated with T2DM. Laughter therapy is effective in delaying diabetic complications and should be used as an adjuvant therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Wolbachia infection in Aedes aegypti mosquitoes alters blood meal excretion and delays oviposition without affecting trypsin activity.

    PubMed

    Pimenta de Oliveira, Sofia; Dantas de Oliveira, Caroline; Viana Sant'Anna, Mauricio Roberto; Carneiro Dutra, Heverton Leandro; Caragata, Eric Pearce; Moreira, Luciano Andrade

    2017-08-01

    Blood feeding in Aedes aegypti is essential for reproduction, but also permits the mosquito to act as a vector for key human pathogens such as the Zika and dengue viruses. Wolbachia pipientis is an endosymbiotic bacterium that can manipulate the biology of Aedes aegypti mosquitoes, making them less competent hosts for many pathogens. Yet while Wolbachia affects other aspects of host physiology, it is unclear whether it influences physiological processes associated with blood meal digestion. To that end, we examined the effects of wMel Wolbachia infection in Ae. aegypti, on survival post-blood feeding, blood meal excretion, rate of oviposition, expression levels of key genes involved in oogenesis, and activity levels of trypsin blood digestion enzymes. We observed that wMel infection altered the rate and duration of blood meal excretion, delayed the onset of oviposition and was associated with a greater number of eggs being laid later. wMel-infected Ae. aegypti also had lower levels of key yolk protein precursor genes necessary for oogenesis. However, all of these effects occurred without a change in trypsin activity. These results suggest that Wolbachia infection may disrupt normal metabolic processes associated with blood feeding and reproduction in Ae. aegypti. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Biological treatment of soils contaminated with hydrophobic organics using slurry- and solid-phase techniques

    NASA Astrophysics Data System (ADS)

    Cassidy, Daniel H.; Irvine, Robert L.

    1995-10-01

    Both slurry-phase and solid-phase bioremediation are effective ex situ soil decontamination methods. Slurrying is energy intensive relative to solid-phase treatment, but provides homogenization and uniform nutrient distribution. Limited contaminant bioavailability at concentrations above the required cleanup level reduces biodegradation rates and renders solid phase bioremediation more cost effective than complete treatment in a bio-slurry reactor. Slurrying followed by solid-phase bioremediation combines the advantages and minimizes the weaknesses of each treatment method when used alone. A biological treatment system consisting of slurrying followed by aeration in solid phase bioreactors was developed and tested in the laboratory using a silty clay loam contaminated with diesel fuel. The first set of experiments was designed to determine the impact of the water content and mixing time during slurrying on the rate an extent of contaminant removal in continuously aerated solid phase bioreactors. The second set of experiments compared the volatile and total diesel fuel removal in solid phase bioreactors using periodic and continuous aeration strategies. Results showed that slurrying for 1.5 hours at a water content less than saturation markedly increased the rate and extent of contaminant biodegradation in the solid phase bioreactors compared with soil having no slurry pretreatment. Slurrying the soil at or above its saturation moisture content resulted in lengthy dewatering times which prohibited aeration, thereby delaying the onset of biological treatment in the solid phase bioreactors. Results also showed that properly operated periodic aeration can provide less volatile contaminant removal and a grater fraction of biological contaminant removal than continuous aeration.

  20. Leveraging delay discounting for health: Can time delays influence food choice?

    PubMed

    Appelhans, Bradley M; French, Simone A; Olinger, Tamara; Bogucki, Michael; Janssen, Imke; Avery-Mamer, Elizabeth F; Powell, Lisa M

    2018-07-01

    Delay discounting, the tendency to choose smaller immediate rewards over larger delayed rewards, is theorized to promote consumption of immediately rewarding but unhealthy foods at the expense of long-term weight maintenance and nutritional health. An untested implication of delay discounting models of decision-making is that selectively delaying access to less healthy foods may promote selection of healthier (immediately available) alternatives, even if they may be less desirable. The current study tested this hypothesis by measuring healthy versus regular vending machine snack purchasing before and during the implementation of a 25-s time delay on the delivery of regular snacks. Purchasing was also examined under a $0.25 discount on healthy snacks, a $0.25 tax on regular snacks, and the combination of both pricing interventions with the 25-s time delay. Across 32,019 vending sales from three separate vending locations, the 25-s time delay increased healthy snack purchasing from 40.1% to 42.5%, which was comparable to the impact of a $0.25 discount (43.0%). Combining the delay and the discount had a roughly additive effect (46.0%). However, the strongest effects were seen under the $0.25 tax on regular snacks (53.7%) and the combination of the delay and the tax (50.2%). Intervention effects varied substantially between vending locations. Importantly, time delays did not harm overall vending sales or revenue, which is relevant to the real-world feasibility of this intervention. More investigation is needed to better understand how the impact of time delays on food choice varies across populations, evaluate the effects of time delays on beverage vending choices, and extend this approach to food choices in contexts other than vending machines. ClinicalTrials.gov, NCT02359916. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Synthesis of valproic acid amides of a melatonin derivative, a piracetam and amantadine for biological tests.

    PubMed

    Chatterjie, N; Alexander, G; Wang, H

    2001-10-01

    Three new amide derivatives of valproic acid have been synthesized and characterized by spectrophotometric studies. The rationale for the preparation of such agents has been based on the observation that chemical combination of the anticonvulsant pharmacophore, valproic acid with amine moieties produces more effective and less toxic amides. The amine components selected in this work also exhibit neuroactivity with the prospect of these agents being biologically active in controlling not just seizures and but also possessing neuroprotective properties. We report here the synthesis and properties of the valproylamides of 5-methoxytryptamine, related to melatonin (1), of N-substituted 2-pyrrolidinone related to piracetam (2), and of adamantylamine related to amantadine (3). In preliminary tests these compounds showed low toxicity and a variety of anticonvulsive properties, including a delay in onset of activity. These compounds and their derivatives are now available to be tested additionally for control of subclinical seizures, enhancement of cognition, behavior modification and alleviation of symptoms and disorders due to neuronal damage.

  2. Performance and emissions characteristics of aqueous alcohol fumes in a DI diesel engine

    NASA Technical Reports Server (NTRS)

    Heisey, J. B.; Lestz, S. S.

    1981-01-01

    A single cylinder DI Diesel engine was fumigated with ethanol and methanol in amounts up to 55% of the total fuel energy. The effects of aqueous alcohol fumigation on engine thermal efficiency, combustion intensity and gaseous exhaust emissions were determined. Assessment of changes in the biological activity of raw particulate and its soluble organic fraction were also made using the Salmonella typhimurium test. Alcohol fumigation improved thermal efficiency slightly at moderate and heavy loads, but increased ignition delay at all operating conditions. Carbon monoxide and unburned hydrocarbon emission generally increased with alcohol fumigation and showed no dependence on alcohol type or quality. Oxide of nitrogen emission showed a strong dependence on alcohol quality; relative emission levels decreased with increasing water content of the fumigant. Particulate mass loading rates were lower for ethanol fueled conditions. However, the biological activity of both the raw particulate and its soluble organic fraction was enhanced by ethanol fumigation at most operating conditions.

  3. Biologic considerations regarding the one and two step procedures in the management of patients with invasive carcinoma of the breast.

    PubMed

    Fisher, E R; Sass, R; Fisher, B

    1985-09-01

    Investigation of the biologic significance of delay between biopsy and mastectomy was performed upon women with invasive carcinoma of the breast in protocol four of the NSABP. Since the period of delay was two weeks or less in approximately 75 per cent, no comment concerning the possible effects of longer periods can be made. Life table analyses failed to reveal any difference in ten year survival rates between patients undergoing radical mastectomy management by the one and two step procedures. Similarly, no difference in adjusted ten year survival rate was observed between women managed by the two step procedure who did or did not have residual tumor identified in the mastectomy specimen after the first step or biopsy. Importantly, the clinical or pathologic stages, sizes of tumor or histologic grades were similar in women managed by the one and two step procedures minimizing selection bias. The material used also allowed for study of the possible causative role of biopsy of the breast on the development of sinus histiocytosis in regional axillary lymph nodes. No difference in degree or types of this nodal reaction could be discerned in the lymph nodes of the mastectomy specimens obtained from patients who had undergone the one and two step procedures. This finding indicates that nodal sinus histiocytosis is indeed related to the neoplastic process, albeit in an undefined manner, rather than the trauma of biopsy per se as has been suggested. These results do not invalidate the use of the one step procedure in the management of patients with carcinoma of the breast. Indeed, it is highly likely that it will be commonly used now that breast-conserving operations appear to represent a viable alternative modality for the primary surgical treatment of carcinoma of the breast. Yet, it is apparent that the one step procedure will be performed for technical and practical rather than biologic reasons.

  4. Individual differences in discount rate are associated with demand for self-administered cocaine, but not sucrose.

    PubMed

    Koffarnus, Mikhail N; Woods, James H

    2013-01-01

    Substance abusers, including cocaine abusers, discount delayed rewards to a greater extent than do matched controls. In the current experiment, individual differences in discounting of delayed rewards in rats (choice of one immediate over three delayed sucrose pellets) were assessed for associations with demand for either sucrose pellets or an intravenous dose of 0.1 mg/kg/infusion cocaine. Twenty-four male Sprague Dawley rats were split into three groups based on sensitivity to delay to reinforcement. Then, demand for sucrose pellets and cocaine was determined across a range of fixed-ratio values. Delay discounting was then reassessed to determine the stability of this measure over the course of the experiment. Individual differences in impulsive choice were positively associated with elasticity of demand for cocaine, a measure of reinforcer value, indicating that rats having higher discount rates also valued cocaine more. Impulsive choice was not associated with the level of cocaine consumption as price approached 0 or with any parameter associated with demand for sucrose. Individual sensitivity to delay was correlated with the initial assessment when reassessed at the end of the experiment, although impulsive choice increased for this cohort of rats as a whole. These findings suggest that impulsive choice in rats is positively associated with valuation of cocaine, but not sucrose. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  5. Drinking status but not acute alcohol consumption influences delay discounting.

    PubMed

    Adams, Sally; Attwood, Angela S; Munafò, Marcus R

    2017-09-01

    The aim of this study was to investigate the following: (a) the effects of acute alcohol on delay discounting; (b) the effects of drinking status on delayed discounting; and (c) whether these effects differ according to reward type (alcohol vs. money). Heavy and light social alcohol users (n = 96) were randomized to receive either an acute dose of alcohol at 0.4 or 0.6 g/kg or placebo in a between-subjects, double-blind design. Delay discounting of alcohol and monetary rewards was measured using a hyperbolic model, with higher scores indicative of greater delay discounting. ANOVA of discount scores indicated a main effect of reward type, where all participants had higher discount scores for alcohol versus money rewards. A main effect of drinking status was also observed, where heavier drinkers had higher discount scores compared with lighter drinkers. We did not observe a main effect of acute alcohol use on delay discounting or the hypothesized interactions between acute alcohol use and drinking status with reward type. Our data suggest that heavier drinkers discount the value of delayed rewards more steeply than lighter drinkers. Delay discounting may therefore be a promising marker of heavy alcohol consumption in social drinkers. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Carrier Dynamics and Application of the Phase Coherent Photorefractive Effect in ZnSe Quantum Wells

    NASA Astrophysics Data System (ADS)

    Dongol, Amit

    The intensity dependent diffraction efficiency of a phase coherent photorefractive (PCP) ZnSe quantum well (QW) is investigated at 80 K in a two-beam four-wave mixing (FWM) configuration using 100 fs laser pulses with a repetition rate of 80 MHz. The observed diffraction efficiencies of the first and second-order diffracted beam are on the order of 10-3 and 10-5, respectively, revealing nearly no intensity dependence. The first-order diffraction is caused by the PCP effect where the probe-pulse is diffracted due to a long-living incoherent electron density grating in the QW. The second-order diffraction is created by a combination of diffraction processes. For negative probe-pulse delay, the exciton polarization is diffracted at the electron grating twice by a cascade effect. For positive delay, the diffracted signal is modified by the destructive interference with a chi(5) generated signal due to a dynamical screening effect. Model calculations of the signal traces based on the optical Bloch equations considering inhomogeneous broadening of exciton energies are in good agreement with the experimental data. To study the carrier dynamics responsible for the occurrence of the PCP effect, threebeam FWM experiments are carried out. The non-collinear wave-vectors k1 , k2 and k3 at central wavelength of 441 nm (~2.81 eV) were resonantly tuned to the heavy-hole exciton transition energy at 20 K. In the FWM experiment the time coincident strong pump pulses k1 and k2 create both an exciton density grating in the QW and an electron-hole pair grating in the GaAs while the delayed weak pulse k3 simultaneously probes the exciton lifetime as well as the electron grating capture time. The model calculations are in good agreement with the experimental results also providing information about the transfer delay of electrons arriving from the substrate to the QW. For negative probe-pulse delay we still observe a diffracted signal due to the long living electron density grating in the QW. The electron grating build-up and decay times are also studied with the modified three-beam FWM set-up. Using an optical shutter for pump pulses k1and k2, the dynamics of the electron grating formation and its decay is continuously probed by a delayed pulse k3. The obtained build-up and decay times are found to depend nearly linearly on the intensity of incident pulses k1 and k2 being on the order of several microseconds at low pump intensities. The PCP effect in ZnSe QW possesses a time-gating capability which can be used for real-time holographic imaging. In this work we demonstrate contrast enhanced real time holographic imaging (CEHI) of floating glass beads and of living unicellular animals (Paramecium and Euglena cells) in aqueous solution. We also demonstrate CEHI of a ~100 im thick wire concealed behind a layer of chicken skin. The results demonstrate the potential of PCP QWs for real-time and depth-resolved imaging of moving micrometer sized biological objects in transparent media or of obscured objects in turbid media.

  7. A money management-based substance use treatment increases valuation of future rewards.

    PubMed

    Black, Anne C; Rosen, Marc I

    2011-01-01

    A positive association between delay discounting and substance use has been documented; substance users tend to discount future rewards more than non-users. However, studies detailing the responsiveness of delay discounting to interventions are lacking, and few have examined how any behavioral intervention affects delay discounting and whether these effects moderate changes in substance abuse. This study assesses the effectiveness of a money management intervention, Advisor-Teller Money Manager (ATM), in reducing delay discounting over time and the relationship of these effects to changes in cocaine use. Ninety psychiatric patients with histories of cocaine and/or alcohol use were randomly assigned to 36-weeks of ATM treatment or to a minimal-attention control condition. Delay discounting and cocaine use were measured throughout the intervention with a 52-week follow up measure of cocaine use. Analyses were conducted of (a) the effect of ATM on slopes of delay discounting and cocaine abstinence and (b) the relationship between change in delay discounting and change in cocaine abstinence. The ATM intervention was associated with significantly less delay discounting and less cocaine use over time relative to controls. Increases in delay discounting were associated with decreased abstinence from cocaine. ATM treatment decreased delay discounting rates and these effects extended to cocaine use. Concrete conceptualizations of future events, as occur in financial planning, with higher perceived probability may account for higher valuation of future rewards in counseled patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. The influence of delaying judgments of learning on metacognitive accuracy: a meta-analytic review.

    PubMed

    Rhodes, Matthew G; Tauber, Sarah K

    2011-01-01

    Many studies have examined the accuracy of predictions of future memory performance solicited through judgments of learning (JOLs). Among the most robust findings in this literature is that delaying predictions serves to substantially increase the relative accuracy of JOLs compared with soliciting JOLs immediately after study, a finding termed the delayed JOL effect. The meta-analyses reported in the current study examined the predominant theoretical accounts as well as potential moderators of the delayed JOL effect. The first meta-analysis examined the relative accuracy of delayed compared with immediate JOLs across 4,554 participants (112 effect sizes) through gamma correlations between JOLs and memory accuracy. Those data showed that delaying JOLs leads to robust benefits to relative accuracy (g = 0.93). The second meta-analysis examined memory performance for delayed compared with immediate JOLs across 3,807 participants (98 effect sizes). Those data showed that delayed JOLs result in a modest but reliable benefit for memory performance relative to immediate JOLs (g = 0.08). Findings from these meta-analyses are well accommodated by theories suggesting that delayed JOL accuracy reflects access to more diagnostic information from long-term memory rather than being a by-product of a retrieval opportunity. However, these data also suggest that theories proposing that the delayed JOL effect results from a memorial benefit or the match between the cues available for JOLs and those available at test may also provide viable explanatory mechanisms necessary for a comprehensive account.

  9. Feedback in Action--The Mechanism of the Iris.

    ERIC Educational Resources Information Center

    Pingnet, B.; And Others

    1988-01-01

    Describes two demonstration experiments. Outlines a demonstration of the general principle of positive and negative feedback and the influence of time delays in feedback circuits. Elucidates the principle of negative feedback with a model of the iris of the eye. Emphasizes the importance of feedback in biological systems. (CW)

  10. Racial/Ethnic Differences in the Predictive Validity of MCAT Scores.

    ERIC Educational Resources Information Center

    Jones, Robert F.; Mitchell, Karen

    Medical College Admission Test (MCAT) score differences were examined for Black and White examinees who entered American medical schools in 1978 and 1979. The incidence of academic difficulty resulting in delayed graduation, withdrawal, or dismissal was also examined. The MCAT provides six scores: biology, chemistry, physics, science problems,…

  11. A Developmental and Genetic Classification for Malformations of Cortical Development: Update 2012

    ERIC Educational Resources Information Center

    Barkovich, A. James; Guerrini, Renzo; Kuzniecky, Ruben I.; Jackson, Graeme D.; Dobyns, William B.

    2012-01-01

    Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics…

  12. The Abusive Environment and the Child's Adaptation.

    ERIC Educational Resources Information Center

    Martin, Harold P.

    The biologic and developmental problems of abused children are usually thought of etiologically in relation to the physical trauma which has been suffered. Indeed, physical trauma can cause death, brain damage, developmental delays and deviations in personality development. The environment in which the abused child grows and develops is a most…

  13. Making the case for early adoption of preventative practices for management of grapevine trunk diseases

    USDA-ARS?s Scientific Manuscript database

    Experimental trials on prevention of trunk diseases Botryosphaeria dieback, Esca, and Eutypa dieback have shown that delayed pruning, double pruning, and applications of the pruning-wound protectant thiophanate-methyl (Topsin) can reduce pruning-wound infections by 25-75%. Despite this biological e...

  14. Effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks.

    PubMed

    Sun, Xiaojuan; Perc, Matjaž; Kurths, Jürgen

    2017-05-01

    In this paper, we study effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks. Our focus is on the impact of two parameters, namely the time delay τ and the probability of partial time delay p delay , whereby the latter determines the probability with which a connection between two neurons is delayed. Our research reveals that partial time delays significantly affect phase synchronization in this system. In particular, partial time delays can either enhance or decrease phase synchronization and induce synchronization transitions with changes in the mean firing rate of neurons, as well as induce switching between synchronized neurons with period-1 firing to synchronized neurons with period-2 firing. Moreover, in comparison to a neuronal network where all connections are delayed, we show that small partial time delay probabilities have especially different influences on phase synchronization of neuronal networks.

  15. A biological study establishing the endotoxin limit of biomaterials for bone regeneration in cranial and femoral implantation of rats.

    PubMed

    Haishima, Yuji; Hasegawa, Chie; Todoki, Kazuo; Sasaki, Kazuo; Niimi, Shingo; Ozono, Satoru

    2017-08-01

    The purpose of this study was to accurately quantify the risk of endotoxin contamination in biomaterials for bone regeneration in order to establish the acceptable endotoxin limit. Collagen sheets containing varying amounts of purified endotoxin from Escherichia coli and dried, heat-killed E. coli or Staphylococcus aureus cells were implanted into cranial or femoral defects in rats. These defects were artificially prepared to a size of 5 × 5 mm or a diameter of 1 mm, respectively. The degree of osteoanagenesis was assessed by soft X-ray radiography and histopathology at 1 and 4 weeks after implantation. The collagen sheet containing the dried E. coli cells showed a dose-dependent delay in cranial and/or femoral osteoanagenesis at endotoxin activities of more than 33.6 EU/mg, at which no inflammatory response was observed. In contrast, no such observation occurred with the collagen sheet containing S. aureus cells. These results suggest that endotoxins may affect the process of osteoanagenesis. Additionally, the no-observed-adverse-effect level was 9.6 EU/mg, corresponding to 255 EU/kg body weight in rats. Interestingly, no delay in osteoanagenesis was induced by the implantation of collagen sheets containing purified endotoxin at any dose tested. This suggested that pure endotoxin implanted into tissues having poor circulation of bodily fluids without bleeding may not be recognized as a foreign substance and may not induce a significant biological response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1514-1524, 2017. © 2016 Wiley Periodicals, Inc.

  16. Functional Outcome of School Children With History of Global Developmental Delay.

    PubMed

    Dornelas, Lílian F; Duarte, Neuza M C; Morales, Nívea M O; Pinto, Rogério M C; Araújo, Renata R H; Pereira, Sílvia A; Magalhães, Lívia C

    2016-07-01

    This study aimed to investigate the functional and developmental outcomes in school age children diagnosed with global developmental delay before 2 years old and to verify the association between their final diagnosis and environmental and biological factors. Forty-five Brazilian children (26 boys), mean age 95.84 (7.72) months, who attended regular school and were diagnosed with global developmental delay before they were 2 years old had their functions evaluated. Children with global developmental delay were diagnosed with several conditions at school age. Students with greater chances of receiving a diagnosis were those whose mothers were younger at the time their children were born (OR = 1.47, CI = 1.04-2.09, P = .03), who had impaired motor performance, specially balance (OR = 1.33, CI = 1.01-1.75, P = .04), and who needed help during cognitive and behavioral tasks at school (OR = 1.08, CI = 1.00-1.17, P = .048). Interdisciplinary evaluation contributed to defining the specific diagnosis and to identifying the necessity of specialized support. © The Author(s) 2016.

  17. δ 13C evidence that high primary productivity delayed recovery from end-Permian mass extinction

    NASA Astrophysics Data System (ADS)

    Meyer, K. M.; Yu, M.; Jost, A. B.; Kelley, B. M.; Payne, J. L.

    2011-02-01

    Euxinia was widespread during and after the end-Permian mass extinction and is commonly cited as an explanation for delayed biotic recovery during Early Triassic time. This anoxic, sulfidic episode has been ascribed to both low- and high-productivity states in the marine water column, leaving the causes of euxinia and the mechanisms underlying delayed recovery poorly understood. Here we use isotopic analysis to examine the changing chemical structure of the water column through the recovery interval and thereby better constrain paleoproductivity. The δ 13C of limestones from 5 stratigraphic sections in south China displays a negative gradient of approximately 4‰ from shallow-to-deep water facies within the Lower Triassic. This intense gradient declines within Spathian and lowermost Middle Triassic strata, coincident with accelerated biotic recovery and carbon cycle stabilization. Model simulations show that high nutrient levels and a vigorous biological pump are required to sustain such a large gradient in δ 13C, indicating that Early Triassic ocean anoxia and delayed recovery of benthic animal ecosystems resulted from too much productivity rather than too little.

  18. Proceedings of the Government Neural Network Applications Workshop Held at Wright-Patterson AFB, Ohio on August 24-26, 1992. Volume 1

    DTIC Science & Technology

    1992-08-01

    history trace of input u(t). (b) A common network struc- 1 ture makes use of the feedforward tapped delay line. For this structure the memory depth D...theories and analyses that will be used world- wide for a long time to come. The reason for this contribution has generally been the government’s need to...that emulate the neural reasoning behavior of biological neural systems (e.g. the human brain). As such, they are loosely based on biological neural

  19. Modelling and simulation techniques for membrane biology.

    PubMed

    Burrage, Kevin; Hancock, John; Leier, André; Nicolau, Dan V

    2007-07-01

    One of the most important aspects of Computational Cell Biology is the understanding of the complicated dynamical processes that take place on plasma membranes. These processes are often so complicated that purely temporal models cannot always adequately capture the dynamics. On the other hand, spatial models can have large computational overheads. In this article, we review some of these issues with respect to chemistry, membrane microdomains and anomalous diffusion and discuss how to select appropriate modelling and simulation paradigms based on some or all the following aspects: discrete, continuous, stochastic, delayed and complex spatial processes.

  20. Periodicity computation of generalized mathematical biology problems involving delay differential equations.

    PubMed

    Jasim Mohammed, M; Ibrahim, Rabha W; Ahmad, M Z

    2017-03-01

    In this paper, we consider a low initial population model. Our aim is to study the periodicity computation of this model by using neutral differential equations, which are recognized in various studies including biology. We generalize the neutral Rayleigh equation for the third-order by exploiting the model of fractional calculus, in particular the Riemann-Liouville differential operator. We establish the existence and uniqueness of a periodic computational outcome. The technique depends on the continuation theorem of the coincidence degree theory. Besides, an example is presented to demonstrate the finding.

  1. Boosted Regeneration and Reduced Denervated Muscle Atrophy by NeuroHeal in a Pre-clinical Model of Lumbar Root Avulsion with Delayed Reimplantation.

    PubMed

    Romeo-Guitart, David; Forés, Joaquim; Navarro, Xavier; Casas, Caty

    2017-09-20

    The "gold standard" treatment of patients with spinal root injuries consists of delayed surgical reconnection of nerves. The sooner, the better, but problems such as injury-induced motor neuronal death and muscle atrophy due to long-term denervation mean that normal movement is not restored. Herein we describe a preclinical model of root avulsion with delayed reimplantation of lumbar roots that was used to establish a new adjuvant pharmacological treatment. Chronic treatment (up to 6 months) with NeuroHeal, a new combination drug therapy identified using a systems biology approach, exerted long-lasting neuroprotection, reduced gliosis and matrix proteoglycan content, accelerated nerve regeneration by activating the AKT pathway, promoted the formation of functional neuromuscular junctions, and reduced denervation-induced muscular atrophy. Thus, NeuroHeal is a promising treatment for spinal nerve root injuries and axonal regeneration after trauma.

  2. Numerical modelling in biosciences using delay differential equations

    NASA Astrophysics Data System (ADS)

    Bocharov, Gennadii A.; Rihan, Fathalla A.

    2000-12-01

    Our principal purposes here are (i) to consider, from the perspective of applied mathematics, models of phenomena in the biosciences that are based on delay differential equations and for which numerical approaches are a major tool in understanding their dynamics, (ii) to review the application of numerical techniques to investigate these models. We show that there are prima facie reasons for using such models: (i) they have a richer mathematical framework (compared with ordinary differential equations) for the analysis of biosystem dynamics, (ii) they display better consistency with the nature of certain biological processes and predictive results. We analyze both the qualitative and quantitative role that delays play in basic time-lag models proposed in population dynamics, epidemiology, physiology, immunology, neural networks and cell kinetics. We then indicate suitable computational techniques for the numerical treatment of mathematical problems emerging in the biosciences, comparing them with those implemented by the bio-modellers.

  3. The effect of visual-motion time delays on pilot performance in a pursuit tracking task

    NASA Technical Reports Server (NTRS)

    Miller, G. K., Jr.; Riley, D. R.

    1976-01-01

    A study has been made to determine the effect of visual-motion time delays on pilot performance of a simulated pursuit tracking task. Three interrelated major effects have been identified: task difficulty, motion cues, and time delays. As task difficulty, as determined by airplane handling qualities or target frequency, increases, the amount of acceptable time delay decreases. However, when relatively complete motion cues are included in the simulation, the pilot can maintain his performance for considerably longer time delays. In addition, the number of degrees of freedom of motion employed is a significant factor.

  4. Using Video to Bridge the Gap Between Problem Behavior and a Delayed Time-out Procedure.

    PubMed

    Coppage, Sara; Meindl, James N

    2017-09-01

    Treatment plans focused on problem behavior often include punishment contingencies to decrease problem behavior. Immediate punishers are typically more effective than delayed punishers, but immediate delivery of a punisher is not always possible. Strategies need to be developed to increase the suppressive effects of delayed punishers. This study demonstrated the effectiveness of a treatment package involving replaying a video recording of problem behavior immediately before delivering a 15 min delayed time-out. This treatment package may prove to be an accessible and inexpensive strategy when using delayed punishers.

  5. Forgetting in immediate serial recall: decay, temporal distinctiveness, or interference?

    PubMed

    Oberauer, Klaus; Lewandowsky, Stephan

    2008-07-01

    Three hypotheses of forgetting from immediate memory were tested: time-based decay, decreasing temporal distinctiveness, and interference. The hypotheses were represented by 3 models of serial recall: the primacy model, the SIMPLE (scale-independent memory, perception, and learning) model, and the SOB (serial order in a box) model, respectively. The models were fit to 2 experiments investigating the effect of filled delays between items at encoding or at recall. Short delays between items, filled with articulatory suppression, led to massive impairment of memory relative to a no-delay baseline. Extending the delays had little additional effect, suggesting that the passage of time alone does not cause forgetting. Adding a choice reaction task in the delay periods to block attention-based rehearsal did not change these results. The interference-based SOB fit the data best; the primacy model overpredicted the effect of lengthening delays, and SIMPLE was unable to explain the effect of delays at encoding. The authors conclude that purely temporal views of forgetting are inadequate. Copyright (c) 2008 APA, all rights reserved.

  6. Grape berry ripening delay induced by a pre-véraison NAA treatment is paralleled by a shift in the expression pattern of auxin- and ethylene-related genes.

    PubMed

    Ziliotto, Fiorenza; Corso, Massimiliano; Rizzini, Fabio Massimo; Rasori, Angela; Botton, Alessandro; Bonghi, Claudio

    2012-10-09

    Auxins act as repressors of ripening inception in grape (véraison), while ethylene and abscisic acid (ABA) play a positive role as inducers of the syndrome. Despite the increasing amount of information made available on this topic, the complex network of interactions among these hormones remains elusive. In order to shed light on these aspects, a holistic approach was adopted to evaluate, at the transcriptomic level, the crosstalk between hormones in grape berries, whose ripening progression was delayed by applying naphtalenacetic acid (NAA) one week before véraison. The NAA treatment caused significant changes in the transcription rate of about 1,500 genes, indicating that auxin delayed grape berry ripening also at the transcriptional level, along with the recovery of a steady state of its intracellular concentration. Hormone indices analysis carried out with the HORMONOMETER tool suggests that biologically active concentrations of auxins were achieved throughout a homeostatic recovery. This occurred within 7 days after the treatment, during which the physiological response was mainly unspecific and due to a likely pharmacological effect of NAA. This hypothesis is strongly supported by the up-regulation of genes involved in auxin conjugation (GH3-like) and action (IAA4- and IAA31-like). A strong antagonistic effect between auxin and ethylene was also observed, along with a substantial 'synergism' between auxins and ABA, although to a lesser extent. This study suggests that, in presence of altered levels of auxins, the crosstalk between hormones involves diverse mechanisms, acting at both the hormone response and biosynthesis levels, creating a complex response network.

  7. Development and biological function of the female gonads and genitalia in IGF-I deficiency -- Laron syndrome as a model.

    PubMed

    Laron, Zvi

    2006-01-01

    Laron syndrome (LS) or primary GH insensitivity is a unique human model to study the effects of congenital IGF-I deficiency. Within our cohort of 63 patients with LS, 15 female patients were regularly followed since birth or infancy, throughout puberty. We observed that they were short at birth, with small genitalia and gonads -- during puberty, developed delayed puberty but eventually reached between 16 and 19 1/2 years full sexual development. Reproduction is unaffected at a young adult age. It is concluded that IGF-I in concert with the sex hormones has a modulatory but not essential function on female sexual development and maturation.

  8. Cancer Risk Assessment for Space Radiation

    NASA Technical Reports Server (NTRS)

    Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

    2001-01-01

    Predicting the occurrence of human cancer following exposure to any agent causing genetic damage is a difficult task. This is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within any given clinically normal individual. The radiation health research priorities for enabling long-duration human exploration of space were established in the 1996 NRC Report entitled 'Radiation Hazards to Crews of Interplanetary Missions: Biological Issues and Research Strategies'. This report emphasized that a 15-fold uncertainty in predicting radiation-induced cancer incidence must be reduced before NASA can commit humans to extended interplanetary missions. That report concluded that the great majority of this uncertainty is biologically based, while a minority is physically based due to uncertainties in radiation dosimetry and radiation transport codes. Since that report, the biologically based uncertainty has remained large, and the relatively small uncertainty associated with radiation dosimetry has increased due to the considerations raised by concepts of microdosimetry. In a practical sense, however, the additional uncertainties introduced by microdosimetry are encouraging since they are in a direction of lowered effective dose absorbed through infrequent interactions of any given cell with the high energy particle component of space radiation. Additional information is contained in the original extended abstract.

  9. Describing-function analysis of a ripple regulator with slew-rate limits and time delays

    NASA Technical Reports Server (NTRS)

    Wester, Gene W.

    1990-01-01

    The effects of time delays and slew-rate limits on the steady-state operating points and performance of a free-running ripple regulator are evaluated using describing-function analysis. The describing function of an ideal comparator (no time delays or slew rate limits) has no phase shift and is independent of frequency. It is found that turn-on delay and turn-off delay have different effects on gain and phase and cannot be combined. Comparator hysteresis affects both gain and phase; likewise, time delays generally affect both gain and phase. It is found that the effective time delay around the feedback loop is one half the sum of turn-on and turn-off delays, regardless of whether the delays are caused by storage time or slew rate limits. Expressions are formulated for the switching frequency, switch duty ratio, dc output, and output ripple. For the case of no hysteresis, a simple, graphical solution for the switching frequency is possible, and the resulting switching frequency is independent of first-order variations of input or load.

  10. Distributed Bandpass Filtering and Signal Demodulation in Cortical Network Models

    NASA Astrophysics Data System (ADS)

    McDonnell, Mark D.

    Experimental recordings of cortical activity often exhibit narrowband oscillations, at various center frequencies ranging in the order of 1-200 Hz. Many neuronal mechanisms are known to give rise to oscillations, but here we focus on a population effect known as sparsely synchronised oscillations. In this effect, individual neurons in a cortical network fire irregularly at slow average spike rates (1-10 Hz), but the population spike rate oscillates at gamma frequencies (greater than 40 Hz) in response to spike bombardment from the thalamus. These cortical networks form recurrent (feedback) synapses. Here we describe a model of sparsely synchronized population oscillations using the language of feedback control engineering, where we treat spiking as noisy feedback. We show, using a biologically realistic model of synaptic current that includes a delayed response to inputs, that the collective behavior of the neurons in the network is like a distributed bandpass filter acting on the network inputs. Consequently, the population response has the character of narrowband random noise, and therefore has an envelope and instantaneous frequency with lowpass characteristics. Given that there exist biologically plausible neuronal mechanisms for demodulating the envelope and instantaneous frequency, we suggest there is potential for similar effects to be exploited in nanoscale electronics implementations of engineered communications receivers.

  11. Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes

    NASA Technical Reports Server (NTRS)

    George, Kerry; Durante, Marco; Willingham, Veronica; Wu, Honglu; Yang, Tracy C.; Cucinotta, Francis A.

    2003-01-01

    Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.

  12. Gas formation and biological effects of biodegradable magnesium in a preclinical and clinical observation

    PubMed Central

    Lee, Kwang-Bok; Bode, Ken; Kwon, Tae-Young; Jeon, Moo Heon

    2018-01-01

    Abstract Magnesium alloys are biodegradable metals receiving increasing attention, but the clinical applications of these materials are delayed by concerns over the rapid corrosion rate and gas formation. Unlike corrosion, which weakens mechanical properties, the gas formation issue has received little attention. Therefore, we evaluated the gas formation and biological effects for Mg implants through preclinical (immersed in Earle’s balanced salt solution and in vivo) and clinical studies. The immersion test examined the gas volume and composition. The in vivo study also examined gas volume and histological analysis. The clinical study examined the gas volume and safety after Mg screw metatarsal fixation. Gas was mainly composed of H2, CO and CO2. Maximum volumes of gas formed after 5 days for in vivo and 7 days in clinical study. Within the clinical examination, two superficial wound complications healed with local wound care. Osteolytic lesions in the surrounding metaphysis of the Mg screw insertion developed in all cases and union occurred at 3 months. Mg implants released gas with variable volumes and composition (H2, CO, and CO2), with no long-term toxic effects on the surrounding tissue. The implants enabled bone healing, although complications of wound breakdown and osteolytic lesions developed. PMID:29707071

  13. [Survivability and morphologic anomalies in higher plants wolffia arrhiza following exposure to heavy ions of the galactic space radiation].

    PubMed

    Nevzgodina, L V; Kaminskaia, E V; Maksimova, E N; Fatsius, R; Sherrer, K; Shtraukh, V

    2000-01-01

    Experimental data on the effects of spaceflight factors, space radiation in particular, on higher plant Wolffia arrhiza firstly exposed in the "Bioblock" assembly and measurements made by physical track detectors of heavy ions (HI) are presented. Death of individual Wolffia plants and morphologic anomalies were the basic evaluation criteria. The peculiar feature of this biological object consists in the possibility to reveal delayed effects after 1-2 months since space flight as Wolffia has a high rate of vegetative reproduction. German investigators through microscopic examination of track detectors performed identification of individual plants affected by HI. With specially developed software and a coordinate system of supposition of biolayers and track detectors with the accuracy of 1 micron, tracks and even separate sections of individual HI tracks were determined in biological objects. Thereafter each Wolffia plant hit by HI was examined and data were compared with other variants. As a result, correlation between Wolffia death rate and morphologic anomalies were determined at different times post flight and topography of HI tracks was found. It is hypothesized that morphological anomalies in Walffia were caused by direct hits of plant germs by heavy ions or close passage of particles.

  14. Visualizing protein interactions and dynamics: evolving a visual language for molecular animation.

    PubMed

    Jenkinson, Jodie; McGill, Gaël

    2012-01-01

    Undergraduate biology education provides students with a number of learning challenges. Subject areas that are particularly difficult to understand include protein conformational change and stability, diffusion and random molecular motion, and molecular crowding. In this study, we examined the relative effectiveness of three-dimensional visualization techniques for learning about protein conformation and molecular motion in association with a ligand-receptor binding event. Increasingly complex versions of the same binding event were depicted in each of four animated treatments. Students (n = 131) were recruited from the undergraduate biology program at University of Toronto, Mississauga. Visualization media were developed in the Center for Molecular and Cellular Dynamics at Harvard Medical School. Stem cell factor ligand and cKit receptor tyrosine kinase were used as a classical example of a ligand-induced receptor dimerization and activation event. Each group completed a pretest, viewed one of four variants of the animation, and completed a posttest and, at 2 wk following the assessment, a delayed posttest. Overall, the most complex animation was the most effective at fostering students' understanding of the events depicted. These results suggest that, in select learning contexts, increasingly complex representations may be more desirable for conveying the dynamic nature of cell binding events.

  15. Infertility in reproductive-age female cancer survivors.

    PubMed

    Levine, Jennifer M; Kelvin, Joanne Frankel; Quinn, Gwendolyn P; Gracia, Clarisa R

    2015-05-15

    Improved survival rates among reproductive-age females diagnosed with cancer have increased the focus on long-term quality of life, including maintenance of the ability to conceive biological children. Cancer-directed therapies such as high-dose alkylating agents and radiation to the pelvis, which deplete ovarian reserve, radiation to the brain, which affects the hypothalamic-pituitary-gonadal axis, and surgical resection of reproductive structures can decrease the likelihood of having biological children. Standard fertility preservation strategies such as embryo and oocyte cryopreservation before the onset of therapy offer the opportunity to conserve fertility, but they may not be feasible because of the urgency to start cancer therapy, financial limitations, and a lack of access to reproductive endocrinologists. Ovarian tissue freezing is considered experimental, with limited data related to pregnancies, but it minimizes treatment delay. Studies evaluating gonadotropin-releasing hormone analogues have had mixed results, although a recent randomized, prospective study in women with breast cancer demonstrated a protective effect. Fertility preservation programs are increasingly being developed within cancer programs. In this article, we describe risks to infertility and options for preservation, raise psychosocial and ethical issues, and propose elements for establishing an effective fertility preservation program. © 2015 American Cancer Society.

  16. Effects of contaminants of emerging concern on Myzus persicae (Sulzer, Hemiptera: Aphididae) biology and on their host plant, Capsicum annuum.

    PubMed

    Pennington, Marcus John; Rothman, Jason A; Jones, Michael Bellinger; McFrederick, Quinn S; Gan, Jay; Trumble, John T

    2018-02-08

    Many countries are utilizing reclaimed wastewater for agriculture as water demands due to drought, rising temperatures, and expanding human populations. Unfortunately, wastewater often contains biologically active, pseudopersistant pharmaceuticals, even after treatment. Runoff from agriculture and effluent from wastewater treatment plants also contribute high concentrations of pharmaceuticals to the environment. This study assessed the effects of common pharmaceuticals on an agricultural pest, the aphid Myzus persicae (Sulzer, Hemiptera: Aphididae). Second instar nymphs were transferred to bell peppers (Capsicum annuum) that were grown hydroponically. Treatment plants were spiked with contaminants of emerging concern (CECs) at environmentally relevant concentrations found in reclaimed wastewater. M. persicae displayed no differences in population growth or microbial community differences due to chemical treatments. Plants, however, displayed significant growth reduction in antibiotic and mixture treatments, specifically in wet root masses. Antibiotic treatment masses were significantly reduced in the total and root wet masses. Mixture treatments displayed an overall reduction in plant root wet mass. Our results suggest that the use of reclaimed wastewater for crop irrigation would not affect aphid populations, but could hinder or delay crop production.

  17. Homo-β-amino acid containing MBP(85–99) analogs alleviate experimental autoimmune encephalomyelitis

    PubMed Central

    Kant, Ravi; Pasi, Shweta; Surolia, Avadhesha

    2015-01-01

    MBP(85–99), an immuno-dominant epitope of myelin basic protein which binds to the major histocompatibility complex haplotype HLA-DR2 is widely implicated in the pathogenesis of multiple sclerosis. J5, an antagonist of MBP(85–99), that blocks the binding of MBP(85–99) to soluble HLA-DR2b much more efficiently than glatiramer acetate (a random copolymer comprising major MHC and T-cell receptor contact residues), was transformed into analogs with superior biological half-lives and antagonistic-activities by substitution of some of its residues with homo-β-amino acids. S18, the best analog obtained ameliorated symptoms of experimental autoimmune encephalomyelitis at least twice more effectively than glatiramer acetate or J5. S18 displayed marked resistance to proteolysis in-vitro; biological impact of which was evident in the form of delayed clinical onset of disease and prolonged therapeutic-benefits. Besides active suppression of MBP(85–99)-reactive CD4+ T-cells in-vitro and in-vivo S18 treatment also generated IL-4 producing CD4+ T-cell clones, through which protective effect could be transferred passively. PMID:25644378

  18. Delays in the operating room: signs of an imperfect system.

    PubMed

    Wong, Janice; Khu, Kathleen Joy; Kaderali, Zul; Bernstein, Mark

    2010-06-01

    Delays in the operating room have a negative effect on its efficiency and the working environment. In this prospective study, we analyzed data on perioperative system delays. One neurosurgeon prospectively recorded all errors, including perioperative delays, for consecutive patients undergoing elective procedures from May 2000 to February 2009. We analyzed the prevalence, causes and impact of perioperative system delays that occurred in one neurosurgeon's practice. A total of 1531 elective surgical cases were performed during the study period. Delays were the most common type of error (33.6%), and more than half (51.4%) of all cases had at least 1 delay. The most common cause of delay was equipment failure. The first cases of the day and cranial cases had more delays than subsequent cases and spinal cases, respectively. A delay in starting the first case was associated with subsequent delays. Delays frequently occur in the operating room and have a major effect on patient flow and resource utilization. Thorough documentation of perioperative delays provides a basis for the development of solutions for improving operating room efficiency and illustrates the principles underlying the causes of operating room delays across surgical disciplines.

  19. DISCOUNTING OF DELAYED AND PROBABILISTIC LOSSES OVER A WIDE RANGE OF AMOUNTS

    PubMed Central

    Green, Leonard; Myerson, Joel; Oliveira, Luís; Chang, Seo Eun

    2014-01-01

    The present study examined delay and probability discounting of hypothetical monetary losses over a wide range of amounts (from $20 to $500,000) in order to determine how amount affects the parameters of the hyperboloid discounting function. In separate conditions, college students chose between immediate payments and larger, delayed payments and between certain payments and larger, probabilistic payments. The hyperboloid function accurately described both types of discounting, and amount of loss had little or no systematic effect on the degree of discounting. Importantly, the amount of loss also had little systematic effect on either the rate parameter or the exponent of the delay and probability discounting functions. The finding that the parameters of the hyperboloid function remain relatively constant across a wide range of amounts of delayed and probabilistic loss stands in contrast to the robust amount effects observed with delayed and probabilistic rewards. At the individual level, the degree to which delayed losses were discounted was uncorrelated with the degree to which probabilistic losses were discounted, and delay and probability loaded on two separate factors, similar to what is observed with delayed and probabilistic rewards. Taken together, these findings argue that although delay and probability discounting involve fundamentally different decision-making mechanisms, nevertheless the discounting of delayed and probabilistic losses share an insensitivity to amount that distinguishes it from the discounting of delayed and probabilistic gains. PMID:24745086

  20. Quantifying restoration success and recovery in a metal-polluted stream: A 17-year assessment of physicochemical and biological responses

    USGS Publications Warehouse

    Clements, W.H.; Vieira, N.K.M.; Church, S.E.

    2010-01-01

    Evaluating the effectiveness of stream restoration is often challenging because of the lack of pre-treatment data, narrow focus on physicochemical measures and insufficient post-restoration monitoring. Even when these fundamental elements are present, quantifying restoration success is difficult because of the challenges associated with distinguishing treatment effects from seasonal variation, episodic events and long-term climatic changes.2. We report results of one of the most comprehensive and continuous records of physical, chemical and biological data available to assess restoration success for a stream ecosystem in North America. Over a 17 year period we measured seasonal and annual changes in metal concentrations, physicochemical characteristics, macroinvertebrate communities, and brown trout Salmo trutta populations in the Arkansas River, a metal-contaminated stream in Colorado, USA.3. Although we observed significant improvements in water quality after treatment, the effectiveness of restoration varied temporally, spatially and among biological response variables. The fastest recovery was observed at stations where restoration eliminated point sources of metal contamination. Recovery of macroinvertebrates was significantly delayed at some stations because of residual sediment contamination and because extreme seasonal and episodic variation in metal concentrations prevented recolonization by sensitive species. Synthesis and applications. Because recovery trajectories after the removal of a stressor are often complex or nonlinear, long-term studies are necessary to assess restoration success within the context of episodic events and changes in regional climate. The observed variation in recovery among chemical and biological endpoints highlights the importance of developing objective criteria to assess restoration success. Although the rapid response of macroinvertebrates to reduced metal concentrations is encouraging, we have previously demonstrated that benthic communities from the Arkansas River remained susceptible to other novel anthropogenic stressors. We suggest that the resistance or resilience of benthic macroinvertebrate communities to novel stressors may be effective indicators of restoration success that can account for the non-additive (e.g. synergistic) nature of compound perturbations. ?? 2010 The Authors. Journal compilation ?? 2010 British Ecological Society.

  1. Semantic effects in sentence recall: the contribution of immediate vs delayed recall in language assessment.

    PubMed

    Polišenská, Kamila; Chiat, Shula; Comer, Amanda; McKenzie, Kirsty

    2014-01-01

    Sentence recall is increasingly used to assess language. It is widely debated what the task is actually testing, but one rarely explored aspect is the contribution of semantics to sentence recall. The few studies that have examined the role of semantics in sentence recall have employed an 'intrusion paradigm', following Potter and Lombardi (1990), and their paradigm relies on interference errors with conclusions based on an analysis of error patterns. We have instead manipulated the semantic plausibility of whole sentences to investigate the effects of semantics on immediate and delayed sentence recall. In Study 1, adults recalled semantically plausible and implausible sentences either immediately or after distracter tasks varying in lexical retrieval demands (backward counting and picture naming). Results revealed significant effects of plausibility, delay, and a significant interaction indicating increasing reliance on semantics as the demands of the distracter tasks increased. Study 2, conducted with 6-year-old children, employed delay conditions that were modified to avoid floor effects (delay with silence and forward counting) and a similar pattern of results emerged. This novel methodology provided robust evidence showing the effectiveness of delayed recall in the assessment of semantics and the effectiveness of immediate recall in the assessment of morphosyntax. The findings from our study clarify the linguistic mechanisms involved in immediate and delayed sentence recall, with implications for the use of recall tasks in language assessment. The reader will be able to: (i) define the difference between immediate and delayed sentence recall and different types of distractors, (ii) explain the utility of immediate and delayed recall sentence recall in language assessment, (iii) discuss suitability of delayed recall for the assessment of semantics. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Effects of Acute and Chronic Flunitrazepam on Delay Discounting in Pigeons

    PubMed Central

    Eppolito, Amy K; France, Charles P; Gerak, Lisa R

    2011-01-01

    Delay to delivery of a reinforcer can decrease responding for that reinforcer and increase responding for smaller reinforcers that are available concurrently and delivered without delay; acute administration of drugs can alter responding for large, delayed reinforcers, although the impact of chronic treatment on delay discounting is not well understood. In this experiment, the effects of repeated administration of the benzodiazepine flunitrazepam were studied in 6 pigeons responding on one key to receive food that was delivered immediately and on a second key to receive a larger amount of food that was delivered following delays which increased across a single session. Pigeons responded predominantly for the large reinforcer when there were no delays and when delays were short; however, as delays increased, responding for the large reinforcer decreased. Acutely, flunitrazepam (0.32, 1.0 and 3.2 mg/kg) dose-dependently increased responding for the large reinforcer, shifting the discounting curve rightward and upward. Repeated administration of flunitrazepam (0.32, 1.0 and 3.2 mg/kg, each for six sessions, separated by one session during which vehicle was administered) did not markedly alter its effects on responding for the large reinforcer, indicating that the development of tolerance to this effect of flunitrazepam is modest under these conditions. PMID:21541119

  3. Effects of the gaseous and liquid water content of the atmosphere on range delay and Doppler frequency

    NASA Technical Reports Server (NTRS)

    Flock, W. L.

    1981-01-01

    When high precision is required for range measurement on Earth space paths, it is necessary to correct as accurately as possible for excess range delays due to the dry air, water vapor, and liquid water content of the atmosphere. Calculations based on representative values of atmospheric parameters are useful for illustrating the order of magnitude of the expected delays. Range delay, time delay, and phase delay are simply and directly related. Doppler frequency variations or noise are proportional to the time rate of change of excess range delay. Tropospheric effects were examined as part of an overall consideration of the capability of precision two way ranging and Doppler systems.

  4. Delayed Response and Biosonar Perception Explain Movement Coordination in Trawling Bats

    PubMed Central

    Giuggioli, Luca; McKetterick, Thomas J.; Holderied, Marc

    2015-01-01

    Animal coordinated movement interactions are commonly explained by assuming unspecified social forces of attraction, repulsion and alignment with parameters drawn from observed movement data. Here we propose and test a biologically realistic and quantifiable biosonar movement interaction mechanism for echolocating bats based on spatial perceptual bias, i.e. actual sound field, a reaction delay, and observed motor constraints in speed and acceleration. We found that foraging pairs of bats flying over a water surface swapped leader-follower roles and performed chases or coordinated manoeuvres by copying the heading a nearby individual has had up to 500 ms earlier. Our proposed mechanism based on the interplay between sensory-motor constraints and delayed alignment was able to recreate the observed spatial actor-reactor patterns. Remarkably, when we varied model parameters (response delay, hearing threshold and echolocation directionality) beyond those observed in nature, the spatio-temporal interaction patterns created by the model only recreated the observed interactions, i.e. chases, and best matched the observed spatial patterns for just those response delays, hearing thresholds and echolocation directionalities found to be used by bats. This supports the validity of our sensory ecology approach of movement coordination, where interacting bats localise each other by active echolocation rather than eavesdropping. PMID:25811627

  5. Analysis of actuator delay and its effect on uncertainty quantification for real-time hybrid simulation

    NASA Astrophysics Data System (ADS)

    Chen, Cheng; Xu, Weijie; Guo, Tong; Chen, Kai

    2017-10-01

    Uncertainties in structure properties can result in different responses in hybrid simulations. Quantification of the effect of these uncertainties would enable researchers to estimate the variances of structural responses observed from experiments. This poses challenges for real-time hybrid simulation (RTHS) due to the existence of actuator delay. Polynomial chaos expansion (PCE) projects the model outputs on a basis of orthogonal stochastic polynomials to account for influences of model uncertainties. In this paper, PCE is utilized to evaluate effect of actuator delay on the maximum displacement from real-time hybrid simulation of a single degree of freedom (SDOF) structure when accounting for uncertainties in structural properties. The PCE is first applied for RTHS without delay to determine the order of PCE, the number of sample points as well as the method for coefficients calculation. The PCE is then applied to RTHS with actuator delay. The mean, variance and Sobol indices are compared and discussed to evaluate the effects of actuator delay on uncertainty quantification for RTHS. Results show that the mean and the variance of the maximum displacement increase linearly and exponentially with respect to actuator delay, respectively. Sensitivity analysis through Sobol indices also indicates the influence of the single random variable decreases while the coupling effect increases with the increase of actuator delay.

  6. The effect of student-centered and teacher-centered instruction with and without conceptual advocacy on biology students' misconceptions, achievement, attitudes toward science, and cognitive retention

    NASA Astrophysics Data System (ADS)

    Gallop, Roger Graham

    The purpose of this study was to investigate the effect of student-centered and teacher-centered instructional strategies with and without conceptual advocacy (CA) on ninth-grade biology students' misconceptions (MIS), biology achievement (ACH), attitudes toward science (ATT), and cognitive retention of scientific method and measurement, spontaneous generation, and characteristics of living things. Students were purposively selected using intact classes and assigned to one of four treatment groups (i.e., student-centered instruction without CA, student-centered instruction with CA, teacher-centered instruction with CA, and teacher-centered instruction without CA). A modified quasi-experimental design was used in which students were not matched in the conventional sense but instead, groups were shown to be equivalent on the dependent measure via a pretest. A 5-day treatment implementation period addressed science conceptions under investigation. The treatment period was based on the number of class periods teachers at the target school actually spend teaching the biological concepts under investigation using traditional instruction. At the end of the treatment period, students were posttested using the Concepts in Biology instrument and Science Questionnaire. Eight weeks after the posttest, these instruments were administered again as a delayed posttest to determine cognitive retention of the correct biological conceptions and attitudes toward science. MANCOVA and follow-up univariate ANCOVA results indicated that student-centered instruction without CA (i.e., Group 1) did not have a significant effect on students' MIS, ACH, and ATT (F = .029, p = .8658; F = .002, p =.9688, F = .292, p = .5897, respectively). On the other hand, student-centered instruction with CA (i.e., Group 2) had a significant effect on students' MIS and ACH (F =10.33, p = .0016 and F = 10.17, p = .0017, respectively), but did not on ATT (F = .433, p = .5117). Teacher-centered instruction with CA (i.e., Group 3) had a significant effect on students' MIS in favor of Group 4 (i.e., control group) (F = 4.11, p = .0444), and did not have a significant effect on ACH and ATT (F = 1.83, p = .1777 and F = 1.89, p = .1709, respectively). Student gender and teacher gender did not have a significant effect on students' MIS, ACH, and ATT. In the cognitive retention model, there was no significant difference among the research factors relative to the 3 dependent measures.

  7. [Epidemiological, clinical and biological features of infantile visceral leishmaniasis at Kairouan hospital (Tunisia): about 240 cases].

    PubMed

    Aissi, W; Ben Hellel, K; Habboul, Z; Ben Sghaier, I; Harrat, Z; Bouratbine, A; Aoun, K

    2015-10-01

    Visceral leishmaniasis (VL) is an important health problem in Tunisia. It is most common in children under five years of age. The governorate of Kairouan (central Tunisia) is one of the most affected foci. The aim of this study was to update the epidemiological, clinical and biological features of the disease. The study concerned all VL cases admitted in the pediatric department of Kairouan hospital during 10 years (from 2004 to 2013). For every patient included in this study and when available, data such as sex, age, geographical origin and the condition of the patient at admission (clinical and biological findings) were collected. The myelogram results were also exploited as well as results of serology, culture, Real-Time polymerase chain reaction (PCR) and isoenzymatic typing of Leishmania isolates. Two hundred and forty cases were recorded. Rural cases (87.1%) were more prevalent than urban ones (12.9%). Age ranged from 2 months to 13 years (median, 18 months). The female/male sex ratio was 1.03. The diagnosis delays ranged from 1 day to 8 months (median, 15 days). The most common clinical symptoms at admission were splenomegaly (97.9%), fever (79.9%) and hepatomegaly (47.3%). The principal biological disturbances were anemia (91.7%), thrombocytopenia (83.9%) and leucopenia (56.1%). Among the different biological tools used for diagnosis confirmation, PCR was the most sensitive (100%). All 43 typed stocks corresponded to Leishmania (L.) infantum species. Although zymodeme MON-1 was predictably the most frequent (27 cases), L. infantum MON-24 and MON-80 were responsible of no negligible numbers of cases (11 and 5 cases respectively). The present study gave an updated epidemiological, clinical and biological profile of infantile VL in Tunisia. The diagnosis delays were considerably shortened compared to previous reports. However, an even earlier diagnosis of cases is needed to improve the disease prognosis. Real-Time PCR showed to be helpful in VL management.

  8. Delay-induced stochastic bifurcations in a bistable system under white noise

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

    Sun, Zhongkui, E-mail: sunzk@nwpu.edu.cn; Fu, Jin; Xu, Wei

    2015-08-15

    In this paper, the effects of noise and time delay on stochastic bifurcations are investigated theoretically and numerically in a time-delayed Duffing-Van der Pol oscillator subjected to white noise. Due to the time delay, the random response is not Markovian. Thereby, approximate methods have been adopted to obtain the Fokker-Planck-Kolmogorov equation and the stationary probability density function for amplitude of the response. Based on the knowledge that stochastic bifurcation is characterized by the qualitative properties of the steady-state probability distribution, it is found that time delay and feedback intensity as well as noise intensity will induce the appearance of stochasticmore » P-bifurcation. Besides, results demonstrated that the effects of the strength of the delayed displacement feedback on stochastic bifurcation are accompanied by the sensitive dependence on time delay. Furthermore, the results from numerical simulations best confirm the effectiveness of the theoretical analyses.« less

  9. Effect of delayed auditory feedback on normal speakers at two speech rates

    NASA Astrophysics Data System (ADS)

    Stuart, Andrew; Kalinowski, Joseph; Rastatter, Michael P.; Lynch, Kerry

    2002-05-01

    This study investigated the effect of short and long auditory feedback delays at two speech rates with normal speakers. Seventeen participants spoke under delayed auditory feedback (DAF) at 0, 25, 50, and 200 ms at normal and fast rates of speech. Significantly two to three times more dysfluencies were displayed at 200 ms (p<0.05) relative to no delay or the shorter delays. There were significantly more dysfluencies observed at the fast rate of speech (p=0.028). These findings implicate the peripheral feedback system(s) of fluent speakers for the disruptive effects of DAF on normal speech production at long auditory feedback delays. Considering the contrast in fluency/dysfluency exhibited between normal speakers and those who stutter at short and long delays, it appears that speech disruption of normal speakers under DAF is a poor analog of stuttering.

  10. Immediate versus delayed self-reporting of symptoms and side effects during chemotherapy: does timing matter?

    PubMed

    Coolbrandt, Annemarie; Van den Heede, Koen; Vanhove, Ellen; De Bom, Ann; Milisen, Koen; Wildiers, Hans

    2011-04-01

    The aim of this study was to examine how patients recall symptoms at a delayed self-report. Accurate insight into toxicity symptoms during chemotherapy is essential so that nurses and doctors can assess therapeutic tolerance and adjust supportive care accordingly. A non-experimental, longitudinal design was employed. Using the Therapy-Related Symptoms Checklist (TRSC), respondents (n = 142) reported their initial symptoms during the first 7 days of the chemotherapy cycle at two different times: (1) each day of the first seven days after the chemotherapy administration (immediate self-report), and (2) at their next hospital visit for chemotherapy (delayed self-report). We compared the number and severity of symptoms and side effects reported in the immediate and delayed self-reports. Respondents reported significantly fewer symptoms and fewer severe symptoms in the delayed self-report. For 22 out of 25 symptoms the delayed-reported grade was significantly lower than the immediate-reported maximum grade. Compared to the immediate-reported median grade, significant differences occurred in only 10 out of the 25 symptoms. In all cases, except fatigue, the delayed-reported grade was significantly higher than the immediate-reported median grade. This study indicates that delayed self-report of chemotherapy side effects is not an appropriate measure of actual symptoms and side effects experienced by patients. Delayed self-report gives a weaker insight into actual symptom burden. Fatigue is at particular risk to be minimized at the delayed self-report. Therefore it is recommended to assess chemotherapy-related symptoms and side effects by means of immediate self-report. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Delay Discounting in C57BL/6J and DBA/2J Mice: Adolescent-Limited and Life-Persistent Patterns of Impulsivity

    PubMed Central

    Pinkston, Jonathan W.; Lamb, R. J.

    2011-01-01

    Impulsivity is a defining characteristic of adolescence. Compared to adults, for example, adolescents engage in higher rates of drug and alcohol experimentation, risky sexual practices, and criminal activity. Such behavior may reflect reduced sensitivity to long-term consequences for behavior during adolescence. Recently, our lab has attempted to refine mouse procedures to study developmental trends in decision making in the laboratory. In the present experiment, we examined sensitivity to delayed rewards in C57BL/6J (B6) and DBA/2J (D2) mice during adolescence and adulthood using an adaptation of a two-week delay discounting procedure developed by Adriani & Laviola (2003) [Behavioral Neuroscience, 117, 695-703]. During training, mice could choose between a 20- or 100-ul drop of milk delivered after a 1-s delay. During testing, the delay to the large drop of milk was increased from 1 to 100 seconds. As the delay to the larger volume increased, preference shifted to the smaller, more immediate option. In adolescence, both strains showed similar shifts in preference. In contrast, adult B6 mice were less sensitive to increasing delays than were adult D2 mice, who continued to perform much as their adolescent counterparts. A subsequent resistance-to-extinction test ruled out the possibility that the slower change in the adult B6 mice was due to perseverative responding. The present findings suggest that B6 and D2 strains may be differentially suited to uncovering the biological mechanism of short-term and long-term patterns of impulsive behavior. PMID:21463022

  12. Effects of computing time delay on real-time control systems

    NASA Technical Reports Server (NTRS)

    Shin, Kang G.; Cui, Xianzhong

    1988-01-01

    The reliability of a real-time digital control system depends not only on the reliability of the hardware and software used, but also on the speed in executing control algorithms. The latter is due to the negative effects of computing time delay on control system performance. For a given sampling interval, the effects of computing time delay are classified into the delay problem and the loss problem. Analysis of these two problems is presented as a means of evaluating real-time control systems. As an example, both the self-tuning predicted (STP) control and Proportional-Integral-Derivative (PID) control are applied to the problem of tracking robot trajectories, and their respective effects of computing time delay on control performance are comparatively evaluated. For this example, the STP (PID) controller is shown to outperform the PID (STP) controller in coping with the delay (loss) problem.

  13. Time-limited effects of emotional arousal on item and source memory.

    PubMed

    Wang, Bo; Sun, Bukuan

    2015-01-01

    Two experiments investigated the time-limited effects of emotional arousal on consolidation of item and source memory. In Experiment 1, participants memorized words (items) and the corresponding speakers (sources) and then took an immediate free recall test. Then they watched a neutral, positive, or negative video 5, 35, or 50 min after learning, and 24 hours later they took surprise memory tests. Experiment 2 was similar to Experiment 1 except that (a) a reality monitoring task was used; (b) elicitation delays of 5, 30, and 45 min were used; and (c) delayed memory tests were given 60 min after learning. Both experiments showed that, regardless of elicitation delay, emotional arousal did not enhance item recall memory. Second, both experiments showed that negative arousal enhanced delayed item recognition memory only at the medium elicitation delay, but not in the shorter or longer delays. Positive arousal enhanced performance only in Experiment 1. Third, regardless of elicitation delay, emotional arousal had little effect on source memory. These findings have implications for theories of emotion and memory, suggesting that emotion effects are contingent upon the nature of the memory task and elicitation delay.

  14. Wigner time delay in photodetachment of Tm-and in photoionization of Yb: A comparative study

    NASA Astrophysics Data System (ADS)

    Saha, Soumyajit; Jose, Jobin; Deshmukh, Pranawa; Dolmatov, Valeriy; Kheifets, Anatoli; Manson, Steven

    2017-04-01

    Preliminary studies of Wigner time delay in photodetachment spectra of negative ions have been reported. Photodetachment time delay for some dipole channels of Tm- and of Cl- were calculated using relativistic random phase approximation (RRPA). Comparisons between photodetachment time delay of Cl- and photoionization time delay of Ar were made. We investigate the photodetachment time delay for all three relativistically split nd -> ɛ f channels of Tm- and for nd -> ɛ f channels of Yb (isoelectronic to Tm-) using RRPA. We study the effect of the shape resonance, brought about by the centrifugal barrier potential, on photodetachment time delay. A negative ion is a good laboratory for studying the effects of shape resonances on time delay since the phase is unaffected by the Coulomb component. Wigner time delay in photodetachment of Tm- and in photoionization of Yb: A comparative study.

  15. Effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks

    NASA Astrophysics Data System (ADS)

    Sun, Xiaojuan; Perc, Matjaž; Kurths, Jürgen

    2017-05-01

    In this paper, we study effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks. Our focus is on the impact of two parameters, namely the time delay τ and the probability of partial time delay pdelay, whereby the latter determines the probability with which a connection between two neurons is delayed. Our research reveals that partial time delays significantly affect phase synchronization in this system. In particular, partial time delays can either enhance or decrease phase synchronization and induce synchronization transitions with changes in the mean firing rate of neurons, as well as induce switching between synchronized neurons with period-1 firing to synchronized neurons with period-2 firing. Moreover, in comparison to a neuronal network where all connections are delayed, we show that small partial time delay probabilities have especially different influences on phase synchronization of neuronal networks.

  16. The effect of visual-motion time-delays on pilot performance in a simulated pursuit tracking task

    NASA Technical Reports Server (NTRS)

    Miller, G. K., Jr.; Riley, D. R.

    1977-01-01

    An experimental study was made to determine the effect on pilot performance of time delays in the visual and motion feedback loops of a simulated pursuit tracking task. Three major interrelated factors were identified: task difficulty either in the form of airplane handling qualities or target frequency, the amount and type of motion cues, and time delay itself. In general, the greater the task difficulty, the smaller the time delay that could exist without degrading pilot performance. Conversely, the greater the motion fidelity, the greater the time delay that could be tolerated. The effect of motion was, however, pilot dependent.

  17. Methodology for Analysis, Modeling and Simulation of Airport Gate-waiting Delays

    NASA Astrophysics Data System (ADS)

    Wang, Jianfeng

    This dissertation presents methodologies to estimate gate-waiting delays from historical data, to identify gate-waiting-delay functional causes in major U.S. airports, and to evaluate the impact of gate operation disruptions and mitigation strategies on gate-waiting delay. Airport gates are a resource of congestion in the air transportation system. When an arriving flight cannot pull into its gate, the delay it experiences is called gate-waiting delay. Some possible reasons for gate-waiting delay are: the gate is occupied, gate staff or equipment is unavailable, the weather prevents the use of the gate (e.g. lightning), or the airline has a preferred gate assignment. Gate-waiting delays potentially stay with the aircraft throughout the day (unless they are absorbed), adding costs to passengers and the airlines. As the volume of flights increases, ensuring that airport gates do not become a choke point of the system is critical. The first part of the dissertation presents a methodology for estimating gate-waiting delays based on historical, publicly available sources. Analysis of gate-waiting delays at major U.S. airports in the summer of 2007 identifies the following. (i) Gate-waiting delay is not a significant problem on majority of days; however, the worst delay days (e.g. 4% of the days at LGA) are extreme outliers. (ii) The Atlanta International Airport (ATL), the John F. Kennedy International Airport (JFK), the Dallas/Fort Worth International Airport (DFW) and the Philadelphia International Airport (PHL) experience the highest gate-waiting delays among major U.S. airports. (iii) There is a significant gate-waiting-delay difference between airlines due to a disproportional gate allocation. (iv) Gate-waiting delay is sensitive to time of a day and schedule peaks. According to basic principles of queueing theory, gate-waiting delay can be attributed to over-scheduling, higher-than-scheduled arrival rate, longer-than-scheduled gate-occupancy time, and reduced gate availability. Analysis of the worst days at six major airports in the summer of 2007 indicates that major gate-waiting delays are primarily due to operational disruptions---specifically, extended gate occupancy time, reduced gate availability and higher-than-scheduled arrival rate (usually due to arrival delay). Major gate-waiting delays are not a result of over-scheduling. The second part of this dissertation presents a simulation model to evaluate the impact of gate operational disruptions and gate-waiting-delay mitigation strategies, including building new gates, implementing common gates, using overnight off-gate parking and adopting self-docking gates. Simulation results show the following effects of disruptions: (i) The impact of arrival delay in a time window (e.g. 7 pm to 9 pm) on gate-waiting delay is bounded. (ii) The impact of longer-than-scheduled gate-occupancy times in a time window on gate-waiting delay can be unbounded and gate-waiting delay can increase linearly as the disruption level increases. (iii) Small reductions in gate availability have a small impact on gate-waiting delay due to slack gate capacity, while larger reductions have a non-linear impact as slack gate capacity is used up. Simulation results show the following effects of mitigation strategies: (i) Implementing common gates is an effective mitigation strategy, especially for airports with a flight schedule not dominated by one carrier, such as LGA. (ii) The overnight off-gate rule is effective in mitigating gate-waiting delay for flights stranded overnight following departure cancellations. This is especially true at airports where the gate utilization is at maximum overnight, such as LGA and DFW. The overnight off-gate rule can also be very effective to mitigate gate-waiting delay due to operational disruptions in evenings. (iii) Self-docking gates are effective in mitigating gate-waiting delay due to reduced gate availability.

  18. Signal functions in delayed reinforcement

    PubMed Central

    Lattal, Kennon A.

    1984-01-01

    Three experiments were conducted with pigeons to examine the role of the signal in delay-of-reinforcement procedures. In the first, a blackout accompanying a period of nonreinforcement increased key-peck response rates maintained by immediate reinforcement. The effects of dissociating the blackout from the delay interval were examined in the second experiment. In three conditions, blackouts and unsignaled delays were negatively correlated or occurred randomly with respect to one another. A signaled delay and an unsignaled delay that omitted the blackouts were studied in two other conditions. All delay-of-reinforcement conditions generally produced response rates lower than those produced by immediate reinforcement. Signaled delays maintained higher response rates than did any of the various unsignaled-delay conditions, with or without dissociated blackouts. The effects of these latter conditions did not differ systematically from one another. The final experiment showed that response rates varied as a function of the frequency with which a blackout accompanied delay intervals. By eliminating a number of methodological difficulties present in previous delay-of-reinforcement experiments, these results suggest the importance of the signal in maintaining responding during delay-of-reinforcement procedures and, conversely, the importance of the delay interval in decreasing responding. PMID:16812387

  19. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low

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

    Kadhim, Munira A

    2012-08-22

    The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program. To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e. less than 0.1 Gy), including the lowest possible dose, that of a single electronmore » track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these "non-targeted responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate non-targeted effects of ionizing radiation with a focus on the induction of genomic instability (GI) in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/CaH and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition in these models on genomic instability. We will specifically focus on the effects of low doses of low LET radiation, down to the dose of 10mGy (0.01Gy) X-rays. Using conventional X-ray and we will be able to assess the role of genetic variation under various conditions at a range of doses down to the very low dose of 0.01Gy. Irradiations will be carried out using facilities in routine operation for such studies. Mechanistic studies of instability in different cell lineages will include the role of cytokines which have been shown to be in the initiation of instability. These studies also aim to uncover the possible mechanism of the initiation, perpetuation and delayed pathways of the instability response using relevant biological endpoints i.e. chromosomal instability, apoptosis induction, cytokine and gene array analysis. Integral to these studies will be an assessment of the role of genetic susceptibility in these responses, using CBA/CaH and C57BL/6J mice. The overall results suggest that low dose low LET X-irradiation induced delayed GI in both CBA/CaH and C57BL/6J haemopoeitic tissue. Using several biological approaches, some key strain and dose-specific differences have been identified in radiation-induced signalling in the initiation and perpetuation of the instability process. Furthermore, the induction of non-targeted radiation effects and genetic dependency may be linked to the use of alternative signalling pathways and mechanisms which have potential implications on evaluation of non-targeted effects in radiation risk assessment.« less

  20. The Effects of Asynchronous Visual Delays on Simulator Flight Performance and the Development of Simulator Sickness Symptomatology

    DTIC Science & Technology

    1986-12-26

    NAVAL TRAINING SYSTEMS CENTER ORLANDO. FLORIDA IT FILE COPY THE EFFECTS OF ASYNCHRONOUS VISUAL DELAYS ON SIMULATOR FLIGHT PERFORMANCE AND THE...ASYNCHRONOUS VISUAL. DELAYS ON SI.WLATOR FLIGHT PERF OMANCE AND THE DEVELOPMENT OF SIMLATOR SICKNESS SYMPTOMATOLOGY K. C. Uliano, E. Y. Lambert, R. S. Kennedy...ACCESSION NO. N63733N SP-01 0785-7P6 I. 4780 11. TITLE (Include Security Classification) The Effects of Asynchronous Visual Delays on Simulator Flight

  1. Solar UV-A and UV-B radiation fluxes at two Alpine stations at different altitudes

    NASA Astrophysics Data System (ADS)

    Blumthaler, M.; Ambach, W.; Rehwald, W.

    1992-03-01

    Daily totals of UV-A and UV-B radiation fluxes and global radiation were measured since 1981 at Jungfraujoch (3576 m) a.s.l.) and in Innsbruck (577 m a.s.l.) in their seasonal course. The altitude effect of annual totals yields 19%/1000 m (UV-B), 11%/1000 m (UV-A) and 9%/1000 m (global radiation) with reference to Innsbruck station. The ratio of the daily totals of UV-B/global radiation shows a significant seasonal course with the maximum in summer, whereas the ratio of the daily totals of UV-A/global radiation shows no significant seasonal variation. The biological effective doses of erythema reaction, delayed tanning and immediate tanning by UV-A and UV-B radiant exposure are reported in the seasonal course at Jungfraujoch and in Innsbruck.

  2. Supercritical CO2 extract of Cinnamomum zeylanicum: chemical characterization and antityrosinase activity.

    PubMed

    Marongiu, Bruno; Piras, Alessandra; Porcedda, Silvia; Tuveri, Enrica; Sanjust, Enrico; Meli, Massimo; Sollai, Francesca; Zucca, Paolo; Rescigno, Antonio

    2007-11-28

    The volatile oil of the bark of Cinnamomum zeylanicum was extracted by means of supercritical CO2 fluid extraction in different conditions of pressure and temperature. Its chemical composition was characterized by GC-MS analysis. Nineteen compounds, which in the supercritical extract represented >95% of the oil, were identified. (E)-Cinnamaldehyde (77.1%), (E)-beta-caryophyllene (6.0%), alpha-terpineol (4.4%), and eugenol (3.0%) were found to be the major constituents. The SFE oil of cinnamon was screened for its biological activity about the formation of melanin in vitro. The extract showed antityrosinase activity and was able to reduce the formation of insoluble flakes of melanin from tyrosine. The oil also delayed the browning effect in apple homogenate. (E)-Cinnamaldehyde and eugenol were found to be mainly responsible of this inhibition effect.

  3. Why Do Rereading Lag Effects Depend on Test Delay?

    ERIC Educational Resources Information Center

    Rawson, Katherine A.

    2012-01-01

    In previous research, rereading after a long lag versus a short lag led to greater performance on delayed tests but not on immediate tests. The current study tested two accounts of why the effects of rereading lag depend on test delay. The "levels of representation" ("LOR") "hypothesis" states that the effects reflect…

  4. Biologically based multistage modeling of radiation effects

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

    William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

    2005-08-30

    This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistagemore » carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of epidemiologic studies using multistage carcinogenesis models that incorporate the ''initiation, promotion, and malignant conversion'' paradigm of carcinogenesis are indicating that promotion of initiated cells is the most important cellular mechanism driving the shape of the age specific hazard for many types of cancer. Second, we have realized that many of the genes that are modified in early stages of the carcinogenic process contribute to one or more of four general cellular pathways that confer a promotional advantage to cells when these pathways are disrupted.« less

  5. Effect of time delay on flying qualities: An update

    NASA Technical Reports Server (NTRS)

    Smith, R. E.; Sarrafian, S. K.

    1986-01-01

    Flying qualities problems of modern, full-authority electronic flight control systems are most often related to the introduction of additional time delay in aircraft response to a pilot input. These delays can have a significant effect on the flying qualities of the aircraft. Time delay effects are reexamined in light of recent flight test experience with aircraft incorporating new technology. Data from the X-29A forward-swept-wing demonstrator, a related preliminary in-flight experiment, and other flight observations are presented. These data suggest that the present MIL-F-8785C allowable-control system time delay specifications are inadequate or, at least, incomplete. Allowable time delay appears to be a function of the shape of the aircraft response following the initial delay. The cockpit feel system is discussed as a dynamic element in the flight control system. Data presented indicate that the time delay associated with a significant low-frequency feel system does not result in the predicted degradation in aircraft flying qualities. The impact of the feel system is discussed from two viewpoints: as a filter in the control system which can alter the initial response shape and, therefore, the allowable time delay, and as a unique dynamic element whose delay contribution can potentially be discounted by special pilot loop closures.

  6. Effect of time delay on surgical performance during telesurgical manipulation.

    PubMed

    Fabrizio, M D; Lee, B R; Chan, D Y; Stoianovici, D; Jarrett, T W; Yang, C; Kavoussi, L R

    2000-03-01

    Telementoring allows a less experienced surgeon to benefit from an expert surgical consultation, reducing cost, travel, and the learning curve associated with new procedures. However, there are several technical limitations that affect practical applications. One potentially serious problem is the time delay that occurs any time data are transferred across long distances. To date, the effect of time delay on surgical performance has not been studied. A two-phase trial was designed to examine the effect of time delay on surgical performance. In the first phase, a series of tasks was performed, and the numbers of robotic movements required for completion was counted. Programmed incremental time delays were made in audiovisual acquisition and robotic controls. The number of errors made while performing each task at various time delay intervals was noted. In the second phase, a remote surgeon in Baltimore performed the tasks 9000 miles away in Singapore. The number of errors made was recorded. As the time delay increased, the number of operator errors increased. The accuracy needed to perform remote robotic procedures was diminished as the time delay increased. A learning curve did exist for each task, but as the time delay interval increased, it took longer to complete the task. Time delay does affect surgical performance. There is an acceptable delay of <700 msec in which surgeons can compensate for this phenomenon. Clinical studies will be needed to evaluate the true impact of time delay.

  7. A correlation of long term effects and radiation quality in the progeny of bystander cells after microbeam radiations: The experimental study of radiotherapy for cancer risk mitigation

    NASA Astrophysics Data System (ADS)

    Autsavapromporn, N.; Konishi, T.; Liu, C.; Plante, I.; Funayama, T.; Usami, N.; Azzam, EI; Suzuki, M.

    2017-06-01

    The goal of this study is to investigate the role of radiation quality and gap junction intercellular communication (GJIC) in the propagation of delayed stressful effects in the progeny of bystander human skin fibroblasts cultures (NB1RGB). Briefly, confluent NB1RGB cells in the presence and absence of gap junction inhibitor (AGA) were exposed to ionizing radiation (IR) with a different linear energy transfer (LET) either 5.35 keV X rays (LET ∼6 keV/μm) or 18.3 MeV/u carbon (LET ∼103 keV/μm) microbeam radiations. Following 20 populations post-irradiation, the progeny of bystander NB1RGB cells were harvested and assayed for several of biological endpoints. Our results showed that expression of stressful effects in the progeny of bystander cells is dependent on LET. The progeny of bystander cells exposed to low-LET X rays showed the persistence of oxidative stress and it was correlated with the increased mutant fraction. Such effect were not observed after high-LET carbon ions. Interestingly, inhibition of GJIC mitigated the toxic effects in the progeny of bystander cells. Together, the results contribute to the understanding of the fundamental radiation biology relating to the high-LET carbon ions to mitigate cancer risk after radiotherapy. Furthermore, GJIC be considered as a critical mediator in the bystander mutagenic effect.

  8. The Effect of Delayed Auditory Feedback on Activity in the Temporal Lobe while Speaking: A Positron Emission Tomography Study

    ERIC Educational Resources Information Center

    Takaso, Hideki; Eisner, Frank; Wise, Richard J. S.; Scott, Sophie K.

    2010-01-01

    Purpose: Delayed auditory feedback is a technique that can improve fluency in stutterers, while disrupting fluency in many nonstuttering individuals. The aim of this study was to determine the neural basis for the detection of and compensation for such a delay, and the effects of increases in the delay duration. Method: Positron emission…

  9. The Effects of Short Interval Delay of Reinforcement Upon Human Discrimination Learning. IMRID Papers and Reports Vol. 4 No. 12.

    ERIC Educational Resources Information Center

    Kral, Paul A.; And Others

    Investigates the effect of delay of reinforcement upon human discrimination learning with particular emphasis on the form of the gradient within the first few seconds of delay. In previous studies subjects are usually required to make an instrumental response to a stimulus, this is followed by the delay interval, and finally, the reinforcement…

  10. The Effects of Methylphenidate on Discounting of Delayed Rewards in ADHD

    PubMed Central

    Shiels, Keri; Hawk, Larry W.; Reynolds, Brady; Mazzullo, Rebecca; Rhodes, Jessica; Pelham, William E.; Waxmonsky, James G.; Gangloff, Brian P.

    2010-01-01

    Impulsivity is a central component of attention-deficit/hyperactivity disorder (ADHD). Delay discounting, or a preference for smaller, immediate rewards over larger, delayed rewards is considered an important aspect of impulsivity, and delay-related impulsivity has been emphasized in etiological models of ADHD. The current study examined whether stimulant medication, an effective treatment for ADHD, reduces discounting of delayed experiential and hypothetical rewards among 49 children (age 9–12 years) with ADHD. Following a practice day, participants completed a 3-day double-blind placebo-controlled acute medication assessment. Active doses were long-acting methylphenidate (Concerta), with the nearest equivalents of 0.3 and 0.6 mg/kg TID immediate-release methylphenidate. On each testing day, participants completed experiential (real-world money in real time) and hypothetical discounting tasks. Relative to placebo, methylphenidate reduced discounting of delayed experiential rewards, but not hypothetical rewards. Broadly consistent with etiological models that emphasize delay-related impulsivity among children with ADHD, these findings provide initial evidence that stimulant medication reduces delay discounting among those with the disorder. The present results also draw attention to task parameters that may influence the sensitivity of various delay discounting measures to medication effects. PMID:19803628

  11. A Retrospective Analysis of Corticosteroid Utilization Before Initiation of Biologic DMARDs Among Patients with Rheumatoid Arthritis in the United States.

    PubMed

    Spivey, Christina A; Griffith, Jenny; Kaplan, Cameron; Postlethwaite, Arnold; Ganguli, Arijit; Wang, Junling

    2018-06-01

    Understanding the effects of corticosteroid utilization prior to initiation of biologic disease-modifying antirheumatic drugs (DMARDs) can inform decision-makers on the appropriate use of these medications. This study examined treatment patterns and associated burden of corticosteroid utilization before initiation of biologic DMARDs among rheumatoid arthritis (RA) patients. A retrospective analysis was conducted of adult RA patients in the US MarketScan Database (2011-2015). The following patterns of corticosteroid utilization were analyzed: whether corticosteroids were used; duration of use (short/long duration defined as < or ≥ 3 months); and dosage (low as < 2.5, medium as 2.5 to < 7.5 and high as ≥ 7.5 mg/day). Effects of corticosteroid use on time to biologic DMARD initiation were examined using Cox proportional hazards models. Likelihood and number of adverse events were examined using logistic and negative binomial regression models. Generalized linear models were used to examine healthcare costs. Independent variables in all models included patient demographics and health characteristics. A total of 25,542 patients were included (40.84% used corticosteroids). Lower hazard of biologic DMARD initiation was associated with corticosteroid use (hazard ratio = 0.89, 95% confidence interval = 0.83-0.96), long duration and lower dose. Corticosteroid users compared to non-users had higher incidence rates of various adverse events including cardiovascular events (P < 0.05). Higher likelihood of adverse events was associated with corticosteroid use and long duration of use, as was increased number of adverse events. Corticosteroid users had a greater annualized mean number of physician visits, hospitalizations, and emergency department (ED) visits than non-users in adjusted analysis. Corticosteroid users compared to non-users had higher mean costs for total healthcare, physician visits, hospitalizations, and ED visits. Among patients with RA, corticosteroid utilization is associated with delayed initiation of biologic DMARDS and higher burden of adverse events and healthcare utilization/costs before the initiation of biologic DMARDs. AbbVie Inc.

  12. Neuromechanical tuning of nonlinear postural control dynamics

    NASA Astrophysics Data System (ADS)

    Ting, Lena H.; van Antwerp, Keith W.; Scrivens, Jevin E.; McKay, J. Lucas; Welch, Torrence D. J.; Bingham, Jeffrey T.; DeWeerth, Stephen P.

    2009-06-01

    Postural control may be an ideal physiological motor task for elucidating general questions about the organization, diversity, flexibility, and variability of biological motor behaviors using nonlinear dynamical analysis techniques. Rather than presenting "problems" to the nervous system, the redundancy of biological systems and variability in their behaviors may actually be exploited to allow for the flexible achievement of multiple and concurrent task-level goals associated with movement. Such variability may reflect the constant "tuning" of neuromechanical elements and their interactions for movement control. The problem faced by researchers is that there is no one-to-one mapping between the task goal and the coordination of the underlying elements. We review recent and ongoing research in postural control with the goal of identifying common mechanisms underlying variability in postural control, coordination of multiple postural strategies, and transitions between them. We present a delayed-feedback model used to characterize the variability observed in muscle coordination patterns during postural responses to perturbation. We emphasize the significance of delays in physiological postural systems, requiring the modulation and coordination of both the instantaneous, "passive" response to perturbations as well as the delayed, "active" responses to perturbations. The challenge for future research lies in understanding the mechanisms and principles underlying neuromechanical tuning of and transitions between the diversity of postural behaviors. Here we describe some of our recent and ongoing studies aimed at understanding variability in postural control using physical robotic systems, human experiments, dimensional analysis, and computational models that could be enhanced from a nonlinear dynamics approach.

  13. Delayed selfing ensures reproductive assurance in Utricularia praeterita and Utricularia babui in Western Ghats.

    PubMed

    Chaudhary, Anjali; Yadav, S R; Tandon, Rajesh

    2018-02-19

    Numerous bladderwort (Utricularia) species are distributed worldwide, but their reproductive biology is rarely investigated. Bladderworts are known to depend on tiny organisms to meet a significant proportion of their energy requirement by trapping them in bladders. However, information on the extent of their reliance on insects for pollination success is limited. We examined the reproductive strategy of two Utricularia species viz. Utricularia praeterita and U. babui, endemic to Western Ghats, India. The main aspects of the investigation involved floral biology, breeding system, pollination mechanism, and reproductive success. Flowers of both the species are structured for outbreeding through entomophilous floral suites, herkogamy, protandrous dichogamy and sensitive lobes of the stigma. With nearly 65% natural fruit-set, both the species appeared to be sufficiently open-pollinated. However, pollinators failed to show in plants of U. praeterita while in U. babui there was an apparent mismatch between the extent of fruit-set and pollinator visits. The study demonstrated that in the absence/insufficient visits of pollinators, the two species resort to autonomous selfing. In U. babui, denser patches of plants appeared to be crucial for attracting the pollinators. Both species are self-compatible, and reproductive success is predominantly achieved by delayed autonomous selfing. The sensitive stigma in the species fails to prevent selfing due to diminished herkogamy during the late anthetic stages. It is inferred that in the pollinator-limited environment, delayed selfing contributes to absolute natural fecundity in U. praeterita, while it produces a mixed progeny in U. babui.

  14. Individual differences in choice (in)flexibility but not impulsivity in the common marmoset: an automated, operant-behavior choice task.

    PubMed

    Adriani, Walter; Romani, Chiara; Manciocco, Arianna; Vitale, Augusto; Laviola, Giovanni

    2013-11-01

    Individual differences in behavioural flexibility are a significant issue in human psychopathology as well as in its animal models. We aimed to investigate individual variations of operant-choice behaviour in the common marmoset (Callithrix jacchus), a small New World primate, using a new operant panel with two hand-poking holes. Experimental subjects (N=16) were presented with a choice between a Small & Soon (SS) vs a Large & Late (LL) food reward. After extensive training (31 daily sessions with no delay, during which a basal, large-reward preference developed), the delay before release of LL was progressively increased (from 0 to 60 s, during 16 daily sessions; indifferent point at delay=9 s). Subjects were classified as either "flexible" or "non-flexible", respectively, based on a decrease (or not) in the preference for LL with increasing delays. Each subject was also classified as "maximizer" (or "non-maximizer") based on capacity (or not) to maximize the food payoff as delay increased. Upon delays shorter than the indifferent point (<9s), none of the subjects showed a shift from LL to SS, denoting a lack of delay-induced, cognitive impulsivity. Individual differences only emerged upon delays longer than the indifferent point (>9 s), when a preference shift could be interpreted as economically-driven. In general, a profile of few unrewarded hand-pokes in reaction to initial delays (i.e., a low motor impulsivity) and of clear-cut basal LL preference seemed to predict elevated flexibility of choices and better food payoff, which was typical of subjects classified as both "flexible & maximizer". These results provide normative data on the marmosets, which can be used as a model for the investigation of 1) individual differences in behavioural flexibility, as well as 2) biological mechanisms rooted in our evolutionary history. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Responsiveness of emergency obstetric care systems in low- and middle-income countries: a critical review of the "third delay".

    PubMed

    Cavallaro, Francesca L; Marchant, Tanya J

    2013-05-01

    We reviewed the evidence on the duration, causes and effects of delays in providing emergency obstetric care to women attending health facilities (the third delay) in low- and middle-income countries. We performed a critical literature review using terms related to obstetric care, birth outcome, delays and developing countries. A manual search of reference lists of key articles was also performed. 69 studies met the inclusion criteria. Most studies reported long delays in providing care, and the mean waiting time for women admitted with complications was as much as 24 h before treatment. The three most cited barriers to providing timely care were shortage of treatment materials, surgery facilities and qualified staff. Existing evidence is insufficient to estimate the effect of delays on birth outcomes. Delays in providing emergency obstetric care seem common in resource-constrained settings but further research is necessary to determine the effect of the third delay on birth outcomes. © 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.

  16. Effects of delay and probability combinations on discounting in humans

    PubMed Central

    Cox, David J.; Dallery, Jesse

    2017-01-01

    To determine discount rates, researchers typically adjust the amount of an immediate or certain option relative to a delayed or uncertain option. Because this adjusting amount method can be relatively time consuming, researchers have developed more efficient procedures. One such procedure is a 5-trial adjusting delay procedure, which measures the delay at which an amount of money loses half of its value (e.g., $1000 is valued at $500 with a 10-year delay to its receipt). Experiment 1 (n = 212) used 5-trial adjusting delay or probability tasks to measure delay discounting of losses, probabilistic gains, and probabilistic losses. Experiment 2 (n = 98) assessed combined probabilistic and delayed alternatives. In both experiments, we compared results from 5-trial adjusting delay or probability tasks to traditional adjusting amount procedures. Results suggest both procedures produced similar rates of probability and delay discounting in six out of seven comparisons. A magnitude effect consistent with previous research was observed for probabilistic gains and losses, but not for delayed losses. Results also suggest that delay and probability interact to determine the value of money. Five-trial methods may allow researchers to assess discounting more efficiently as well as study more complex choice scenarios. PMID:27498073

  17. Effects of time delay and pitch control sensitivity in the flared landing

    NASA Technical Reports Server (NTRS)

    Berthe, C. J.; Chalk, C. R.; Wingarten, N. C.; Grantham, W.

    1986-01-01

    Between December 1985 and January 1986, a flared landing program was conducted, using the USAF Total In-Flight simulator airplane, to examine time delay effects in a formal manner. Results show that as pitch sensitivity is increased, tolerance to time delay decreases. With the proper selection of pitch sensitivity, Level I performance was maintained with time delays ranging from 150 milliseconds to greater than 300 milliseconds. With higher sensitivity, configurations with Level I performance at 150 milliseconds degraded to level 2 at 200 milliseconds. When metrics of time delay and pitch sensitivity effects are applied to enhance previously developed predictive criteria, the result is an improved prediction technique which accounts for significant closed loop items.

  18. A Job with a Future? Delay Discounting, Magnitude Effects, and Domain Independence of Utility for Career Decisions.

    ERIC Educational Resources Information Center

    Schoenfelder, Thomas E.; Hantula, Donald A.

    2003-01-01

    Seniors (n=20) assessed two job offers with differences in domain (salary/tasks), delay (career-long earnings), and magnitude (initial salary offer). Contrary to discounted utility theory, choices reflected nonconstant discount rates for future salary/tasks (delay effect), lower discount rates for salary/preferred tasks (magnitude effect), and a…

  19. Determining delayed admission to intensive care unit for mechanically ventilated patients in the emergency department.

    PubMed

    Hung, Shih-Chiang; Kung, Chia-Te; Hung, Chih-Wei; Liu, Ber-Ming; Liu, Jien-Wei; Chew, Ghee; Chuang, Hung-Yi; Lee, Wen-Huei; Lee, Tzu-Chi

    2014-08-23

    The adverse effects of delayed admission to the intensive care unit (ICU) have been recognized in previous studies. However, the definitions of delayed admission varies across studies. This study proposed a model to define "delayed admission", and explored the effect of ICU-waiting time on patients' outcome. This retrospective cohort study included non-traumatic adult patients on mechanical ventilation in the emergency department (ED), from July 2009 to June 2010. The primary outcomes measures were 21-ventilator-day mortality and prolonged hospital stays (over 30 days). Models of Cox regression and logistic regression were used for multivariate analysis. The non-delayed ICU-waiting was defined as a period in which the time effect on mortality was not statistically significant in a Cox regression model. To identify a suitable cut-off point between "delayed" and "non-delayed", subsets from the overall data were made based on ICU-waiting time and the hazard ratio of ICU-waiting hour in each subset was iteratively calculated. The cut-off time was then used to evaluate the impact of delayed ICU admission on mortality and prolonged length of hospital stay. The final analysis included 1,242 patients. The time effect on mortality emerged after 4 hours, thus we deduced ICU-waiting time in ED > 4 hours as delayed. By logistic regression analysis, delayed ICU admission affected the outcomes of 21 ventilator-days mortality and prolonged hospital stay, with odds ratio of 1.41 (95% confidence interval, 1.05 to 1.89) and 1.56 (95% confidence interval, 1.07 to 2.27) respectively. For patients on mechanical ventilation at the ED, delayed ICU admission is associated with higher probability of mortality and additional resource expenditure. A benchmark waiting time of no more than 4 hours for ICU admission is recommended.

  20. GPU accelerated real-time confocal fluorescence lifetime imaging microscopy (FLIM) based on the analog mean-delay (AMD) method

    PubMed Central

    Kim, Byungyeon; Park, Byungjun; Lee, Seungrag; Won, Youngjae

    2016-01-01

    We demonstrated GPU accelerated real-time confocal fluorescence lifetime imaging microscopy (FLIM) based on the analog mean-delay (AMD) method. Our algorithm was verified for various fluorescence lifetimes and photon numbers. The GPU processing time was faster than the physical scanning time for images up to 800 × 800, and more than 149 times faster than a single core CPU. The frame rate of our system was demonstrated to be 13 fps for a 200 × 200 pixel image when observing maize vascular tissue. This system can be utilized for observing dynamic biological reactions, medical diagnosis, and real-time industrial inspection. PMID:28018724

  1. Parameter estimation and sensitivity analysis for a mathematical model with time delays of leukemia

    NASA Astrophysics Data System (ADS)

    Cândea, Doina; Halanay, Andrei; Rǎdulescu, Rodica; Tǎlmaci, Rodica

    2017-01-01

    We consider a system of nonlinear delay differential equations that describes the interaction between three competing cell populations: healthy, leukemic and anti-leukemia T cells involved in Chronic Myeloid Leukemia (CML) under treatment with Imatinib. The aim of this work is to establish which model parameters are the most important in the success or failure of leukemia remission under treatment using a sensitivity analysis of the model parameters. For the most significant parameters of the model which affect the evolution of CML disease during Imatinib treatment we try to estimate the realistic values using some experimental data. For these parameters, steady states are calculated and their stability is analyzed and biologically interpreted.

  2. The effects of the framing of time on delay discounting.

    PubMed

    DeHart, William Brady; Odum, Amy L

    2015-01-01

    We examined the effects of the framing of time on delay discounting. Delay discounting is the process by which delayed outcomes are devalued as a function of time. Time in a titrating delay discounting task is often framed in calendar units (e.g., as 1 week, 1 month, etc.). When time is framed as a specific date, delayed outcomes are discounted less compared to the calendar format. Other forms of framing time; however, have not been explored. All participants completed a titrating calendar unit delay-discounting task for money. Participants were also assigned to one of two delay discounting tasks: time as dates (e.g., June 1st, 2015) or time in units of days (e.g., 5000 days), using the same delay distribution as the calendar delay-discounting task. Time framed as dates resulted in less discounting compared to the calendar method, whereas time framed as days resulted in greater discounting compared to the calendar method. The hyperboloid model fit best compared to the hyperbola and exponential models. How time is framed may alter how participants attend to the delays as well as how the delayed outcome is valued. Altering how time is framed may serve to improve adherence to goals with delayed outcomes. © Society for the Experimental Analysis of Behavior.

  3. The role of strategic attention deployment in development of self-regulation: predicting preschoolers' delay of gratification from mother-toddler interactions.

    PubMed

    Sethi, A; Mischel, W; Aber, J L; Shoda, Y; Rodriguez, M L

    2000-11-01

    Toddlers' use of effective attention deployment strategies to cope with separation from the mother and with maternal behavior predicted the use of effective delay-of-gratification strategies at age 5, even though the contexts, measures, and manifest behaviors were different. Toddlers who used distraction strategies during a brief separation from the mother were able, at age 5, to delay immediate gratification longer for more valued rewards. Toddlers who explored at a distance from a controlling mother when she tried to engage the child also delayed longer and used more effective delay strategies at age 5, compared with toddlers who did not distance themselves. Toddlers whose mothers were not controlling showed the opposite pattern: Those who did not distance themselves from the mother's bids had longer preschool delay times and more effective strategies. Strategic attention deployment was shown to be an enduring self-regulatory skill visible in early development across domains, measures, and over time.

  4. Photon-Counting H33D Detector for Biological Fluorescence Imaging

    PubMed Central

    Michalet, X.; Siegmund, O.H.W.; Vallerga, J.V.; Jelinsky, P.; Millaud, J.E.; Weiss, S.

    2010-01-01

    We have developed a photon-counting High-temporal and High-spatial resolution, High-throughput 3-Dimensional detector (H33D) for biological imaging of fluorescent samples. The design is based on a 25 mm diameter S20 photocathode followed by a 3-microchannel plate stack, and a cross delay line anode. We describe the bench performance of the H33D detector, as well as preliminary imaging results obtained with fluorescent beads, quantum dots and live cells and discuss applications of future generation detectors for single-molecule imaging and high-throughput study of biomolecular interactions. PMID:20151021

  5. Comparison principle for impulsive functional differential equations with infinite delays and applications

    NASA Astrophysics Data System (ADS)

    Li, Xiaodi; Shen, Jianhua; Akca, Haydar; Rakkiyappan, R.

    2018-04-01

    We introduce the Razumikhin technique to comparison principle and establish some comparison results for impulsive functional differential equations (IFDEs) with infinite delays, where the infinite delays may be infinite time-varying delays or infinite distributed delays. The idea is, under the help of Razumikhin technique, to reduce the study of IFDEs with infinite delays to the study of scalar impulsive differential equations (IDEs) in which the solutions are easy to deal with. Based on the comparison principle, we study the qualitative properties of IFDEs with infinite delays , which include stability, asymptotic stability, exponential stability, practical stability, boundedness, etc. It should be mentioned that the developed results in this paper can be applied to IFDEs with not only infinite delays but also persistent impulsive perturbations. Moreover, even for the special cases of non-impulsive effects or/and finite delays, the criteria prove to be simpler and less conservative than some existing results. Finally, two examples are given to illustrate the effectiveness and advantages of the proposed results.

  6. Functional model of biological neural networks.

    PubMed

    Lo, James Ting-Ho

    2010-12-01

    A functional model of biological neural networks, called temporal hierarchical probabilistic associative memory (THPAM), is proposed in this paper. THPAM comprises functional models of dendritic trees for encoding inputs to neurons, a first type of neuron for generating spike trains, a second type of neuron for generating graded signals to modulate neurons of the first type, supervised and unsupervised Hebbian learning mechanisms for easy learning and retrieving, an arrangement of dendritic trees for maximizing generalization, hardwiring for rotation-translation-scaling invariance, and feedback connections with different delay durations for neurons to make full use of present and past informations generated by neurons in the same and higher layers. These functional models and their processing operations have many functions of biological neural networks that have not been achieved by other models in the open literature and provide logically coherent answers to many long-standing neuroscientific questions. However, biological justifications of these functional models and their processing operations are required for THPAM to qualify as a macroscopic model (or low-order approximate) of biological neural networks.

  7. The delaying effect of stigma on mental health help-seeking in Sri Lanka.

    PubMed

    Fernando, Sunera M; Deane, Frank P; McLeod, Hamish J

    2017-03-01

    Mental health stigma has been associated with delays in seeking treatment. To describe perceived stigma experienced by patients and carers in Sri Lanka and to determine the effects of stigma on help-seeking delay. Survey of outpatients and family carers (n = 118 dyads) attending two psychiatric hospitals in Sri Lanka, using the Disclosure and Discrimination subscales of the Stigma Scale. Stigma was positively related to help-seeking delay for carers but not patients. Public stigma experienced by carers accounted for 23% of the variance in help-seeking delay. Reducing stigma may reduce help-seeking delays during the course of treatment. © 2016 John Wiley & Sons Australia, Ltd.

  8. Revealing determinants of two-phase dynamics of P53 network under gamma irradiation based on a reduced 2D relaxation oscillator model.

    PubMed

    Demirkıran, Gökhan; Kalaycı Demir, Güleser; Güzeliş, Cüneyt

    2018-02-01

    This study proposes a two-dimensional (2D) oscillator model of p53 network, which is derived via reducing the multidimensional two-phase dynamics model into a model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the impact of p53-regulators on cell fate decision. First, the authors identify a 6D core oscillator module, then reduce this module into a 2D oscillator model while preserving the qualitative behaviours. The introduced 2D model is shown to be an excitable relaxation oscillator. This oscillator provides a mechanism that leads diverse modes underpinning cell fate, each corresponding to a cell state. To investigate the effects of p53 inhibitors and the intrinsic time delay of Wip1 on the characteristics of oscillations, they introduce also a delay differential equation version of the 2D oscillator. They observe that the suppression of p53 inhibitors decreases the amplitudes of p53 oscillation, though the suppression increases the sustained level of p53. They identify Wip1 and P53DINP1 as possible targets for cancer therapies considering their impact on the oscillator, supported by biological findings. They model some mutations as critical changes of the phase space characteristics. Possible cancer therapeutic strategies are then proposed for preventing these mutations' effects using the phase space approach.

  9. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs.

    PubMed

    Erb, Samuel J; Schappi, Jeffrey M; Rasenick, Mark M

    2016-09-16

    Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Because antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5-hydroxytryptamine transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction, where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Bactericidal activity of OPC-67683 against drug-tolerant Mycobacterium tuberculosis.

    PubMed

    Saliu, Oluwabunmi Y; Crismale, Catina; Schwander, Stephan K; Wallis, Robert S

    2007-11-01

    There is an urgent need for drugs that hasten sterilization in tuberculosis; however, we presently lack indicators of this activity to guide early drug development. We previously described a novel in vitro assay to study mycobacterial phenotypic drug tolerance, in which sterilizing activity could be assessed. OPC-67,683 is a novel imidazooxazole that accelerates sterilization in the mouse tuberculosis model. The present study was conducted to determine the activity of OPC-67,683 in the in vitro tolerance model using drug-tolerant clinical Mycobacterium tuberculosis strains. Tolerance was assessed in Bactec radiometric culture as: (i) delayed decline in growth index during 14 days of drug exposure; (ii) shorter time to positivity of subcultures following drug exposure. Four isolates were selected from among 16 surveyed, based on delayed killing by isoniazid and OPC-67,683. Unlike isoniazid and rifampicin, whose rates of killing were concentration-independent, OPC-67,683 showed concentration-dependent effects that, at the highest dose levels tested (1.0 microg/mL), were superior to isoniazid and equal to rifampicin. The sterilizing activity of OPC-67683 against drug-tolerant M. tuberculosis in the Bactec model is consistent with its activity in mice. Further studies are warranted to examine the effects of OPC-67683 on mycobacterial persistence in tuberculous patients and to determine the biological basis of tolerance in the model.

  11. Delayed childbearing: determining responsibilities for prime gamete quality.

    PubMed

    Campagne, Daniel M

    2013-01-01

    Delayed parenting affects fertility in women and in men, and cryopreservation of oocytes and sperm is becoming the latest trend as a solution for those who want or need to postpone procreation, in an attempt to avoid the damage medical conditions or time itself produces in gametes. Although "social freezing" is considered legitimate, its ethical and social aspects are in need of an overdue medical, public and legal debate. Assisted reproduction and cryopreservation, in combination with womb outsourcing, have opened the door to biological ectogenesis and the subsequent question of whether delayed childbearing means we should formally separate procreation from sexual activity. This article briefly summarizes what cryotechniques are capable of presently and in the near future, to separate fact from fiction. It names the implications for and discusses the practically virgin subject of the underlying responsibilities of delayed parenting techniques towards the child-to-be-not only the unborn but also the not-yet-conceived child. Considering the medical, economic, legal and social consequences of these rapidly growing developments in reproduction, several reasons point at the need to formally separate procreation from sexual activity, specifying responsibilities in the first while respecting personal choice in the second.

  12. Impacts of Wake Effect and Time Delay on the Dynamic Analysis of Wind Farms Models

    ERIC Educational Resources Information Center

    El-Fouly, Tarek H. M.; El-Saadany, Ehab F.; Salama, Magdy M. A.

    2008-01-01

    This article investigates the impacts of proper modeling of the wake effects and wind speed delays, between different wind turbines' rows, on the dynamic performance accuracy of the wind farms models. Three different modeling scenarios were compared to highlight the impacts of wake effects and wind speed time-delay models. In the first scenario,…

  13. Comprehensive Care for Joint Replacement Model (CJR); Delay of Effective Date. Final rule; delay of effective date.

    PubMed

    2017-05-19

    This final rule finalizes May 20, 2017 as the effective date of the final rule titled "Advancing Care Coordination Through Episode Payment Models (EPMs); Cardiac Rehabilitation Incentive Payment Model; and Changes to the Comprehensive Care for Joint Replacement Model (CJR)" originally published in the January 3, 2017 Federal Register. This final rule also finalizes a delay of the applicability date of the regulations at 42 CFR part 512 from July 1, 2017 to January 1, 2018 and delays the effective date of the specific CJR regulations listed in the DATES section from July 1, 2017 to January 1, 2018.

  14. An optimal control model approach to the design of compensators for simulator delay

    NASA Technical Reports Server (NTRS)

    Baron, S.; Lancraft, R.; Caglayan, A.

    1982-01-01

    The effects of display delay on pilot performance and workload and of the design of the filters to ameliorate these effects were investigated. The optimal control model for pilot/vehicle analysis was used both to determine the potential delay effects and to design the compensators. The model was applied to a simple roll tracking task and to a complex hover task. The results confirm that even small delays can degrade performance and impose a workload penalty. A time-domain compensator designed by using the optimal control model directly appears capable of providing extensive compensation for these effects even in multi-input, multi-output problems.

  15. Delay and death-thought accessibility: a meta-analysis.

    PubMed

    Steinman, Christopher T; Updegraff, John A

    2015-12-01

    The dual-process component of Terror Management Theory (TMT) proposes that different types of threats lead to increases in death-thought accessibility (DTA) after different delay intervals. Experimental studies of terror management threats' effect on DTA were collected and coded for their use of explicitly death-related (vs. not explicitly death-related) threats, and for their use of delay and task-switching during the delay. Results reveal that studies using death-related threats achieved larger DTA effect-sizes when they included more task-switching or a longer delay between the threat and the DTA measurement. In contrast, studies using threats that were not explicitly death-related achieved smaller DTA effect-sizes when they included more task-switching between the threat and the DTA measurement. These findings provide partial support for the dual-process component's predictions regarding delay and DTA. Limitations and future directions are discussed. © 2015 by the Society for Personality and Social Psychology, Inc.

  16. Combined effects of THC and caffeine on working memory in rats.

    PubMed

    Panlilio, Leigh V; Ferré, Sergi; Yasar, Sevil; Thorndike, Eric B; Schindler, Charles W; Goldberg, Steven R

    2012-04-01

    Cannabis and caffeine are two of the most widely used psychoactive substances. Δ(9) -Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. Rats were given THC (0, 1 and 3 mg·kg(-1) , i.p.) along with caffeine (0, 1, 3 and 10 mg·kg(-1) , i.p.), the selective adenosine A(1) -receptor antagonist CPT (0, 3 and 10 mg·kg(-1) ) or the selective adenosine A(2A) -receptor antagonist SCH58261 (0 and 5 mg·kg(-1) ) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. THC alone produced memory deficits at 3 mg·kg(-1) . The initial exposure to caffeine (10 mg·kg(-1) ) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg(-1) ) was combined with caffeine (10 mg·kg(-1) ) or CPT (10 mg·kg(-1) ), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

  17. Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives.

    PubMed

    Hampel, Harald; Frank, Richard; Broich, Karl; Teipel, Stefan J; Katz, Russell G; Hardy, John; Herholz, Karl; Bokde, Arun L W; Jessen, Frank; Hoessler, Yvonne C; Sanhai, Wendy R; Zetterberg, Henrik; Woodcock, Janet; Blennow, Kaj

    2010-07-01

    Advances in therapeutic strategies for Alzheimer's disease that lead to even small delays in onset and progression of the condition would significantly reduce the global burden of the disease. To effectively test compounds for Alzheimer's disease and bring therapy to individuals as early as possible there is an urgent need for collaboration between academic institutions, industry and regulatory organizations for the establishment of standards and networks for the identification and qualification of biological marker candidates. Biomarkers are needed to monitor drug safety, to identify individuals who are most likely to respond to specific treatments, to stratify presymptomatic patients and to quantify the benefits of treatments. Biomarkers that achieve these characteristics should enable objective business decisions in portfolio management and facilitate regulatory approval of new therapies.

  18. Setting Adolescents up for Success: Promoting a Policy to Delay High School Start Times

    ERIC Educational Resources Information Center

    Barnes, Margaux; Davis, Krista; Mancini, Mackenzie; Ruffin, Jasmine; Simpson, Tina; Casazza, Krista

    2016-01-01

    Background: A unique biological shift in sleep cycles occurs during adolescence causing later sleep and wake times. This shift is not matched by a concurrent modification in school start times, resulting in sleep curtailment for a large majority of adolescents. Chronic inadequate sleep is associated with poor academic performance including…

  19. Influence of a constant magnetic field on thrombocytes. [delay of blood coagulation time

    NASA Technical Reports Server (NTRS)

    Meyerova, Y. A.

    1974-01-01

    In an experiment on white mice it was found that a constant electromagnetic field with strength of 250-275 oersteds is biologically active at an exposure of 55 minutes. Qualitative and morphological changes in thrombocytes 1-3 days following exposure reduced their numbers, prolonged blood coagulation time and increased the number of leucocytes.

  20. Father Involvement and Maternal Depressive Symptoms in Families of Children with Disabilities or Delays

    ERIC Educational Resources Information Center

    Laxman, Daniel J.; McBride, Brent A.; Jeans, Laurie M.; Dyer, William J.; Santos, Rosa M.; Kern, Justin L.; Sugimura, Niwako; Curtiss, Sarah L.; Weglarz-Ward, Jenna M.

    2015-01-01

    This study examined the longitudinal association between fathers' early involvement in routine caregiving, literacy, play, and responsive caregiving activities at 9 months and maternal depressive symptoms at 4 years. Data for 3,550 children and their biological parents were drawn from the Early Childhood Longitudinal Study-Birth Cohort data set.…

  1. Psychophysiology of Delayed Extinction and Reconsolidation in Humans

    DTIC Science & Technology

    2015-04-01

    2013). Reconsolidation in a human fear conditioning study: a test of extinction as updating mechanism. Biological Psychology , 92(1), 43–50. doi...strengths of various pharmacological and behavioral, reconsolidation-blocking interventions could be tested . We completed testing for two...conductance, when assessing renewal and reinstatement. Mifepristone was tested as a second pharmacological intervention. After adjusting for initial

  2. Cognitive Functioning in Toddlerhood: The Role of Gestational Age, Attention Capacities, and Maternal Stimulation

    ERIC Educational Resources Information Center

    de Jong, Marjanneke; Verhoeven, Marjolein; Hooge, Ignace T. C.; Maingay-Visser, Arnoldina P. G. F.; Spanjerberg, Louise; van Baar, Anneloes L.

    2018-01-01

    Why do many preterm children show delays in development? An integrated model of biological risk, children's capacities, and maternal stimulation was investigated in relation to cognitive functioning at toddler age. Participants were 200 Dutch children (gestational age = 32-41 weeks); 51% boys, 96% Dutch nationality, 71.5% highly educated mothers.…

  3. Cocaine administration dose-dependently increases sexual desire and decreases condom use likelihood: The role of delay and probability discounting in connecting cocaine with HIV.

    PubMed

    Johnson, Matthew W; Herrmann, Evan S; Sweeney, Mary M; LeComte, Robert S; Johnson, Patrick S

    2017-02-01

    Although cocaine use has been linked to sexual HIV risk behavior for decades, the direct effects of cocaine on sexual desire and sexual decision-making are unexamined. Research suggests delay discounting (devaluation of future outcomes) and probability discounting (devaluation of uncertain outcomes) play roles in condom use decisions. This study examined the effect of cocaine administration on sexual desire, hypothetical condom use, and discounting tasks. This double-blind, within-subjects study compared the effects of 0, 125, and 250 mg/70 kg oral cocaine HCl in 12 cocaine users. Measures included sexual desire and other subjective ratings, the Sexual Delay Discounting Task, the Sexual Probability Discounting Task, and monetary delay and probability discounting tasks. Cocaine caused dose-related increases in sexual desire and prototypical stimulant abuse-liability ratings. Relative to placebo, cocaine did not significantly alter condom use likelihood when condoms were immediately available or when sex was associated with 100% certainty of sexually transmitted infection (STI). In contrast, cocaine dose-dependently strengthened the effect of delay (sexual delay discounting) and STI uncertainty (sexual probability discounting) in decreasing condom use likelihood. Cocaine caused no significant change in monetary delay and probability discounting. This is the first study showing that cocaine administration increases sexual desire. Detrimental effects of cocaine on sexual risk were only observed when safer sex required delay, or STI risk was uncertain (representative of many real-world scenarios), suggesting a critical role of discounting processes. Lack of monetary effects highlights the importance of studying clinically relevant outcomes when examining drug effects on behavioral processes.

  4. Effects of delay and probability combinations on discounting in humans.

    PubMed

    Cox, David J; Dallery, Jesse

    2016-10-01

    To determine discount rates, researchers typically adjust the amount of an immediate or certain option relative to a delayed or uncertain option. Because this adjusting amount method can be relatively time consuming, researchers have developed more efficient procedures. One such procedure is a 5-trial adjusting delay procedure, which measures the delay at which an amount of money loses half of its value (e.g., $1000 is valued at $500 with a 10-year delay to its receipt). Experiment 1 (n=212) used 5-trial adjusting delay or probability tasks to measure delay discounting of losses, probabilistic gains, and probabilistic losses. Experiment 2 (n=98) assessed combined probabilistic and delayed alternatives. In both experiments, we compared results from 5-trial adjusting delay or probability tasks to traditional adjusting amount procedures. Results suggest both procedures produced similar rates of probability and delay discounting in six out of seven comparisons. A magnitude effect consistent with previous research was observed for probabilistic gains and losses, but not for delayed losses. Results also suggest that delay and probability interact to determine the value of money. Five-trial methods may allow researchers to assess discounting more efficiently as well as study more complex choice scenarios. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. A Comparison of the Effects of Brief Rules, a Timer, and Preferred Toys on Self-Control

    ERIC Educational Resources Information Center

    Newquist, Matthew H.; Dozier, Claudia L.; Neidert, Pamela L.

    2012-01-01

    Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining…

  6. Neural congruence between intertemporal and interpersonal self-control: Evidence from delay and social discounting.

    PubMed

    Hill, Paul F; Yi, Richard; Spreng, R Nathan; Diana, Rachel A

    2017-11-15

    Behavioral studies using delay and social discounting as indices of self-control and altruism, respectively, have revealed functional similarities between farsighted and social decisions. However, neural evidence for this functional link is lacking. Twenty-five young adults completed a delay and social discounting task during fMRI scanning. A spatiotemporal partial least squares analysis revealed that both forms of discounting were well characterized by a pattern of brain activity in areas comprising frontoparietal control, default, and mesolimbic reward networks. Both forms of discounting appear to draw on common neurocognitive mechanisms, regardless of whether choices involve intertemporal or interpersonal outcomes. We also observed neural profiles differentiating between high and low discounters. High discounters were well characterized by increased medial temporal lobe and limbic activity. In contrast, low discount rates were associated with activity in the medial prefrontal cortex and right temporoparietal junction. This pattern may reflect biological mechanisms underlying behavioral heterogeneity in discount rates. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The Triplet State

    NASA Astrophysics Data System (ADS)

    Zahlan, A. B.

    2010-01-01

    Preface; List of participants; Part I. Spin-orbit Coupling and Intersystem Crossing: 1. Spin-orbit interactions in organic molecules; 2. Singlet-triplet transitions in organic molecules; 3. Triplet decay and intersystem crossing in aromatic hydrocarbons; 4. Statistical aspects of resonance energy transfer; Discussion; Part II. Magnetic Resonance and Magnetic Interactions: 5. Magnetic resonance spectra of organic molecules in triplet states in single crystals; 6. Magnetic interactions related to phosphorescence; 7. ESR investigations of naphthalene-d8:Naphthalene-h8 mixed crystals; 8. Biradicals and polyradicals in the nitroxide series; 9. Changes induced in the phosphorescent radiation of aromatic molecules by paramagnetic resonance in their metastable triplet states; 10. Paramagnetic resonance of the triplet state of tetramethylpyrazine; 11. On magnetic dipole contributions to the intrinsic S0 = T1 transition in simple aromatics; Discussion; Part III. Photochemistry: 12. The kinetics of energy transfer from the triplet state in rigid solutions; 13. Triplet states in gas-phase photochemistry; 14. Biphotonic photochemistry, involving the triplet state: polarisation of the effective T-T transition and solvent effects; 15. Direct and sensitised photo-oxidation of aromatic hydrocarbons in boric acid glass; Discussion; Part IV. Radiationless Transitions: 16. Radiationless transitions in gaseous benzene; 17. Low-lying excited triplet states and intersystem crossing in aromatic hydrocarbons; 18. De-excitation rates of triplet states in condensed media; 19. Lifetimes of the triplet state of aromatic hydrocarbons in the vapour phase; Discussion; Part V. Triplet Excitons: 20. Some comments on the properties of triplet excitons in molecular crystals; 21. Exact treatment of coherent and incoherent triplet exciton migration; 22. Magnetic susceptibility of a system of triplet excitons: Würster's Blue Perchlorate; 23. A study of triplet excitons in anthracene crystals under laser excitation; 24. The electronic states in crystaline anthracene; Discussion; Part VI. Delayed Fluorescent and Phosphorescence: 25. Delayed fluorescence of solutions; 26. The kinetics of the excited states of anthracene and phenanthrene vapor; 27. Optical investigations of the triplet states of naphthalene in different crystalline environments; 28. Excitation of the triplet states of organic molecules; 29. The delayed luminescence and triplet quantum yields of pyrene solutions; 30. Triplet state studies of some polyphenyls in rigid glasses; 31. Decay time of delayed fluorescence of anthracene as a function of temperature (2-30ºK); 32. Energy transfer between benzene and biacetyl and the lifetime of triplet benzene in the gas phase; 33. Charge transfer triplet state of molecular complexes. 34. Flash-photolytic detection of triplet acridine formed by energy transfer from biacetyl; 35. Extinction coefficients of triplet-triplet transitions between 3000 and 8800 A in anthracene; 36. Anthracene triplet-triplet annihilation rate constant; Discussion; Part VII. Triplet State Related to Biology: 37. ESR and optical studies of some triplet states of biological interest; 38. The triplet state of DNA; 39. Some characteristics of the triplet states of the nucleic bases; Discussion; Indexes.

  8. The perspective effects of various seed coating substances on rice seed variety Khao DAWK Mali 105 storability I: the case study of physiological properties.

    PubMed

    Thobunluepop, P; Pawelzik, E; Vearasilp, S

    2008-10-01

    This study aimed to evaluate the perspective changes of several physiological performances of rice seeds cv. KDML 105 which were coated with various seed coating substances [chemical fungicide, captan (CA) and biological coating polymers; chitosan-lignosulphonate polymer (CL) and eugenol incorporated into chitosan-lignosulphonate polymer (E + CL)] during storage (12 months). CA significantly increased seed moisture content and seed water activity through out the storage period. The qualities and viability of the seeds were seriously declined by this treatment. Moreover, CA inhibited the shoot and root development, seedling dry weight accumulation, delayed the seed germination and seedling growth rate. CA treated seeds were susceptible to stress conditions that declined the seed germination potential under cold, high moisture and temperature stress conditions. Nevertheless, CL and E + CL coating polymer could maintain seed storability, which significantly improved seed germination and seedling performances. These improvements were attributed to maintain the nutritive reserve and dehydrogenase activity in seeds. Moreover, the biological seed treatment stimulated the embryo growth and so speeding up the seedling emergence when compared untreated seeds.

  9. A burgeoning science of embryological genetics demands a modern ethics.

    PubMed

    Edwards, R G

    2007-09-01

    This brief article discusses the nature of recent scientific advances in reproductive biomedicine and genetics, their moral implications and their effects on society. The pace of research has amplified exponentially, leading society into situations incomprehended by our ancestors. Early studies on reproductive biology in animals, and clinical methods such as artificial insemination by donor spermatozoa, were introduced several centuries ago and led to prolonged ethical disagreements. The 20th century witnessed the introduction of controlled ovulation in laboratory animals, the fertilization of the oocyte and preimplantation embryology in mammalian species. The second half of this century produced an avalanche of knowledge on genetics, developmental biology, the fertilization of the human oocyte in vitro, test-tube babies, preimplantation genetic diagnosis, designer babies, stem cells and a deeper understanding of molecular differentiation in the human embryo. The ethical and legal aspects of these items have led to intense debates on their rights and wrongs. The future may have even more bizarre possibilities such as producing medicines in cow's milk or trees and delaying death for many years.

  10. Metabolic profiling of body fluids and multivariate data analysis.

    PubMed

    Trezzi, Jean-Pierre; Jäger, Christian; Galozzi, Sara; Barkovits, Katalin; Marcus, Katrin; Mollenhauer, Brit; Hiller, Karsten

    2017-01-01

    Metabolome analyses of body fluids are challenging due pre-analytical variations, such as pre-processing delay and temperature, and constant dynamical changes of biochemical processes within the samples. Therefore, proper sample handling starting from the time of collection up to the analysis is crucial to obtain high quality samples and reproducible results. A metabolomics analysis is divided into 4 main steps: 1) Sample collection, 2) Metabolite extraction, 3) Data acquisition and 4) Data analysis. Here, we describe a protocol for gas chromatography coupled to mass spectrometry (GC-MS) based metabolic analysis for biological matrices, especially body fluids. This protocol can be applied on blood serum/plasma, saliva and cerebrospinal fluid (CSF) samples of humans and other vertebrates. It covers sample collection, sample pre-processing, metabolite extraction, GC-MS measurement and guidelines for the subsequent data analysis. Advantages of this protocol include: •Robust and reproducible metabolomics results, taking into account pre-analytical variations that may occur during the sampling process•Small sample volume required•Rapid and cost-effective processing of biological samples•Logistic regression based determination of biomarker signatures for in-depth data analysis.

  11. Implications of Plasmodium vivax Biology for Control, Elimination, and Research

    PubMed Central

    Olliaro, Piero L.; Barnwell, John W.; Barry, Alyssa; Mendis, Kamini; Mueller, Ivo; Reeder, John C.; Shanks, G. Dennis; Snounou, Georges; Wongsrichanalai, Chansuda

    2016-01-01

    This paper summarizes our current understanding of the biology of Plasmodium vivax, how it differs from Plasmodium falciparum, and how these differences explain the need for P. vivax-tailored interventions. The article further pinpoints knowledge gaps where investments in research are needed to help identify and develop such specific interventions. The principal obstacles to reduce and eventually eliminate P. vivax reside in 1) its higher vectorial capacity compared with P. falciparum due to its ability to develop at lower temperature and over a shorter sporogonic cycle in the vector, allowing transmission in temperate zones and making it less sensitive to vector control measures that are otherwise effective on P. falciparum; 2) the presence of dormant liver forms (hypnozoites), sustaining multiple relapsing episodes from a single infectious bite that cannot be diagnosed and are not susceptible to any available antimalarial except primaquine, with routine deployment restricted by toxicity; 3) low parasite densities, which are difficult to detect with current diagnostics leading to missed diagnoses and delayed treatments (and protracted transmission), coupled with 4) transmission stages (gametocytes) occurring early in acute infections, before infection is diagnosed. PMID:27799636

  12. Differential Effects of the Cannabinoid Agonist WIN55,212-2 on Delay and Trace Eyeblink Conditioning

    PubMed Central

    Steinmetz, Adam B.; Freeman, John H.

    2014-01-01

    Central cannabinoid-1 receptors (CB1R) play a role in the acquisition of delay eyeblink conditioning but not trace eyeblink conditioning in humans and animals. However, it is not clear why trace conditioning is immune to the effects of cannabinoid receptor compounds. The current study examined the effects of variants of delay and trace conditioning procedures to elucidate the factors that determine the effects of CB1R agonists on eyeblink conditioning. In Experiment 1 rats were administered the cannabinoid agonist WIN55,212-2 during delay, long delay, or trace conditioning. Rats were impaired during delay and long delay but not trace conditioning; the impairment was greater for long delay than delay conditioning. Trace conditioning was further examined in Experiment 2 by manipulating the trace interval and keeping constant the conditioned stimulus (CS) duration. It was found that when the trace interval was 300 ms or less WIN55,212-2 administration impaired the rate of learning. Experiment 3 tested whether the trace interval duration or the relative durations of the CS and trace interval were critical parameters influencing the effects of WIN55,212-2 on eyeblink conditioning. Rats were not impaired with a 100 ms CS, 200 ms trace paradigm but were impaired with a 1000 ms CS, 500 ms trace paradigm, indicating that the duration of the trace interval does not matter but the proportion of the interstimulus interval occupied by the CS relative to the trace period is critical. Taken together the results indicate that cannabinoid agonists affect cerebellar learning the CS is longer than the trace interval. PMID:24128358

  13. Cocaine dependent individuals discount future rewards more than future losses for both cocaine and monetary outcomes.

    PubMed

    Johnson, Matthew W; Bruner, Natalie R; Johnson, Patrick S

    2015-01-01

    Cocaine dependence and other forms of drug dependence are associated with steeper devaluation of future outcomes (delay discounting). Although studies in this domain have typically assessed choices between monetary gains (e.g., receive less money now versus receive more money after a delay), delay discounting is also applicable to decisions involving losses (e.g., small loss now versus larger delayed loss), with gains typically discounted more than losses (the "sign effect"). It is also known that drugs are discounted more than equivalently valued money. In the context of drug dependence, however, relatively little is known about the discounting of delayed monetary and drug losses and the presence of the sign effect. In this within-subject, laboratory study, delay discounting for gains and losses was assessed for cocaine and money outcomes in cocaine-dependent individuals (n=89). Both cocaine and monetary gains were discounted at significantly greater rates than cocaine and monetary losses, respectively (i.e., the sign effect). Cocaine gains were discounted significantly more than monetary gains, but cocaine and monetary losses were discounted similarly. Results suggest that cocaine is discounted by cocaine-dependent individuals in a systematic manner similar to other rewards. Because the sign effect was shown for both cocaine and money, delayed aversive outcomes may generally have greater impact than delayed rewards in shaping present behavior in this population. Copyright © 2014. Published by Elsevier Ltd.

  14. Time delays in flight simulator visual displays

    NASA Technical Reports Server (NTRS)

    Crane, D. F.

    1980-01-01

    It is pointed out that the effects of delays of less than 100 msec in visual displays on pilot dynamic response and system performance are of particular interest at this time because improvements in the latest computer-generated imagery (CGI) systems are expected to reduce CGI displays delays to this range. Attention is given to data which quantify the effects of display delays in the range of 0-100 msec on system stability and performance, and pilot dynamic response for a particular choice of aircraft dynamics, display, controller, and task. The conventional control system design methods are reviewed, the pilot response data presented, and data for long delays, all suggest lead filter compensation of display delay. Pilot-aircraft system crossover frequency information guides compensation filter specification.

  15. Study on Effects of the Stochastic Delay Probability for 1d CA Model of Traffic Flow

    NASA Astrophysics Data System (ADS)

    Xue, Yu; Chen, Yan-Hong; Kong, Ling-Jiang

    Considering the effects of different factors on the stochastic delay probability, the delay probability has been classified into three cases. The first case corresponding to the brake state has a large delay probability if the anticipant velocity is larger than the gap between the successive cars. The second one corresponding to the following-the-leader rule has intermediate delay probability if the anticipant velocity is equal to the gap. Finally, the third case is the acceleration, which has minimum delay probability. The fundamental diagram obtained by numerical simulation shows the different properties compared to that by the NaSch model, in which there exist two different regions, corresponding to the coexistence state, and jamming state respectively.

  16. An ethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents

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

    Mercado-Feliciano, Minerva; Cora, Michelle C.; Witt, Kristine L.

    2012-09-01

    Black cohosh rhizome (Actaea racemosa) is used as a remedy for pain and gynecological ailments; modern preparations are commonly sold as ethanolic extracts available as dietary supplements. Black cohosh was nominated to the National Toxicology Program (NTP) for toxicity testing due to its widespread use and lack of safety data. Several commercially available black cohosh extracts (BCE) were characterized by the NTP, and one with chemical composition closest to formulations available to consumers was used for all studies. Female B6C3F1/N mice and Wistar Han rats were given 0, 15 (rats only), 62.5 (mice only), 125, 250, 500, or 1000 mg/kg/daymore » BCE by gavage for 90 days starting at weaning. BCE induced dose-dependent hematological changes consistent with a non-regenerative macrocytic anemia and increased frequencies of peripheral micronucleated red blood cells (RBC) in both species. Effects were more severe in mice, which had decreased RBC counts in all treatment groups and increased micronucleated RBC at doses above 125 mg/kg. Dose-dependent thymus and liver toxicity was observed in rats but not mice. No biologically significant effects were observed in other organs. Puberty was delayed 2.9 days at the highest treatment dose in rats; a similar magnitude delay in mice occurred in the 125 and 250 mg/kg groups but not at the higher doses. An additional uterotrophic assay conducted in mice exposed for 3 days to 0.001, 0.01, 0.1, 1, 10, 100 and 500 mg/kg found no estrogenic or anti-estrogenic activity. These are the first studies to observe adverse effects of BCE in rodents. -- Highlights: ► Mice and rats were dosed with black cohosh extract for 90 days starting at weaning. ► Hematological changes were consistent with a non-regenerative macrocytic anemia. ► Peripheral micronucleated red blood cell frequencies increased. ► Puberty was delayed 2.9 days in rats. ► No estrogenic/anti-estrogenic activity was seen in the uterotrophic assay.« less

  17. Effects of delay to reinforcement on the choice between cocaine and food in rhesus monkeys.

    PubMed

    Woolverton, William L; Anderson, Karen G

    2006-05-01

    Although a delay between behavior and reinforcer has been shown to weaken behavior, little is known about the effects of delay on drug choice. The present study examined effects of delay between lever press and reinforcer presentation on the choice between a drug and non-drug reinforcer and between different drug doses. Monkeys (n=4) were allowed to choose 32 times/day between cocaine and four food pellets. The delay between lever press and a preferred dose of cocaine (0.05 mg/kg/injection) was increased systematically from 0 to 240 s, while the delay to food remained at 0 s. A second group of monkeys (n=4) was allowed to choose between 0.05 mg/kg/injection and a lower dose of cocaine (0.025 mg/kg/injection). Next, a delay that resulted in less than 20% choice of 0.05 mg/kg/injection cocaine was selected and delay to the alternative was varied. Results were similar across groups. The choice of 0.05 mg/kg/injection approximated 100% at 0 delay and decreased to near 0 as delay increased. As the delay to alternative was subsequently increased from 0 to 240 s, choice of 0.05 mg/kg/injection increased, though full cocaine choice was not generally restored. The delay estimated to maintain 50% choice (indifference point) was lower for the cocaine-food choice (mean=64 s) than for the cocaine-cocaine choice (mean=207 s). This experiment demonstrates that the choice between cocaine and a non-drug or drug alternative can be modified by increasing the interval between behavior and drug injection. Overall, the results are consistent with a temporal discounting model of drug choice.

  18. Influenza vaccine delivery delays from the perspective of primary care physicians.

    PubMed

    O'Leary, Sean T; Barrow, Jennifer C; McQuillan, Lon; Daley, Matthew F; Crane, Lori A; Beaty, Brenda L; Babbel, Christine I; Dickinson, L Miriam; Kempe, Allison

    2011-06-01

    The effects of delayed influenza vaccine delivery on primary practices are currently unknown. To describe, among primary care physicians nationally regarding the 2006-2007 influenza season: (1) how physicians defined influenza vaccine delay; (2) the extent of reported vaccine delays; and (3) the perceived effects of vaccine delays. Between March and June 2007, a total of 1268 primary care physicians nationally were surveyed. Survey response was 74% (n=940). The majority of physicians (79%) defined "influenza vaccine delay" as not receiving vaccine by November 1. Fifty-three percent reported a vaccine delay. Providers reported the following as effects of delays: reduced satisfaction of patients or parents in the practice (72%); decreased percentage in their practice who received the vaccination (65%); disruption of scheduling influenza clinics (55%); increased referral of patients elsewhere for vaccination (55%); and negative financial impact caused by unused vaccine (46%). Those who reported experiencing delays more often reported not meeting demand for vaccine (adjusted risk ratio [ARR]=1.83, 95% CI=1.64, 2.07); that grocery stores, retail outlets, or pharmacies had vaccine before their practices did (ARR=1.82, 95% CI=1.53, 2.26); not receiving all vaccine that was ordered (ARR=1.19, 95% CI=1.06, 1.36); and having leftover vaccine (ARR=1.17, 95% CI=1.04, 1.32). During the 2006-2007 influenza season, a non-shortage season, the majority of respondents reported experiencing an influenza vaccine delivery delay. Experiencing a delay was thought to decrease vaccination use, increase referrals elsewhere, and have a negative financial impact on practices. Delayed delivery of influenza vaccine is disruptive for primary care practices, and it consequently may affect vaccination coverage. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Accommodating Adolescent Sleep-Wake Patterns: The Effects of Shifting the Timing of Sleep on Training Effectiveness

    PubMed Central

    Miller, Nita Lewis; Tvaryanas, Anthony P.; Shattuck, Lawrence G.

    2012-01-01

    Study Objective: This study evaluated the effect of accommodating adolescent sleep-wake patterns by altering the timing of the major sleep period of US Army recruits. Design: The quasi-experimental study compared recruits assigned to one of two training companies: one with a customary sleep regimen (20:30 to 04:30) while the other employed a phase-delayed sleep regimen (23:00 to 07:00), the latter aligning better with biologically driven sleep-wake patterns of adolescents. Setting: The study was conducted during Basic Combat Training (BCT) at Fort Leonard Wood, Missouri. Trainees: The study included 392 trainees: 209 received the intervention, while 183 composed the Comparison group. Measurements and Results: Demographic and psychophysiological measures were collected on all trainees. Weekly assessments of subjective fatigue and mood, periodic physical fitness, marksmanship scores, and attrition rates from BCT were studied. Actigraphy was collected on approximately 24% of trainees. Based on actigraphy, trainees on the phase-delayed sleep schedule obtained 31 m more sleep/night than trainees on the customary sleep schedule. The Intervention group reported less total mood disturbance relative to baseline. Improvements in marksmanship correlated positively with average nightly sleep during the preceding week when basic marksmanship skills were taught. No differences were seen in physical fitness or attrition rates. In contrast to the Intervention group, the Comparison group was 2.3 times more likely to experience occupationally significant fatigue and 5.5 times more likely to report poor sleep quality. Conclusions: Accommodating adolescent sleep patterns significantly improves mental health and performance in the training environment. Citation: Miller NL; Tvaryanas AP; Shattuck LG. Accommodating adolescent sleep-wake patterns: the effects of shifting the timing of sleep on training effectiveness. SLEEP 2012;35(8):1123-1136. PMID:22851808

  20. Testing of resveratrol microemulsion photostability and protective effect against UV induced oxidative stress.

    PubMed

    Juškaitė, Vaida; Ramanauskienė, Kristina; Briedis, Vitalis

    2017-06-27

    Resveratrol is well known for its antioxidant activity and susceptibility to ultraviolet radiation. Development of formulations providing improved stability and relevant drug delivery of resveratrol is still a challenging task. The aim of this study was to determine protective characteristics of formulated microemulsions by evaluating photoisomerization of resveratrol and to investigate the effects of resveratrol on human keratinocyte cells under oxidative stress caused by ultraviolet radiation. Incorporation of resveratrol into microemulsions resulted in increased photostability of active compounds and the results demonstrated that photodegradation of resveratrol was significantly delayed. Results of biopharmaceutical evaluation in vitro demonstrated that up to 60 % of resveratrol was released from microemulsions within 6 hours under a constant release rate profile. In vivo biological testing confirmed the ability of resveratrol to protect cells from oxidative stress and to increase cell viability. It was concluded that microemulsions might be considered in the development of UV light sensitive compounds.

  1. Numerical solution of a conspicuous consumption model with constant control delay☆

    PubMed Central

    Huschto, Tony; Feichtinger, Gustav; Hartl, Richard F.; Kort, Peter M.; Sager, Sebastian; Seidl, Andrea

    2011-01-01

    We derive optimal pricing strategies for conspicuous consumption products in periods of recession. To that end, we formulate and investigate a two-stage economic optimal control problem that takes uncertainty of the recession period length and delay effects of the pricing strategy into account. This non-standard optimal control problem is difficult to solve analytically, and solutions depend on the variable model parameters. Therefore, we use a numerical result-driven approach. We propose a structure-exploiting direct method for optimal control to solve this challenging optimization problem. In particular, we discretize the uncertainties in the model formulation by using scenario trees and target the control delays by introduction of slack control functions. Numerical results illustrate the validity of our approach and show the impact of uncertainties and delay effects on optimal economic strategies. During the recession, delayed optimal prices are higher than the non-delayed ones. In the normal economic period, however, this effect is reversed and optimal prices with a delayed impact are smaller compared to the non-delayed case. PMID:22267871

  2. Generalized binomial τ-leap method for biochemical kinetics incorporating both delay and intrinsic noise

    NASA Astrophysics Data System (ADS)

    Leier, André; Marquez-Lago, Tatiana T.; Burrage, Kevin

    2008-05-01

    The delay stochastic simulation algorithm (DSSA) by Barrio et al. [Plos Comput. Biol. 2, 117(E) (2006)] was developed to simulate delayed processes in cell biology in the presence of intrinsic noise, that is, when there are small-to-moderate numbers of certain key molecules present in a chemical reaction system. These delayed processes can faithfully represent complex interactions and mechanisms that imply a number of spatiotemporal processes often not explicitly modeled such as transcription and translation, basic in the modeling of cell signaling pathways. However, for systems with widely varying reaction rate constants or large numbers of molecules, the simulation time steps of both the stochastic simulation algorithm (SSA) and the DSSA can become very small causing considerable computational overheads. In order to overcome the limit of small step sizes, various τ-leap strategies have been suggested for improving computational performance of the SSA. In this paper, we present a binomial τ-DSSA method that extends the τ-leap idea to the delay setting and avoids drawing insufficient numbers of reactions, a common shortcoming of existing binomial τ-leap methods that becomes evident when dealing with complex chemical interactions. The resulting inaccuracies are most evident in the delayed case, even when considering reaction products as potential reactants within the same time step in which they are produced. Moreover, we extend the framework to account for multicellular systems with different degrees of intercellular communication. We apply these ideas to two important genetic regulatory models, namely, the hes1 gene, implicated as a molecular clock, and a Her1/Her 7 model for coupled oscillating cells.

  3. Interference effects on commonly used memory tasks.

    PubMed

    Brophy, Linda M; Jackson, Martin; Crowe, Simon F

    2009-02-01

    This paper reports two studies which investigated the effect of interference on delayed recall scores of the WMS-III and other commonly used memory measures. In Study 1, participants completed the immediate and delayed components of the WMS-III, with or without the introduction of conceptually similar memory tasks between the recall trials. In Study 2, this order of administration was reversed, with the WMS-III subtests used as the interference items. The results indicated that the introduction of interference items during the delay negatively affected delayed recall performance on almost all sub-tests. In addition, equal effects of proactive and retroactive interference were demonstrated. These findings raise concerns regarding the standardization process for memory tasks and highlight the need to consider interference effects in clinical practice, and stand as a caution in the use of memory-related materials during the delay interval in memory testing.

  4. Modified Primers for the Identification of Nonpathogenic Fusarium oxysporum Isolates That Have Biological Control Potential against Fusarium Wilt of Cucumber in Taiwan

    PubMed Central

    Wang, Chaojen; Lin, Yisheng; Lin, Yinghong; Chung, Wenhsin

    2013-01-01

    Previous investigations demonstrated that Fusarium oxysporum (Fo), which is not pathogenic to cucumbers, could serve as a biological control agent for managing Fusarium wilt of cucumber caused by Fo f. sp. cucumerinum (Foc) in Taiwan. However, thus far it has not been possible to separate the populations of pathogenic Fo from the nonpathogenic isolates that have biological control potential through their morphological characteristics. Although these two populations can be distinguished from one another using a bioassay, the work is laborious and time-consuming. In this study, a fragment of the intergenic spacer (IGS) region of ribosomal DNA from an Fo biological control agent, Fo366, was PCR-amplified with published general primers, FIGS11/FIGS12 and sequenced. A new primer, NPIGS-R, which was designed based on the IGS sequence, was paired with the FIGS11 primer. These primers were then evaluated for their specificity to amplify DNA from nonpathogenic Fo isolates that have biological control potential. The results showed that the modified primer pair, FIGS11/NPIGS-R, amplified a 500-bp DNA fragment from five of seven nonpathogenic Fo isolates. These five Fo isolates delayed symptom development of cucumber Fusarium wilt in greenhouse bioassay tests. Seventy-seven Fo isolates were obtained from the soil and plant tissues and then subjected to amplification using the modified primer pair; six samples showed positive amplification. These six isolates did not cause symptoms on cucumber seedlings when grown in peat moss infested with the isolates and delayed disease development when the same plants were subsequently inoculated with a virulent isolate of Foc. Therefore, the modified primer pair may prove useful for the identification of Fo isolates that are nonpathogenic to cucumber which can potentially act as biocontrol agents for Fusarium wilt of cucumber. PMID:23762289

  5. Egg-laying environment modulates offspring responses to predation risk in an amphibian.

    PubMed

    Tóth, Zoltán; Hettyey, Attila

    2018-05-01

    Predator-induced plasticity has been in the focus of evolutionary ecological research in the last decades, but the consequences of temporal variation in the presence of cues predicting offspring environment have remained controversial. This is partly due to the fact that the role of early environmental effects has scarcely been scrutinized in this context while also controlling for potential maternal effects. In this study, we investigated how past environmental conditions, that is different combinations of risky or safe adult (prenatal) and oviposition (early post-natal) environments, affected offspring's plastic responses in hatching time and locomotor activity to predation risk during development in the smooth newt (Lissotriton vulgaris). We found that females did not adjust their reproductive investment to the perceived level of risk in the adult environment, and this prenatal environment had generally negligible effect on offspring phenotype. However, when predator cues were absent during oviposition, larvae raised in the presence of predator cues delayed their hatching and exhibited a decreased activity compared to control larvae developing without predator cues, which responses are advantageous when predators pose a threat to hatched larvae. In the presence of predator cues during oviposition, the difference in hatching time persisted, but the difference in general locomotor activity disappeared between risk-exposed and control larvae. Our findings provide clear experimental evidence that fine-scale temporal variation in a predictive cue during and after egg-laying interactively affects offspring phenotype, and highlight the importance of the early post-natal environment, which may exert a substantial influence on progeny's phenotype also under natural conditions. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

  6. Behavioral effects of delayed timeouts from reinforcement.

    PubMed

    Byrne, Tom; Poling, Alan

    2017-03-01

    Timeouts are sometimes used in applied settings to reduce target responses, and in some circumstances delays are unavoidably imposed between the onset of a timeout and the offset of the response that produces it. The present study examined the effects of signaled and unsignaled timeouts in rats exposed to concurrent fixed-ratio 1 fixed-ratio 1 schedules of food delivery, where each response on one lever, the location of which changed across conditions, produced both food and a delayed 10-s timeout. Delays of 0 to 38 s were examined. Delayed timeouts often, but not always, substantially reduced the number of responses emitted on the lever that produced timeouts relative to the number emitted on the lever that did not produce timeouts. In general, greater sensitivity was observed to delayed timeouts when they were signaled. These results demonstrate that delayed timeouts, like other delayed consequences, can affect behavior, albeit less strongly than immediate consequences. © 2017 Society for the Experimental Analysis of Behavior.

  7. Effects of stochastic time-delayed feedback on a dynamical system modeling a chemical oscillator.

    PubMed

    González Ochoa, Héctor O; Perales, Gualberto Solís; Epstein, Irving R; Femat, Ricardo

    2018-05-01

    We examine how stochastic time-delayed negative feedback affects the dynamical behavior of a model oscillatory reaction. We apply constant and stochastic time-delayed negative feedbacks to a point Field-Körös-Noyes photosensitive oscillator and compare their effects. Negative feedback is applied in the form of simulated inhibitory electromagnetic radiation with an intensity proportional to the concentration of oxidized light-sensitive catalyst in the oscillator. We first characterize the system under nondelayed inhibitory feedback; then we explore and compare the effects of constant (deterministic) versus stochastic time-delayed feedback. We find that the oscillatory amplitude, frequency, and waveform are essentially preserved when low-dispersion stochastic delayed feedback is used, whereas small but measurable changes appear when a large dispersion is applied.

  8. Effects of stochastic time-delayed feedback on a dynamical system modeling a chemical oscillator

    NASA Astrophysics Data System (ADS)

    González Ochoa, Héctor O.; Perales, Gualberto Solís; Epstein, Irving R.; Femat, Ricardo

    2018-05-01

    We examine how stochastic time-delayed negative feedback affects the dynamical behavior of a model oscillatory reaction. We apply constant and stochastic time-delayed negative feedbacks to a point Field-Körös-Noyes photosensitive oscillator and compare their effects. Negative feedback is applied in the form of simulated inhibitory electromagnetic radiation with an intensity proportional to the concentration of oxidized light-sensitive catalyst in the oscillator. We first characterize the system under nondelayed inhibitory feedback; then we explore and compare the effects of constant (deterministic) versus stochastic time-delayed feedback. We find that the oscillatory amplitude, frequency, and waveform are essentially preserved when low-dispersion stochastic delayed feedback is used, whereas small but measurable changes appear when a large dispersion is applied.

  9. Advanced Transport Delay Compensation Algorithms: Results of Delay Measurement and Piloted Performance Tests

    NASA Technical Reports Server (NTRS)

    Guo, Liwen; Cardullo, Frank M.; Kelly, Lon C.

    2007-01-01

    This report summarizes the results of delay measurement and piloted performance tests that were conducted to assess the effectiveness of the adaptive compensator and the state space compensator for alleviating the phase distortion of transport delay in the visual system in the VMS at the NASA Langley Research Center. Piloted simulation tests were conducted to assess the effectiveness of two novel compensators in comparison to the McFarland predictor and the baseline system with no compensation. Thirteen pilots with heterogeneous flight experience executed straight-in and offset approaches, at various delay configurations, on a flight simulator where different predictors were applied to compensate for transport delay. The glideslope and touchdown errors, power spectral density of the pilot control inputs, NASA Task Load Index, and Cooper-Harper rating of the handling qualities were employed for the analyses. The overall analyses show that the adaptive predictor results in slightly poorer compensation for short added delay (up to 48 ms) and better compensation for long added delay (up to 192 ms) than the McFarland compensator. The analyses also show that the state space predictor is fairly superior for short delay and significantly superior for long delay than the McFarland compensator.

  10. An alternative approach to solar system exploration providing safety of human mission to Mars.

    PubMed

    Gitelson, J I; Bartsev, S I; Mezhevikin, V V; Okhonin, V A

    2003-01-01

    For systematic human Mars exploration, meeting crew safety requirements, it seems perspective to assemble into a spacecraft: an electrical rocket, a well-shielded long-term life support system, and a manipulator-robots operating in combined "presence effect" and "master-slave" mode. The electrical spacecraft would carry humans to the orbit of Mars, providing short distance (and low signal time delay) between operator and robot-manipulators, which are landed on the surface of the planet. Long-term hybrid biological and physical/chemical LSS could provide environment supporting human health and well being. Robot-manipulators operating in "presence effect" and "master-slave" mode exclude necessity of human landing on Martian surface decreasing the level of risk for crew. Since crewmen would not have direct contact with the Martian environment then the problem of mutual biological protection is essentially reduced. Lightweight robot-manipulators, without heavy life support systems and without the necessity of returning to the mother vessel, could be sent as scouts to different places on the planet surface, scanning the most interesting for exobiological research site. Some approximate estimations of electric spacecraft, long-term hybrid LSS, radiation protection and mission parameters are conducted and discussed. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  11. Medicinal plants for the treatment of obesity: ethnopharmacological approach and chemical and biological studies

    PubMed Central

    de Freitas Junior, Luciano Mamede; de Almeida Jr, Eduardo B

    2017-01-01

    Obesity is a global epidemic that has shown a steady increase in morbimortality indicators; it is considered a social problem and entails serious health risks. One of the alternatives in the treatment of obesity is the traditional use of medicinal plants, which supports the research and development of obesity phytotherapy. In this article, we provide information about ethnopharmacological species used to treat obesity, through an electronic search of the periodical databases Web of Science, Scopus, PubMed and Scielo, considering the period 1996-2015 and using the descriptors “plants for obesity”, “ethnopharmacology for obesity” and “anti-obesity plants” in both Portuguese and English. We analyzed and organized data on 76 plant species, cataloged per the taxonomy, geographic distribution, botanical aspects, popular use, and chemical and biological studies of the listed plants. The anti-obesity effect of the cataloged species was reported, describing actions on the delay of fat absorption, suppression of enzymatic activities, mediation of lipid levels and increase of lipolytic effects, attributed mainly to phenolic compounds. Given these findings, ethnopharmacological approaches are relevant scientific tools in the selection of plant species for studies that demonstrate anti-obesity action. Deeper botanical, chemical, pre-clinical and clinical studies are particularly necessary for species that present phenolic compounds in their chemical structure. PMID:28559960

  12. [Effect of trampling disturbance on soil infiltration of biological soil crusts].

    PubMed

    Shi, Ya Fang; Zhao, Yun Ge; Li, Chen Hui; Wang, Shan Shan; Yang, Qiao Yun; Xie, Shen Qi

    2017-10-01

    The effect of trampling disturbance on soil infiltration of biological soil crusts was investigated by using simulated rainfall. The results showed that the trampling disturbance significantly increased soil surface roughness. The increasing extent depended on the disturbance intensity. Soil surface roughness values at 50% disturbance increased by 91% compared with the undisturbed treatment. The runoff was delayed by trampling disturbance. A linear increase in the time of runoff yield was observed along with the increasing disturbance intensity within 20%-50%. The time of runoff yield at 50% disturbance increased by 169.7% compared with the undisturbed treatment. Trampling disturbance increased soil infiltration and consequently decreased the runoff coefficient. The cumulative infiltration amount at 50% disturbance increased by 12.6% compared with the undisturbed treatment. Soil infiltration significant decreased when biocrusts were removed. The cumulative infiltration of the treatment of biocrusts removal decreased by 30.2% compared with the undisturbed treatment. Trampling disturbance did not significantly increase the soil loss when the distur bance intensity was lower than 50%, while the biocrusts removal resulted in 10 times higher in soil erosion modulus. The trampling disturbance of lower than 50% on biocrusts might improve soil infiltration and reduce the risk of runoff, thus might improve the soil moisture without obviously increa sing the soil loss.

  13. Visualizing Protein Interactions and Dynamics: Evolving a Visual Language for Molecular Animation

    PubMed Central

    Jenkinson, Jodie; McGill, Gaël

    2012-01-01

    Undergraduate biology education provides students with a number of learning challenges. Subject areas that are particularly difficult to understand include protein conformational change and stability, diffusion and random molecular motion, and molecular crowding. In this study, we examined the relative effectiveness of three-dimensional visualization techniques for learning about protein conformation and molecular motion in association with a ligand–receptor binding event. Increasingly complex versions of the same binding event were depicted in each of four animated treatments. Students (n = 131) were recruited from the undergraduate biology program at University of Toronto, Mississauga. Visualization media were developed in the Center for Molecular and Cellular Dynamics at Harvard Medical School. Stem cell factor ligand and cKit receptor tyrosine kinase were used as a classical example of a ligand-induced receptor dimerization and activation event. Each group completed a pretest, viewed one of four variants of the animation, and completed a posttest and, at 2 wk following the assessment, a delayed posttest. Overall, the most complex animation was the most effective at fostering students' understanding of the events depicted. These results suggest that, in select learning contexts, increasingly complex representations may be more desirable for conveying the dynamic nature of cell binding events. PMID:22383622

  14. Amphetamine increases schedule-induced drinking reduced by negative punishment procedures.

    PubMed

    Pérez-Padilla, Angeles; Pellón, Ricardo

    2003-05-01

    d-Amphetamine has been reported to increase schedule-induced drinking punished by lick-dependent signalled delays in food delivery. This might reflect a drug-behaviour interaction dependent on the type of punisher, because no such effect has been found when drinking was reduced by lick-contingent electric shocks. However, the anti-punishment effect of amphetamine could be mediated by other behavioural processes, such as a loss of discriminative control or an increase in the value of delayed reinforcers. To test the effects of d-amphetamine on the acquisition and maintenance of schedule-induced drinking reduced by unsignalled delays in food delivery. Rats received 10-s unsignalled delays initiated by each lick after polydipsia was induced by a fixed-time 30-s food reinforcement schedule or from the outset of the experiment. Yoked-control rats received these same delays but independently of their own behaviour. d-Amphetamine (0.1-3.0 mg/kg) was then tested IP. d-Amphetamine dose-dependently increased and then decreased punished schedule-induced drinking. The drug led to dose-dependent reductions when the delays were not contingent or when they were applied from the outset of training. These results support the contention that d-amphetamine has an increasing effect on schedule-induced drinking that has been previously reduced by a negative punishment procedure. This effect cannot be attributed to other potentially involved processes, and therefore support the idea that drug effects on punished behaviour depend on punishment being delays in food or shock deliveries.

  15. The effect of reinforcer magnitude on probability and delay discounting of experienced outcomes in a computer game task in humans.

    PubMed

    Greenhow, Anna K; Hunt, Maree J; Macaskill, Anne C; Harper, David N

    2015-09-01

    Delay and uncertainty of receipt both reduce the subjective value of reinforcers. Delay has a greater impact on the subjective value of smaller reinforcers than of larger ones while the reverse is true for uncertainty. We investigated the effect of reinforcer magnitude on discounting of delayed and uncertain reinforcers using a novel approach: embedding relevant choices within a computer game. Participants made repeated choices between smaller, certain, immediate outcomes and larger, but delayed or uncertain outcomes while experiencing the result of each choice. Participants' choices were generally well described by the hyperbolic discounting function. Smaller numbers of points were discounted more steeply than larger numbers as a function of delay but not probability. The novel experiential choice task described is a promising approach to investigating both delay and probability discounting in humans. © Society for the Experimental Analysis of Behavior.

  16. Firing patterns transition and desynchronization induced by time delay in neural networks

    NASA Astrophysics Data System (ADS)

    Huang, Shoufang; Zhang, Jiqian; Wang, Maosheng; Hu, Chin-Kun

    2018-06-01

    We used the Hindmarsh-Rose (HR) model (Hindmarsh and Rose, 1984) to study the effect of time delay on the transition of firing behaviors and desynchronization in neural networks. As time delay is increased, neural networks exhibit diversity of firing behaviors, including regular spiking or bursting and firing patterns transitions (FPTs). Meanwhile, the desynchronization of firing and unstable bursting with decreasing amplitude in neural system, are also increasingly enhanced with the increase of time delay. Furthermore, we also studied the effect of coupling strength and network randomness on these phenomena. Our results imply that time delays can induce transition and desynchronization of firing behaviors in neural networks. These findings provide new insight into the role of time delay in the firing activities of neural networks, and can help to better understand the firing phenomena in complex systems of neural networks. A possible mechanism in brain that can cause the increase of time delay is discussed.

  17. Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys

    PubMed Central

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2015-01-01

    Opioid abusers discount delayed reinforcers more rapidly than non-users; however, it is unclear whether chronic drug administration or its discontinuation impact discounting. This study examined daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered 1 food pellet immediately; responding on another lever delivered 2 food pellets either immediately or after a delay (30–120 sec) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032–5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e., rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g., decrease in the number of trials completed as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest factors other than, or in addition to, changes in discounting might play a role. PMID:26397762

  18. Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

    PubMed Central

    Piskin, Ahmet; Altunkaynak, Berrin Zühal; Çιtlak, Atilla; Sezgin, Hicabi; Yazιcι, Ozgür; Kaplan, Süleyman

    2013-01-01

    It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed (3 days after injury) neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair. PMID:25206663

  19. Effects of the delay and duration of self-generated wind on behavioral compensation in unilaterally cercus-ablated crickets, Gryllus bimaculatus.

    PubMed

    Takuwa, Hiroyuki; Mori, Daichi; Ozaki, Naoko; Kanou, Masamichi

    2013-05-01

    The effects of the delay and duration of wind self-generated during walking on the compensational recovery of escape direction were investigated in unilaterally cercus-ablated crickets, Gryllus bimaculatus. Artificial self-generated winds (self-stimulations; hereafter, SSts) from a nozzle set in front of a cricket placed on a styrofoam ball for stationary walking were used for training after unilateral cercus ablation. The delay and duration of artificial SSts were separately controlled. When the stimulus duration was fixed to 100 msec, the crickets trained with artificial SSts of 1000 msec delay showed a compensational recovery of the escape direction. However, no such compensational recovery was observed in crickets trained with artificial SSts of 1200, 1500, and 2000 msec delays. The relationship between the delay and duration of artificial SSts for compensational recovery was investigated. An artificial SSt with a longer delay required a longer-duration air current to cause a recovery of the escape direction. In contrast, an artificial SSt with a shorter delay was effective even when the duration was short. On the basis of the results obtained in the present study, we propose a hypothesis to explain the initial step for the compensation, that is, how the delay and duration of SSts are traded in terms of the compensational recovery of the escape direction.

  20. Isolated Lung Perfusion as an Adjuvant Treatment of Colorectal Cancer Lung Metastases: A Preclinical Study in a Pig Model

    PubMed Central

    Pagès, Pierre-Benoit; Facy, Olivier; Mordant, Pierre; Ladoire, Sylvain; Magnin, Guy; Lokiec, Francois; Ghiringhelli, Francois; Bernard, Alain

    2013-01-01

    Background The lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP). We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP. Methods First, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative) and delayed (1 month) tolerance of two concentrations of the molecule administered via ILP was tested on 19 adult pigs using hemodynamic, biological and histological criteria. Results In vitro, gemcitabine (GEM) was the most efficient drug against selected CRC cell lines. In vivo, GEM was administered via ILP at regular (20 µg/ml) or high (100 µg/ml) concentrations. GEM administration was associated with transient and dose-dependant pulmonary vasoconstriction, leading to a voluntary decrease in pump inflow in order to maintain a stable pulmonary artery pressure. After this modulation, ILP using GEM was not associated with any systemic leak, systemic damage, and acute or delayed histological pulmonary toxicity. Pharmacokinetics studies revealed dose-dependant uptake associated with heterogenous distribution of the molecule into the lung parenchyma, and persistent cytotoxicity of venous effluent. Conclusions GEM is effective against CRC cells even after a short exposure. ILP with GEM is a safe and reproducible technique. PMID:23527205

  1. Lethal Forethought: Delayed Reward Discounting Differentiates High- and Low-Lethality Suicide Attempts in Old Age

    PubMed Central

    Dombrovski, Alexandre Y.; Szanto, Katalin; Siegle, Greg J.; Wallace, Meredith L.; Forman, Steven D.; Sahakian, Barbara; Reynolds, Charles F.; Clark, Luke

    2011-01-01

    Background The decision to commit suicide may be impulsive, but lethal suicidal acts often involve planning and forethought. People who attempt suicide make disadvantageous decisions in other contexts, but nothing is known about the way they decide about the future. Can the willingness to postpone future gratification differentiate between individuals prone to serious, premeditated and less serious, unplanned suicidal acts? Methods Four groups of depressed participants aged 60+ made choices between smaller immediate and larger delayed monetary rewards: 15 who made high-lethality suicide attempts, 14 who made low-lethality suicide attempts, 12 who seriously contemplated suicide, and 42 people with depression but no history of suicidal thoughts. The reference group was 31 psychiatrically healthy elders. Results Individuals who had made low-lethality attempts displayed an exaggerated preference for immediate rewards compared to non-suicidal depressed and healthy controls. Those who had carried out high-lethality suicide attempts were more willing to delay future rewards, compared to low-lethality attempters. Better planned suicide attempts were also associated with willingness to wait for larger rewards. These effects were unchanged after accounting for education, global cognitive function, substance use disorders, psychotropic medications, and possible brain injury from attempts. Discount rates were correlated with having debt but were not significantly associated with income, hopelessness, depressive severity, premorbid IQ, age at first attempt, or choice of violent means. Conclusions While clinicians often focus on impulsivity in patients at risk for suicide, these data suggest that identifying biological characteristics and treatments for non-impulsive suicidal older people may be even more important. PMID:21329911

  2. Feasibility of retinoids for the treatment of emphysema study.

    PubMed

    Roth, Michael D; Connett, John E; D'Armiento, Jeanine M; Foronjy, Robert F; Friedman, Paul J; Goldin, Jonathan G; Louis, Thomas A; Mao, Jenny T; Muindi, Josephia R; O'Connor, George T; Ramsdell, Joe W; Ries, Andrew L; Scharf, Steven M; Schluger, Neil W; Sciurba, Frank C; Skeans, Melissa A; Walter, Robert E; Wendt, Christine H; Wise, Robert A

    2006-11-01

    Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema. One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels <- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period. No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild. No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.

  3. Individual Differences in Sleep Timing Relate to Melanopsin-Based Phototransduction in Healthy Adolescents and Young Adults.

    PubMed

    van der Meijden, Wisse P; Van Someren, Jamie L; Te Lindert, Bart H W; Bruijel, Jessica; van Oosterhout, Floor; Coppens, Joris E; Kalsbeek, Andries; Cajochen, Christian; Bourgin, Patrice; Van Someren, Eus J W

    2016-06-01

    Individual differences in sleep timing have been widely recognized and are of particular relevance in adolescents and young adults who often show mild to severely delayed sleep. The biological mechanisms underlying the between-subject variance remain to be determined. Recent human genetics studies showed an association between sleep timing and melanopsin gene variation, but support for functional effects on downstream pathways and behavior was not demonstrated before. We therefore investigated the association between the autonomic (i.e., pupil diameter) and behavioral (i.e., sleep timing) readouts of two different downstream brain areas, both affected by the same melanopsin-dependent retinal phototransduction: the olivary pretectal nucleus (OPN) and the suprachiasmatic nucleus (SCN). Our study population included 71 healthy individuals within an age range with known vulnerability to a delayed sleep phase (16.8-35.7 y, 37 males, 34 females). Pupillometry was performed to estimate functionality of the intrinsic melanopsin-signaling circuitry based on the OPN-mediated post-illumination pupil response (PIPR) to blue light. Sleep timing was quantified by estimating the SCN-mediated mid-sleep timing in three different ways in parallel: using a chronotype questionnaire, a sleep diary, and actigraphy. All three measures consistently showed that those individuals with a later mid-sleep timing had a more pronounced PIPR (0.03 < P < 0.05), indicating a stronger blue-light responsiveness of the intrinsic melanopsin-based phototransduction circuitry. Trait-like individual differences in the melanopsin phototransduction circuitry contribute to individual differences in sleep timing. Blue light-sensitive young individuals are more prone to delayed sleep. © 2016 Associated Professional Sleep Societies, LLC.

  4. Impulsive choice and pre-exposure to delays: iv. effects of delay- and immediacy-exposure training relative to maturational changes in impulsivity.

    PubMed

    Renee Renda, C; Rung, Jillian M; Hinnenkamp, Jay E; Lenzini, Stephanie N; Madden, Gregory J

    2018-04-23

    Impulsive choice describes preference for smaller, sooner rewards over larger, later rewards. Excessive delay discounting (i.e., rapid devaluation of delayed rewards) underlies some impulsive choices, and is observed in many maladaptive behaviors (e.g., substance abuse, gambling). Interventions designed to reduce delay discounting may provide therapeutic gains. One such intervention provides rats with extended training with delayed reinforcers. When compared to a group given extended training with immediate reinforcers, delay-exposed rats make significantly fewer impulsive choices. To what extent is this difference due to delay-exposure training shifting preference toward self-control or immediacy-exposure training (the putative control group) shifting preference toward impulsivity? The current study compared the effects of delay- and immediacy-exposure training to a no-training control group and evaluated within-subject changes in impulsive choice across 51 male Wistar rats. Delay-exposed rats made significantly fewer impulsive choices than immediacy-exposed and control rats. Between-group differences in impulsive choice were not observed in the latter two groups. While delay-exposed rats showed large, significant pre- to posttraining reductions in impulsive choice, immediacy-exposed and control rats showed small reductions in impulsive choice. These results suggest that extended training with delayed reinforcers reduces impulsive choice, and that extended training with immediate reinforcers does not increase impulsive choice. © 2018 Society for the Experimental Analysis of Behavior.

  5. Cost-effectiveness of early compared to late inhaled nitric oxide therapy in near-term infants.

    PubMed

    Armstrong, Edward P; Dhanda, Rahul

    2010-12-01

    The purpose of this study was to determine the cost-effectiveness of early versus late inhaled nitric oxide (INO) therapy in neonates with hypoxic respiratory failure initially managed on conventional mechanical ventilation. A decision analytic model was created to compare the use of early INO compared to delayed INO for neonates receiving mechanical ventilation due to hypoxic respiratory failure. The perspective of the model was that of a hospital. Patients who did not respond to either early or delayed INO were assumed to have been treated with extracorporeal membrane oxygenation (ECMO). The effectiveness measure was defined as a neonate discharged alive without requiring ECMO therapy. A Monte Carlo simulation of 10,000 cases was conducted using first and second order probabilistic analysis. Direct medical costs that differed between early versus delayed INO treatment were estimated until time to hospital discharge. The proportion of successfully treated patients and costs were determined from the probabilistic sensitivity analysis. The mean (± SD) effectiveness rate for early INO was 0.75 (± 0.08) and 0.61 (± 0.09) for delayed INO. The mean hospital cost for early INO was $21,462 (± $2695) and $27,226 (± $3532) for delayed INO. In 87% of scenarios, early INO dominated delayed INO by being both more effective and less costly. The acceptability curve between products demonstrated that early INO had over a 90% probability of being the most cost-effective treatment across a wide range of willingness to pay values. This analysis indicated that early INO therapy was cost-effective in neonates with hypoxic respiratory failure requiring mechanical ventilation compared to delayed INO by reducing the probability of developing severe hypoxic respiratory failure. There was a 90% or higher probability that early INO was more cost-effective than delayed INO across a wide range of willingness to pay values in this analysis.

  6. Monostable traveling waves for a time-periodic and delayed nonlocal reaction-diffusion equation

    NASA Astrophysics Data System (ADS)

    Li, Panxiao; Wu, Shi-Liang

    2018-04-01

    This paper is concerned with a time-periodic and delayed nonlocal reaction-diffusion population model with monostable nonlinearity. Under quasi-monotone or non-quasi-monotone assumptions, it is known that there exists a critical wave speed c_*>0 such that a periodic traveling wave exists if and only if the wave speed is above c_*. In this paper, we first prove the uniqueness of non-critical periodic traveling waves regardless of whether the model is quasi-monotone or not. Further, in the quasi-monotone case, we establish the exponential stability of non-critical periodic traveling fronts. Finally, we illustrate the main results by discussing two types of death and birth functions arising from population biology.

  7. Transport of gadolinium- and arsenic-based pharmaceuticals in saturated soil under various redox conditions.

    PubMed

    Menahem, Adi; Dror, Ishai; Berkowitz, Brian

    2016-02-01

    The release of pharmaceuticals and personal care products (PPCPs) to the soil-water environment necessitates understanding of PPCP transport behavior under conditions that account for dynamic flow and varying redox states. This study investigates the transport of two organometallic PPCPs, Gd-DTPA and roxarsone (arsenic compound) and their metal salts (Gd(NO3)3, AsNaO2); Gd-DTPA is used widely as a contrasting agent for MRI, while roxarsone is applied extensively as a food additive in the broiler poultry industry. Here, we present column experiments using sand and Mediterranean red sandy clay soil, performed under several redox conditions. The metal salts were almost completely immobile. In contrast, transport of Gd-DTPA and roxarsone was affected by the soil type. Roxarsone was also affected by the different redox conditions, showing delayed breakthrough curves as the redox potential became more negative due to biological activity (chemically-strong reducing conditions did not affect the transport). Mechanisms that include adsorptive retardation for aerobic and nitrate-reducing conditions, and non-adsorptive retardation for iron-reducing, sulfate-reducing and biologically-strong reducing conditions, are suggested to explain the roxarsone behavior. Gd-DTPA is found to be a stable complex, with potential for high mobility in groundwater systems, whereas roxarsone transport through groundwater systems is affected by redox environments, demonstrating high mobility under aerobic and nitrate-reducing conditions and delayed transport under iron-reducing, sulfate-reducing and biologically-strong reducing conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Regulation of blood-testis barrier by actin binding proteins and protein kinases

    PubMed Central

    Li, Nan; Tang, Elizabeth I.; Cheng, C. Yan

    2016-01-01

    The blood-testis barrier (BTB) is an important ultrastructure in the testis since the onset of spermatogenesis coincides with the establishment of a functional barrier in rodents and humans. It is also noted that a delay in the assembly of a functional BTB following treatment of neonatal rats with drugs such as diethylstilbestrol or adjudin also delays the first wave of spermiation. While the BTB is one of the tightest blood-tissue barriers, it undergoes extensive remodeling, in particular at stage VIII of the epithelial cycle to facilitate the transport of preleptotene spermatocytes connected in clones across the immunological barrier. Without this timely transport of preleptotene spermatocytes derived from type B spermatogonia, meiosis will be arrested, causing aspermatogenesis. Yet the biology and regulation of the BTB remains largely unexplored since the morphological studies in the 1970s. Recent studies, however, have shed new light on the biology of the BTB. Herein, we critically evaluate some of these findings, illustrating that the Sertoli cell BTB is regulated by actin binding proteins (ABPs), likely supported by non-receptor protein kinases, to modulate the organization of actin microfilament bundles at the site. Furthermore, microtubule (MT)-based cytoskeleton is also working in concert with the actin-based cytoskeleton to confer BTB dynamics. This timely review provides an update on the unique biology and regulation of the BTB based on the latest findings in the field, focusing on the role of ABPs and non-receptor protein kinases. PMID:26628556

  9. Predicting flight delay based on multiple linear regression

    NASA Astrophysics Data System (ADS)

    Ding, Yi

    2017-08-01

    Delay of flight has been regarded as one of the toughest difficulties in aviation control. How to establish an effective model to handle the delay prediction problem is a significant work. To solve the problem that the flight delay is difficult to predict, this study proposes a method to model the arriving flights and a multiple linear regression algorithm to predict delay, comparing with Naive-Bayes and C4.5 approach. Experiments based on a realistic dataset of domestic airports show that the accuracy of the proposed model approximates 80%, which is further improved than the Naive-Bayes and C4.5 approach approaches. The result testing shows that this method is convenient for calculation, and also can predict the flight delays effectively. It can provide decision basis for airport authorities.

  10. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

    PubMed Central

    Azzam, Edouard I.; Jay-Gerin, Jean-Paul; Pain, Debkumar

    2013-01-01

    Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes. PMID:22182453

  11. Mean, covariance, and effective dimension of stochastic distributed delay dynamics

    NASA Astrophysics Data System (ADS)

    René, Alexandre; Longtin, André

    2017-11-01

    Dynamical models are often required to incorporate both delays and noise. However, the inherently infinite-dimensional nature of delay equations makes formal solutions to stochastic delay differential equations (SDDEs) challenging. Here, we present an approach, similar in spirit to the analysis of functional differential equations, but based on finite-dimensional matrix operators. This results in a method for obtaining both transient and stationary solutions that is directly amenable to computation, and applicable to first order differential systems with either discrete or distributed delays. With fewer assumptions on the system's parameters than other current solution methods and no need to be near a bifurcation, we decompose the solution to a linear SDDE with arbitrary distributed delays into natural modes, in effect the eigenfunctions of the differential operator, and show that relatively few modes can suffice to approximate the probability density of solutions. Thus, we are led to conclude that noise makes these SDDEs effectively low dimensional, which opens the possibility of practical definitions of probability densities over their solution space.

  12. The use of delay in multitrack production

    NASA Astrophysics Data System (ADS)

    Case, Alexander U.

    2003-04-01

    Delay, inevitable whenever sound propagates through space, is too often the bane of the acoustician's practice. An audible echo generally relegates a music performance hall-no matter how beautiful it otherwise might sound-to the lowest status. Multitrack music production on the other hand, with its aggressive use of overdubbing, editing, and signal processing, is not bound by those rules of time and space which determine the sound of a hall. In the recording studio, where music is synthesized for playback over loudspeakers, the delay is employed as a powerful, multipurpose tool. It is not avoided. It is in fact embraced. Echoes are used on purpose, strategically, to enhance the loudspeaker listening experience. Moreover, the humble delay is the basis for many nonecho effects. Flanging, chorus, and pitch shifting are delay-based effects regularly used in audio engineering practice. This paper discusses some of the more common delay-based effects, reviewing their technical structure, the psychoacoustic motivation behind them, and the musical value they create.

  13. Effect of guar gum on hunger and satiety after meals of differing fat content: relationship with gastric emptying.

    PubMed

    French, S J; Read, N W

    1994-01-01

    To determine whether the satiating effects of fiber are due to delaying gastric emptying or slowing absorption of meals, 3% guar gum was added to high- and low-fat soups and gastric emptying rate, hunger, and satiety were measured in eight male volunteers. Guar gum delayed the emptying of the low-fat soup but the small delays in the return of hunger and decline of fullness were significantly correlated with the gastric emptying, suggesting mediation by gastric mechanoreceptors. The high-fat soup also emptied more slowly but this had no effect on the return of hunger or the decline in fullness. The delays in the return of hunger and decline of fullness were far greater when guar gum was added to the fatty soup; these delays were not correlated with the small additional delay in gastric emptying. This is more compatible with slowed absorption and prolonged contact of nutrients with intestinal chemoreceptors.

  14. Delay or probability discounting in a model of impulsive behavior: effect of alcohol.

    PubMed Central

    Richards, J B; Zhang, L; Mitchell, S H; de Wit, H

    1999-01-01

    Little is known about the acute effects of drugs of abuse on impulsivity and self-control. In this study, impulsivity was assessed in humans using a computer task that measured delay and probability discounting. Discounting describes how much the value of a reward (or punisher) is decreased when its occurrence is either delayed or uncertain. Twenty-four healthy adult volunteers ingested a moderate dose of ethanol (0.5 or 0.8 g/kg ethanol: n = 12 at each dose) or placebo before completing the discounting task. In the task the participants were given a series of choices between a small, immediate, certain amount of money and $10 that was either delayed (0, 2, 30, 180, or 365 days) or probabilistic (i.e., certainty of receipt was 1.0, .9, .75, .5, or .25). The point at which each individual was indifferent between the smaller immediate or certain reward and the $10 delayed or probabilistic reward was identified using an adjusting-amount procedure. The results indicated that (a) delay and probability discounting were well described by a hyperbolic function; (b) delay and probability discounting were positively correlated within subjects; (c) delay and probability discounting were moderately correlated with personality measures of impulsivity; and (d) alcohol had no effect on discounting. PMID:10220927

  15. Memory of Gender and Gait Direction from Biological Motion: Gender Fades Away but Directions Stay

    ERIC Educational Resources Information Center

    Poom, Leo

    2012-01-01

    The delayed discrimination methodology has been used to demonstrate a high-fidelity nondecaying visual short-term memory (VSTM) for so-called preattentive basic features. In the current Study, I show that the nondecaying high VSTM precision is not restricted to basic features by using the same method to measure memory precision for gait direction…

  16. Linking Assessment and Intervention for Developmental/Functional Outcomes of Premature, Low-Birth-Weight Children

    ERIC Educational Resources Information Center

    Xu, Yaoying; Filler, John W.

    2005-01-01

    Prematurity and low birth weight (LBW) are two major biological factors that put infants and young children at high risk for developmental delays or disabilities. While survival rates for premature and LBW children have improved, incidence figures have changed little over the past 20 years; in fact, the incidence of LBW has increased. Although the…

  17. Lifespan Changes in Working Memory in Fragile X Premutation Males

    ERIC Educational Resources Information Center

    Cornish, Kim M.; Kogan, Cary S.; Li, Lexin; Turk, Jeremy; Jacquemont, Sebastien; Hagerman, Randi J.

    2009-01-01

    Fragile X syndrome is the world's most common hereditary cause of developmental delay in males and is now well characterized at the biological, brain and cognitive levels. The disorder is caused by the silencing of a single gene on the X chromosome, the "FMR1" gene. The premutation (carrier) status, however, is less well documented but has an…

  18. Starlings uphold principles of economic rationality for delay and probability of reward.

    PubMed

    Monteiro, Tiago; Vasconcelos, Marco; Kacelnik, Alex

    2013-04-07

    Rationality principles are the bedrock of normative theories of decision-making in biology and microeconomics, but whereas in microeconomics, consistent choice underlies the notion of utility; in biology, the assumption of consistent selective pressures justifies modelling decision mechanisms as if they were designed to maximize fitness. In either case, violations of consistency contradict expectations and attract theoretical interest. Reported violations of rationality in non-humans include intransitivity (i.e. circular preferences) and lack of independence of irrelevant alternatives (changes in relative preference between options when embedded in different choice sets), but the extent to which these observations truly represent breaches of rationality is debatable. We tested both principles with starlings (Sturnus vulgaris), training subjects either with five options differing in food delay (exp. 1) or with six options differing in reward probability (exp. 2), before letting them choose repeatedly one option out of several binary and trinary sets of options. The starlings conformed to economic rationality on both tests, showing strong stochastic transitivity and no violation of the independence principle. These results endorse the rational choice and optimality approaches used in behavioural ecology, and highlight the need for functional and mechanistic enquiring when apparent violations of such principles are observed.

  19. Language acquisition with limited input: Romanian institution and foster care.

    PubMed

    Windsor, Jennifer; Glaze, Leslie E; Koga, Sebastian F

    2007-10-01

    To provide the first detailed information about native language abilities of children who are or had been institutionalized. The language of ten 30-month-old children raised in Romanian orphanages was compared with that of 30 chronological-age-matched peers: 10 children who had moved recently from orphanages to foster care, 10 children in foster families for at least 1 year, and 10 children raised in their biological families. Ten language measures were obtained from communication during play and from parent/caregiver report. Children who were institutionalized and children in foster care for a brief time showed substantial language delays, with some of these children not yet producing intelligible words. Children in foster care for at least 1 year approximated the expressive output and receptive language of children who had never been institutionalized; however, they showed lower expressive grammatical abilities. Within the group of children who were institutionalized, the presence of a preferred caregiver and a measure of development, greater height, were associated with greater language output. Although children in orphanages produced fewer complex forms than children in biological families, there were no systematic qualitative differences in language structure across groups. Foster care facilitated language growth after substantial language delays associated with institutionalization.

  20. Starlings uphold principles of economic rationality for delay and probability of reward

    PubMed Central

    Monteiro, Tiago; Vasconcelos, Marco; Kacelnik, Alex

    2013-01-01

    Rationality principles are the bedrock of normative theories of decision-making in biology and microeconomics, but whereas in microeconomics, consistent choice underlies the notion of utility; in biology, the assumption of consistent selective pressures justifies modelling decision mechanisms as if they were designed to maximize fitness. In either case, violations of consistency contradict expectations and attract theoretical interest. Reported violations of rationality in non-humans include intransitivity (i.e. circular preferences) and lack of independence of irrelevant alternatives (changes in relative preference between options when embedded in different choice sets), but the extent to which these observations truly represent breaches of rationality is debatable. We tested both principles with starlings (Sturnus vulgaris), training subjects either with five options differing in food delay (exp. 1) or with six options differing in reward probability (exp. 2), before letting them choose repeatedly one option out of several binary and trinary sets of options. The starlings conformed to economic rationality on both tests, showing strong stochastic transitivity and no violation of the independence principle. These results endorse the rational choice and optimality approaches used in behavioural ecology, and highlight the need for functional and mechanistic enquiring when apparent violations of such principles are observed. PMID:23390098

  1. Multispectral analog-mean-delay fluorescence lifetime imaging combined with optical coherence tomography

    PubMed Central

    Nam, Hyeong Soo; Kang, Woo Jae; Lee, Min Woo; Song, Joon Woo; Kim, Jin Won; Oh, Wang-Yuhl; Yoo, Hongki

    2018-01-01

    The pathophysiological progression of chronic diseases, including atherosclerosis and cancer, is closely related to compositional changes in biological tissues containing endogenous fluorophores such as collagen, elastin, and NADH, which exhibit strong autofluorescence under ultraviolet excitation. Fluorescence lifetime imaging (FLIm) provides robust detection of the compositional changes by measuring fluorescence lifetime, which is an inherent property of a fluorophore. In this paper, we present a dual-modality system combining a multispectral analog-mean-delay (AMD) FLIm and a high-speed swept-source optical coherence tomography (OCT) to simultaneously visualize the cross-sectional morphology and biochemical compositional information of a biological tissue. Experiments using standard fluorescent solutions showed that the fluorescence lifetime could be measured with a precision of less than 40 psec using the multispectral AMD-FLIm without averaging. In addition, we performed ex vivo imaging on rabbit iliac normal-looking and atherosclerotic specimens to demonstrate the feasibility of the combined FLIm-OCT system for atherosclerosis imaging. We expect that the combined FLIm-OCT will be a promising next-generation imaging technique for diagnosing atherosclerosis and cancer due to the advantages of the proposed label-free high-precision multispectral lifetime measurement. PMID:29675330

  2. The Effects of Inflation and Interest Rates on Delay Discounting in Human Behavior

    ERIC Educational Resources Information Center

    Kawashima, Kentaro

    2006-01-01

    Interest and inflation rates may be major determinants of delay discounting, but these variables have not been controlled in past experiments because they depend on macroeconomic conditions. This study uses a computer game-like task to investigate the effects of inflation rates on people's subjective valuation of delayed rewards. During the task,…

  3. Reversing the Signaled Magnitude Effect in Delayed Matching to Sample: Delay-Specific Remembering?

    ERIC Educational Resources Information Center

    White, K. Geoffrey; Brown, Glenn S.

    2011-01-01

    Pigeons performed a delayed matching-to-sample task in which large or small reinforcers for correct remembering were signaled during the retention interval. Accuracy was low when small reinforcers were signaled, and high when large reinforcers were signaled (the signaled magnitude effect). When the reinforcer-size cue was switched from small to…

  4. The Effects of Time Delay and Increasing Prompt Hierarchy Strategies on the Acquisition of Purchasing Skills by Students with Severe Handicaps.

    ERIC Educational Resources Information Center

    McDonnell, John

    1987-01-01

    Two teaching strategies (constant time delay and increasing prompt hierarchy assistance) were compared in teaching four severely handicapped high school students to purchase snack items at a convenience store and fast food restaurant. Results indicated the time delay procedure was more effective. (DB)

  5. The Effect of D-Cycloserine on Immediate vs. Delayed Extinction of Learned Fear

    ERIC Educational Resources Information Center

    Langton, Julia M.; Richardson, Rick

    2010-01-01

    We compared the effect of D-cycloserine (DCS) on immediate (10 min after conditioning) and delayed (24 h after conditioning) extinction of learned fear in rats. DCS facilitated both immediate and delayed extinction when the drug was administered after extinction training. However, DCS did not facilitate immediate extinction when administered prior…

  6. Caregivers as Teachers: Using Constant Time Delay To Teach Adults How To Use Constant Time Delay.

    ERIC Educational Resources Information Center

    Wall, Maureen E.; Gast, David L.

    1997-01-01

    A study involving four caregivers evaluated the effectiveness of a systematic instructional procedure known as constant time delay (CTD) in teaching caregivers how to use CTD to teach their adolescent or adult children, siblings, or clients with disabilities, response chain skills. Results found the procedure to be effective. (CR)

  7. The Effects of Four-Hour Delay of PUnishment under Two Conditions of Verbal Instruction

    ERIC Educational Resources Information Center

    Verna, Gary B.

    1977-01-01

    The effects of 4-hour delay of punishment (withdrawal of reward) on response inhibition was studied with 24 fourth-grade children. Results showed that verbal expression of the punishment contingency allows the 10-year-old child to profit from 4-hour delayed punishment as much as immediate punishment. (Author/JMB)

  8. Mesos-scale modeling of irradiation in pressurized water reactor concrete biological shields

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

    Le Pape, Yann; Huang, Hai

    Neutron irradiation exposure causes aggregate expansion, namely radiation-induced volumetric expansion (RIVE). The structural significance of RIVE on a portion of a prototypical pressurized water reactor (PWR) concrete biological shield (CBS) is investigated by using a meso- scale nonlinear concrete model with inputs from an irradiation transport code and a coupled moisture transport-heat transfer code. RIVE-induced severe cracking onset appears to be triggered by the ini- tial shrinkage-induced cracking and propagates to a depth of > 10 cm at extended operation of 80 years. Relaxation of the cement paste stresses results in delaying the crack propagation by about 10 years.

  9. A modeling study on the influence of blood flow regulation on skin temperature pulsations

    NASA Astrophysics Data System (ADS)

    Tang, Yanliang; Mizeva, Irina; He, Ying

    2017-04-01

    Nowadays together with known optic techniques of microcirculation blood flow monitoring, skin temperature measurements are developed as well. In this paper, a simple one-dimensional bioheat transfer model was developed to analyse the heat wave transport in biological tissue, where an arteriole vessel with pulsatile blood is located. The simulated results show that the skin temperature oscillation amplitudes attenuate with the increase of blood flow oscillation frequency which gives the same tendency as that in the experiments. The parameter analyses further show that the amplitude of oscillation is also influenced by oscillation amplitude of blood and effective thermal conductivity. When oscillation amplitude of blood flow and effective thermal conductivity increase, the amplitude of skin temperature oscillation increases nonlinearly. Variation of effective thermal convective influence to the time delay of the thermal wave on the skin surface and distort it. Combination of two measurement techniques: one for estimation blood flow oscillations in the microvessels and other to the skin temperature measurement can produce additional information about the skin properties.

  10. [Blood fluidity and omega-3 fatty acids].

    PubMed

    Ernst, E

    1991-01-01

    Omega-3 fatty acids are highly unsaturated fatty acids with a first (counted from the methyl end) double bound at the third carbon atom. Their biological effects--mainly changes of blood lipids and of the eicosanoid pattern--are due to a competitive inhibition of omega-6 fatty acids within the prostaglandin metabolism. Hemorheological effects have also been described repeatedly. A placebo-controlled, double blind study shows that red cell deformability is raised and blood viscosity decreased by omega-3 fatty acids in stepwise increasing doses. When the dose is further increased there is a drop of plasma viscosity and red cell aggregation. An open study with hyperlipoproteinemic patients confirms these effects: After 21 days of 8 capsules Ameu per day there is a significant reduction of plasma viscosity. After 56 days treatment (same dosage) blood viscosity drops and red cell deformability increases significantly. At present the evidence is growing to suggest that omega-3 fatty acids can delay atherogenesis. The above data allow the hypothesis that hemorheology may be involved in this.

  11. Mechanistic insights into the effect of nanoparticles on zebrafish hatch.

    PubMed

    Ong, Kimberly Jessica; Zhao, Xinxin; Thistle, Maria E; Maccormack, Tyson J; Clark, Rhett J; Ma, Guibin; Martinez-Rubi, Yadienka; Simard, Benoit; Loo, Joachim Say Chye; Veinot, Jonathan G C; Goss, Greg G

    2014-05-01

    Aquatic organisms are susceptible to waterborne nanoparticles (NP) and there is only limited understanding of the mechanisms by which these emerging contaminants may affect biological processes. This study used silicon (nSi), cadmium selenide (nCdSe), silver (nAg) and zinc NPs (nZnO) as well as single-walled carbon nanotubes (SWCNT) to assess NP effects on zebrafish (Danio rerio) hatch. Exposure of 10 mg/L nAg and nCdSe delayed zebrafish hatch and 100 mg/L of nCdSe as well as 10 and 100 mg/L of uncoated nZnO completely inhibited hatch and the embryos died within the chorion. Both the morphology and the movement of the embryos were not affected, and it was determined that the main mechanism of hatch inhibition by NPs is likely through the interaction of NPs with the zebrafish hatching enzyme. Furthermore, it was concluded that the observed effects arose from the NPs themselves and not their dissolved metal components.

  12. Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies.

    PubMed

    Pérez-Sánchez, Almudena; Barrajón-Catalán, Enrique; Herranz-López, María; Micol, Vicente

    2018-03-24

    The skin is the body's largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

  13. Sodium benzoate induced developmental defects, oxidative stress and anxiety-like behaviour in zebrafish larva.

    PubMed

    Gaur, Himanshu; Purushothaman, Srinithi; Pullaguri, Narasimha; Bhargava, Yogesh; Bhargava, Anamika

    2018-07-20

    Sodium benzoate (SB) is a common food preservative. Its FDA described safety limit is 1000 ppm. Lately, increased use of SB has prompted investigations regarding its effects on biological systems. Data regarding toxicity of SB is divergent and controversial with studies reporting both harmful and beneficial effects. Therefore, we did a systematic dose dependent toxicity study of SB using zebrafish vertebrate animal model. We also investigated oxidative stress and anxiety-like behaviour in zebrafish larva treated with SB. Our results indicate that SB induced developmental (delayed hatching), morphological (pericardial edema, yolk sac edema and tail bending), biochemical (oxidative stress) and behavioural (anxiety-like behaviour) abnormalities in developing zebrafish larva. LC 50 of SB induced toxicity was approximately 400 ppm after 48 h of SB exposure. Our study strongly supports its harmful effects on vertebrates at increasing doses. Thus, we suggest caution in the excessive use of this preservative in processed and convenience foods. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Acute ethanol effects on neural encoding of reward size and delay in the nucleus accumbens

    PubMed Central

    Gutman, Andrea L.

    2016-01-01

    Acute ethanol administration can cause impulsivity, resulting in increased preference for immediately available rewards over delayed but more valuable alternatives. The manner in which reward size and delay are represented in neural firing is not fully understood, and very little is known about ethanol effects on this encoding. To address this issue, we used in vivo electrophysiology to characterize neural firing in the core of the nucleus accumbens (NAcc) in rats responding for rewards that varied in size or delay after vehicle or ethanol administration. The NAcc is a central element in the circuit that governs decision-making and importantly, promotes choice of delayed rewards. We found that NAcc firing in response to reward-predictive cues encoded anticipated reward value after vehicle administration, but ethanol administration disrupted this encoding, resulting in a loss of discrimination between immediate and delayed rewards in cue-evoked neural responses. In addition, NAcc firing occurring at the time of the operant response (lever pressing) was inversely correlated with behavioral response latency, such that increased firing rates were associated with decreased latencies to lever press. Ethanol administration selectively attenuated this lever press-evoked firing when delayed but not immediate rewards were expected. These effects on neural firing were accompanied by increased behavioral latencies to respond for delayed rewards. Our results suggest that ethanol effects on NAcc cue- and lever press-evoked encoding may contribute to ethanol-induced impulsivity. PMID:27169507

  15. Delay-dependent coupling for a multi-agent LTI consensus system with inter-agent delays

    NASA Astrophysics Data System (ADS)

    Qiao, Wei; Sipahi, Rifat

    2014-01-01

    Delay-dependent coupling (DDC) is considered in this paper in a broadly studied linear time-invariant multi-agent consensus system in which agents communicate with each other under homogeneous delays, while attempting to reach consensus. The coupling among the agents is designed here as an explicit parameter of this delay, allowing couplings to autonomously adapt based on the delay value, and in order to guarantee stability and a certain degree of robustness in the network despite the destabilizing effect of delay. Design procedures, analysis of convergence speed of consensus, comprehensive numerical studies for the case of time-varying delay, and limitations are presented.

  16. Effect of metrology time delay on overlay APC

    NASA Astrophysics Data System (ADS)

    Carlson, Alan; DiBiase, Debra

    2002-07-01

    The run-to-run control strategy of lithography APC is primarily composed of a feedback loop as shown in the diagram below. It is known that the insertion of a time delay in a feedback loop can cause degradation in control performance and could even cause a stable system to become unstable, if the time delay becomes sufficiently large. Many proponents of integrated metrology methods have cited the damage caused by metrology time delays as the primary justification for moving from a stand-alone to integrated metrology. While there is little dispute over the qualitative form of this argument, there has been very light published about the quantitative effects under real fab conditions - precisely how much control is lost due to these time delays. Another issue regarding time delays is that the length of these delays is not typically fixed - they vary from lot to lot and in some cases this variance can be large - from one hour on the short side to over 32 hours on the long side. Concern has been expressed that the variability in metrology time delays can cause undesirable dynamics in feedback loops that make it difficult to optimize feedback filters and gains and at worst could drive a system unstable. By using data from numerous fabs, spanning many sizes and styles of operation, we have conducted a quantitative study of the time delay effect on overlay run- to-run control. Our analysis resulted in the following conclusions: (1) There is a significant and material relationship between metrology time delay and overlay control under a variety of real world production conditions. (2) The run-to-run controller can be configured to minimize sensitivity to time delay variations. (3) The value of moving to integrated metrology can be quantified.

  17. PARAMETRIC ANALYSIS OF DELAYED PRIMARY AND CONDITIONED REINFORCERS

    PubMed Central

    Leon, Yanerys; Borrero, John C.; DeLeon, Iser G.

    2016-01-01

    We examined the effects of delayed reinforcement on the responding of individuals with intellectual disabilities. Three conditions were evaluated: (a) food reinforcement, (b) token reinforcement with a postsession exchange opportunity, and (c) token reinforcement with a posttrial exchange opportunity. Within each condition, we assessed responding given (a) a no-reinforcement baseline, (b) immediate reinforcement, and (c) delayed reinforcement, in which responses produced a reinforcer after 1 of 6 delays. Results suggest that delayed food produced greater response persistence than did delayed tokens. PMID:27174440

  18. Facilitating tolerance of delayed reinforcement during functional communication training.

    PubMed

    Fisher, W W; Thompson, R H; Hagopian, L P; Bowman, L G; Krug, A

    2000-01-01

    Few clinical investigations have addressed the problem of delayed reinforcement. In this investigation, three individuals whose destructive behavior was maintained by positive reinforcement were treated using functional communication training (FCT) with extinction (EXT). Next, procedures used in the basic literature on delayed reinforcement and self-control (reinforcer delay fading, punishment of impulsive responding, and provision of an alternative activity during reinforcer delay) were used to teach participants to tolerate delayed reinforcement. With the first case, reinforcer delay fading alone was effective at maintaining low rates of destructive behavior while introducing delayed reinforcement. In the second case, the addition of a punishment component reduced destructive behavior to near-zero levels and facilitated reinforcer delay fading. With the third case, reinforcer delay fading was associated with increases in masturbation and head rolling, but prompting and praising the individual for completing work during the delay interval reduced all problem behaviors and facilitated reinforcer delay fading.

  19. Polynucleotide phosphorylase has an impact on cell biology of Campylobacter jejuni

    PubMed Central

    Haddad, Nabila; Tresse, Odile; Rivoal, Katell; Chevret, Didier; Nonglaton, Quentin; Burns, Christopher M.; Prévost, Hervé; Cappelier, Jean M.

    2012-01-01

    Polynucleotide phosphorylase (PNPase), encoded by the pnp gene, is known to degrade mRNA, mediating post-transcriptional regulation and may affect cellular functions. The role of PNPase is pleiotropic. As orthologs of the two major ribonucleases (RNase E and RNase II) of Escherichia coli are missing in the Campylobacter jejuni genome, in the current study the focus has been on the C. jejuni ortholog of PNPase. The effect of PNPase mutation on C. jejuni phenotypes and proteome was investigated. The inactivation of the pnp gene reduced significantly the ability of C. jejuni to adhere and to invade Ht-29 cells. Moreover, the pnp mutant strain exhibited a decrease in C. jejuni swimming ability and chick colonization. To explain effects of PNPase on C. jejuni 81-176 phenotype, the proteome of the pnp mutant and parental strains were compared. Overall, little variation in protein production was observed. Despite the predicted role of PNPase in mRNA regulation, the pnp mutation did not induce profound proteomic changes suggesting that other ribonucleases in C. jejuni might ensure this biological function in the absence of PNPase. Nevertheless, synthesis of proteins which are involved in virulence (LuxS, PEB3), motility (N-acetylneuraminic acid synthetase), stress-response (KatA, DnaK, Hsp90), and translation system (EF-Tu, EF-G) were modified in the pnp mutant strain suggesting a more specific role of PNPase in C. jejuni. In conclusion, PNPase deficiency induces limited but important consequences on C. jejuni biology that could explain swimming limitation, chick colonization delay, and the decrease of cell adhesion/invasion ability. PMID:22919622

  20. Chromatically encoded high-speed photography of cavitation bubble dynamics inside inhomogeneous ophthalmic tissue

    NASA Astrophysics Data System (ADS)

    Tinne, N.; Matthias, B.; Kranert, F.; Wetzel, C.; Krüger, A.; Ripken, T.

    2016-03-01

    The interaction effect of photodisruption, which is used for dissection of biological tissue with fs-laser pulses, has been intensively studied inside water as prevalent sample medium. In this case, the single effect is highly reproducible and, hence, the method of time-resolved photography is sufficiently applicable. In contrast, the reproducibility significantly decreases analyzing more solid and anisotropic media like biological tissue. Therefore, a high-speed photographic approach is necessary in this case. The presented study introduces a novel technique for high-speed photography based on the principle of chromatic encoding. For illumination of the region of interest within the sample medium, the light paths of up to 12 LEDs with various emission wavelengths are overlaid via optical filters. Here, MOSFET-electronics provide a LED flash with a duration <100 ns; the diodes are externally triggered with a distinct delay for every LED. Furthermore, the different illumination wavelengths are chromatically separated again for detection via camera chip. Thus, the experimental setup enables the generation of a time-sequence of <= 12 images of a single cavitation bubble dynamics. In comparison to conventional time-resolved photography, images in sample media like water and HEMA show the significant advantages of this novel illumination technique. In conclusion, the results of this study are of great importance for the fundamental evaluation of the laser-tissue interaction inside anisotropic biological tissue and for the optimization of the surgical process with high-repetition rate fs-lasers. Additionally, this application is also suitable for the investigation of other microscopic, ultra-fast events in transparent inhomogeneous materials.

  1. Causes of and contributors to infant mortality in a rural community of North India: evidence from verbal and social autopsy

    PubMed Central

    Rai, Sanjay Kumar; Kant, Shashi; Srivastava, Rahul; Gupta, Priti; Misra, Puneet; Pandav, Chandrakant Sambhaji; Singh, Arvind Kumar

    2017-01-01

    Objective To identify the medical causes of death and contribution of non-biological factors towards infant mortality by a retrospective analysis of routinely collected data using verbal and social autopsy tools. Setting The study site was Health and Demographic Surveillance System (HDSS), Ballabgarh, North India Participants All infant deaths during the years 2008–2012 were included for verbal autopsy and infant deaths from July 2012 to December 2012 were included for social autopsy. Outcome measures Cause of death ascertained by a validated verbal autopsy tool and level of delay based on a three-delay model using the INDEPTH social autopsy tool were the main outcome measures. The level of delay was defined as follows: level 1, delay in identification of danger signs and decision making to seek care; level 2, delay in reaching a health facility from home; level 3, delay in getting healthcare at the health facility. Results The infant mortality rate during the study period was 46.5/1000 live births. Neonatal deaths contributed to 54.3% of infant deaths and 39% occurred on the first day of life. Birth asphyxia (31.5%) followed by low birth weight (LBW)/prematurity (26.5%) were the most common causes of neonatal death, while infection (57.8%) was the most common cause of post-neonatal death. Care-seeking was delayed among 50% of neonatal deaths and 41.2% of post-neonatal deaths. Delay at level 1 was most common and occurred in 32.4% of neonatal deaths and 29.4% of post-neonatal deaths. Deaths due to LBW/prematurity were mostly followed by delay at level 1. Conclusion A high proportion of preventable infant mortality still exists in an area which is under continuous health and demographic surveillance. There is a need to enhance home-based preventive care to enable the mother to identify and respond to danger signs. Verbal autopsy and social autopsy could be routinely done to guide policy interventions aimed at reduction of infant mortality. PMID:28801384

  2. Myths, models and mitigation of resistance to pesticides.

    PubMed Central

    Hoy, M A

    1998-01-01

    Resistance to pesticides in arthropod pests is a significant economic, ecological and public health problem. Although extensive research has been conducted on diverse aspects of pesticide resistance and we have learned a great deal during the past 50 years, to some degree the discussion about 'resistance management' has been based on 'myths'. One myth involves the belief that we can manage resistance. I will maintain that we can only attempt to mitigate resistance because resistance is a natural evolutionary response to environmental stresses. As such, resistance will remain an ongoing dilemma in pest management and we can only delay the onset of resistance to pesticides. 'Resistance management' models and tactics have been much discussed but have been tested and deployed in practical pest management programmes with only limited success. Yet the myth persists that better models will provide a 'solution' to the problem. The reality is that success in using mitigation models is limited because these models are applied to inappropriate situations in which the critical genetic, ecological, biological or logistic assumptions cannot be met. It is difficult to predict in advance which model is appropriate to a particular situation; if the model assumptions cannot be met, applying the model sometimes can increase the rate of resistance development rather than slow it down. Are there any solutions? I believe we already have one. Unfortunately, it is not a simple or easy one to deploy. It involves employing effective agronomic practices to develop and maintain a healthy crop, monitoring pest densities, evaluating economic injury levels so that pesticides are applied only when necessary, deploying and conserving biological control agents, using host-plant resistance, cultural controls of the pest, biorational pest controls, and genetic control methods. As a part of a truly multi-tactic strategy, it is crucial to evaluate the effect of pesticides on natural enemies in order to preserve them in the cropping system. Sometimes, pesticide-resistant natural enemies are effective components of this resistance mitigation programme. Another name for this resistance mitigation model is integrated pest management (IPM). This complex model was outlined in some detail nearly 40 years ago by V. M. Stern and colleagues. To deploy the IPM resistance mitigation model, we must admit that pest management and resistance mitigation programmes are not sustainable if based on a single-tactic strategy. Delaying resistance, whether to traditional pesticides or to transgenic plants containing toxin genes from Bacillus thuringiensis, will require that we develop multi-tactic pest management programmes that incorporate all appropriate pest management approaches. Because pesticides are limited resources, and their loss can result in significant social and economic costs, they should be reserved for situations where they are truly needed--as tools to subdue an unexpected pest population outbreak. Effective multi-tactic IPM programmes delay resistance (= mitigation) because the number and rates of pesticide applications will be reduced. PMID:10021775

  3. Neighborhood Environment and Cognition in Older Adults: A Systematic Review.

    PubMed

    Besser, Lilah M; McDonald, Noreen C; Song, Yan; Kukull, Walter A; Rodriguez, Daniel A

    2017-08-01

    Some evidence suggests that treating vascular risk factors and performing mentally stimulating activities may delay cognitive impairment onset in older adults. Exposure to a complex neighborhood environment may be one mechanism to help delay cognitive decline. PubMed, Web of Science, and ProQuest Dissertation and Theses Global database were systematically reviewed, identifying 25 studies published from February 1, 1989 to March 5, 2016 (data synthesized, May 3, 2015 to October 7, 2016). The review was restricted to quantitative studies focused on: (1) neighborhood social and built environment and cognition; and (2) community-dwelling adults aged ≥45 years. The majority of studies were cross-sectional, U.S.-based, and found at least one significant association. The diversity of measures and neighborhood definitions limited the synthesis of findings in many instances. Evidence was moderately strong for an association between neighborhood SES and cognition, and modest for associations between neighborhood demographics, design, and destination accessibility and cognition. Most studies examining effect modification found significant associations, with some evidence for effect modification of the neighborhood SES-cognition association by individual-level SES. No studies had low risk of bias and many tested multiple associations that increased the chance of a statistically significant finding. Considering the studies to date, the evidence for an association between neighborhood characteristics and cognition is modest. Future studies should include longitudinal measures of neighborhood characteristics and cognition; examine potential effect modifiers, such as sex and disability; and study mediators that may help elucidate the biological mechanisms linking neighborhood environment and cognition. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Interventions to Slow Aging in Humans: Are We Ready?

    PubMed Central

    Longo, Valter D; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M; Caruso, Calogero; Curiel, Tyler J; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K; Johnson, Thomas E; Kennedy, Brian K; Kenyon, Cynthia; Klein, Samuel; Kopchick, John J; Lepperdinger, Guenter; Madeo, Frank; Mirisola, Mario G; Mitchell, James R; Passarino, Giuseppe; Rudolph, Karl L; Sedivy, John M; Shadel, Gerald S; Sinclair, David A; Spindler, Stephen R; Suh, Yousin; Vijg, Jan; Vinciguerra, Manlio; Fontana, Luigi

    2015-01-01

    The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR–S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting. PMID:25902704

  5. [Effect of pulse magnetic field on distribution of neuronal action potential].

    PubMed

    Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

    2014-08-25

    The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

  6. Accommodating adolescent sleep-wake patterns: the effects of shifting the timing of sleep on training effectiveness.

    PubMed

    Miller, Nita Lewis; Tvaryanas, Anthony P; Shattuck, Lawrence G

    2012-08-01

    This study evaluated the effect of accommodating adolescent sleep-wake patterns by altering the timing of the major sleep period of US Army recruits. The quasi-experimental study compared recruits assigned to one of two training companies: one with a customary sleep regimen (20:30 to 04:30) while the other employed a phase-delayed sleep regimen (23:00 to 07:00), the latter aligning better with biologically driven sleep-wake patterns of adolescents. The study was conducted during Basic Combat Training (BCT) at Fort Leonard Wood, Missouri. TRAINEES: The study included 392 trainees: 209 received the intervention, while 183 composed the Comparison group. Demographic and psychophysiological measures were collected on all trainees. Weekly assessments of subjective fatigue and mood, periodic physical fitness, marksmanship scores, and attrition rates from BCT were studied. Actigraphy was collected on approximately 24% of trainees. Based on actigraphy, trainees on the phase-delayed sleep schedule obtained 31 m more sleep/night than trainees on the customary sleep schedule. The Intervention group reported less total mood disturbance relative to baseline. Improvements in marksmanship correlated positively with average nightly sleep during the preceding week when basic marksmanship skills were taught. No differences were seen in physical fitness or attrition rates. In contrast to the Intervention group, the Comparison group was 2.3 times more likely to experience occupationally significant fatigue and 5.5 times more likely to report poor sleep quality. Accommodating adolescent sleep patterns significantly improves mental health and performance in the training environment.

  7. Novel Nipah virus immune-antagonism strategy revealed by experimental and computational study.

    PubMed

    Seto, Jeremy; Qiao, Liang; Guenzel, Carolin A; Xiao, Sa; Shaw, Megan L; Hayot, Fernand; Sealfon, Stuart C

    2010-11-01

    Nipah virus is an emerging pathogen that causes severe disease in humans. It expresses several antagonist proteins that subvert the immune response and that may contribute to its pathogenicity. Studies of its biology are difficult due to its high pathogenicity and requirement for biosafety level 4 containment. We integrated experimental and computational methods to elucidate the effects of Nipah virus immune antagonists. Individual Nipah virus immune antagonists (phosphoprotein and V and W proteins) were expressed from recombinant Newcastle disease viruses, and the responses of infected human monocyte-derived dendritic cells were determined. We developed an ordinary differential equation model of the infectious process that that produced results with a high degree of correlation with these experimental results. In order to simulate the effects of wild-type virus, the model was extended to incorporate published experimental data on the time trajectories of immune-antagonist production. These data showed that the RNA-editing mechanism utilized by the wild-type Nipah virus to produce immune antagonists leads to a delay in the production of the most effective immune antagonists, V and W. Model simulations indicated that this delay caused a disconnection between attenuation of the antiviral response and suppression of inflammation. While the antiviral cytokines were efficiently suppressed at early time points, some early inflammatory cytokine production occurred, which would be expected to increase vascular permeability and promote virus spread and pathogenesis. These results suggest that Nipah virus has evolved a unique immune-antagonist strategy that benefits from controlled expression of multiple antagonist proteins with various potencies.

  8. Immunomodulatory effects of Agaricus blazei Murill in Balb/cByJ mice.

    PubMed

    Chan, You; Chang, Tim; Chan, Chi Ho; Yeh, Yi Chun; Chen, Chien Wei; Shieh, Biehuoy; Li, Ching

    2007-06-01

    Agaricus blazei Murill has been reported to possess biological effects that include immunomodulatory and tumoricidal activities, but its potential effects have not been systematically analyzed in vivo. We evaluated the immunomodulatory effects of A. blazei in Balb/cByJ mice. 160 male Balb/cByJ mice were divided into four groups and treated with various quantities of intragastric A. blazei extract or distilled water for 8 to 10 weeks. Nine parameters, relating to general immune function or adaptive immunity against immunogen chicken oval albumin, were determined. The results revealed that mice receiving A. blazei extract exhibited significantly greater serum immunoglobulin G levels, increased T-cell numbers in spleen, and elevated phagocytic capability compared with controls. Consumption of A. blazei was also associated with significant increases in oval albumin-specific serum immunoglobulin G level, delayed-type hypersensitivity, splenocyte proliferation rate, and tumor necrosis factor-alpha secretion by splenocytes. Consumption of A. blazei extract was associated with significant enhancement of seven out of nine immune functions tested. We conclude that A. blazei Murill possesses a wide range of immunomodulatory effects in vivo.

  9. Could the RTS,S/AS01 meningitis safety signal really be a protective effect of rabies vaccine?

    PubMed

    Gessner, Bradford D; Knobel, Darryn L; Conan, Anne; Finn, Adam

    2017-02-01

    The RTS,S/AS01 malaria vaccine has been associated with meningitis and cerebral malaria safety signals. Key characteristics of the meningitis signal include presence, in the 5-17month but not the 6-12week age group, of delayed and variable meningitis onset after vaccination, and multiple etiologies. For both meningitis and cerebral malaria, the 5-17month old age group control arm had abnormally low incidences while other arms in both age groups had meningitis and cerebral malaria incidences similar to background rates. No single hypothesis postulating an adverse effect from RTS,S/AS01 unites these observations. Unlike the 6-12week group, the control population in the 5-17month old age group received rabies vaccine. This raises the possibility that non-specific rabies vaccine effects had a protective effect against central nervous system infection, a hypothesis consistent with the epidemiologic data. The lack of a confirmed biologic mechanism for such an effect emphasizes the need for additional studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Inhibition of insulin fibrillation by osmolytes: Mechanistic Insights

    NASA Astrophysics Data System (ADS)

    Choudhary, Sinjan; Kishore, Nand; Hosur, Ramakrishna V.

    2015-11-01

    We have studied here using a number of biophysical tools the effects of osmolytes, betaine, citrulline, proline and sorbitol which differ significantly in terms of their physical characteristics such as, charge distribution, polarity, H-bonding abilities etc, on the fibrillation of insulin. Among these, betaine, citrulline, and proline are very effective in decreasing the extent of fibrillation. Proline also causes a substantial delay in the onset of fibrillation in the concentration range (50-250 mM) whereas such an effect is seen for citrulline only at 250 mM, and in case of betaine this effect is not seen at all in the whole concentration range. The enthalpies of interaction at various stages of fibrillation process have suggested that the preferential exclusion of the osmolyte and its polar interaction with the protein are important in inhibition. The results indicate that the osmolytes are most effective when added prior to the elongation stage of fibrillation. These observations have significant biological implications, since insulin fibrillation is known to cause injection amyloidosis and our data may help in designing lead drug molecules and development of potential therapeutic strategies.

  11. Relations among Temperament, Self-regulatory Strategies and Gender in Predicting Delay of Gratification.

    PubMed

    Hong, Fang; Doan, Stacey N; Lopez, Angelica; Evans, Gary W

    2017-01-01

    Self-regulation is associated with many positive outcomes, but there is limited information about individual difference regarding children's spontaneous use of strategies to self-regulate and the relative success of those strategies. In the current study, we examined whether temperament and gender are associated with self-regulation and explored the types of spontaneous strategies children use during Mischel's delay of gratification protocol. In addition, we investigated whether spontaneous strategy use during the task could moderate the effects of temperament on self-regulation and whether temperament would mediate the effect of gender on self-regulation. Participants were 349 9-year-olds (182 boys, M age = 9.18, SD = 1.17). Mothers reported on children's temperament and the Delay of Gratification task was used to assess self-regulation. Both temperament and child's gender were significantly associated with children's delay time. Girls were able to delay longer than boys, and children scoring high on activity level were less able to delay. Activity level also mediated the relationship between gender and delay time. Finally, we found an interaction effect between activity level and certain strategies in relation to self-regulatory behavior.

  12. Relations among Temperament, Self-regulatory Strategies and Gender in Predicting Delay of Gratification

    PubMed Central

    Hong, Fang; Doan, Stacey N.; Lopez, Angelica; Evans, Gary W.

    2017-01-01

    Self-regulation is associated with many positive outcomes, but there is limited information about individual difference regarding children’s spontaneous use of strategies to self-regulate and the relative success of those strategies. In the current study, we examined whether temperament and gender are associated with self-regulation and explored the types of spontaneous strategies children use during Mischel’s delay of gratification protocol. In addition, we investigated whether spontaneous strategy use during the task could moderate the effects of temperament on self-regulation and whether temperament would mediate the effect of gender on self-regulation. Participants were 349 9-year-olds (182 boys, Mage = 9.18, SD = 1.17). Mothers reported on children’s temperament and the Delay of Gratification task was used to assess self-regulation. Both temperament and child’s gender were significantly associated with children’s delay time. Girls were able to delay longer than boys, and children scoring high on activity level were less able to delay. Activity level also mediated the relationship between gender and delay time. Finally, we found an interaction effect between activity level and certain strategies in relation to self-regulatory behavior. PMID:29163300

  13. Biphasic Effects of Alcohol on Delay and Probability Discounting

    PubMed Central

    Bidwell, L. Cinnamon; MacKillop, James; Murphy, James G.; Grenga, Andrea; Swift, Robert M.; McGeary, John E.

    2014-01-01

    Delay discounting and probability discounting are behavioral economic indices of impulsive and risky decision making that have been associated with addictive behavior, but the acute biphasic effects of alcohol on these decision-making processes are not well understood. This study sought to investigate the biphasic effects of alcohol on delay and probability discounting across the ascending and descending limbs of the breath alcohol concentration (BAC) curve, which are respectively characterized by the stimulant and sedative effects of alcohol. Delay and probability discounting were measured at four time points (Baseline, Ascending, Descending, and Endpoint) across the BAC curve at two target alcohol doses (40 mg/dl and 80 mg/dl) in healthy adults (N = 23 and 27, for both doses, respectively). There was no significant effect of alcohol on delay discounting at either dose. Alcohol significantly affected probability discounting, such that reduced discounting for uncertain rewards was evident during the descending limb of the BAC curve at the lower dose (p<.05) and during both the ascending and descending limb of the BAC curve at the higher dose (p<.05). Thus, alcohol resulted in increased risky decision making, particularly during the descending limb which is primarily characterized by the sedative effects of alcohol. These findings suggest that the biphasic effects of alcohol across the ascending and descending limbs of the BAC have differential effects on behavior related to decision-making for probabilistic, but not delayed, rewards. Parallels to and distinctions from previous findings are discussed. PMID:23750692

  14. Effects of Reinforcer Probability, Delay, and Response Requirements on the Choices of Rats and Pigeons: Possible Species Differences

    ERIC Educational Resources Information Center

    Mazur, James E.

    2005-01-01

    In Experiment 1 with rats, a left lever press led to a 5-s delay and then a possible reinforcer. A right lever press led to an adjusting delay and then a certain reinforcer. This delay was adjusted over trials to estimate an indifference point, or a delay at which the two alternatives were chosen about equally often. Indifference points increased…

  15. OPPORTUNITY COSTS OF REWARD DELAYS AND THE DISCOUNTING OF HYPOTHETICAL MONEY AND CIGARETTES

    PubMed Central

    Johnson, Patrick S.; Herrmann, Evan S.; Johnson, Matthew W.

    2015-01-01

    Humans are reported to discount delayed rewards at lower rates than nonhumans. However, nonhumans are studied in tasks that restrict reinforcement during delays, whereas humans are typically studied in tasks that do not restrict reinforcement during delays. In nonhuman tasks, the opportunity cost of restricted reinforcement during delays may increase delay discounting rates. The present within-subjects study used online crowdsourcing (Amazon Mechanical Turk, or MTurk) to assess the discounting of hypothetical delayed money (and cigarettes in smokers) under four hypothetical framing conditions differing in the availability of reinforcement during delays. At one extreme, participants were free to leave their computer without returning, and engage in any behavior during reward delays (modeling typical human tasks). At the opposite extreme, participants were required to stay at their computer and engage in little other behavior during reward delays (modeling typical nonhuman tasks). Discounting rates increased as an orderly function of opportunity cost. Results also indicated predominantly hyperbolic discounting, the “magnitude effect,” steeper discounting of cigarettes than money, and positive correlations between discounting rates of these commodities. This is the first study to test the effects of opportunity costs on discounting, and suggests that procedural differences may partially account for observed species differences in discounting. PMID:25388973

  16. Opportunity costs of reward delays and the discounting of hypothetical money and cigarettes.

    PubMed

    Johnson, Patrick S; Herrmann, Evan S; Johnson, Matthew W

    2015-01-01

    Humans are reported to discount delayed rewards at lower rates than nonhumans. However, nonhumans are studied in tasks that restrict reinforcement during delays, whereas humans are typically studied in tasks that do not restrict reinforcement during delays. In nonhuman tasks, the opportunity cost of restricted reinforcement during delays may increase delay discounting rates. The present within-subjects study used online crowdsourcing (Amazon Mechanical Turk, or MTurk) to assess the discounting of hypothetical delayed money (and cigarettes in smokers) under four hypothetical framing conditions differing in the availability of reinforcement during delays. At one extreme, participants were free to leave their computer without returning, and engage in any behavior during reward delays (modeling typical human tasks). At the opposite extreme, participants were required to stay at their computer and engage in little other behavior during reward delays (modeling typical nonhuman tasks). Discounting rates increased as an orderly function of opportunity cost. Results also indicated predominantly hyperbolic discounting, the "magnitude effect," steeper discounting of cigarettes than money, and positive correlations between discounting rates of these commodities. This is the first study to test the effects of opportunity costs on discounting, and suggests that procedural differences may partially account for observed species differences in discounting. © Society for the Experimental Analysis of Behavior.

  17. The Value of Clean Air: Comparing Discounting of Delayed Air Quality and Money Across Magnitudes.

    PubMed

    Berry, Meredith S; Friedel, Jonathan E; DeHart, William B; Mahamane, Salif; Jordan, Kerry E; Odum, Amy L

    2017-06-01

    The detrimental health effects of exposure to air pollution are well established. Fostering behavioral change concerning air quality may be challenging because the detrimental health effects of exposure to air pollution are delayed. Delay discounting, a measure of impulsive choice, encapsulates this process of choosing between the immediate conveniences of behaviors that increase pollution and the delayed consequences of prolonged exposure to poor air quality. In Experiment 1, participants completed a series of delay-discounting tasks for air quality and money. We found that participants discounted delayed air quality more than money. In Experiment 2, we investigated whether the common finding that large amounts of money are discounted less steeply than small amounts of money generalized to larger and smaller improvements in air quality. Participants discounted larger improvements in air quality less steeply than smaller improvements, indicating that the discounting of air quality shares a similar process as the discounting of money. Our results indicate that the discounting of delayed money is strongly related to the discounting of delayed air quality and that similar mechanisms may be involved in the discounting of these qualitatively different outcomes. These data are also the first to demonstrate the malleability of delay discounting of air quality, and provide important public health implications for decreasing delay discounting of air quality.

  18. How does signal fade on photo-stimulable storage phosphor imaging plates when scanned with a delay and what is the effect on image quality?

    PubMed

    Ang, Dan B; Angelopoulos, Christos; Katz, Jerald O

    2006-11-01

    The goals of this in vitro study were to determine the effect of signal fading of DenOptix photo-stimulable storage phosphor imaging plates scanned with a delay and to determine the effect on the diagnostic quality of the image. In addition, we sought to correlate signal fading with image spatial resolution and average pixel intensity values. Forty-eight images were obtained of a test specimen apparatus and scanned at 6 delayed time intervals: immediately scanned, 1 hour, 8 hours, 24 hours, 72 hours, and 168 hours. Six general dentists using Vixwin2000 software performed a measuring task to determine the location of an endodontic file tip and root apex. One-way ANOVA with repeated measures was used to determine the effect of signal fading (delayed scan time) on diagnostic image quality and average pixel intensity value. There was no statistically significant difference in diagnostic image quality resulting from signal fading. No difference was observed in spatial resolution of the images. There was a statistically significant difference in the pixel intensity analysis of an 8-step aluminum wedge between immediate scanning and 24-hour delayed scan time. There was an effect of delayed scanning on the average pixel intensity value. However, there was no effect on image quality and raters' ability to perform a clinical identification task. Proprietary software of the DenOptix digital imaging system demonstrates an excellent ability to process a delayed scan time signal and create an image of diagnostic quality.

  19. Heterogeneity of residuals from comparison of GNSS and raytracing based troposphere slant total delays, as an indicator of hydrometeors

    NASA Astrophysics Data System (ADS)

    Hordyniec, Paweł; Rohm, Witold; Kapłon, Jan

    2017-04-01

    Post-fit residuals from Precise Point Positioning (PPP) carry the troposphere information except of multipath and residual antenna Phase Centre Variations (PCVs), when precise satellite orbits and clocks were introduced. Slant total delay (STD) of GNSS signal is a sum of a priori slant hydrostatic delay, estimated wet delay, asymetry introduced by the estimated zenith total delay (ZTD) horizontal gradients and a post-fit residual reduced by the systematic (site-dependant) effect. It was revealed, that application of reduced post-fit residuls to the slant total delays obtained from GNSS data processing increases the discrepancy with slant delays from raytracing (RT) through the Numerical Weather Model (NWM). One of the possible sources of that effect is neglected influence of hydrometeors in raytracing procedures. If the assumption of hydrometeor information existence in the PPP post-fit residuals is correct, we expect the diversity of slant delay discrepancies for satellite-receiver rays pointing or not the hydrometeors. Paper presents the spatial and temporal correlation analysis of the slant delay residuals (GNSS - RT) with hydrometeor phenomena recorded during the COST ES1206 GNSS4SWEC benchmark period (May 5th - June 29th, 2013). It presents the discussion of the results from different GNSS PPP slant delay estimation approaches including coordinates unconstraining or heavy constraining, and the calculation of slant delays with and without ZTD horizontal gradients estimation.

  20. Effect of delayed reinforcement on skill acquisition during discrete-trial instruction: Implications for treatmen-integrity errors in academic settings.

    PubMed

    Carroll, Regina A; Kodak, Tiffany; Adolf, Kari J

    2016-03-01

    We used an adapted alternating treatments design to compare skill acquisition during discrete-trial instruction using immediate reinforcement, delayed reinforcement with immediate praise, and delayed reinforcement for 2 children with autism spectrum disorder. Participants acquired the skills taught with immediate reinforcement; however, delayed reinforcement decreased the efficiency and effectiveness of discrete-trial instruction. We discuss the importance of evaluating the influence of treatment-integrity errors on skill acquisition during discrete-trial instruction. © 2015 Society for the Experimental Analysis of Behavior.

  1. Delay discounting of qualitatively different reinforcers in rats.

    PubMed

    Calvert, Amanda L; Green, Leonard; Myerson, Joel

    2010-03-01

    Humans discount larger delayed rewards less steeply than smaller rewards, whereas no such magnitude effect has been observed in rats (and pigeons). It remains possible that rats' discounting is sensitive to differences in the quality of the delayed reinforcer even though it is not sensitive to amount. To evaluate this possibility, Experiment 1 examined discounting of qualitatively different food reinforcers: highly preferred versus nonpreferred food pellets. Similarly, Experiment 2 examined discounting of highly preferred versus nonpreferred liquid reinforcers. In both experiments, an adjusting-amount procedure was used to determine the amount of immediate reinforcer that was judged to be of equal subjective value to the delayed reinforcer. The amount and quality of the delayed reinforcer were varied across conditions. Discounting was well described by a hyperbolic function, but no systematic effects of the quantity or the quality of the delayed reinforcer were observed.

  2. Examination of a Regressive Prompt-Delay Procedure for Improving Sight-Word Reading

    ERIC Educational Resources Information Center

    Daly, Edward J., III.; Hess, Polly M.; Sommerhalder, Mackenzie; Strong, Whitney; Johnsen, Mallory; O'Connor, Maureen A.; Young, Nicholas D.

    2016-01-01

    The current two-experiment study examined the effects of a regressive prompt-delay procedure on sight-word reading of four elementary school students. In contrast to traditional progressive prompt-delay procedures in which the latency of prompts is increased, the regressive prompt-delay latency is decreased over time. Data indicate that…

  3. Strategic Attention Deployment for Delay of Gratification in Working and Waiting Situations.

    ERIC Educational Resources Information Center

    Peake, Philip K.; Hebl, Michelle; Mischel, Walter

    2002-01-01

    Two studies examined whether effects of attention to rewards during a delay of gratification task in waiting situations affects preschoolers' ability to delay gratification in working situations. Findings show that when work provides distraction, attention on rewards reduces delay time whether working or waiting; when work is not engaging,…

  4. Delay Discounting of Losses in Alcohol Use Disorders and Antisocial Psychopathology: Effects of a Working Memory Load.

    PubMed

    Gerst, Kyle R; Gunn, Rachel L; Finn, Peter R

    2017-10-01

    Alcohol use disorders (AUDs) are associated with increased discounting of delayed rewards and reduced executive working memory (eWM) capacity. This association is amplified when comorbid with antisocial psychopathology (AP). Furthermore, recent studies suggest that reduced WM capacity is associated with disinhibited decisions reflected by increased impulsive decision making on the delay discounting of rewards task. While discounting of delayed rewards is well studied, the discounting of delayed losses has received significantly less experimental attention. The current study investigated (i) the rate of discounting of delayed losses in individuals with AUD only (n = 61), AUD with comorbid AP (n = 79) and healthy controls (n = 64); (ii) the relationship between eWM capacity and discounting of delayed losses; and (iii) the effect of a WM load on discounting of delayed losses. Discounting performance was assessed using a computerized discounting of delayed losses task. Results showed that the AUD-only and AUD-AP groups had higher rates of discounting of delayed losses and lower eWM capacity compared to the control groups. Lower individual eWM capacity was associated with increased discounting of delayed losses. However, WM load did not increase discounting rates overall. These results support the hypothesis that greater discounting of delayed losses is associated with AUD and comorbid AP problems and lower individual eWM capacity. Copyright © 2017 by the Research Society on Alcoholism.

  5. Joint cartilage thickness and automated determination of bone age and bone health in juvenile idiopathic arthritis.

    PubMed

    Twilt, Marinka; Pradsgaard, Dan; Spannow, Anne Helene; Horlyck, Arne; Heuck, Carsten; Herlin, Troels

    2017-08-10

    BoneXpert is an automated method to calculate bone maturation and bone health index (BHI) in children with juvenile idiopathic arthritis (JIA). Cartilage thickness can also be seen as an indicator for bone health and arthritis damage. The objective of this study was to evaluate the relation between cartilage thickness, bone maturation and bone health in patients with JIA. Patients with JIA diagnosed according ILAR criteria included in a previous ultrasonography (US) study were eligible if hand radiographs were taken at the same time as the US examination. Of the 95 patients 67 met the inclusion criteria. Decreased cartilage thickness was seen in 27% of the examined joints. Decreased BHI was seen in half of the JIA patient, and delayed bone maturation was seen in 33% of patients. A combination of decreased BHI and bone age was seen in 1 out of 5 JIA patients. Decreased cartilage thickness in the knee, wrist and MCP joint was negatively correlated with delayed bone maturation but not with bone health index. Delayed bone maturation and decreased BHI were not related to a thinner cartilage, but a thicker cartilage. No relation with JADAS 10 was found. The rheumatologist should remain aware of delayed bone maturation and BHI in JIA patients with cartilage changes, even in the biologic era.

  6. A COMPREHENSIVE STUDY OF THE NEUTRON ACTIVATION ANALYSIS OF URANIUM BY DELAYED-NEUTRON COUNTING

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

    Dyer, F.F.; Emery, J.F.; Leddicotte, G.W.

    The method of neutron activation analysis of U by delayed-neutron counting was investigated in order to ascertain if the method would be suitable for routine application to such analyses. It was shown that the method can be used extensively and routinely for the determination of U. Emphasis was placed on the determination of U in the types of sample materials encountered in nuclear technology. Determinations of U were made on such materials as ores, granite, sea sediments, biological tissue, graphite, and metal alloys. The method is based upon the fact that delayed neutrons are emitted from fission products from themore » interaction of neutrons with U/sup 235/. Since the U/sup 235/ component of U undergoes most of the fissions when a sample is in a neutron flux, the method is predominately one for the determination of U/sup 235/. The total U in a sample or the isotopic composition of the U in a sample can be determined provided there is a prior knowledge of one of these quantities. The U/sup 235/ content of a test sample is obtained by comparing its delayed-neutron count to that obtained with a comparator sample containing a known quantity of U/sup 235/. (auth)« less

  7. The Trade-Off Mechanism in Mammalian Circadian Clock Model with Two Time Delays

    NASA Astrophysics Data System (ADS)

    Yan, Jie; Kang, Xiaxia; Yang, Ling

    Circadian clock is an autonomous oscillator which orchestrates the daily rhythms of physiology and behaviors. This study is devoted to explore how a positive feedback loop affects the dynamics of mammalian circadian clock. We simplify an experimentally validated mathematical model in our previous work, to a nonlinear differential equation with two time delays. This simplified mathematical model incorporates the pacemaker of mammalian circadian clock, a negative primary feedback loop, and a critical positive auxiliary feedback loop, Rev-erbα/Cry1 loop. We perform analytical studies of the system. Delay-dependent conditions for the asymptotic stability of the nontrivial positive steady state of the model are investigated. We also prove the existence of Hopf bifurcation, which leads to self-sustained oscillation of mammalian circadian clock. Our theoretical analyses show that the oscillatory regime is reduced upon the participation of the delayed positive auxiliary loop. However, further simulations reveal that the auxiliary loop can enable the circadian clock gain widely adjustable amplitudes and robust period. Thus, the positive auxiliary feedback loop may provide a trade-off mechanism, to use the small loss in the robustness of oscillation in exchange for adaptable flexibility in mammalian circadian clock. The results obtained from the model may gain new insights into the dynamics of biological oscillators with interlocked feedback loops.

  8. Spatial gradients of protein-level time delays set the pace of the traveling segmentation clock waves

    PubMed Central

    Ay, Ahmet; Holland, Jack; Sperlea, Adriana; Devakanmalai, Gnanapackiam Sheela; Knierer, Stephan; Sangervasi, Sebastian; Stevenson, Angel; Özbudak, Ertuğrul M.

    2014-01-01

    The vertebrate segmentation clock is a gene expression oscillator controlling rhythmic segmentation of the vertebral column during embryonic development. The period of oscillations becomes longer as cells are displaced along the posterior to anterior axis, which results in traveling waves of clock gene expression sweeping in the unsegmented tissue. Although various hypotheses necessitating the inclusion of additional regulatory genes into the core clock network at different spatial locations have been proposed, the mechanism underlying traveling waves has remained elusive. Here, we combined molecular-level computational modeling and quantitative experimentation to solve this puzzle. Our model predicts the existence of an increasing gradient of gene expression time delays along the posterior to anterior direction to recapitulate spatiotemporal profiles of the traveling segmentation clock waves in different genetic backgrounds in zebrafish. We validated this prediction by measuring an increased time delay of oscillatory Her1 protein production along the unsegmented tissue. Our results refuted the need for spatial expansion of the core feedback loop to explain the occurrence of traveling waves. Spatial regulation of gene expression time delays is a novel way of creating dynamic patterns; this is the first report demonstrating such a control mechanism in any tissue and future investigations will explore the presence of analogous examples in other biological systems. PMID:25336742

  9. Neuropsychiatrie of biologische psychiatrie; een toekomstvisie in historisch perspectief.

    PubMed

    Verhoeven, W M; Tuinier, S

    1999-06-01

    Neuropsychiatry or Biological Psychiatry There is an urgent need to reconsider the position of psychiatry within the neurosciences because of the exploding knowledge about the relationship between brain and behaviour and the delay in implementation of new findings due to the separation of neurology and psychiatry. Biological psychiatry and psychopharmacology originate from the discovery by chance of psycho-active compounds in the early fifties and have contributed to the scientification of psychiatry. The impact of biological psychiatry for the pathophysiology of psychiatric disorders, however, is limited as a result of its biased orientation on neurotransmitters and receptors. The neuropsychiatric paradigm integrates knowledge from several domains, such as functional neuroanatomy, genetics and endocrinology and opens new vistas for the involvement of neuronal circuits in the initiation and maintenance of behavioural disturbances. In addition, novel and more specific treatment modalities may emerge.

  10. Spatio-temporal dynamics of action-effect associations in oculomotor control.

    PubMed

    Riechelmann, Eva; Pieczykolan, Aleksandra; Horstmann, Gernot; Herwig, Arvid; Huestegge, Lynn

    2017-10-01

    While there is ample evidence that actions are guided by anticipating their effects (ideomotor control) in the manual domain, much less is known about the underlying characteristics and dynamics of effect-based oculomotor control. Here, we address three open issues. 1) Is action-effect anticipation in oculomotor control reflected in corresponding spatial saccade characteristics in inanimate environments? 2) Does the previously reported dependency of action latency on the temporal effect delay (action-effect interval) also occur in the oculomotor domain? 3) Which temporal effect delay is optimally suited to develop strong action-effect associations over time in the oculomotor domain? Participants executed left or right free-choice saccades to peripheral traffic lights, causing an (immediate or delayed) action-contingent light switch in the upper vs. lower part of the traffic light. Results indicated that saccades were spatially shifted toward the location of the upcoming change, indicating anticipation of the effect (location). Saccade latency was affected by effect delay, suggesting that corresponding time information is integrated into event representations. Finally, delayed (vs. immediate) effects were more effective in strengthening action-effect associations over the course of the experiment, likely due to greater saliency of perceptual changes occurring during target fixation as opposed to changes during saccades (saccadic suppression). Overall, basic principles underlying ideomotor control appear to generalize to the oculomotor domain. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Procedural Adaptations for Use of Constant Time Delay to Teach Highly Motivating Words to Beginning Braille Readers

    ERIC Educational Resources Information Center

    Ivy, Sarah E.; Guerra, Jennifer A.; Hatton, Deborah D.

    2017-01-01

    Introduction: Constant time delay is an evidence-based practice to teach sight word recognition to students with a variety of disabilities. To date, two studies have documented its effectiveness for teaching braille. Methods: Using a multiple-baseline design, we evaluated the effectiveness of constant time delay to teach highly motivating words to…

  12. The Role of Strategic Attention Deployment in Development of Self-Regulation: Predicting Preschoolers' Delay of Gratification from Mother-Toddler Interactions.

    ERIC Educational Resources Information Center

    Sethi, Anita; Mischel, Walter; Aber, J. Lawrence; Shoda, Yuichi; Rodriguez, Monica Larrea

    2000-01-01

    Examined role of toddlers' attention deployment strategies in predicting 5-year-olds' delay-of-gratification strategies. Found that toddlers' use of effective attention deployment strategies to cope with separation from mother and with maternal behavior (controlling or noncontrolling) predicted effective delay-of-gratification strategies at age 5,…

  13. Retention of Esperanto Is Affected by Delay-Interval Task and Item Closure: A Partial Resolution of the Delay-Retention Effect

    ERIC Educational Resources Information Center

    Brosvic, Gary M.; Epstein, Michael L.; Dihoff, Roberta E.; Cook, Michael L.

    2006-01-01

    The present studies were undertaken to examine the effects of manipulating delay-interval task (Study 1) and timing of feedback (Study 2) on acquisition and retention. Participants completed a 100-item cumulative final examination, which included 50 items from each laboratory examination, plus 50 entirely new items. Acquisition and retention were…

  14. The effects of time delay in man-machine control systems: Implications for design of flight simulator Visual-Display-Delay compensation

    NASA Technical Reports Server (NTRS)

    Crane, D. F.

    1984-01-01

    When human operators are performing precision tracking tasks, their dynamic response can often be modeled by quasilinear describing functions. That fact permits analysis of the effects of delay in certain man machine control systems using linear control system analysis techniques. The analysis indicates that a reduction in system stability is the immediate effect of additional control system delay, and that system characteristics moderate or exaggerate the importance of the delay. A selection of data (simulator and flight test) consistent with the analysis is reviewed. Flight simulator visual-display delay compensation, designed to restore pilot aircraft system stability, was evaluated in several studies which are reviewed here. The studies range from single-axis, tracking-task experiments (with sufficient subjects and trials to establish the statistical significance of the results) to a brief evaluation of compensation of a computer generated imagery (CGI) visual display system in a full six degree of freedom simulation. The compensation was effective, improvements in pilot performance and workload or aircraft handling qualities rating (HQR) were observed. Results from recent aircraft handling qualities research literature, which support the compensation design approach, are also reviewed.

  15. Non-target organism effects tests on Vip3A and their application to the ecological risk assessment for cultivation of MIR162 maize.

    PubMed

    Raybould, Alan; Vlachos, Demetra

    2011-06-01

    Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) provide economic, environmental and health benefits by maintaining or increasing crop yields with fewer applications of insecticide. To sustain these benefits, it is important to delay the evolution of insect resistance to the proteins, and to ensure that the proteins do not harm non-target organisms, particularly those that may control secondary pests that would otherwise flourish because of reduced insecticide applications. Vip3A is a Bt vegetative insecticidal protein that is active against lepidopterous pests. It has a different mode of action from other proteins for control of Lepidoptera in current Bt crops, and when combined with these proteins, it should help to delay the evolution of pest resistance to Bt crops. This paper presents data on the effects of Vip3A on non-target organisms, and an ecological risk assessment of MIR162 maize, which expresses Vip3Aa20. Laboratory studies indicate few adverse effects of Vip3A to non-target organisms: 11 of 12 species tested showed no adverse effects when exposed to high concentrations of Vip3A relative to estimated exposures resulting from cultivation of MIR162 maize. Daphnia magna exposed to Vip3Aa20 were unaffected in terms of survival or fecundity, but grew slightly more slowly than unexposed controls. The data indicate that cultivation of MIR162 maize poses negligible risk to non-target organisms, and that crops producing Vip3A are unlikely to adversely affect biological control organisms such that benefits from reduced insecticide applications are lost.

  16. The importance of explicitly mapping instructional analogies in science education

    NASA Astrophysics Data System (ADS)

    Asay, Loretta Johnson

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With Analogies (TWA) model (Glynn, 1991) is one of the models frequently cited in the variety of research about analogies. The TWA model outlines steps for instruction, including the step of explicitly mapping the features of the source to the target. An experimental study was conducted to examine the effects of explicitly mapping the features of the source and target in an analogy during computer-based instruction about electrical circuits. Explicit mapping was compared to no mapping and to a control with no analogy. Participants were ninth- and tenth-grade biology students who were each randomly assigned to one of three conditions (no analogy module, analogy module, or explicitly mapped analogy module) for computer-based instruction. Subjects took a pre-test before the instruction, which was used to assign them to a level of previous knowledge about electrical circuits for analysis of any differential effects. After the instruction modules, students took a post-test about electrical circuits. Two weeks later, they took a delayed post-test. No advantage was found for explicitly mapping the analogy. Learning patterns were the same, regardless of the type of instruction. Those who knew the least about electrical circuits, based on the pre-test, made the most gains. After the two-week delay, this group maintained the largest amount of their gain. Implications exist for science education classrooms, as analogy use should be based on research about effective practices. Further studies are suggested to foster the building of research-based models for classroom instruction with analogies.

  17. Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response.

    PubMed

    Perez, Felipe P; Zhou, Ximing; Morisaki, Jorge; Jurivich, Donald

    2008-04-01

    Hormesis may result when mild repetitive stress increases cellular defense against diverse injuries. This process may also extend in vitro cellular proliferative life span as well as delay and reverse some of the age-dependent changes in both replicative and non-replicative cells. This study evaluated the potential hormetic effect of non-thermal repetitive electromagnetic field shock (REMFS) and its impact on cellular aging and mortality in primary human T lymphocytes and fibroblast cell lines. Unlike previous reports employing electromagnetic radiation, this study used a long wave length, low energy, and non-thermal REMFS (50MHz/0.5W) for various therapeutic regimens. The primary outcomes examined were age-dependent morphological changes in cells over time, cellular death prevention, and stimulation of the heat shock response. REMFS achieved several biological effects that modified the aging process. REMFS extended the total number of population doublings of mouse fibroblasts and contributed to youthful morphology of cells near their replicative lifespan. REMFS also enhanced cellular defenses of human T cells as reflected in lower cell mortality when compared to non-treated T cells. To determine the mechanism of REMFS-induced effects, analysis of the cellular heat shock response revealed Hsp90 release from the heat shock transcription factor (HSF1). Furthermore, REMFS increased HSF1 phosphorylation, enhanced HSF1-DNA binding, and improved Hsp70 expression relative to non-REMFS-treated cells. These results show that non-thermal REMFS activates an anti-aging hormetic effect as well as reduces cell mortality during lethal stress. Because the REMFS configuration employed in this study can potentially be applied to whole body therapy, prospects for translating these data into clinical interventions for Alzheimer's disease and other degenerative conditions with aging are discussed.

  18. [Iron deficiency anaemia: clinical presentation, biological diagnosis and management].

    PubMed

    Espanel, C; Kafando, E; Hérault, B; Petit, A; Herault, O; Binet, C

    2007-05-01

    The iron deficiency is the first cause of anaemia. In healthy young adult, anemia is well tolerated because of its progressive installation. The most common symptoms of anemia are pallor, fatigue and dyspnea. In biological exams, anemia is classically associated with microcytosis and hypochromia. The origins of microcytic anemia are iron deficiency, inflammatory aetiologies, thalassemia and sideroblastic anaemia. The iron-deficiency diagnosis includes two explorations: biological and clinical. The biological exploration is based on interpretation of serum biologics tests as blood iron, ferritin, transferrin with saturation, total iron-binding capacity and its soluble receptors. This interpretation is simple if it is not associated with clinical disorders influencing the internal iron cycle. The clinical exploration must always be followed by a careful assessment of the underlying cause as blood loss. The most common causes in women of reproductive age are gynaecologic. In men and menopausal women, the gastrointestinal tract bleeding is source of anemia. Therapeutic management of anemia is oral iron therapy. Etiological diagnostic of microcytosis is essential before iron therapy. If not, the treatment could be inefficient or it could mask or delay the etiological diagnostic.

  19. Attosecond-resolution Hong-Ou-Mandel interferometry.

    PubMed

    Lyons, Ashley; Knee, George C; Bolduc, Eliot; Roger, Thomas; Leach, Jonathan; Gauger, Erik M; Faccio, Daniele

    2018-05-01

    When two indistinguishable photons are each incident on separate input ports of a beamsplitter, they "bunch" deterministically, exiting via the same port as a direct consequence of their bosonic nature. This two-photon interference effect has long-held the potential for application in precision measurement of time delays, such as those induced by transparent specimens with unknown thickness profiles. However, the technique has never achieved resolutions significantly better than the few-femtosecond (micrometer) scale other than in a common-path geometry that severely limits applications. We develop the precision of Hong-Ou-Mandel interferometry toward the ultimate limits dictated by statistical estimation theory, achieving few-attosecond (or nanometer path length) scale resolutions in a dual-arm geometry, thus providing access to length scales pertinent to cell biology and monoatomic layer two-dimensional materials.

  20. Using Electroencephalography for Treatment Guidance in Major Depressive Disorder.

    PubMed

    Wade, Elizabeth C; Iosifescu, Dan V

    2016-09-01

    Given the high prevalence of treatment-resistant depression and the long delays in finding effective treatments via trial and error, valid biomarkers of treatment outcome with the ability to guide treatment selection represent one of the most important unmet needs in mood disorders. A large body of research has investigated, for this purpose, biomarkers derived from electroencephalography (EEG), using resting state EEG or evoked potentials. Most studies have focused on specific EEG features (or combinations thereof), whereas more recently machine-learning approaches have been used to define the EEG features with the best predictive abilities without a priori hypotheses. While reviewing these different approaches, we have focused on the predictor characteristics and the quality of the supporting evidence. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.

    PubMed

    Kogan, Samuel; Sood, Aditya; Garnick, Mark S

    2017-04-01

    Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.

  2. Tolerable hearing-aid delays: IV. effects on subjective disturbance during speech production by hearing-impaired subjects.

    PubMed

    Stone, Michael A; Moore, Brian C J

    2005-04-01

    We assessed the effects of time delay in a hearing aid on subjective disturbance and reading rates while the user of the aid was speaking, using hearing-impaired subjects and real-time processing. The time delay was constant across frequency. A digital signal processor was programmed as a four-channel, fast-acting, wide-dynamic-range compression hearing aid. One of four delays could be selected on the aid to produce a total delay of 13, 21, 30, or 40 msec between microphone and receiver. Twenty-five subjects, mostly with near-symmetric hearing impairment of cochlear origin, were fitted bilaterally with behind-the-ear aids connected to the processor. The aids were programmed with insertion gains prescribed by the CAMEQ loudness equalization procedure for each subject and ear. Subjects were asked to read aloud from scripts: speech production rates were measured and subjective ratings of the disturbance of the delay were obtained. Subjects required some training to recognize the effects of the delay to rate it consistently. Subjective disturbance increased progressively with increasing delay and was a nonmonotonic function of low-frequency hearing loss. Subjects with mild or severe low-frequency hearing loss were generally less disturbed by the delay than those with moderate loss. Disturbance ratings tended to decrease over successive tests. Word production rates were not significantly affected by delay over the range of delays tested. The results follow a pattern similar to those presented in , obtained using a simulation of hearing loss and normally hearing subjects, except for the nonmonotonic variation of disturbance with low-frequency hearing loss. We hypothesize that disturbance is maximal when the levels in the ear canal of the low-frequency components are similar for the unaided and aided sounds. A rating of 3, which is probably just acceptable, was obtained for delays ranging from 14 to 30 msec, depending on the hearing loss. Some acclimatization to the subjective disturbance occurred over a time scale of about 1 hour.

  3. Role of delay-based reward in the spatial cooperation

    NASA Astrophysics Data System (ADS)

    Wang, Xu-Wen; Nie, Sen; Jiang, Luo-Luo; Wang, Bing-Hong; Chen, Shi-Ming

    2017-01-01

    Strategy selection in games, a typical decision making, usually brings noticeable reward for players which have discounted value if the delay appears. The discounted value is measure: earning sooner with a small reward or later with a delayed larger reward. Here, we investigate effects of delayed rewards on the cooperation in structured population. It is found that delayed reward supports the spreading of cooperation in square lattice, small-world and random networks. In particular, intermediate reward differences between delays impel the highest cooperation level. Interestingly, cooperative individuals with the same delay time steps form clusters to resist the invasion of defects, and cooperative individuals with lowest delay reward survive because they form the largest clusters in the lattice.

  4. Delayed, but not immediate, feedback after multiple-choice questions increases performance on a subsequent short-answer, but not multiple-choice, exam: evidence for the dual-process theory of memory.

    PubMed

    Sinha, Neha; Glass, Arnold Lewis

    2015-01-01

    Three experiments, two performed in the laboratory and one embedded in a college psychology lecture course, investigated the effects of immediate versus delayed feedback following a multiple-choice exam on subsequent short answer and multiple-choice exams. Performance on the subsequent multiple-choice exam was not affected by the timing of the feedback on the prior exam; however, performance on the subsequent short answer exam was better following delayed than following immediate feedback. This was true regardless of the order in which immediate versus delayed feedback was given. Furthermore, delayed feedback only had a greater effect than immediate feedback on subsequent short answer performance following correct, confident responses on the prior exam. These results indicate that delayed feedback cues a student's prior response and increases subsequent recollection of that response. The practical implication is that delayed feedback is better than immediate feedback during academic testing.

  5. Market-based control strategy for long-span structures considering the multi-time delay issue

    NASA Astrophysics Data System (ADS)

    Li, Hongnan; Song, Jianzhu; Li, Gang

    2017-01-01

    To solve the different time delays that exist in the control device installed on spatial structures, in this study, discrete analysis using a 2 N precise algorithm was selected to solve the multi-time-delay issue for long-span structures based on the market-based control (MBC) method. The concept of interval mixed energy was introduced from computational structural mechanics and optimal control research areas, and it translates the design of the MBC multi-time-delay controller into a solution for the segment matrix. This approach transforms the serial algorithm in time to parallel computing in space, greatly improving the solving efficiency and numerical stability. The designed controller is able to consider the issue of time delay with a linear controlling force combination and is especially effective for large time-delay conditions. A numerical example of a long-span structure was selected to demonstrate the effectiveness of the presented controller, and the time delay was found to have a significant impact on the results.

  6. Delayed neutron spectral data for Hansen-Roach energy group structure

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

    Campbell, J.M.; Spriggs, G.D.

    A detailed knowledge of delayed neutron spectra is important in reactor physics. It not only allows for an accurate estimate of the effective delayed neutron fraction {beta}{sub eff} but also is essential to calculating important reactor kinetic parameters, such as effective group abundances and the ratio of {beta}{sub eff} to the prompt neutron generation time. Numerous measurements of delayed neutron spectra for various delayed neutron precursors have been performed and reported in the literature. However, for application in reactor physics calculations, these spectra are usually lumped into one of the traditional six groups of delayed neutrons in accordance to theirmore » half-lives. Subsequently, these six-group spectra are binned into energy intervals corresponding to the energy intervals of a chosen nuclear cross-section set. In this work, the authors present a set of delayed neutron spectra that were formulated specifically to match Keepin`s six-group parameters and the 16-energy-group Hansen-Roach cross sections.« less

  7. Biological Perspectives of Delayed Fracture Healing

    PubMed Central

    Hankenson, KD; Zmmerman, G; Marcucio, R

    2015-01-01

    Fracture healing is a complex biological process that requires interaction among a series of different cell types. Maintaining the appropriate temporal progression and spatial pattern is essential to achieve robust healing. We can temporally assess the biological phases via gene expression, protein analysis, histologically, or non-invasively using biomarkers as well as imaging techniques. However, determining what leads to normal verses abnormal healing is more challenging. Since the ultimate outcome of the process of fracture healing is to restore the original functions of bone, assessment of fracture healing should include not only monitoring the restoration of structure and mechanical function, but also an evaluation of the restoration of normal bone biology. Currently very few non-invasive measures of the biology of healing exist; however, recent studies that have correlated non-invasive measures with fracture healing outcome in humans have shown that serum TGFbeta1 levels appear to be an indicator of healing vs non-healing. In the future, developing additional serum measures to assess biological healing will improve the reliability and permit us to assess stages of fracture healing. Additionally, new functional imaging technologies could prove useful for better understanding both normal fracture healing and predicting dysfunctional healing in human patients. PMID:24857030

  8. Biological floating bed and bio-contact oxidation processes for landscape water treatment: simultaneous removal of Microcystis aeruginosa, TOC, nitrogen and phosphorus.

    PubMed

    Su, Jun Feng; Liang, Dong Hui; Fu, Le; Wei, Li; Ma, Min

    2018-06-13

    The aim of this study was to identify algicidal bacteria J25 against the Microcystis aeruginosa (90.14%), Chlorella (78.75%), Scenedesmus (not inhibited), and Oscillatoria (90.12%). Meanwhile, we evaluate the SOD activity and efficiency of denitrification characteristics with Acinetobacter sp. J25. A novel hybrid bioreactor combined biological floating bed with bio-contact oxidation (BFBO) was designed for treating the landscape water, and the average removal efficiencies of nitrate-N, ammonia-N, nitrite-N, TN, TP, TOC, and algal cells were 91.14, 50, 87.86, 88.83, 33.07, 53.95, and 53.43%, respectively. A 454-pyrosequencing technology was employed to investigate the microbial communities of the BFBO reactor samples. The results showed that Acinetobacter sp. J25 was the dominant contributor for effective removal of N, algal cells, and TOC in the BFBO reactor. And the relative abundance of Acinetobacter showed increase trend with the delay of reaction time. Graphical abstract Biological floating bed and bio-contact oxidation (BFBO) as a novel hybrid bioreactor designed for simultaneous removal Microcystis aeruginosa, TOC, nitrogen, and phosphorus. And high-throughput sequencing data demonstrated that Acinetobacter sp. J25 was the dominate species in the reactor and played key roles in the removal of N, TOC, and M. aeruginosa. Proposed reaction mechanism of the BFBO.

  9. [Central nervous tuberculosis in patients non-VIH: seven case reports].

    PubMed

    Mazodier, K; Bernit, E; Faure, V; Rovery, C; Gayet, S; Seux, V; Donnet, A; Brouqui, P; Disdier, P; Schleinitz, N; Kaplanski, G; Veit, V; Harlé, J-R

    2003-02-01

    Tuberculosis involving the central nervous system (CNS) is rarely observed in non immuno-compromised hosts. We report herin the various clinical, biological and radiological manifestations observed in 7 patients with CNS tuberculosis. Clinical and biological records of 7 patients with CNS tuberculosis were retrospectively studied. All patients had encephalic CT-scan and MRI in the course of the disease. 5 women and 2 men with a mean age of 38.4 years initially initially presented with headache (n = 6), fever (n = 5), meningeal irritation (n = 3), localizing neurological signs (n = 1). Lumbar punction revealed lymphocytic meningitis (n = 6/7). Mycobacterium tuberculosis or bovis was isolated in 3 patients only. Cerebral tomodensitography or magnetic resonance imaging were initially normal in most of cases (n = 4/7), but discovered in the course of disease basilar meningitis (n = 6), hydrocephalus (n = 6), abcess or tuberculoma (n = 4). In all the patients, initiation of the treatment was complicated by clinical and/or biological deterioration, called paradoxal reaction, leading in all cases to glucocorticoid adjunction, with various final results. Indeed, 4 patients developed neurological sequelae. No patient died. CNS tuberculosis is a rare disease in non immunocompromised patients whose diagnostic may be difficult due to the absence of specific clinical symptoms, negative initial radiological examination, as well as delayed and often negative bacterial isolation. Paradoxal reaction appeared to be frequent despite specific antibiotherapy and underlines the beneficial effects of addictive corticosteroids.

  10. A compensation controller based on a regional pole-assignment method for AMD control systems with a time-varying delay

    NASA Astrophysics Data System (ADS)

    Li, Zuohua; Chen, Chaojun; Teng, Jun; Wang, Ying

    2018-04-01

    Active mass damper/driver (AMD) control system has been proposed as an effective tool for high-rise buildings to resist strong dynamic loads. However, such disadvantage as time-varying delay in AMD control systems impedes their application in practices. Time-varying delay, which has an effect on the performance and stability of single-degree-of-freedom (SDOF) and multi-degree-of-freedom (MDOF) systems, is considered in the paper. In addition, a new time-delay compensation controller based on regional pole-assignment method is presented. To verify its effectiveness, the proposed method is applied to a numerical example of a ten-storey frame and an experiment of a single span four-storey steel frame. Both numerical and experimental results demonstrate that the proposed method can enhance the performances of an AMD control system with time-varying delays.

  11. Sphingolipids as New Biomarkers for Assessment of Delayed-Type Hypersensitivity and Response to Triptolide

    PubMed Central

    Qu, Feng; Wu, Cai-Sheng; Hou, Jin-Feng; Jin, Ying; Zhang, Jin-Lan

    2012-01-01

    Background Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and pathological mechanisms of treating these diseases may be attributable to sphingolipid metabolism. Methods High performance liquid chromatography-tandem mass spectrometry was employed to target and measure 43 core sphingolipids in the plasma, kidneys, livers and spleens of BALB/c mice from four experimental groups: control, delayed-type hypersensitivity (DTH) model, DTH+triptolide, and control+triptolide. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify potential biomarkers associated with variance between groups. Relationships between the identified biomarkers and disease markers were evaluated by Spearman correlation. Results As a treatment to hypersensitivity disease, triptolide significantly inhibit the ear swelling and recover the reduction of splenic index caused by DTH. The sphingolipidomic result revealed marked alterations in sphingolipid levels between groups that were associated with the effects of the disease and triptolide treatment. Based on this data, 23 potential biomarkers were identified by OPLS-DA, and seven of these biomarkers correlated markedly with the disease markers (p<0.05) by Spearman correlation. Conclusions These data indicate that differences in sphingolipid levels in plasma and tissues are related to DTH and treatment with triptolide. Restoration of proper sphingolipid levels may attribute to the therapeutic effect of triptolide treatment. Furthermore, these findings demonstrate that targeted sphingolipidomic analysis followed by multivariate analysis presents a novel strategy for the identification of biomarkers in biological samples. PMID:23300675

  12. Positive parenting mitigates the effects of poor self-regulation on body mass index trajectories from ages 4-15 years.

    PubMed

    Connell, Lauren E; Francis, Lori A

    2014-08-01

    This study sought to determine whether parenting style moderates the effects of delay of gratification on body mass index (BMI) trajectories from ages 4-15 years. Longitudinal data were analyzed for 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (i.e., authoritative, authoritarian, permissive, and neglectful) was created from measures of mothers' sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4-15 years. There was a significant interaction effect of parenting and ability to delay on BMI growth from 4-15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting by delay group. Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles.

  13. Positive parenting mitigates the effects of poor self-regulation on BMI trajectories from age 4 to 15 years

    PubMed Central

    Connell, Lauren E.; Francis, Lori A.

    2014-01-01

    Objective This study sought to determine whether parenting style moderated the effects of delay of gratification on BMI trajectories from age 4 to 15 years. Methods Longitudinal data were analyzed on 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (authoritative, authoritarian, permissive, neglectful) was created from measures of mothers’ sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4 to 15 years. Results There was a significant interaction effect of parenting and ability to delay on BMI growth from 4 to 15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting x delay group. Conclusions Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles. PMID:23977874

  14. Investigating the Influences of Language Delay and/or Familial Risk for Dyslexia on Brain Structure in 5-Year-Olds

    PubMed Central

    Raschle, Nora Maria; Becker, Bryce Larkin Chessell; Smith, Sara; Fehlbaum, Lynn Valérie; Wang, Yingying; Gaab, Nadine

    2017-01-01

    Abstract Early language delay has often been associated with atypical language/literacy development. Neuroimaging studies further indicate functional disruptions during language and print processing in school-age children with a retrospective report of early language delay. Behavioral data of 114 5-year-olds with a retrospective report of early language delay in infancy (N = 34) and those without (N = 80) and with a familial risk for dyslexia and those without are presented. Behaviorally, children with a retrospective report of early language delay exhibited reduced performance in language/reading-related measures. A voxel-based morphometry analysis in a subset (N = 46) demonstrated an association between reduced gray matter volume and early language delay in left-hemispheric middle temporal, occipital, and frontal regions. Alterations in middle temporal cortex in children with a retrospective report of early language delay were observed regardless of familial risk for dyslexia. Additionally, while children with isolated familial risk for dyslexia showed gray matter reductions in temporoparietal and occipitotemporal regions, these effects were most profound in children with both risk factors. An interaction effect of early language delay and familial risk was revealed in temporoparietal, occipital, and frontal cortex. Our findings support a cumulative effect of early behavioral and genetic risk factors on brain development and may ultimately inform diagnosis/treatment. PMID:26585334

  15. Effect of Interocular Delay on Disparity-Selective V1 Neurons: Relationship to Stereoacuity and the Pulfrich Effect

    PubMed Central

    Read, Jenny C. A.; Cumming, Bruce G.

    2006-01-01

    The temporal properties of disparity-sensitive neurons place important temporal constraints on stereo matching. We examined these constraints by measuring the responses of disparity-selective neurons in striate cortex of awake behaving monkeys to random-dot stereograms that contained interocular delays. Disparity selectivity was gradually abolished by increasing interocular delay (when the delay exceeds the integration time, the inputs from the 2 eyes become uncorrelated). The amplitude of the disparity-selective response was a Gaussian function of interocular delay, with a mean of 16 ms (±5 ms, SD). Psychophysical measures of stereoacuity, in both monkey and human observers, showed a closely similar dependency on time, suggesting that temporal integration in V1 neurons is what determines psychophysical matching constraints over time. There was a slight but consistent asymmetry in the neuronal responses, as if the optimum stimulus is one in which the right stimulus leads by about 4 ms. Because all recordings were made in the left hemisphere, this probably reflects nasotemporal differences in conduction times; psychophysical data are compatible with this interpretation. In only a few neurons (5/72), interocular delay caused a change in the preferred disparity. Such tilted disparity/delay profiles have been invoked previously to explain depth perception in the stroboscopic version of the Pulfrich effect (and other variants). However, the great majority of the neurons did not show tilted disparity/delay profiles. This suggests that either the activity of these neurons is ignored when viewing Pulfrich stimuli, or that current theories relating neuronal properties to perception in the Pulfrich effect need to be reevaluated. PMID:15788521

  16. Local Bifurcations and Optimal Theory in a Delayed Predator-Prey Model with Threshold Prey Harvesting

    NASA Astrophysics Data System (ADS)

    Tankam, Israel; Tchinda Mouofo, Plaire; Mendy, Abdoulaye; Lam, Mountaga; Tewa, Jean Jules; Bowong, Samuel

    2015-06-01

    We investigate the effects of time delay and piecewise-linear threshold policy harvesting for a delayed predator-prey model. It is the first time that Holling response function of type III and the present threshold policy harvesting are associated with time delay. The trajectories of our delayed system are bounded; the stability of each equilibrium is analyzed with and without delay; there are local bifurcations as saddle-node bifurcation and Hopf bifurcation; optimal harvesting is also investigated. Numerical simulations are provided in order to illustrate each result.

  17. Delays in new drug applications in Japan and industrial R&D strategies.

    PubMed

    Hirai, Y; Kinoshita, H; Kusama, M; Yasuda, K; Sugiyama, Y; Ono, S

    2010-02-01

    The gap between Japan and both the United States (US) and the European Union (EU) with regard to access to new drugs is becoming a major issue in Japan. We analyzed the time lags involved in new drug application (NDA) and biological license application submissions in Japan, the US, and the EU in order to identify the causes of delayed access. The time lag related to submission of applications ("submission lag") was longer for in-licensed products and for non-Japanese companies. Factors related to costs of clinical studies and potential volumes of sales were not associated with the submission lag. A bridging strategy (extrapolative use of foreign clinical data in the clinical data package based on International Conference on Harmonisation guideline E5) seemed to reduce submission lag, but the association between the two diminished when the cause-and-effect relationship was specifically investigated. These results suggest that multinational companies are likely to place more emphasis on the choice of development strategies that successfully lead to their goal rather than on direct costs and expected sales when deciding to introduce their pharmaceutical products in Japan. Our findings indicate that the clinical development guidances that helps pharmaceutical companies decide on investment and strategies are also the key to narrowing the gap in access to new drugs.

  18. On the robustness of vocal development: an examination of infants with moderate-to-severe hearing loss and additional risk factors.

    PubMed

    Nathani, Suneeti; Oller, D Kimbrough; Neal, A Rebecca

    2007-12-01

    Onset of canonical babbling by 10 months of age is surprisingly robust in infancy, suggesting that there must be deep biological forces that keep the development of this key vocal capability on course. This study further evaluated the robustness of canonical babbling and other aspects of prelinguistic vocal development. Longitudinal observation was conducted on 4 infants who were at risk for abnormal vocal development because of bilateral moderate-to-severe sensorineural hearing loss and additional risk factors for developmental delay. Two of the infants were delayed in the onset of canonical babbling and showed greater fluctuation in canonical babbling ratios following its onset than did typically developing infants. On the same measures, the remaining 2 infants were within normal limits, although their age of onset for canonical babbling was later than the mean for typically developing infants. Volubility was not notably different from typically developing infants. Differences from typically developing infants were, however, observed in proportions of various prelinguistic syllable types produced across time. Results provided further evidence of robustness of canonical babbling and indicated the need for a large parametric study evaluating effects of varying degrees of hearing loss and other risk factors on vocal development.

  19. Now for Me, Later for Us? Effects of Group Context on Temporal Discounting

    PubMed Central

    Charlton, Shawn R.; Yi, Richard; Porter, Caitlin; Carter, Anne E.; Bickel, Warren; Rachlin, Howard

    2013-01-01

    Delayed rewards are less valuable than immediate rewards. This well-established finding has focused almost entirely on individual outcomes. However, are delayed rewards similarly discounted if they are shared by a group? The current article reports on three experiments exploring the effect of group context on delay discounting. Results indicate that discount rates of individual and group rewards were highly correlated, but that respondents were more willing to wait (decreased discounting) for shared outcomes than for individual outcomes. An explanatory model is proposed suggesting that decreased discount rates in group contexts may be due to the way the effects of both delay and social discounting are combined. That is, in a group context, a person values both a future reward (discounted by delay) and a present reward to another person (discounted by the social distance between them). The results are explained by a combined discount function containing a delay factor and a factor representing the social distance between the decision maker and group members. Practical implications of the fact that shared consequences can increase individual self-control are also discussed. PMID:23641123

  20. The Effects of Embedded Skill Instruction on the Acquisition of Target and Nontarget Skills in Preschoolers with Developmental Delays.

    ERIC Educational Resources Information Center

    Daugherty, Stefanie; Grisham-Brown, Jennifer; Hemmeter, Mary Louise

    2001-01-01

    In the current study, a constant time delay (CTD) procedure was embedded in classroom activities and routines to teach counting to three preschool children with speech and language delays. CTD was effective in teaching numbers to all three children. One child out of two also was able to acquire non-target information. (Contains references.) (CR)

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