Time delays between core power production and external detector response from Monte Carlo calculations

International Nuclear Information System (INIS)

Valentine, T.E.; Mihalczo, J.T.

1996-01-01

One primary concern for design of safety systems for reactors is the time response of external detectors to changes in the core. This paper describes a way to estimate the time delay between the core power production and the external detector response using Monte Carlo calculations and suggests a technique to measure the time delay. The Monte Carlo code KENO-NR was used to determine the time delay between the core power production and the external detector response for a conceptual design of the Advanced Neutron Source (ANS) reactor. The Monte Carlo estimated time delay was determined to be about 10 ms for this conceptual design of the ANS reactor

Lesions Responsible for Delayed Oral Transit Time in Post-stroke Dysphagia.

Science.gov (United States)

Moon, Hyun Im; Yoon, Seo Yeon; Yi, Tae Im; Jeong, Yoon Jeong; Cho, Tae Hwan

2017-10-11

Some stroke patients show oral phase dysphagia, characterized by a markedly prolonged oral transit time that hinders oral feeding. The aim of this study was to clarify the clinical characteristics and lesions responsible for delayed swallowing. We reviewed 90 patients with stroke. The oral processing time plus the postfaucial aggregation time required to swallow semisolid food was assessed. The patients were divided into two groups according to oral transit time, and we analyzed the differences in characteristics such as demographic factors, lesion factors, and cognitive function. Logistic regression analyses were performed to examine the predictors of delayed oral transit time. Lesion location and volume were measured on brain magnetic resonance images. We generated statistic maps of lesions related to delayed oral phase in swallowing using voxel-based lesion symptom mapping (VLSM). The group of patients who showed delayed oral transit time had significantly low cognitive function. Also, in a regression model, delayed oral phase was predicted with low K-MMSE (Korean version of the Mini Mental Status Exam). Using VLSM, we found the lesion location to be associated with delayed oral phase after adjusting for K-MMSE score. Although these results did not reach statistical significance, they showed the lesion pattern with predominant distribution in the left frontal lobe. Delayed oral phase in post-stroke patients was not negligible clinically. Patients' cognitive impairments affect the oral transit time. When adjusting it, we found a trend that the lesion responsible for delayed oral phase was located in the left frontal lobe, though the association did not reach significance. The delay might be related to praxis function.

Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants.

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Maria Sellitto

Full Text Available Celiac disease (CD is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8 and the environmental trigger (gluten are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to

Impulsive Delayed Reward Discounting as a Genetically-Influenced Target for Drug Abuse Prevention: A Critical Evaluation

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Joshua C. Gray

2015-09-01

Full Text Available This review evaluates the viability of delayed reward discounting (DRD, an index of how much an individual devalues a future reward based on its delay in time, for genetically-informed drug abuse prevention. A review of the literature suggests that impulsive DRD is robustly associated with drug addiction and meets most of the criteria for being an endophenotype, albeit with mixed findings for specific molecular genetic influences. Several modes of experimental manipulation have been demonstrated to reduce DRD acutely. These include behavioral strategies, such as mindfulness, reward bundling, and episodic future thinking; pharmacological interventions, including noradrengic agonists, adrenergic agonists, and multiple monoamine agonists; and neuromodulatory interventions, such as transcranial magnetic stimulation and transcranial direct current stimulation. However, the generalization of these interventions to positive clinical outcomes remains unclear and no studies to date have examined interventions on DRD in the context of prevention. Collectively, these findings suggest it would be premature to target DRD for genetically-informed prevention. Indeed, given the evidence of environmental contributions such as early life adversity to impulsive DRD, whether genetically-informed secondary prevention would ever be warranted is debatable. However, progress in identifying polymorphisms associated with DRD preference could further clarify the underlying biological systems implicated in impulsive DRD for further progress in pharmacological and neuromodulatory interventions. Furthermore, independent of genetically-informed prevention, impulsive DRD is a qualitatively different risk factor from existing prevention programs and is generally worthy of investigation as a novel and promising drug abuse prevention target.

Adjoint method provides phase response functions for delay-induced oscillations.

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Kotani, Kiyoshi; Yamaguchi, Ikuhiro; Ogawa, Yutaro; Jimbo, Yasuhiko; Nakao, Hiroya; Ermentrout, G Bard

2012-07-27

Limit-cycle oscillations induced by time delay are widely observed in various systems, but a systematic phase-reduction theory for them has yet to be developed. Here we present a practical theoretical framework to calculate the phase response function Z(θ), a fundamental quantity for the theory, of delay-induced limit cycles with infinite-dimensional phase space. We show that Z(θ) can be obtained as a zero eigenfunction of the adjoint equation associated with an appropriate bilinear form for the delay differential equations. We confirm the validity of the proposed framework for two biological oscillators and demonstrate that the derived phase equation predicts intriguing multimodal locking behavior.

Genetic and histological studies on the delayed systemic movement of Tobacco Mosaic Virus in Arabidopsis thaliana

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Matus José

2008-09-01

Full Text Available Abstract Background Viral infections and their spread throughout a plant require numerous interactions between the host and the virus. While new functions of viral proteins involved in these processes have been revealed, current knowledge of host factors involved in the spread of a viral infection is still insufficient. In Arabidopsis thaliana, different ecotypes present varying susceptibilities to Tobacco mosaic virus strain U1 (TMV-U1. The rate of TMV-U1 systemic movement is delayed in ecotype Col-0 when compared with other 13 ecotypes. We followed viral movement through vascular tissue in Col-0 plants by electronic microscopy studies. In addition, the delay in systemic movement of TMV-U1 was genetically studied. Results TMV-U1 reaches apical leaves only after 18 days post rosette inoculation (dpi in Col-0, whereas it is detected at 9 dpi in the Uk-4 ecotype. Genetic crosses between Col-0 and Uk-4 ecotypes, followed by analysis of viral movement in F1 and F2 populations, revealed that this delayed movement correlates with a recessive, monogenic and nuclear locus. The use of selected polymorphic markers showed that this locus, denoted DSTM1 (Delayed Systemic Tobamovirus Movement 1, is positioned on the large arm of chromosome II. Electron microscopy studies following the virion's route in stems of Col-0 infected plants showed the presence of curved structures, instead of the typical rigid rods of TMV-U1. This was not observed in the case of TMV-U1 infection in Uk-4, where the observed virions have the typical rigid rod morphology. Conclusion The presence of defectively assembled virions observed by electron microscopy in vascular tissue of Col-0 infected plants correlates with a recessive delayed systemic movement trait of TMV-U1 in this ecotype.

Effect of Phase Response Curve Skew on Synchronization with and without Conduction Delays

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Carmen eCanavier

2013-12-01

Full Text Available A central problem in cortical processing including sensory binding and attentional gating is how neurons can synchronize their responses with zero or near-zero time lag. For a spontaneously firing neuron, an input from another neuron can delay or advance the next spike by different amounts depending upon the timing of the input relative to the previous spike. This information constitutes the phase response curve (PRC. We present a simple graphical method for determining the effect of PRC shape on synchronization tendencies and illustrate it using type 1 PRCs, which consist entirely of advances (delays in response to excitation (inhibition. We obtained the following generic solutions for type 1 PRCs, which include the pulse coupled leaky integrate and fire model. For pairs with mutual excitation, exact synchrony can be stable for strong coupling because of the stabilizing effect of the causal limit region of the PRC in which an input triggers a spike immediately upon arrival. However, synchrony is unstable for short delays, because delayed inputs arrive during a refractory period and cannot trigger an immediate spike. Right skew destabilizes antiphase and enables modes with time lags that grow as the conduction delay is increased. Therefore, right skew favors near-synchrony at short conduction delays and a gradual transition between synchrony and antiphase for pairs coupled by mutual excitation. For pairs with mutual inhibition, zero time lag synchrony is stable for conduction delays ranging from zero to a substantial fraction of the period for pairs. However, for right skew there is a preferred antiphase mode at short delays. In contrast to mutual excitation, left skew destabilizes antiphase for mutual inhibition so that synchrony dominates at short delays as well. These pairwise synchronization tendencies constrain the synchronization properties of neurons embedded in larger networks.

Genetic and epigenetic features in radiation sensitivity. Part I: Cell signalling in radiation response

International Nuclear Information System (INIS)

Bourguignon, Michel H.; Gisone, Pablo A.; Perez, Maria R.; Michelin, Severino; Dubner, Diana; Giorgio, Marina di; Carosella, Edgardo D.

2005-01-01

Recent progress especially in the field of gene identification and expression has attracted greater attention to genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. It has been proposed that the occurrence and severity of the adverse reactions to radiation therapy are also influenced by such genetic susceptibility. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation offering a better likelihood of cure for malignant tumours. This paper, the first of two parts, reviews the main mechanisms involved in cell response to ionising radiation. DNA repair machinery and cell signalling pathways are considered and their role in radiosensitivity is analysed. The implication of non-targeted and delayed effects in radiosensitivity is also discussed. (orig.)

Diagnostic outcome following routine genetics clinic referral for the assessment of global developmental delay.

LENUS (Irish Health Repository)

Shahdadpuri, R

2012-02-01

The aim of this study was to ascertain the diagnostic yield following a routine genetics clinic referral for the assessment of global developmental delay. Detailed retrospective review of 119 complete consecutive case notes of patients referred to one single clinical geneticist over a 14 month time period was undertaken (n = 119; 54 males, 65 females). The age at initial review ranged from 2 months to 37 years 3 months (mean 8 y 3 mo [SD 7 y 10 mo]). We made a diagnosis in 36\\/119 (30%); 21\\/36 were new diagnoses and 15\\/36 were confirmations of diagnoses. We removed a wrong diagnostic label in 8\\/119 (7%). In 3\\/8 we were able to achieve a diagnosis but in 5\\/8 no alternative diagnosis was reached. We had a better diagnostic rate where the patients were dysmorphic (odds ratio [OR] 1.825; 95% confidence interval [CI] 1.065 to 3.128, p = 0.044). In the majority, the diagnosis was made by clinical examination only. Molecular diagnosis was reached in seven cases. Five cases were confirmed by cytogenetic analysis. Brain magnetic resonance imaging (MRI) revealed a diagnosis in three cases. This study confirms the importance of a clinical genetics assessment in the investigation of global developmental delay.

Resistance to Change of Responding Maintained by Unsignaled Delays to Reinforcement: A Response-Bout Analysis

Science.gov (United States)

Podlesnik, Christopher A.; Jimenez-Gomez, Corina; Ward, Ryan D.; Shahan, Timothy A.

2006-01-01

Previous experiments have shown that unsignaled delayed reinforcement decreases response rates and resistance to change. However, the effects of different delays to reinforcement on underlying response structure have not been investigated in conjunction with tests of resistance to change. In the present experiment, pigeons responded on a…

Delayed system response times affect immediate physiology and the dynamics of subsequent button press behavior.

Science.gov (United States)

Kohrs, Christin; Hrabal, David; Angenstein, Nicole; Brechmann, André

2014-11-01

System response time research is an important issue in human-computer interactions. Experience with technical devices and general rules of human-human interactions determine the user's expectation, and any delay in system response time may lead to immediate physiological, emotional, and behavioral consequences. We investigated such effects on a trial-by-trial basis during a human-computer interaction by measuring changes in skin conductance (SC), heart rate (HR), and the dynamics of button press responses. We found an increase in SC and a deceleration of HR for all three delayed system response times (0.5, 1, 2 s). Moreover, the data on button press dynamics was highly informative since subjects repeated a button press with more force in response to delayed system response times. Furthermore, the button press dynamics could distinguish between correct and incorrect decisions and may thus even be used to infer the uncertainty of a user's decision. Copyright © 2014 Society for Psychophysiological Research.

Time delay and duration of ionospheric total electron content responses to geomagnetic disturbances

Directory of Open Access Journals (Sweden)

J. Liu

2010-03-01

Full Text Available Although positive and negative signatures of ionospheric storms have been reported many times, global characteristics such as the time of occurrence, time delay and duration as well as their relations to the intensity of the ionospheric storms have not received enough attention. The 10 years of global ionosphere maps (GIMs of total electron content (TEC retrieved at Jet Propulsion Laboratory (JPL were used to conduct a statistical study of the time delay of the ionospheric responses to geomagnetic disturbances. Our results show that the time delays between geomagnetic disturbances and TEC responses depend on season, magnetic local time and magnetic latitude. In the summer hemisphere at mid- and high latitudes, the negative storm effects can propagate to the low latitudes at post-midnight to the morning sector with a time delay of 4–7 h. As the earth rotates to the sunlight, negative phase retreats to higher latitudes and starts to extend to the lower latitude toward midnight sector. In the winter hemisphere during the daytime and after sunset at mid- and low latitudes, the negative phase appearance time is delayed from 1–10 h depending on the local time, latitude and storm intensity compared to the same area in the summer hemisphere. The quick response of positive phase can be observed at the auroral area in the night-side of the winter hemisphere. At the low latitudes during the dawn-noon sector, the ionospheric negative phase responses quickly with time delays of 5–7 h in both equinoctial and solsticial months.

Our results also manifest that there is a positive correlation between the intensity of geomagnetic disturbances and the time duration of both the positive phase and negative phase. The durations of both negative phase and positive phase have clear latitudinal, seasonal and magnetic local time (MLT dependence. In the winter hemisphere, long durations for the positive phase are 8–11 h and 12–14 h during the daytime at

Time delay and duration of ionospheric total electron content responses to geomagnetic disturbances

Directory of Open Access Journals (Sweden)

J. Liu

2010-03-01

Full Text Available Although positive and negative signatures of ionospheric storms have been reported many times, global characteristics such as the time of occurrence, time delay and duration as well as their relations to the intensity of the ionospheric storms have not received enough attention. The 10 years of global ionosphere maps (GIMs of total electron content (TEC retrieved at Jet Propulsion Laboratory (JPL were used to conduct a statistical study of the time delay of the ionospheric responses to geomagnetic disturbances. Our results show that the time delays between geomagnetic disturbances and TEC responses depend on season, magnetic local time and magnetic latitude. In the summer hemisphere at mid- and high latitudes, the negative storm effects can propagate to the low latitudes at post-midnight to the morning sector with a time delay of 4–7 h. As the earth rotates to the sunlight, negative phase retreats to higher latitudes and starts to extend to the lower latitude toward midnight sector. In the winter hemisphere during the daytime and after sunset at mid- and low latitudes, the negative phase appearance time is delayed from 1–10 h depending on the local time, latitude and storm intensity compared to the same area in the summer hemisphere. The quick response of positive phase can be observed at the auroral area in the night-side of the winter hemisphere. At the low latitudes during the dawn-noon sector, the ionospheric negative phase responses quickly with time delays of 5–7 h in both equinoctial and solsticial months. Our results also manifest that there is a positive correlation between the intensity of geomagnetic disturbances and the time duration of both the positive phase and negative phase. The durations of both negative phase and positive phase have clear latitudinal, seasonal and magnetic local time (MLT dependence. In the winter hemisphere, long durations for the positive phase are 8–11 h and 12–14 h during the daytime at middle

Is pupillary response a reliable index of word recognition? Evidence from a delayed lexical decision task.

Science.gov (United States)

Haro, Juan; Guasch, Marc; Vallès, Blanca; Ferré, Pilar

2017-10-01

Previous word recognition studies have shown that the pupillary response is sensitive to a word's frequency. However, such a pupillary effect may be due to the process of executing a response, instead of being an index of word processing. With the aim of exploring this possibility, we recorded the pupillary responses in two experiments involving a lexical decision task (LDT). In the first experiment, participants completed a standard LDT, whereas in the second they performed a delayed LDT. The delay in the response allowed us to compare pupil dilations with and without the response execution component. The results showed that pupillary response was modulated by word frequency in both the standard and the delayed LDT. This finding supports the reliability of using pupillometry for word recognition research. Importantly, our results also suggest that tasks that do not require a response during pupil recording lead to clearer and stronger effects.

Response to Competitive Entry: A Rationale for Delayed Defensive Reaction

OpenAIRE

Ajay Kalra; Surendra Rajiv; Kannan Srinivasan

1998-01-01

Empirical studies examining responses to new product entries come to the puzzling conclusion that, in general, an incumbent reacts to a new entrant after a significant delay. Even easy-to-implement price cuts are observed after significant lag following entry. These findings seem to contradict the existing literature that either implicitly assumes or strongly advocates immediate defensive responses to limit competitive encroachment. When a competing firm enters the market, consumers may be un...

Genetic Influences on Response to Alcohol and Response to Pharmacotherapies for Alcoholism

Science.gov (United States)

Enoch, Mary-Anne

2014-01-01

Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5′ and 3′ functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs / ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage. PMID:24220019

Periodic solutions of delayed predator-prey model with the Beddington-DeAngelis functional response

Energy Technology Data Exchange (ETDEWEB)

Huo Haifeng [Institute of Applied Mathematics, Lanzhou University of Technology, Lanzhou, Gansu 730050 (China)]. E-mail: hfhuo@lut.cn; Li Wantong [Department of Mathematics, Lanzhou University Lanzhou, Gansu 730000 (China)]. E-mail: wtli@lzu.edu.cn; Nieto, Juan J. [Departamento de Analisis Matematico, Facultad de Matematicas, Universidad de Santiago de Compostela 15782 (Spain)]. E-mail: amnieto@usc.es

2007-07-15

By using the continuation theorem based on Gaines and Mawhin's coincidence degree, sufficient and realistic conditions are obtained for the global existence of positive periodic solutions for a delayed predator-prey model with the Beddington-DeAngelis functional response. Our results are applicable to state dependent and distributed delays.

Changes in the long-term delayed response of platinum self-powered detector with irradiation

International Nuclear Information System (INIS)

Parent, G.; Serdula, K.J.; Eng, P.

1989-01-01

Two long-term delayed response characteristics have been observed for platinum, Pt, detectors in the Gentilly-2 600 MW(e) CANDU PHWR reactor. The first effect is a dip in the signal two to three hours after a shutdown, due to the (n,beta) interactions of Mn-55 and Ni-64 which exist as impurities in the detector assembly. The second effect is an increase of the delayed fraction of the signal. The low neutron absorption cross-section of Pt-196 combined with the conversion of the Pt-194 and Pt-195 results in build-up of the Pt-196. The long half-lives associated with the beta-emission in the transmutation of Pt-196 to Hg-198 or Hg-199 give rise to the observed long-term delayed response

Genetics Home Reference: SADDAN

Science.gov (United States)

... view the expand/collapse boxes. Description SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a ... Genetic Testing (1 link) Genetic Testing Registry: Severe achondroplasia with developmental delay and acanthosis nigricans Other Diagnosis ...

Delayed response task performance as a function of age in cynomolgus monkeys (Macaca fascicularis)

DEFF Research Database (Denmark)

Darusman, H S; Call, J; Sajuthi, D

2014-01-01

We compared delayed response task performance in young, middle-aged, and old cynomolgus monkeys using three memory tests that have been used with non-human primates. Eighteen cynomolgus monkeys-6 young (4-9 years), 6 middle-aged (10-19 years), and 6 old (above 20 years)-were tested. In general......, the old monkeys scored significantly worse than did the animals in the two other age groups. Longer delays between stimulus presentation and response increased the performance differences between the old and younger monkeys. The old monkeys in particular showed signs of impaired visuo-spatial memory...

Electroencephalographic Response to Sodium Nitrite May Predict Delayed Cerebral Ischemia After Severe Subarachnoid Hemorrhage.

Science.gov (United States)

Garry, Payashi S; Rowland, Matthew J; Ezra, Martyn; Herigstad, Mari; Hayen, Anja; Sleigh, Jamie W; Westbrook, Jon; Warnaby, Catherine E; Pattinson, Kyle T S

2016-11-01

Aneurysmal subarachnoid hemorrhage often leads to death and poor clinical outcome. Injury occurring during the first 72 hours is termed "early brain injury," with disruption of the nitric oxide pathway playing an important pathophysiologic role in its development. Quantitative electroencephalographic variables, such as α/δ frequency ratio, are surrogate markers of cerebral ischemia. This study assessed the quantitative electroencephalographic response to a cerebral nitric oxide donor (intravenous sodium nitrite) to explore whether this correlates with the eventual development of delayed cerebral ischemia. Unblinded pilot study testing response to drug intervention. Neuroscience ICU, John Radcliffe Hospital, Oxford, United Kingdom. Fourteen World Federation of Neurosurgeons grades 3, 4, and 5 patients (mean age, 52.8 yr [range, 41-69 yr]; 11 women). IV sodium nitrite (10 μg/kg/min) for 1 hour. Continuous electroencephalographic recording for 2 hours. The alpha/delta frequency ratio was measured before and during IV sodium nitrite infusion. Seven of 14 patients developed delayed cerebral ischemia. There was a +30% to +118% (range) increase in the alpha/delta frequency ratio in patients who did not develop delayed cerebral ischemia (p frequency ratio in those patients who did develop delayed cerebral ischemia (range, +11% to -31%) (p = 0.006, multivariate analysis accounting for major confounds). Administration of sodium nitrite after severe subarachnoid hemorrhage differentially influences quantitative electroencephalographic variables depending on the patient's susceptibility to development of delayed cerebral ischemia. With further validation in a larger sample size, this response may be developed as a tool for risk stratification after aneurysmal subarachnoid hemorrhage.

State estimation for Markov-type genetic regulatory networks with delays and uncertain mode transition rates

International Nuclear Information System (INIS)

Liang Jinling; Lam, James; Wang Zidong

2009-01-01

This Letter is concerned with the robust state estimation problem for uncertain time-delay Markovian jumping genetic regulatory networks (GRNs) with SUM logic, where the uncertainties enter into both the network parameters and the mode transition rate. The nonlinear functions describing the feedback regulation are assumed to satisfy the sector-like conditions. The main purpose of the problem addressed is to design a linear estimator to approximate the true concentrations of the mRNA and protein through available measurement outputs. By resorting to the Lyapunov functional method and some stochastic analysis tools, it is shown that if a set of linear matrix inequalities (LMIs) is feasible, the desired state estimator, that can ensure the estimation error dynamics to be globally robustly asymptotically stable in the mean square, exists. The obtained LMI conditions are dependent on both the lower and the upper bounds of the delays. An illustrative example is presented to demonstrate the feasibility of the proposed estimation schemes.

A Novel Energy Saving Algorithm with Frame Response Delay Constraint in IEEE 802.16e

Science.gov (United States)

Nga, Dinh Thi Thuy; Kim, Mingon; Kang, Minho

Sleep-mode operation of a Mobile Subscriber Station (MSS) in IEEE 802.16e effectively saves energy consumption; however, it induces frame response delay. In this letter, we propose an algorithm to quickly find the optimal value of the final sleep interval in sleep-mode in order to minimize energy consumption with respect to a given frame response delay constraint. The validations of our proposed algorithm through analytical results and simulation results suggest that our algorithm provide a potential guidance to energy saving.

Genetic variation of transgenerational plasticity of offspring germination in response to salinity stress and the seed transcriptome of Medicago truncatula.

Science.gov (United States)

Vu, Wendy T; Chang, Peter L; Moriuchi, Ken S; Friesen, Maren L

2015-04-01

Transgenerational plasticity provides phenotypic variation that contributes to adaptation. For plants, the timing of seed germination is critical for offspring survival in stressful environments, as germination timing can alter the environmental conditions a seedling experiences. Stored seed transcripts are important determinants of seed germination, but have not previously been linked with transgenerational plasticity of germination behavior. In this study we used RNAseq and growth chamber experiments of the model legume M. trucantula to test whether parental exposure to salinity stress influences the expression of stored seed transcripts and early offspring traits and test for genetic variation. We detected genotype-dependent parental environmental effects (transgenerational plasticity) on the expression levels of stored seed transcripts, seed size, and germination behavior of four M. truncatula genotypes. More than 50% of the transcripts detected in the mature, ungerminated seed transcriptome were annotated as regulating seed germination, some of which are involved in abiotic stress response and post-embryonic development. Some genotypes showed increased seed size in response to parental exposure to salinity stress, but no parental environmental influence on germination timing. In contrast, other genotypes showed no seed size differences across contrasting parental conditions but displayed transgenerational plasticity for germimation timing, with significantly delayed germination in saline conditions when parental plants were exposed to salinity. In genotypes that show significant transgenerational plastic germination response, we found significant coexpression networks derived from salt responsive transcripts involved in post-transcriptional regulation of the germination pathway. Consistent with the delayed germination response to saline conditions in these genotypes, we found genes associated with dormancy and up-regulation of abscisic acid (ABA). Our results

Patients and acute coronary syndrome - Prehospital delay and mental and emotional delaying responses - a qualitative study

DEFF Research Database (Denmark)

Lorentzen, Vibeke; Larsen, Birte Hedegaard

2016-01-01

to identify and discuss patient’s mental and emotional responses, including interpretations and delaying strategies concerning Acute Coronary Syndrome symptoms, with a view to elucidating patterns in the pre-hospital decision-making process of female and male persons to contact medical services...... cardinal. Male participants often used expletives and expressed symptoms in concrete terms. Women expressed symptoms in vaguer terms. Both genders used linguistic metaphors. The implications for nursing emphasised the impact of prodromal symptoms, mental and emotional withdrawal, and linguistic...

Patients and acute coronary syndrome - Prehospital delay and mental and emotional delaying responses - a qualitative study

DEFF Research Database (Denmark)

Lorentzen, Vibeke; Larsen, Birte Hedegaard

2016-01-01

cardinal. Male participants often used expletives and expressed symptoms in concrete terms. Women expressed symptoms in vaguer terms. Both genders used linguistic metaphors. The implications for nursing emphasised the impact of prodromal symptoms, mental and emotional withdrawal, and linguistic...... to identify and discuss patient’s mental and emotional responses, including interpretations and delaying strategies concerning Acute Coronary Syndrome symptoms, with a view to elucidating patterns in the pre-hospital decision-making process of female and male persons to contact medical services...

Frequency adaptation in controlled stochastic resonance utilizing delayed feedback method: two-pole approximation for response function.

Science.gov (United States)

Tutu, Hiroki

2011-06-01

Stochastic resonance (SR) enhanced by time-delayed feedback control is studied. The system in the absence of control is described by a Langevin equation for a bistable system, and possesses a usual SR response. The control with the feedback loop, the delay time of which equals to one-half of the period (2π/Ω) of the input signal, gives rise to a noise-induced oscillatory switching cycle between two states in the output time series, while its average frequency is just smaller than Ω in a small noise regime. As the noise intensity D approaches an appropriate level, the noise constructively works to adapt the frequency of the switching cycle to Ω, and this changes the dynamics into a state wherein the phase of the output signal is entrained to that of the input signal from its phase slipped state. The behavior is characterized by power loss of the external signal or response function. This paper deals with the response function based on a dichotomic model. A method of delay-coordinate series expansion, which reduces a non-Markovian transition probability flux to a series of memory fluxes on a discrete delay-coordinate system, is proposed. Its primitive implementation suggests that the method can be a potential tool for a systematic analysis of SR phenomenon with delayed feedback loop. We show that a D-dependent behavior of poles of a finite Laplace transform of the response function qualitatively characterizes the structure of the power loss, and we also show analytical results for the correlation function and the power spectral density.

Ocean acidification genetics - Genetics and genomics of response to ocean acidification

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — We are applying a variety of genetic tools to assess the response of our ocean resources to ocean acidification, including gene expression techniques, identification...

Quantitative genetics of migration syndromes: a study of two barn swallow populations.

Science.gov (United States)

Teplitsky, C; Mouawad, N G; Balbontin, J; De Lope, F; Møller, A P

2011-09-01

Migration is a complex trait although little is known about genetic correlations between traits involved in such migration syndromes. To assess the migratory responses to climate change, we need information on genetic constraints on evolutionary potential of arrival dates in migratory birds. Using two long-term data sets on barn swallows Hirundo rustica (from Spain and Denmark), we show for the first time in wild populations that spring arrival dates are phenotypically and genetically correlated with morphological and life history traits. In the Danish population, length of outermost tail feathers and wing length were negatively genetically correlated with arrival date. In the Spanish population, we found a negative genetic correlation between arrival date and time elapsed between arrival date and laying date, constraining response to selection that favours both early arrival and shorter delays. This results in a decreased rate of adaptation, not because of constraints on arrival date, but constraints on delay before breeding, that is, a trait that can be equally important in the context of climate change. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Genetic polymorphisms and lipid response to dietary changes in humans

NARCIS (Netherlands)

Weggemans, R.M.; Zock, P.L.; Ordovas, J.M.; Ramos-Galluzzi, J.; Katan, M.B.

2001-01-01

Previous studies on the effects of genetic polymorphisms on the serum cholesterol response to dietary treatments were often inconsistent and frequently involved small numbers of subjects. We studied the effect of 10 genetic polymorphisms on the responses of serum cholesterol to saturated and trans

Plant genetic and molecular responses to water deficit

Directory of Open Access Journals (Sweden)

Silvio Salvi

2011-02-01

Full Text Available Plant productivity is severely affected by unfavourable environmental conditions (biotic and abiotic stresses. Among others, water deficit is the plant stress condition which mostly limits the quality and the quantity of plant products. Tolerance to water deficit is a polygenic trait strictly dependent on the coordinated expression of a large set of genes coding for proteins directly involved in stress-induced protection/repair mechanisms (dehydrins, chaperonins, enzymes for the synthesis of osmoprotectants and detoxifying compounds, and others as well as genes involved in transducing the stress signal and regulating gene expression (transcription factors, kinases, phosphatases. Recently, research activities in the field evolved from the study of single genes directly involved in cellular stress tolerance (functional genes to the identification and characterization of key regulatory genes involved in stress perception and transduction and able to rapidly and efficiently activate the complex gene network involved in the response to stress. The complexity of the events occurring in response to stress have been recently approached by genomics tools; in fact the analysis of transcriptome, proteome and metabolome of a plant tissue/cell in response to stress already allowed to have a global view of the cellular and molecular events occurring in response to water deficit, by the identification of genes activated and co-regulated by the stress conditions and the characterization of new signalling pathways. Moreover the recent application of forward and reverse genetic approaches, trough mutant collection development, screening and characterization, is giving a tremendous impulse to the identification of gene functions with key role in stress tolerance. The integration of data obtained by high-throughput genomic approaches, by means of powerful informatic tools, is allowing nowadays to rapidly identify of major genes/QTLs involved in stress tolerance

Lactic acid delays the inflammatory response of human monocytes

Energy Technology Data Exchange (ETDEWEB)

Peter, Katrin, E-mail: katrin.peter@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Rehli, Michael, E-mail: michael.rehli@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Singer, Katrin, E-mail: katrin.singer@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Renner-Sattler, Kathrin, E-mail: kathrin.renner-sattler@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Kreutz, Marina, E-mail: marina.kreutz@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany)

2015-02-13

Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors.

Lactic acid delays the inflammatory response of human monocytes

International Nuclear Information System (INIS)

Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

2015-01-01

Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors

Response of an oscillatory differential delay equation to a single stimulus.

Science.gov (United States)

Mackey, Michael C; Tyran-Kamińska, Marta; Walther, Hans-Otto

2017-04-01

Here we analytically examine the response of a limit cycle solution to a simple differential delay equation to a single pulse perturbation of the piecewise linear nonlinearity. We construct the unperturbed limit cycle analytically, and are able to completely characterize the perturbed response to a pulse of positive amplitude and duration with onset at different points in the limit cycle. We determine the perturbed minima and maxima and period of the limit cycle and show how the pulse modifies these from the unperturbed case.

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

Science.gov (United States)

Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

Effect of processing time delay on the dose response of Kodak EDR2 film.

Science.gov (United States)

Childress, Nathan L; Rosen, Isaac I

2004-08-01

Kodak EDR2 film is a widely used two-dimensional dosimeter for intensity modulated radiotherapy (IMRT) measurements. Our clinical use of EDR2 film for IMRT verifications revealed variations and uncertainties in dose response that were larger than expected, given that we perform film calibrations for every experimental measurement. We found that the length of time between film exposure and processing can affect the absolute dose response of EDR2 film by as much as 4%-6%. EDR2 films were exposed to 300 cGy using 6 and 18 MV 10 x 10 cm2 fields and then processed after time delays ranging from 2 min to 24 h. An ion chamber measured the relative dose for these film exposures. The ratio of optical density (OD) to dose stabilized after 3 h. Compared to its stable value, the film response was 4%-6% lower at 2 min and 1% lower at 1 h. The results of the 4 min and 1 h processing time delays were verified with a total of four different EDR2 film batches. The OD/dose response for XV2 films was consistent for time periods of 4 min and 1 h between exposure and processing. To investigate possible interactions of the processing time delay effect with dose, single EDR2 films were irradiated to eight different dose levels between 45 and 330 cGy using smaller 3 x 3 cm2 areas. These films were processed after time delays of 1, 3, and 6 h, using 6 and 18 MV photon qualities. The results at all dose levels were consistent, indicating that there is no change in the processing time delay effect for different doses. The difference in the time delay effect between the 6 and 18 MV measurements was negligible for all experiments. To rule out bias in selecting film regions for OD measurement, we compared the use of a specialized algorithm that systematically determines regions of interest inside the 10 x 10 cm2 exposure areas to manually selected regions of interest. There was a maximum difference of only 0.07% between the manually and automatically selected regions, indicating that the use of

Delays in early neuropsychic development: Approaches to diagnosis

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N. N. Zavadenko

2015-01-01

Full Text Available The population frequency of neuropsychic developmental delays in infants is estimated at nearly 10%; that of global intellectual disability (mental retardation is at 1-3%. Delayed development is denned as a substantial retardation as compared to the standard indicators in any of the basic spheres: motor, communicative, cognitive, adaptive-behavioral, and socioemotional ones. Global developmental delay is characterized by a significant lag in two or more spheres. The use of current diagnostic techniques, such as the Bayley or Griffiths scales, can provide an objective quantitative assessment of both an infant's overall development and indicators in individual spheres. At the preliminary examination stage, it is expedient to carry out a Denver developmental screening test that may be directly used in a doctor's consulting room. The causes of global developmental delay/intellectual disability in infants may be perinatal central nervous system (CNS lesions; brain malformations; intrauterine infections; intrauterine intoxications; early-onset psychoneurological diseases (neuroinfections, CNS injuries, epilepsies, autism spectrum disorders, etc.; congenital hypothyroidism; genetic diseases. Among all genetic causes of global developmental delay/intellectual disability, there are chromosomal anomalies (25-30%, monogenic diseases (metabolic diseases, neuroectodermal syndromes, diseases with predominant grey and white matter involvement. The diagnostic possibilities of current genetic methods are considered.

Researcher responsibilities and genetic counseling for pure-bred dog populations.

Science.gov (United States)

Bell, Jerold S

2011-08-01

Breeders of dogs have ethical responsibilities regarding the testing and management of genetic disease. Molecular genetics researchers have their own responsibilities, highlighted in this article. Laboratories offering commercial genetic testing should have proper sample identification and quality control, official test result certificates, clear explanations of test results and reasonably priced testing fees. Providing test results to a publicly-accessible genetic health registry allows breeders and the public to search for health-tested parents to reduce the risk of producing or purchasing affected offspring. Counseling on the testing and elimination of defective genes must consider the effects of genetic selection on the population. Recommendations to breed quality carriers to normal-testing dogs and replacing them with quality normal-testing offspring will help to preserve breeding lines and breed genetic diversity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Impulsive-choice patterns for food in genetically lean and obese Zucker rats.

Science.gov (United States)

Boomhower, Steven R; Rasmussen, Erin B; Doherty, Tiffany S

2013-03-15

Behavioral-economic studies have shown that differences between lean and obese Zuckers in food consumption depend on the response requirement for food. Since a response requirement inherently increases the delay to reinforcement, differences in sensitivity to delay may also be a relevant mechanism of food consumption in the obese Zucker rat. Furthermore, the endocannabinoid neurotransmitter system has been implicated in impulsivity, but studies that attempt to characterize the effects of cannabinoid drugs (e.g., rimonabant) on impulsive choice may be limited by floor effects. The present study aimed to characterize impulsive-choice patterns for sucrose using an adjusting-delay procedure in genetically lean and obese Zuckers. Ten lean and ten obese Zucker rats chose between one lever that resulted in one pellet after a standard delay (either 1 s or 5 s) and a second lever that resulted in two or three pellets after an adjusting delay. After behavior stabilized under baseline, rimonabant (0-10 mg/kg) was administered prior to some choice sessions in the two-pellet condition. Under baseline, obese Zuckers made more impulsive choices than leans in three of the four standard-delay/pellet conditions. Additionally, in the 2-pellet condition, rimonabant increased impulsive choice in lean rats in the 1-s standard-delay condition; however, rimonabant decreased impulsive choice in obese rats in the 1-s and 5-s standard-delay conditions. These data suggest that genetic factors that influence impulsive choice are stronger in some choice conditions than others, and that the endocannabinoid system may be a relevant neuromechanism. Copyright © 2012 Elsevier B.V. All rights reserved.

Bifurcation and Stability in a Delayed Predator-Prey Model with Mixed Functional Responses

Science.gov (United States)

Yafia, R.; Aziz-Alaoui, M. A.; Merdan, H.; Tewa, J. J.

2015-06-01

The model analyzed in this paper is based on the model set forth by Aziz Alaoui et al. [Aziz Alaoui & Daher Okiye, 2003; Nindjin et al., 2006] with time delay, which describes the competition between the predator and prey. This model incorporates a modified version of the Leslie-Gower functional response as well as that of Beddington-DeAngelis. In this paper, we consider the model with one delay consisting of a unique nontrivial equilibrium E* and three others which are trivial. Their dynamics are studied in terms of local and global stabilities and of the description of Hopf bifurcation at E*. At the third trivial equilibrium, the existence of the Hopf bifurcation is proven as the delay (taken as a parameter of bifurcation) that crosses some critical values.

"The stone which the builders rejected...": Delay of reinforcement and response rate on fixed-interval and related schedules.

Science.gov (United States)

Wearden, J H; Lejeune, Helga

2006-02-28

The article deals with response rates (mainly running and peak or terminal rates) on simple and on some mixed-FI schedules and explores the idea that these rates are determined by the average delay of reinforcement for responses occurring during the response periods that the schedules generate. The effects of reinforcement delay are assumed to be mediated by a hyperbolic delay of reinforcement gradient. The account predicts that (a) running rates on simple FI schedules should increase with increasing rate of reinforcement, in a manner close to that required by Herrnstein's equation, (b) improving temporal control during acquisition should be associated with increasing running rates, (c) two-valued mixed-FI schedules with equiprobable components should produce complex results, with peak rates sometimes being higher on the longer component schedule, and (d) that effects of reinforcement probability on mixed-FI should affect the response rate at the time of the shorter component only. All these predictions were confirmed by data, although effects in some experiments remain outside the scope of the model. In general, delay of reinforcement as a determinant of response rate on FI and related schedules (rather than temporal control on such schedules) seems a useful starting point for a more thorough analysis of some neglected questions about performance on FI and related schedules.

Mouse genetic approaches applied to the normal tissue radiation response

International Nuclear Information System (INIS)

Haston, Christina K.

2012-01-01

The varying responses of inbred mouse models to radiation exposure present a unique opportunity to dissect the genetic basis of radiation sensitivity and tissue injury. Such studies are complementary to human association studies as they permit both the analysis of clinical features of disease, and of specific variants associated with its presentation, in a controlled environment. Herein I review how animal models are studied to identify specific genetic variants influencing predisposition to radiation-induced traits. Among these radiation-induced responses are documented strain differences in repair of DNA damage and in extent of tissue injury (in the lung, skin, and intestine) which form the base for genetic investigations. For example, radiation-induced DNA damage is consistently greater in tissues from BALB/cJ mice, than the levels in C57BL/6J mice, suggesting there may be an inherent DNA damage level per strain. Regarding tissue injury, strain specific inflammatory and fibrotic phenotypes have been documented for principally, C57BL/6 C3H and A/J mice but a correlation among responses such that knowledge of the radiation injury in one tissue informs of the response in another is not evident. Strategies to identify genetic differences contributing to a trait based on inbred strain differences, which include linkage analysis and the evaluation of recombinant congenic (RC) strains, are presented, with a focus on the lung response to irradiation which is the only radiation-induced tissue injury mapped to date. Such approaches are needed to reveal genetic differences in susceptibility to radiation injury, and also to provide a context for the effects of specific genetic variation uncovered in anticipated clinical association studies. In summary, mouse models can be studied to uncover heritable variation predisposing to specific radiation responses, and such variations may point to pathways of importance to phenotype development in the clinic.

Genetic and epigenetic control of plant heat responses

Directory of Open Access Journals (Sweden)

Junzhong eLiu

2015-04-01

Full Text Available Plants have evolved sophisticated genetic and epigenetic regulatory systems to respond quickly to unfavorable environmental conditions such as heat, cold, drought, and pathogen infections. In particular, heat greatly affects plant growth and development, immunity and circadian rhythm, and poses a serious threat to the global food supply. According to temperatures exposing, heat can be usually classified as warm ambient temperature (about 22-27℃, high temperature (27-30℃ and extremely high temperature (37-42℃, also known as heat stress for the model plant Arabidopsis thaliana. The genetic mechanisms of plant responses to heat have been well studied, mainly focusing on elevated ambient temperature-mediated morphological acclimation and acceleration of flowering, modulation of plant immunity and circadian clock by high temperatures, and thermotolerance to heat stress. Recently, great progress has been achieved on epigenetic regulation of heat responses, including DNA methylation, histone modifications, histone variants, ATP-dependent chromatin remodeling, histone chaperones, small RNAs, long non-coding RNAs and other undefined epigenetic mechanisms. These epigenetic modifications regulate the expression of heat-responsive genes and function to prevent heat-related damage. This review focuses on recent progresses regarding the genetic and epigenetic control of heat responses in plants, and pays more attention to the role of the major epigenetic mechanisms in plant heat responses. Further research perspectives are also discussed.

Genetic influence demonstrated for MEG-recorded somatosensory evoked responses

NARCIS (Netherlands)

van 't Ent, D.; van Soelen, I.L.C.; Stam, K.J.; de Geus, E.J.C.; Boomsma, D.I.

2010-01-01

We tested for a genetic influence on magnetoencephalogram (MEG)-recorded somatosensory evoked fields (SEFs) in 20 monozygotic (MZ) and 14 dizygotic (DZ) twin pairs. Previous electroencephalogram (EEG) studies that demonstrated a genetic contribution to evoked responses generally focused on

Delay-range-dependent exponential H∞ synchronization of a class of delayed neural networks

International Nuclear Information System (INIS)

Karimi, Hamid Reza; Maass, Peter

2009-01-01

This article aims to present a multiple delayed state-feedback control design for exponential H ∞ synchronization problem of a class of delayed neural networks with multiple time-varying discrete delays. On the basis of the drive-response concept and by introducing a descriptor technique and using Lyapunov-Krasovskii functional, new delay-range-dependent sufficient conditions for exponential H ∞ synchronization of the drive-response structure of neural networks are driven in terms of linear matrix inequalities (LMIs). The explicit expression of the controller gain matrices are parameterized based on the solvability conditions such that the drive system and the response system can be exponentially synchronized. A numerical example is included to illustrate the applicability of the proposed design method.

Detection of thermogenesis in rodents in response to anti-obesity drugs and genetic modification

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Jonathan R S Arch

2013-04-01

Full Text Available Many compounds and genetic manipulations are claimed to confer resistance to obesity in rodents by raising energy expenditure. Examples taken from recent and older literature, demonstrate that such claims are often based on measurements of energy expenditure after body composition has changed and depend on comparisons of energy expenditure divided by body weight. This is misleading because white adipose tissue has less influence than lean tissue on energy expenditure. Application of this approach to human data would suggest that human obesity is usually due to a low metabolic rate, which is not an accepted view. Increased energy expenditure per animal is a surer way of demonstrating thermogenesis, but even then it is important to know whether this is due to altered body composition (repartitioning, or increased locomotor activity rather than thermogenesis per se. Regression analysis offers other approaches. The thermogenic response to some compounds has a rapid onset and so cannot be due to altered body composition. These compounds usually mimic or activate the sympathetic nervous system. Thermogenesis occurs in, but may not be confined to, brown adipose tissue. It should not be assumed that weight loss in response to these treatments is due to thermogenesis unless there is a sustained increase in 24-h energy expenditure. Thyroid hormones and fibroblast growth factor 21 also raise energy expenditure before they affect body composition. Some treatments and genetic modifications alter the diurnal rhythm of energy expenditure. It is important to establish whether this is due to altered locomotor activity or efficiency of locomotion. There are no good examples of compounds that do not affect short-term energy expenditure but have a delayed effect. How and under what conditions a genetic modification or compound increases energy expenditure influences the decision on whether to seek drugs for the target or take a candidate drug into clinical studies.

Behavioral variability, elimination of responses, and delay-of-reinforcement gradients in SHR and WKY rats

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Killeen Peter R

2007-11-01

Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is characterized by a pattern of inattention, hyperactivity, and impulsivity that is cross-situational, persistent, and produces social and academic impairment. Research has shown that reinforcement processes are altered in ADHD. The dynamic developmental theory has suggested that a steepened delay-of-reinforcement gradient and deficient extinction of behavior produce behavioral symptoms of ADHD and increased behavioral variability. Method The present study investigated behavioral variability and elimination of non-target responses during acquisition in an animal model of ADHD, the spontaneously hypertensive rat (SHR, using Wistar Kyoto (WKY rats as controls. The study also aimed at providing a novel approach to measuring delay-of-reinforcement gradients in the SHR and the WKY strains. The animals were tested in a modified operant chamber presenting 20 response alternatives. Nose pokes in a target hole produced water according to fixed interval (FI schedules of reinforcement, while nose pokes in the remaining 19 holes either had no consequences or produced a sound or a short flickering of the houselight. The stimulus-producing holes were included to test whether light and sound act as sensory reinforcers in SHR. Data from the first six sessions testing FI 1 s were used for calculation of the initial distribution of responses. Additionally, Euclidean distance (measured from the center of each hole to the center of the target hole and entropy (a measure of variability were also calculated. Delay-of-reinforcement gradients were calculated across sessions by dividing the fixed interval into epochs and determining how much reinforcement of responses in one epoch contributed to responding in the next interval. Results Over the initial six sessions, behavior became clustered around the target hole. There was greater initial variability in SHR behavior, and slower elimination of

Plant responses to precipitation in desert ecosystems: integrating functional types, pulses, thresholds, and delays.

Science.gov (United States)

Ogle, Kiona; Reynolds, James F

2004-10-01

The 'two-layer' and 'pulse-reserve' hypotheses were developed 30 years ago and continue to serve as the standard for many experiments and modeling studies that examine relationships between primary productivity and rainfall variability in aridlands. The two-layer hypothesis considers two important plant functional types (FTs) and predicts that woody and herbaceous plants are able to co-exist in savannas because they utilize water from different soil layers (or depths). The pulse-reserve model addresses the response of individual plants to precipitation and predicts that there are 'biologically important' rain events that stimulate plant growth and reproduction. These pulses of precipitation may play a key role in long-term plant function and survival (as compared to seasonal or annual rainfall totals as per the two-layer model). In this paper, we re-evaluate these paradigms in terms of their generality, strengths, and limitations. We suggest that while seasonality and resource partitioning (key to the two-layer model) and biologically important precipitation events (key to the pulse-reserve model) are critical to understanding plant responses to precipitation in aridlands, both paradigms have significant limitations. Neither account for plasticity in rooting habits of woody plants, potential delayed responses of plants to rainfall, explicit precipitation thresholds, or vagaries in plant phenology. To address these limitations, we integrate the ideas of precipitation thresholds and plant delays, resource partitioning, and plant FT strategies into a simple 'threshold-delay' model. The model contains six basic parameters that capture the nonlinear nature of plant responses to pulse precipitation. We review the literature within the context of our threshold-delay model to: (i) develop testable hypotheses about how different plant FTs respond to pulses; (ii) identify weaknesses in the current state-of-knowledge; and (iii) suggest future research directions that will

Genetic Testing Accounts of Autonomy, Responsibility and Blame

DEFF Research Database (Denmark)

Arribas-Ayllon, M.; Sarangi, Srikant; Clarke, Angus

Advances in molecular genetics have led to the increasing availability of genetic testing for a variety of inherited disorders. While this new knowledge presents many obvious health benefits to prospective individuals and their families it also raises complex ethical and moral dilemmas for famili......, the assessment of competence and maturity, the ability to engage in shared decision-making through acts of disclosure and choice, are just some of the issues that are examined in detail....... as well as genetic professionals. This book explores the ways in which genetic testing generates not only probabilities of potential futures, but also enjoys new forms of social, individual and professional responsibility. Concerns about confidentiality and informed consent involving children...

Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

Science.gov (United States)

Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

2015-03-01

Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

Auditory Brainstem Response Wave Amplitude Characteristics as a Diagnostic Tool in Children with Speech Delay with Unknown Causes

Directory of Open Access Journals (Sweden)

Susan Abadi

2016-09-01

Full Text Available Speech delay with an unknown cause is a problem among children. This diagnosis is the last differential diagnosis after observing normal findings in routine hearing tests. The present study was undertaken to determine whether auditory brainstem responses to click stimuli are different between normally developing children and children suffering from delayed speech with unknown causes. In this cross-sectional study, we compared click auditory brainstem responses between 261 children who were clinically diagnosed with delayed speech with unknown causes based on normal routine auditory test findings and neurological examinations and had >12 months of speech delay (case group and 261 age- and sex-matched normally developing children (control group. Our results indicated that the case group exhibited significantly higher wave amplitude responses to click stimuli (waves I, III, and V than did the control group (P=0.001. These amplitudes were significantly reduced after 1 year (P=0.001; however, they were still significantly higher than those of the control group (P=0.001. The significant differences were seen regardless of the age and the sex of the participants. There were no statistically significant differences between the 2 groups considering the latency of waves I, III, and V. In conclusion, the higher amplitudes of waves I, III, and V, which were observed in the auditory brainstem responses to click stimuli among the patients with speech delay with unknown causes, might be used as a diagnostic tool to track patients’ improvement after treatment.

Effect of delayed response in growth on the dynamics of a chemostat model with impulsive input

International Nuclear Information System (INIS)

Jiao Jianjun; Yang Xiaosong; Chen Lansun; Cai Shaohong

2009-01-01

In this paper, a chemostat model with delayed response in growth and impulsive perturbations on the substrate is considered. Using the discrete dynamical system determined by the stroboscopic map, we obtain a microorganism-extinction periodic solution, further, the globally attractive condition of the microorganism-extinction periodic solution is obtained. By the use of the theory on delay functional and impulsive differential equation, we also obtain the permanent condition of the investigated system. Our results indicate that the discrete time delay has influence to the dynamics behaviors of the investigated system, and provide tactical basis for the experimenters to control the outcome of the chemostat. Furthermore, numerical analysis is inserted to illuminate the dynamics of the system affected by the discrete time delay.

The Cost of Delaying Approval of Golden Rice

NARCIS (Netherlands)

Wesseler, J.H.H.; Kaplan, S.; Zilberman, D.

2014-01-01

More than 250,000 children go blind every year because of Vitamin A deficiency. Vitamin A intake can be enhanced by consuming Golden Rice—a genetically engineered variety of rice. It was available for commercialization in 2002, but approval has been delayed. We estimate that this delay has resulted

Effect of Unsaturated Flow on Delayed Response of Unconfined Aquifiers to Pumping

Science.gov (United States)

Tartakovsky, G.; Neuman, S. P.

2005-12-01

A new analytical solution is presented for the delayed response process characterizing flow to a partially penetrating well in an unconfined aquifer. The new solution generalizes that of Neuman [1972, 1974] by accounting for unsaturated flow above the water table. Axially symmetric three-dimensional flow in the unsaturated zone is described by a linearized version of Richards' equation in which hydraulic conductivity and water content vary exponentially with incremental capillary pressure head relative to its air entry value (defining the interface between the saturated and unsaturated zones). Unsaturated soil properties are characterized by an exponent κ having the dimension of inverse length and a dimensionless exponent κD = κb where b is initial saturated thickness. Our treatment of the unsaturated zone is similar to that of Kroszynski and Dagan [1975] who however have ignored internal (artesian) aquifer storage. It has been suggested by Boulton [1954, 1963, 1970] and Neuman [1972, 1974], and is confirmed by our solution, that internal storage is required to reproduce the early increase in drawdown characterizing delayed response to pumping in typical aquifers. According to our new solution such aquifers are characterized by relatively large κ_ D values, typically 10 or larger; in the limit as κD tends to infinity (the soil unsaturated water retention capacity becomes insignificant and/or aquifer thickness become large), unsaturated flow becomes unimportant and our solution reduces to that of Neuman. In typical cases corresponding to κD larger than or equal to 10, unsaturated flow is found to have little impact on early and late dimensionless time behaviors of drawdown measured wholly or in part at some distance below the water table; unsaturated flow causes drawdown to increase slightly at intermediate dimensionless time values that represent transition from an early artesian dominated to a late water-table dominated flow regime. The increase in drawdown

Behavioral effects of delayed timeouts from reinforcement.

Science.gov (United States)

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.

Genetic analysis of Myanmar Vigna species in responses to salt ...

African Journals Online (AJOL)

Genetic analysis of Myanmar Vigna species in responses to salt stress at the ... of reduction was highly dependent on different genotypes and salinity levels. ... the mechanism of salt tolerance and for the provision of genetic resources for ...

Probing the limits of delay intolerance: preliminary young adult data from the Delay Frustration Task (DeFT).

Science.gov (United States)

Bitsakou, Paraskevi; Antrop, Inge; Wiersema, Jan Roelf; Sonuga-Barke, Edmund J S

2006-02-15

Delay intolerance/aversion is one amongst a number of candidate neuropsychological endophenotypes for ADHD. Pilot data suggest that, because of potential ceiling effects, simple choice measures of delay tolerance used for children are probably not appropriate for adolescents and adults. The Delay Frustration Task (DeFT) is a new measure of delay intolerance, designed to be used in a similar form with adolescents and adults as well as children. In it delay frustration is indexed as the number and duration of responses made on a response key during a series of unpredictable and unsignalled delay periods, which interrupt the completion of a simple computer-based tests. The aim of this study was to provide preliminary data on the applicability of the task in a sample of young adults. The DeFT was administered to 49 male and female undergraduate students selected from a normal population-base. Their mean age was 23.14 (S.D.=1.54). Three measures of delay frustration were recorded across time intervals during the response window; the number of responses, their duration and their combined product (total time button was pressed) was calculated for each second interval bin during the post-response delay period. The AARS and HADS were used as screening questionnaires for ADHD and anxiety behaviour, respectively. The results indicated that young adults with high-ADHD symptoms scores pressed the button more than those with low ADHD scores during the post-response delay condition. While both groups increased responding across time within intervals this was significantly more marked in the high-ADHD symptom group. These effects became more pronounced when anxiety was controlled. Young adults with high-ADHD symptoms appear to be more sensitive to the imposition of unscheduled and unsignalled delay during a simple maths test. DeFT may provide a useful index of delay tolerance in young adults with ADHD. Future research needs to examine DeFT performance in different age groups and

Missing and delayed auditory responses in young and older children with autism spectrum disorders

Directory of Open Access Journals (Sweden)

J. Christopher eEdgar

2014-06-01

Full Text Available Background: The development of left and right superior temporal gyrus (STG 50ms (M50 and 100ms (M100 auditory responses in typically developing children (TD and in children with autism spectrum disorder (ASD was examined. It was hypothesized that (1 M50 responses would be observed equally often in younger and older children, (2 M100 responses would be observed more often in older than younger children indicating later development of secondary auditory areas, and (3 M100 but not M50 would be observed less often in ASD than TD in both age groups, reflecting slower maturation of later developing auditory areas in ASD. Methods: 35 typically developing controls, 63 ASD without language impairment (ASD-LI, and 38 ASD with language impairment (ASD+LI were recruited.The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6 to 10-years-old and older groups (11 to 15-years-old. Results: Although M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD-LI and ASD+LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD+LI (90% vs 66%, p=0.04, with no differences between TD and ASD-LI (90% vs 76% p=0.14 or between ASD-LI and ASD+LI (76% vs 66%, p=0.53. In older subjects, whereas no differences were observed between TD and ASD+LI, responses were observed more often in ASD-LI than ASD+LI. Conclusions: Although present in all groups, M50 responses were delayed in ASD, suggesting delayed development of earlier developing auditory areas. Examining the TD data, findings indicated that by 11 years a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment.

Genetic architecture of a hormonal response to gene knockdown in honey bees.

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Ihle, Kate E; Rueppell, Olav; Huang, Zachary Y; Wang, Ying; Fondrk, M Kim; Page, Robert E; Amdam, Gro V

2015-01-01

Variation in endocrine signaling is proposed to underlie the evolution and regulation of social life histories, but the genetic architecture of endocrine signaling is still poorly understood. An excellent example of a hormonally influenced set of social traits is found in the honey bee (Apis mellifera): a dynamic and mutually suppressive relationship between juvenile hormone (JH) and the yolk precursor protein vitellogenin (Vg) regulates behavioral maturation and foraging of workers. Several other traits cosegregate with these behavioral phenotypes, comprising the pollen hoarding syndrome (PHS) one of the best-described animal behavioral syndromes. Genotype differences in responsiveness of JH to Vg are a potential mechanistic basis for the PHS. Here, we reduced Vg expression via RNA interference in progeny from a backcross between 2 selected lines of honey bees that differ in JH responsiveness to Vg reduction and measured JH response and ovary size, which represents another key aspect of the PHS. Genetic mapping based on restriction site-associated DNA tag sequencing identified suggestive quantitative trait loci (QTL) for ovary size and JH responsiveness. We confirmed genetic effects on both traits near many QTL that had been identified previously for their effect on various PHS traits. Thus, our results support a role for endocrine control of complex traits at a genetic level. Furthermore, this first example of a genetic map of a hormonal response to gene knockdown in a social insect helps to refine the genetic understanding of complex behaviors and the physiology that may underlie behavioral control in general. © The American Genetic Association. 2015.

Finite-time hybrid projective synchronization of the drive-response complex networks with distributed-delay via adaptive intermittent control

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Cheng, Lin; Yang, Yongqing; Li, Li; Sui, Xin

2018-06-01

This paper studies the finite-time hybrid projective synchronization of the drive-response complex networks. In the model, general transmission delays and distributed delays are also considered. By designing the adaptive intermittent controllers, the response network can achieve hybrid projective synchronization with the drive system in finite time. Based on finite-time stability theory and several differential inequalities, some simple finite-time hybrid projective synchronization criteria are derived. Two numerical examples are given to illustrate the effectiveness of the proposed method.

Stability in a Simple Food Chain System with Michaelis-Menten Functional Response and Nonlocal Delays

Directory of Open Access Journals (Sweden)

Wenzhen Gan

2013-01-01

Full Text Available This paper is concerned with the asymptotical behavior of solutions to the reaction-diffusion system under homogeneous Neumann boundary condition. By taking food ingestion and species' moving into account, the model is further coupled with Michaelis-Menten type functional response and nonlocal delay. Sufficient conditions are derived for the global stability of the positive steady state and the semitrivial steady state of the proposed problem by using the Lyapunov functional. Our results show that intraspecific competition benefits the coexistence of prey and predator. Furthermore, the introduction of Michaelis-Menten type functional response positively affects the coexistence of prey and predator, and the nonlocal delay is harmless for stabilities of all nonnegative steady states of the system. Numerical simulations are carried out to illustrate the main results.

Investigating the Impact of Cognitive Load and Motivation on Response Control in Relation to Delay Discounting in Children with ADHD.

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Martinelli, Mary K; Mostofsky, Stewart H; Rosch, Keri S

2017-10-01

Attention-deficit/hyperactivity disorder (ADHD) is characterized by deficits in impulse control across a range of behaviors, from simple actions to those involving complex decision-making (e.g., preference for smaller-sooner versus larger later rewards). This study investigated whether changes in motor response control with increased cognitive load and motivational contingencies are associated with decision-making in the form of delay discounting among 8-12 year old children with and without ADHD. Children with ADHD (n = 26; 8 girls) and typically developing controls (n = 40; 11 girls) completed a standard go/no-go (GNG) task, a GNG task with motivational contingencies, a GNG task with increased cognitive load, and two measures of delay discounting: a real-time task in which the delays and immediately consumable rewards are experienced in real-time, and a classic task involving choices about money at longer delays. Children with ADHD, particularly girls, exhibited greater delay discounting than controls during the real-time discounting task, whereas diagnostic groups did not significantly differ on the classic discounting task. The effect of cognitive load on response control was uniquely associated with greater discounting on the real-time task for children with ADHD, but not for control children. The effect of motivational contingencies on response control was not significantly associated with delay discounting for either diagnostic group. The findings from this study help to inform our understanding of the factors that influence deficient self-control in ADHD, suggesting that impairments in cognitive control may contribute to greater delay discounting in ADHD.

Genetic influences on phase synchrony of brain oscillations supporting response inhibition.

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Müller, Viktor; Anokhin, Andrey P; Lindenberger, Ulman

2017-05-01

Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0-300 and 301-600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

Dissecting genetic architecture of startle response in Drosophila melanogaster using multi-omics information.

Science.gov (United States)

Xue, Angli; Wang, Hongcheng; Zhu, Jun

2017-09-28

Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful system to investigate the genetic underpinnings of variation in startle behavior. Since mechanically induced, startle responses and environmental conditions can be readily quantified and precisely controlled. The 156 wild-derived fully sequenced lines of the Drosophila Genetic Reference Panel (DGRP) were used to identify SNPs and transcripts associated with variation in startle behavior. The results validated highly significant effects of 33 quantitative trait SNPs (QTSs) and 81 quantitative trait transcripts (QTTs) directly associated with phenotypic variation of startle response. We also detected QTT variation controlled by 20 QTSs (tQTSs) and 73 transcripts (tQTTs). Association mapping based on genomic and transcriptomic data enabled us to construct a complex genetic network that underlies variation in startle behavior. Based on principles of evolutionary conservation, human orthologous genes could be superimposed on this network. This study provided both genetic and biological insights into the variation of startle response behavior of Drosophila melanogaster, and highlighted the importance of genetic network to understand the genetic architecture of complex traits.

Hopf bifurcation in a reaction-diffusive two-species model with nonlocal delay effect and general functional response

International Nuclear Information System (INIS)

Han, Renji; Dai, Binxiang

2017-01-01

Highlights: • We model general two-dimensional reaction-diffusion with nonlocal delay. • The existence of unique positive steady state is studied. • The bilinear form for the proposed system is given. • The existence, direction of Hopf bifurcation are given by symmetry method. - Abstract: A nonlocal delayed reaction-diffusive two-species model with Dirichlet boundary condition and general functional response is investigated in this paper. Based on the Lyapunov–Schmidt reduction, the existence, bifurcation direction and stability of Hopf bifurcating periodic orbits near the positive spatially nonhomogeneous steady-state solution are obtained, where the time delay is taken as the bifurcation parameter. Moreover, the general results are applied to a diffusive Lotka–Volterra type food-limited population model with nonlocal delay effect, and it is found that diffusion and nonlocal delay can also affect the other dynamic behavior of the system by numerical experiments.

Monitoring adaptive genetic responses to environmental change

DEFF Research Database (Denmark)

Hansen, M.M.; Olivieri, I.; Waller, D.M.

2012-01-01

Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how...... for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We...

Dynamics of a viral infection model with delayed CTL response and immune circadian rhythm

International Nuclear Information System (INIS)

Bai Zhenguo; Zhou Yicang

2012-01-01

This paper studies the global dynamics of a viral infection model that takes into account circadian rhythm and time delay in the CTL response. It is shown that the basic reproduction numbers, R 0 and R 1 , determine the outcome of viral infection. Numerical simulations demonstrate that the changes in the amplitude of lytic component can generate a variety of dynamical patterns, ranging from simple daily oscillation to multi-day dynamics and eventually chaos, whereas time delay can alter the period of oscillation for the larger level of periodic forcing. These results can help to explain the viral oscillation behaviors, which were observed in chronic HBV and HCV infection patients.

Updates in the genetic evaluation of the child with global developmental delay or intellectual disability.

Science.gov (United States)

Flore, Leigh Anne; Milunsky, Jeff M

2012-12-01

Global developmental delay (GDD) and intellectual disability (ID) occur in up to 3% of the general population and are even more commonly encountered in the setting of the pediatric neurology clinic. New advances in technology and in the understanding of genetic disorders have led to changes in the diagnostic approach to a child with unexplained GDD or ID. Chromosomal microarray has become a first-line test for evaluation of patients in this population and has both significantly increased diagnostic yield and introduced new challenges in the interpretation of copy number variants of uncertain significance. The G-banded karyotype is now frequently utilized as an adjunct to the microarray rather than as a first-line test in individuals with GDD or ID. Fragile X DNA testing continues to be recommended in the initial evaluation of the child with GDD or ID. The presence or absence of certain cardinal features (such as microcephaly or macrocephaly, seizures, autism, abnormal neurologic examination, and facial dysmorphism) can be utilized to direct single-gene molecular testing. The availability of next-generation and massively parallel sequencing technologies has enabled the use of genetic testing panels, in which dozens of genes associated with GDD or ID may be rapidly analyzed. Most recently, the clinical availability of whole-genome and whole-exome sequencing has opened new possibilities for the evaluation of individuals with GDD or ID who have previously eluded a genetic diagnosis. Consultation with a medical geneticist is recommended when progressing beyond first-tier analyses to most efficiently prioritize testing. Copyright © 2012 Elsevier Inc. All rights reserved.

Bistable responses in bacterial genetic networks: Designs and dynamical consequences

Science.gov (United States)

Tiwari, Abhinav; Ray, J. Christian J.; Narula, Jatin; Igoshin, Oleg A.

2011-01-01

A key property of living cells is their ability to react to stimuli with specific biochemical responses. These responses can be understood through the dynamics of underlying biochemical and genetic networks. Evolutionary design principles have been well studied in networks that display graded responses, with a continuous relationship between input signal and system output. Alternatively, biochemical networks can exhibit bistable responses so that over a range of signals the network possesses two stable steady states. In this review, we discuss several conceptual examples illustrating network designs that can result in a bistable response of the biochemical network. Next, we examine manifestations of these designs in bacterial master-regulatory genetic circuits. In particular, we discuss mechanisms and dynamic consequences of bistability in three circuits: two-component systems, sigma-factor networks, and a multistep phosphorelay. Analyzing these examples allows us to expand our knowledge of evolutionary design principles for networks with bistable responses. PMID:21385588

Incorporating time-delays in S-System model for reverse engineering genetic networks.

Science.gov (United States)

Chowdhury, Ahsan Raja; Chetty, Madhu; Vinh, Nguyen Xuan

2013-06-18

In any gene regulatory network (GRN), the complex interactions occurring amongst transcription factors and target genes can be either instantaneous or time-delayed. However, many existing modeling approaches currently applied for inferring GRNs are unable to represent both these interactions simultaneously. As a result, all these approaches cannot detect important interactions of the other type. S-System model, a differential equation based approach which has been increasingly applied for modeling GRNs, also suffers from this limitation. In fact, all S-System based existing modeling approaches have been designed to capture only instantaneous interactions, and are unable to infer time-delayed interactions. In this paper, we propose a novel Time-Delayed S-System (TDSS) model which uses a set of delay differential equations to represent the system dynamics. The ability to incorporate time-delay parameters in the proposed S-System model enables simultaneous modeling of both instantaneous and time-delayed interactions. Furthermore, the delay parameters are not limited to just positive integer values (corresponding to time stamps in the data), but can also take fractional values. Moreover, we also propose a new criterion for model evaluation exploiting the sparse and scale-free nature of GRNs to effectively narrow down the search space, which not only reduces the computation time significantly but also improves model accuracy. The evaluation criterion systematically adapts the max-min in-degrees and also systematically balances the effect of network accuracy and complexity during optimization. The four well-known performance measures applied to the experimental studies on synthetic networks with various time-delayed regulations clearly demonstrate that the proposed method can capture both instantaneous and delayed interactions correctly with high precision. The experiments carried out on two well-known real-life networks, namely IRMA and SOS DNA repair network in

Permanence of a Semi-Ratio-Dependent Predator-Prey System with Nonmonotonic Functional Response and Time Delay

Directory of Open Access Journals (Sweden)

Xuepeng Li

2009-01-01

Full Text Available Sufficient conditions for permanence of a semi-ratio-dependent predator-prey system with nonmonotonic functional response and time delay ̇1(=1([1(−11(1(−(−12(2(/(2+21(],  ̇2(=2([2(−21(2(/1(], are obtained, where 1( and 2( stand for the density of the prey and the predator, respectively, and ≠0 is a constant. (≥0 stands for the time delays due to negative feedback of the prey population.

Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases

DEFF Research Database (Denmark)

Sørensen, Signe Bek; Nielsen, J V; Bo Bojesen, Anders

2016-01-01

BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. AIM......2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers...... in an explorative analysis. CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms...

Latitude-dependent delay in the responses of the equatorial electrojet and Sq currents to X-class solar flares

Science.gov (United States)

Nogueira, Paulo A. B.; Abdu, Mangalathayil A.; Souza, Jonas R.; Denardini, Clezio M.; Barbosa Neto, Paulo F.; Serra de Souza da Costa, João P.; Silva, Ana P. M.

2018-01-01

We have analyzed low-latitude ionospheric current responses to two intense (X-class) solar flares that occurred on 13 May 2013 and 11 March 2015. Sudden intensifications, in response to solar flare radiation impulses, in the Sq and equatorial electrojet (EEJ) currents, as detected by magnetometers over equatorial and low-latitude sites in South America, are studied. In particular we show for the first time that a 5 to 8 min time delay is present in the peak effect in the EEJ, with respect that of Sq current outside the magnetic equator, in response to the flare radiation enhancement. The Sq current intensification peaks close to the flare X-ray peak, while the EEJ peak occurs 5 to 8 min later. We have used the Sheffield University Plasmasphere-Ionosphere Model at National Institute for Space Research (SUPIM-INPE) to simulate the E-region conductivity enhancement as caused by the flare enhanced solar extreme ultraviolet (EUV) and soft X-rays flux. We propose that the flare-induced enhancement in neutral wind occurring with a time delay (with respect to the flare radiation) could be responsible for a delayed zonal electric field disturbance driving the EEJ, in which the Cowling conductivity offers enhanced sensitivity to the driving zonal electric field.

Interocular suppression in strabismic amblyopia results in an attenuated and delayed hemodynamic response function in early visual cortex.

Science.gov (United States)

Farivar, Reza; Thompson, Benjamin; Mansouri, Behzad; Hess, Robert F

2011-12-20

Factors such as strabismus or anisometropia during infancy can disrupt normal visual development and result in amblyopia, characterized by reduced visual function in an otherwise healthy eye and often associated with persistent suppression of inputs from the amblyopic eye by those from the dominant eye. It has become evident from fMRI studies that the cortical response to stimulation of the amblyopic eye is also affected. We were interested to compare the hemodynamic response function (HRF) of early visual cortex to amblyopic vs. dominant eye stimulation. In the first experiment, we found that stimulation of the amblyopic eye resulted in a signal that was both attenuated and delayed in its time to peak. We postulated that this delay may be due to suppressive effects of the dominant eye and, in our second experiment, measured the cortical response of amblyopic eye stimulation under two conditions--where the dominant eye was open and seeing a static pattern (high suppression) or where the dominant eye was patched and closed (low suppression). We found that the HRF in response to amblyopic eye stimulation depended on whether the dominant eye was open. This effect was manifested as both a delayed HRF under the suppressed condition and an amplitude reduction.

Host genetic variation influences gene expression response to rhinovirus infection.

Directory of Open Access Journals (Sweden)

Minal Çalışkan

2015-04-01

Full Text Available Rhinovirus (RV is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs, namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5 and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3. The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

Host genetic variation influences gene expression response to rhinovirus infection.

Science.gov (United States)

Çalışkan, Minal; Baker, Samuel W; Gilad, Yoav; Ober, Carole

2015-04-01

Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs) in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs), namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5) and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomes.

Science.gov (United States)

Wilhelm, C J; Mitchell, S H

2008-10-01

Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be because of factors that predate drug exposure (e.g. genetics). This study examined the role of genetics by comparing impulsivity measures in ethanol-naive rats selectively bred based on their high [high alcohol drinking (HAD)] or low [low alcohol drinking (LAD)] consumption of ethanol. Replicates 1 and 2 of the HAD and LAD rats, developed by the University of Indiana Alcohol Research Center, completed two different discounting tasks. Delay discounting examines sensitivity to rewards that are delayed in time and is commonly used to assess 'choice' impulsivity. Probability discounting examines sensitivity to the uncertain delivery of rewards and has been used to assess risk taking and risk assessment. High alcohol drinking rats discounted delayed and probabilistic rewards more steeply than LAD rats. Discount rates associated with probabilistic and delayed rewards were weakly correlated, while bias was strongly correlated with discount rate in both delay and probability discounting. The results suggest that selective breeding for high alcohol consumption selects for animals that are more sensitive to delayed and probabilistic outcomes. Sensitivity to delayed or probabilistic outcomes may be predictive of future drinking in genetically predisposed individuals.

A Shared Genetic Basis for Self-Limited Delayed Puberty and Idiopathic Hypogonadotropic Hypogonadism

Science.gov (United States)

Zhu, Jia; Choa, Ruth E.-Y.; Guo, Michael H.; Plummer, Lacey; Buck, Cassandra; Palmert, Mark R.; Hirschhorn, Joel N.; Seminara, Stephanie B.

2015-01-01

Context: Delayed puberty (DP) is a common issue and, in the absence of an underlying condition, is typically self limited. Alhough DP seems to be heritable, no specific genetic cause for DP has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder characterized by absent or stalled pubertal development. Objective: The objective of this retrospective study, conducted at academic medical centers, was to determine whether variants in IHH genes contribute to the pathogenesis of DP. Subjects and Outcome Measures: Potentially pathogenic variants in IHH genes were identified in two cohorts: 1) DP family members of an IHH proband previously found to have a variant in an IHH gene, with unaffected family members serving as controls, and 2) DP individuals with no family history of IHH, with ethnically matched control subjects drawn from the Exome Aggregation Consortium. Results: In pedigrees with an IHH proband, the proband's variant was shared by 53% (10/19) of DP family members vs 12% (4/33) of unaffected family members (P = .003). In DP subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in IHH genes vs 5.6% (1 907/33 855) of controls (P = .01). Potentially pathogenic variants were found in multiple DP subjects for the genes IL17RD and TAC3. Conclusions: These findings suggest that variants in IHH genes can contribute to the pathogenesis of self-limited DP. Thus, at least in some cases, self-limited DP shares an underlying pathophysiology with IHH. PMID:25636053

Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change

Science.gov (United States)

Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

2014-01-01

Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data. PMID:24454550

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

Science.gov (United States)

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-04-01

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

Delayed Puberty

DEFF Research Database (Denmark)

Kolby, Nanna; Busch, Alexander Siegfried; Juul, Anders

2017-01-01

. The underlying reasons for the large variation in the age at pubertal onset are not fully established; however, nutritional status and socioeconomic and environmental factors are known to be influencing, and a significant amount of influencing genetic factors have also been identified. The challenges...... optimal in discriminating especially CDGP from HH. Management of the delayed puberty depends on the etiology. For boys with CDGP an observational period will often reveal imminent puberty. If puberty is not progressing spontaneously, sex steroid replacement is effective in stimulating the development...

Forced phase-locked response of a nonlinear system with time delay after Hopf bifurcation

International Nuclear Information System (INIS)

Ji, J.C.; Hansen, Colin H.

2005-01-01

The trivial equilibrium of a nonlinear autonomous system with time delay may become unstable via a Hopf bifurcation of multiplicity two, as the time delay reaches a critical value. This loss of stability of the equilibrium is associated with two coincident pairs of complex conjugate eigenvalues crossing the imaginary axis. The resultant dynamic behaviour of the corresponding nonlinear non-autonomous system in the neighbourhood of the Hopf bifurcation is investigated based on the reduction of the infinite-dimensional problem to a four-dimensional centre manifold. As a result of the interaction between the Hopf bifurcating periodic solutions and the external periodic excitation, a primary resonance can occur in the forced response of the system when the forcing frequency is close to the Hopf bifurcating periodic frequency. The method of multiple scales is used to obtain four first-order ordinary differential equations that determine the amplitudes and phases of the phase-locked periodic solutions. The first-order approximations of the periodic solutions are found to be in excellent agreement with those obtained by direct numerical integration of the delay-differential equation. It is also found that the steady state solutions of the nonlinear non-autonomous system may lose their stability via either a pitchfork or Hopf bifurcation. It is shown that the primary resonance response may exhibit symmetric and asymmetric phase-locked periodic motions, quasi-periodic motions, chaotic motions, and coexistence of two stable motions

Understanding delayed T-cell priming, lung recruitment, and airway luminal T-cell responses in host defense against pulmonary tuberculosis.

Science.gov (United States)

Shaler, Christopher R; Horvath, Carly; Lai, Rocky; Xing, Zhou

2012-01-01

Mycobacterium tuberculosis (M.tb), the causative bacterium of pulmonary tuberculosis (TB), is a serious global health concern. Central to M.tb effective immune avoidance is its ability to modulate the early innate inflammatory response and prevent the establishment of adaptive T-cell immunity for nearly three weeks. When compared with other intracellular bacterial lung pathogens, such as Legionella pneumophila, or even closely related mycobacterial species such as M. smegmatis, this delay is astonishing. Customarily, the alveolar macrophage (AM) acts as a sentinel, detecting and alerting surrounding cells to the presence of an invader. However, in the case of M.tb, this may be impaired, thus delaying the recruitment of antigen-presenting cells (APCs) to the lung. Upon uptake by APC populations, M.tb is able to subvert and delay the processing of antigen, MHC class II loading, and the priming of effector T cell populations. This delay ultimately results in the deferred recruitment of effector T cells to not only the lung interstitium but also the airway lumen. Therefore, it is of upmost importance to dissect the mechanisms that contribute to the delayed onset of immune responses following M.tb infection. Such knowledge will help design the most effective vaccination strategies against pulmonary TB.

Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

Science.gov (United States)

Solomon, P R; Groccia-Ellison, M E

1996-06-01

Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

Heritability of brain activity related to response inhibition: a longitudinal genetic study in adolescent twins

Science.gov (United States)

Anokhin, Andrey P.; Golosheykin, Simon; Grant, Julia D.; Heath, Andrew C.

2017-01-01

The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. PMID:28300615

Exploring genetic responsibility for the self, family and kin in the case of hereditary raised cholesterol.

Science.gov (United States)

Weiner, Kate

2011-06-01

This paper explores the notion of genetic responsibility, i.e. the responsibility to know and manage one's own genome for oneself and the sake of others, focusing particularly on responsibilities to family and kin. It also considers wider ideas about the emergence of new forms of biological subjectivities with which the concept of genetic responsibility is associated. The paper draws on a UK-based study concerned with lay constructions of familial hypercholesterolaemia (FH), a treatable inherited form of high cholesterol, which involved qualitative interviews with 31 people with the condition recruited through a specialist outpatient clinic. The paper is an attempt to open out discussions about the significance of genetic responsibility and biological subjectivity. I argue that in this study, FH was not associated with a notable family narrative of illness or a strongly defined specific disease community, and no clear sense emerged of obligations to kin or others derived through genetic risks or genetic connections. While responsibilities concerned with the welfare of oneself and one's existing offspring were enunciated, obligations to other potential or actual kin, e.g. to tell and encourage kin to manage their risks, were much less clearly defined. Drawing on these findings, I start to address questions about the pervasiveness of genetic responsibility and genetic identity and the contexts in which they might be significant. Copyright © 2010 Elsevier Ltd. All rights reserved.

Genetics Home Reference: biotin-thiamine-responsive basal ganglia disease

Science.gov (United States)

... BTBGD thiamine metabolism dysfunction syndrome 2 thiamine-responsive encephalopathy thiamine transporter-2 deficiency THMD2 Related Information How ... genetic testing? What is precision medicine? What is newborn screening? New Pages LMNA-related congenital muscular dystrophy ...

Multilevel linear modelling of the response-contingent learning of young children with significant developmental delays.

Science.gov (United States)

Raab, Melinda; Dunst, Carl J; Hamby, Deborah W

2018-02-27

The purpose of the study was to isolate the sources of variations in the rates of response-contingent learning among young children with multiple disabilities and significant developmental delays randomly assigned to contrasting types of early childhood intervention. Multilevel, hierarchical linear growth curve modelling was used to analyze four different measures of child response-contingent learning where repeated child learning measures were nested within individual children (Level-1), children were nested within practitioners (Level-2), and practitioners were nested within the contrasting types of intervention (Level-3). Findings showed that sources of variations in rates of child response-contingent learning were associated almost entirely with type of intervention after the variance associated with differences in practitioners nested within groups were accounted for. Rates of child learning were greater among children whose existing behaviour were used as the building blocks for promoting child competence (asset-based practices) compared to children for whom the focus of intervention was promoting child acquisition of missing skills (needs-based practices). The methods of analysis illustrate a practical approach to clustered data analysis and the presentation of results in ways that highlight sources of variations in the rates of response-contingent learning among young children with multiple developmental disabilities and significant developmental delays. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Factors Responsible for the Diagnostic Delay in Oral Cancer Patients: A Hospital Based Sociodemographic Study in Kolkata

Directory of Open Access Journals (Sweden)

Pramitasri Bhattacharyya

2016-12-01

Full Text Available Introduction Oral cancer is a challenging health problem globally. Delay in diagnosis is an important factor in determining the outcome of the disease. It is a major determinant of mortality and morbidity of oral cancer patients. Present observational study was conducted with the objective of finding the factors responsible for delay in diagnosis of oral cancer in patients. Materials and Methods Hospital based observational study where patient register was used as data source from 15th Nov, 2013-15th Jan, 2014. Results Among the causes for delay in reporting to hospital, financial constraint (84% and illiteracy (56.5% have been found to contribute the most. The risk of primary delay is 3.53 times more among illiterate in comparison with literate. Age, gender, stage of cancer, religion, caste, tobacco use and delayed referral from the first physician were the other factors found to be significant in relation to primary delay. Discussion Early diagnosis is a major factor for favorable outcome of a disease and several factors hinder early diagnosis. Some of these factors can be easily modified through Information, Education and Communication (IEC. Conclusion Some important factors that lead to delay are identified and some of them are preventable. So, IEC regarding cancer among general population will not only provide knowledge to them, but also will break myths regarding cancer and reduce the burden of disease. These identified predictors of delay may be used for designing an educational intervention program for patients with oral cancers.

Unraveling the "new morbidity": adolescent parenting and developmental delays.

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Borkowski, J G; Whitman, T L; Passino, A W; Rellinger, E A; Sommer, K; Keogh, D

1992-01-01

Baumeister's concept of the "new morbidity" pertains to the linkages between poverty, adolescent mothers, and a series of developmental delays in their children. Outlined are three possible causes of the mild mental retardation and learning disabilities that are found disproportionately among the offspring of adolescents. First, there may be a direct genetic transmission of mild mental retardation. Second, adolescent mothers are likely to have a lack of support from a social network, be unprepared cognitively and emotionally to assume responsibility for child rearing, and to look to an infant to meet their own needs. Third, the interaction of genetic and environmental deficits leads to a parenting style that deprives the child of stimulation that could potentially overcome these deficits. A secure mother-infant attachment relationship provides the foundation for the development of social, emotional, attentional, and self-regulatory processes. When this attachment relationship is insecure, as a result of the mother's unreadiness to parent, the child cannot proceed to exploration of the environment--a critical component of cognitive development. If the infant has a difficult temperament, the risk of physical and emotional abuse increases, further compromising the child's future development. By 3 years of age, many of these children are showing declines in mental functioning, delays in receptive language skills, and poor motor and social skills. Research is urged to identify events in this chain that can be targeted for early intervention.

Predictive display design for the vehicles with time delay in dynamic response

Science.gov (United States)

Efremov, A. V.; Tiaglik, M. S.; Irgaleev, I. H.; Efremov, E. V.

2018-02-01

The two ways for the improvement of flying qualities are considered: the predictive display (PD) and the predictive display integrated with the flight control system (FCS). The both ways allow to transforming the controlled element dynamics in the crossover frequency range, to improve the accuracy of tracking and to suppress the effect of time delay in the vehicle response too. The technique for optimization of the predictive law is applied to the landing task. The results of the mathematical modeling and experimental investigations carried out for this task are considered in the paper.

Genetic response in masseter muscle after orthognathic surgery in comparison with healthy controls - A Microarray study.

Science.gov (United States)

Marewski, Maya; Petto, Carola; Schneider, Matthias; Harzer, Winfried

2017-04-01

One third of adult patients with orthognathic surgery of a prognathic or retrognathic mandible show relapse. The sagittal split osteotomy of the mandible leads to a displacement of both parts up to 10 mm without any changes of muscle attachment. Changed mandible length needs adaptation of muscle capacity because of changed force to moment ratio. The aim of this Microarray study was to analyze the general genetic response of masseter muscle in patients with retrognathism or prognathism of the mandible six months after surgery in comparison with healthy untreated controls. We found in tissue samples from masseter muscle a reduction of different entities between patients and controls but less in retrognathic than in prognathic patients (274/429). The different entities to controls in prognathia were reduced from 1862 to 1749 but increased in retrognathia from 1070 to 1563. We have to consider that the total amount of different entities to the controls is higher in patients with prognathic mandible (7364) because of their strong genetic controlled development compared with that in patients with retrognathic mandible (4126), which is more environmentally influenced. It can be concluded that function follows form after surgical change with high inheritance. In retrognathic patients the adaptation could be delayed or the capacity of regeneration potential is not sufficient. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

DMPD: The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 10669111 The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Qur...e The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Authors Qur

Integration of population genetic structure and plant response to climate change: sustaining genetic resources through evaluation of projected threats

Science.gov (United States)

Bryce A. Richardson; Marcus V. Warwell; Mee-Sook Kim; Ned B. Klopfenstein; Geral I. McDonald

2010-01-01

To assess threats or predict responses to disturbances, or both, it is essential to recognize and characterize the population structures of forest species in relation to changing environments. Appropriate management of these genetic resources in the future will require (1) understanding the existing genetic diversity/variation and population structure of forest trees...

Permanence of a predator-prey discrete system with Holling-IV functional response and distributed delays.

Science.gov (United States)

Zhang, X; Wu, Z; Zhou, T

2016-01-01

A predator-prey discrete-time model with Holling-IV functional response and distributed delays is investigated in this paper. By using the comparison theorem of the difference equation and some analysis technique, some sufficient conditions are obtained for the permanence of the discrete predator-prey system. Two examples are given to illustrate the feasibility of the obtained result.

Time-Delay System Identification Using Genetic Algorithm

DEFF Research Database (Denmark)

Yang, Zhenyu; Seested, Glen Thane

2013-01-01

problem through an identification approach using the real coded Genetic Algorithm (GA). The desired FOPDT/SOPDT model is directly identified based on the measured system's input and output data. In order to evaluate the quality and performance of this GA-based approach, the proposed method is compared...

[SOS response of DNA repair and genetic cell instability under hypoxic conditions].

Science.gov (United States)

Vasil'eva, S V; Strel'tsova, D A

2011-01-01

The SOS DNA repair pathway is induced in E. coli as a multifunctional cell response to a wide variety of signals: UV, X or gamma-irradiation, mitomycin C or nalidixic acid treatment, thymine starvation, etc. Triggering of the system can be used as a general and early sign of DNA damage. Additionally, the SOS-response is known to be an "error-prone" DNA repair pathway and one of the sources of genetic instability. Hypoxic conditions are established to be the major factor of genetic instability as well. In this paper we for the first time studied the SOS DNA repair response under hypoxic conditions induced by the well known aerobic SOS-inducers. The SOS DNA repair response was examined as a reaction of E. coli PQ37 [sfiA::lacZ] cells to UVC, NO-donating agents and 4NQO. Here we provide evidence that those agents were able to induce the SOS DNA repair response in E. coli at anaerobic growth conditions. The process does not depend on the transcriptional activity of the universal protein of E. col anaerobic growth Fnr [4Fe-4S]2+ or can not be referred to as an indicator of genetic instability in hypoxic conditions.

Immediate and delayed effects of radiation on the genetic endowment of the butterfly, Acraea horta L

International Nuclear Information System (INIS)

Balinsky, B.I.

1981-01-01

Pupae of the butterfly Acraea horta were irradiated with X or gamma rays with doses of 3 000 R, 7 000 R and 15 000 R. Even after the highest doses most of the pupae remained vital, butterflies emerged, and a proportion of them mated and produced offspring. The consequences for the offspring of the irradiated pupae were increased mortality, especially mortality of the eggs, decreased vitality, infertility in some cases, and various morphological abnormalities. The genetic nature of the morphological abnormalities could not be analysed, as some of the affected individuals did not breed, and other abnormalities proved not to be heritable. As a result of decreased virtality and increased mortality the offspring of the more heavily irradiated pupae died out after two (in the case of doses of 15 000 R) or three (in the case of doses of 7 000 R) post-irradiation generations. Some of the offspring of pupae receiving 3 000 R were capable of breeding indefinitely. Morphological abnormalities and increased mortality occured in the second and third post-irradiation generations (as well as in the first), after the previous one or two generations appeared to be completely normal and viable. This was not due to segregation of recessive mutations, but seems to be expressions of a delayed effect of the damage caused to the genotype by the radiation. The possible mechanism of such a delayed effect of the radiation is briefly discussed [af

Experience of Comamonas Acidovorans Keratitis with Delayed Onset and Treatment Response in Immunocompromised Cornea

OpenAIRE

Lee, Sang Mok; Kim, Mee Kum; Lee, Jae Lim; Wee, Won Ryang; Lee, Jin Hak

2008-01-01

Purpose To report 2 cases of Comamonas Acidovorans keratitis in immunocompromised cornea. Methods A complete review of the medical records of the two cases of Comamonas acidovorans keratitis. Results We found some similarities in clinical courses of two cases. Both of them showed development of keratitis during the management with corticosteroids, delayed onset, slow response to antibiotics, and relatively less affected corneal epithelium. Conclusions Comamonas Acidovorans is known as a less ...

Delayed plastic responses to anodal tDCS in older adults

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Hakuei eFujiyama

2014-06-01

Full Text Available Despite the abundance of research reporting the neurophysiological and behavioral effects of transcranial direct current stimulation (tDCS in healthy young adults and clinical populations, the extent of potential neuroplastic changes induced by tDCS in healthy older adults is not well understood. The present study compared the extent and time course of anodal tDCS-induced plastic changes in primary motor cortex (M1 in young and older adults. Furthermore, as it has been suggested that neuroplasiticity and associated learning depends on the brain-derived neurotrophic factor (BDNF gene polymorphisms, we also assessed the impact of BDNF polymorphism on these effects. Corticospinal excitability was examined using transcranial magnetic stimulation before and following (0, 10, 20, 30 min anodal tDCS (30 min, 1 mA or sham in young and older adults. While the overall extent of increases in corticospinal excitability induced by anodal tDCS did not vary reliably between young and older adults, older adults exhibited a delayed response; the largest increase in corticospinal excitability occurred 30 min following stimulation for older adults, but immediately post-stimulation for the young group. BDNF genotype did not result in significant differences in the observed excitability increases for either age group. The present study suggests that tDCS-induced plastic changes are delayed as a result of healthy aging, but that the overall efficacy of the plasticity mechanism remains unaffected.

Social Reinforcement Delays in Free-Flying Honey Bees (Apis mellifera L.)

Science.gov (United States)

Craig, David Philip Arthur; Grice, James W.; Varnon, Chris A.; Gibson, B.; Sokolowski, Michel B. C.; Abramson, Charles I.

2012-01-01

Free-flying honey bees (Apis mellifera L.) reactions were observed when presented with varying schedules of post-reinforcement delays of 0 s, 300 s, or 600 s. We measured inter-visit-interval, response length, inter-response-time, and response rate. Honey bees exposed to these post-reinforcement delay intervals exhibit one of several patterns compared to groups not encountering delays, and had longer inter-visit-intervals. We observed no group differences in inter-response time. Honey bees with higher response rates tended to not finish the experiment. The removal of the delay intervals increased response rates for those subjects that completed the trials. PMID:23056425

Airport Flight Departure Delay Model on Improved BN Structure Learning

Science.gov (United States)

Cao, Weidong; Fang, Xiangnong

An high score prior genetic simulated annealing Bayesian network structure learning algorithm (HSPGSA) by combining genetic algorithm(GA) with simulated annealing algorithm(SAA) is developed. The new algorithm provides not only with strong global search capability of GA, but also with strong local hill climb search capability of SAA. The structure with the highest score is prior selected. In the mean time, structures with lower score are also could be choice. It can avoid efficiently prematurity problem by higher score individual wrong direct growing population. Algorithm is applied to flight departure delays analysis in a large hub airport. Based on the flight data a BN model is created. Experiments show that parameters learning can reflect departure delay.

A genetic dissection of the photophobic response of Paramecium tetraurelia.

Science.gov (United States)

Hinrichsen, Robert; Peters, Christian

2013-05-01

Paramecium tetraurelia displayed two behavioral responses upon the initiation of a light stimulus at 7 x 10(4) lux. The cells exhibited a photophobic response in the form of behavioral avoiding reactions, followed by an increase in forward swimming velocity that was significantly higher than prior to the light stimulus activation. It was determined that an intensity of approximately 6.5 x 10(3) lux was required to initiate a moderate avoidance behavioral response. Following the avoiding response, a gradual increase in speed occurred as the intensity increased, indicating that increased swimming speeds are dependent on the light intensity. Two mutants, pawnA and Dancer, were utilized since they affect known Ca(2+)-currents of the cell. The use of pawnA cells, which lack voltage-dependent Ca(2+) channel activity, showed that the two responses to light could be genetically separated, in that the cells showed no avoiding reactions, but did increase their swimming speed. The Dancer cells, which display exaggerated Ca(2+) channel activity, exhibited similar initial avoiding responses as the wild type cells, however did not increase their swimming speed as the intensity of the light was increased. This phenotype as replicated in wildtype cells that had been placed in 25 μM 8-Br-cGMP. These data demonstrate that the photophobic light response of Paramecium tetraurelia can be genetically dissected as a means of elucidating the molecular mechanisms of the light response. Copyright © 2013 Elsevier GmbH. All rights reserved.

Motor Asymmetry and Substantia Nigra Volume Are Related to Spatial Delayed Response Performance in Parkinson Disease

Science.gov (United States)

Foster, Erin R.; Black, Kevin J.; Antenor-Dorsey, Jo Ann V.; Perlmutter, Joel S.; Hershey, Tamara

2008-01-01

Studies suggest motor deficit asymmetry may help predict the pattern of cognitive impairment in individuals with Parkinson disease (PD). We tested this hypothesis using a highly validated and sensitive spatial memory task, spatial delayed response (SDR), and clinical and neuroimaging measures of PD asymmetry. We predicted SDR performance would be…

Modeling of delays in PKPD: classical approaches and a tutorial for delay differential equations.

Science.gov (United States)

Koch, Gilbert; Krzyzanski, Wojciech; Pérez-Ruixo, Juan Jose; Schropp, Johannes

2014-08-01

In pharmacokinetics/pharmacodynamics (PKPD) the measured response is often delayed relative to drug administration, individuals in a population have a certain lifespan until they maturate or the change of biomarkers does not immediately affects the primary endpoint. The classical approach in PKPD is to apply transit compartment models (TCM) based on ordinary differential equations to handle such delays. However, an alternative approach to deal with delays are delay differential equations (DDE). DDEs feature additional flexibility and properties, realize more complex dynamics and can complementary be used together with TCMs. We introduce several delay based PKPD models and investigate mathematical properties of general DDE based models, which serve as subunits in order to build larger PKPD models. Finally, we review current PKPD software with respect to the implementation of DDEs for PKPD analysis.

Fructans from aged garlic extract produce a delayed immunoadjuvant response to ovalbumin antigen in BALB/c mice.

Science.gov (United States)

Chandrashekar, Puthanapura M; Venkatesh, Yeldur P

2012-02-01

Garlic (Allium sativum) is known for its innumerable biological activities including immunomodulation. Aged garlic extract (AGE), an odorless garlic preparation, has been shown to have superior immunomodulatory properties over raw garlic extract. Although garlic is a very rich source of fructans (17%, fresh weight basis), AGE contains only 0.22% of raw garlic fructans. Aged garlic fructans (AGF) have recently been shown to possess immunomodulatory activities in vitro. Natural adjuvants capable of eliciting better immune response of a model antigen are important in developing newer vaccines. In the present study, the adjuvant activity of AGF has been investigated in BALB/c mice using ovalbumin (OVA, 30 µg) as an experimental antigen. The body weights of animals did not change significantly indicating that the administration of garlic fructans is well-tolerated. AGF produce a significant humoral (serum IgG) response to OVA in BALB/c mice administered mucosally by either intranasal or oral route--a delayed response appearing on 50th day at a dose of 30 µg AGF by intranasal route. However, the serum IgG response was seen earlier on 35th day at a dose of 100 µg AGF by oral route. Higher concentrations of AGF (>50 µg) were inhibitory for adjuvant activity by intranasal administration. These observations indicate that AGF display immunoadjuvant activity for a test antigen though the humoral immune response is delayed.

Genetics of growth habit and photoperiodic response to flowering ...

Indian Academy of Sciences (India)

2014-04-16

Apr 16, 2014 ... 3Department of Agricultural Entomology, University of Agricultural Sciences, Gandhi Krishi Vignana Kendra,. Bangalore 560 065, India. [Keerthi C. M., Ramesh S., Byregowda M., Rao A. M., Rajendra Prasad B. S. and Vaijayanthi P. V. 2014 Genetics of growth habit and photoperiodic response to flowering ...

Task-specific modulation of human auditory evoked responses in a delayed-match-to-sample task

Directory of Open Access Journals (Sweden)

Feng eRong

2011-05-01

Full Text Available In this study, we focus our investigation on task-specific cognitive modulation of early cortical auditory processing in human cerebral cortex. During the experiments, we acquired whole-head magnetoencephalography (MEG data while participants were performing an auditory delayed-match-to-sample (DMS task and associated control tasks. Using a spatial filtering beamformer technique to simultaneously estimate multiple source activities inside the human brain, we observed a significant DMS-specific suppression of the auditory evoked response to the second stimulus in a sound pair, with the center of the effect being located in the vicinity of the left auditory cortex. For the right auditory cortex, a non-invariant suppression effect was observed in both DMS and control tasks. Furthermore, analysis of coherence revealed a beta band (12 ~ 20 Hz DMS-specific enhanced functional interaction between the sources in left auditory cortex and those in left inferior frontal gyrus, which has been shown to involve in short-term memory processing during the delay period of DMS task. Our findings support the view that early evoked cortical responses to incoming acoustic stimuli can be modulated by task-specific cognitive functions by means of frontal-temporal functional interactions.

Genetic evolution, plasticity, and bet-hedging as adaptive responses to temporally autocorrelated fluctuating selection: A quantitative genetic model.

Science.gov (United States)

Tufto, Jarle

2015-08-01

Adaptive responses to autocorrelated environmental fluctuations through evolution in mean reaction norm elevation and slope and an independent component of the phenotypic variance are analyzed using a quantitative genetic model. Analytic approximations expressing the mutual dependencies between all three response modes are derived and solved for the joint evolutionary outcome. Both genetic evolution in reaction norm elevation and plasticity are favored by slow temporal fluctuations, with plasticity, in the absence of microenvironmental variability, being the dominant evolutionary outcome for reasonable parameter values. For fast fluctuations, tracking of the optimal phenotype through genetic evolution and plasticity is limited. If residual fluctuations in the optimal phenotype are large and stabilizing selection is strong, selection then acts to increase the phenotypic variance (bet-hedging adaptive). Otherwise, canalizing selection occurs. If the phenotypic variance increases with plasticity through the effect of microenvironmental variability, this shifts the joint evolutionary balance away from plasticity in favor of genetic evolution. If microenvironmental deviations experienced by each individual at the time of development and selection are correlated, however, more plasticity evolves. The adaptive significance of evolutionary fluctuations in plasticity and the phenotypic variance, transient evolution, and the validity of the analytic approximations are investigated using simulations. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Exposing College Students to Exercise: The Training Interventions and Genetics of Exercise Response (TIGER) Study

Science.gov (United States)

Sailors, Mary H.; Jackson, Andrew S.; McFarlin, Brian K.; Turpin, Ian; Ellis, Kenneth J.; Foreyt, John P.; Hoelscher, Deanna M.; Bray, Molly S.

2010-01-01

Objective: The Training Interventions and Genetics of Exercise Response (TIGER) study is an exercise program designed to introduce sedentary college students to regular physical activity and to identify genetic factors that influence response to exercise. Participants: A multiracial/ethnic cohort (N = 1,567; 39% male), age 18 to 35 years,…

The micropolitics of responsibility vis-à-vis autonomy: parental accounts of childhood genetic testing and (non)disclosure.

Science.gov (United States)

Arribas-Ayllon, Michael; Sarangi, Srikant; Clarke, Angus

2008-03-01

Genetic testing and (non)disclosure of genetic information present ethical and moral dilemmas for the management of parental responsibility vis-à-vis the child's autonomy. Ethical guidelines aimed at professionals currently seek to defer childhood testing where there is no clear medical or psychosocial benefit. This version of autonomy is derived from a bioethical paradigm which brackets the individual rights and capacities of the child. In this paper we focus on situated parental accounts of responsibility/autonomy to understand the complex forms of relational work -i.e. the micropolitics of balancing rights and responsibilities - involving a range of inherited genetic disorders. Interviews (n= 20) were conducted with parents whose genetic condition may have had consequences for their children. Using rhetorical discourse analysis, we show how parents draw upon a number of rhetorical/discoursal devices to produce accounts where genetic responsibility is actually or potentially transmitted to the child. We identify three kinds of accounting practice: (1) aligned responsibility; (2) deferred responsibility; and (3) misaligned responsibility. Each of these practices demonstrates how parents position themselves responsibly by foregrounding figures and events onto which the child's autonomy is selectively mapped. Rather than simple representations, we regard these accounts as complex moral performances that seek alignment with broader bioethical discourses.

Impact of genetic polymorphisms on clinical response to antithrombotics

Directory of Open Access Journals (Sweden)

Kena J Lanham

2010-06-01

Full Text Available Kena J Lanham1,2, Julie H Oestreich3, Steven P Dunn1,2, Steven R Steinhubl41Pharmacy Services, UK HealthCare, University of Kentucky, Lexington, Kentucky, USA; 2Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA; 3Department of Pharmacy Practice, College of Pharmacy, University of Nebraska, Omaha, Nebraska, USA; 4The Medicines Company, Zurich, Switzerland and The Geisinger Clinic, Danville, Pennsylvania, USAAbstract: Antithrombotic therapy, including anticoagulants as well as antiplatelet drugs, is an important component in the treatment of cardiovascular disease. Variability in response to such medications, of which pharmacogenetic response is a major source, can decrease or enhance the benefits expected. This review is a comprehensive assessment of the literature published to date on the effects of genetic polymorphisms on the actions of a variety of antithrombotic medications, including warfarin, clopidogrel, prasugrel, and aspirin. Literature evaluating surrogate markers in addition to the impact of pharmacogenetics on clinical outcomes has been reviewed. The results of the studies are conflicting as to what degree pharmacogenetics will affect medication management in cardiovascular disease. Additional research is necessary to discover, characterize, and prospectively evaluate genetic and non-genetic factors that impact antithrombotic treatment in order to maximize the effectiveness and limit the harmful effects of these valuable agents.Keywords: aspirin, warfarin, clopidogrel, prasugrel, pharmacogenetic, antithrombotic, antiplatelet

Functional Dissociation of Confident and Not-Confident Errors in the Spatial Delayed Response Task Demonstrates Impairments in Working Memory Encoding and Maintenance in Schizophrenia

Directory of Open Access Journals (Sweden)

Jutta S. Mayer

2018-05-01

Full Text Available Even though extensively investigated, the nature of working memory (WM deficits in patients with schizophrenia (PSZ is not yet fully understood. In particular, the contribution of different WM sub-processes to the severe WM deficit observed in PSZ is a matter of debate. So far, most research has focused on impaired WM maintenance. By analyzing different types of errors in a spatial delayed response task (DRT, we have recently demonstrated that incorrect yet confident responses (which we labeled as false memory errors rather than incorrect/not-confident responses reflect failures of WM encoding, which was also impaired in PSZ. In the present study, we provide further evidence for a functional dissociation between confident and not-confident errors by manipulating the demands on WM maintenance, i.e., the length over which information has to be maintained in WM. Furthermore, we investigate whether these functionally distinguishable WM processes are impaired in PSZ. Twenty-four PSZ and 24 demographically matched healthy controls (HC performed a spatial DRT in which the length of the delay period was varied between 1, 2, 4, and 6 s. In each trial, participants also rated their level of response confidence. Across both groups, longer delays led to increased rates of incorrect/not-confident responses, while incorrect/confident responses were not affected by delay length. This functional dissociation provides additional support for our proposal that false memory errors (i.e., confident errors reflect problems at the level of WM encoding, while not-confident errors reflect failures of WM maintenance. Schizophrenic patients showed increased numbers of both confident and not-confident errors, suggesting that both sub-processes of WM—encoding and maintenance—are impaired in schizophrenia. Combined with the delay length-dependent functional dissociation, we propose that these impairments in schizophrenic patients are functionally distinguishable.

Genetic Components of Root Architecture Remodeling in Response to Salt Stress

KAUST Repository

Julkowska, Magdalena; Koevoets, Iko Tamar; Mol, Selena; Hoefsloot, Huub CJ; Feron, Richard; Tester, Mark A.; Keurentjes, Joost J.B.; Korte, Arthur; Haring, Michel A; de Boer, Gert-Jan; Testerink, Christa

2017-01-01

Salinity of the soil is highly detrimental to plant growth. Plants respond by a redistribution of root mass between main and lateral roots, yet the genetic machinery underlying this process is still largely unknown. Here, we describe the natural variation among 347 Arabidopsis thaliana accessions in root system architecture (RSA) and identify the traits with highest natural variation in their response to salt. Salt-induced changes in RSA were associated with 100 genetic loci using genome-wide association studies (GWAS). Two candidate loci associated with lateral root development were validated and further investigated. Changes in CYP79B2 expression in salt stress positively correlated with lateral root development in accessions, and cyp79b2 cyp79b3 double mutants developed fewer and shorter lateral roots under salt stress, but not in control conditions. By contrast, high HKT1 expression in the root repressed lateral root development, which could be partially rescued by addition of potassium. The collected data and Multi-Variate analysis of multiple RSA traits, available through the Salt_NV_Root App, capture root responses to salinity. Together, our results provide a better understanding of effective RSA remodeling responses, and the genetic components involved, for plant performance in stress conditions.

Genetic Components of Root Architecture Remodeling in Response to Salt Stress

KAUST Repository

Julkowska, Magdalena

2017-11-07

Salinity of the soil is highly detrimental to plant growth. Plants respond by a redistribution of root mass between main and lateral roots, yet the genetic machinery underlying this process is still largely unknown. Here, we describe the natural variation among 347 Arabidopsis thaliana accessions in root system architecture (RSA) and identify the traits with highest natural variation in their response to salt. Salt-induced changes in RSA were associated with 100 genetic loci using genome-wide association studies (GWAS). Two candidate loci associated with lateral root development were validated and further investigated. Changes in CYP79B2 expression in salt stress positively correlated with lateral root development in accessions, and cyp79b2 cyp79b3 double mutants developed fewer and shorter lateral roots under salt stress, but not in control conditions. By contrast, high HKT1 expression in the root repressed lateral root development, which could be partially rescued by addition of potassium. The collected data and Multi-Variate analysis of multiple RSA traits, available through the Salt_NV_Root App, capture root responses to salinity. Together, our results provide a better understanding of effective RSA remodeling responses, and the genetic components involved, for plant performance in stress conditions.

HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS

NARCIS (Netherlands)

Roberts, Susanna; Keers, Robert; Lester, Kathryn J.; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E.; Herren, Chantal; Hogendoorn, Sanne M.; Hudson, Jennifer L.; Krause, Karen; Lyneham, Heidi J.; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C.; Wong, Chloe C. Y.

2015-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive

Evaluation of mature cow weight: genetic correlations with traits used in selection indices, correlated responses, and genetic trends in Nelore cattle.

Science.gov (United States)

Boligon, A A; Carvalheiro, R; Albuquerque, L G

2013-01-01

Genetic correlations of selection indices and the traits considered in these indices with mature weight (MW) of Nelore females and correlated responses were estimated to determine whether current selection practices will result in an undesired correlated response in MW. Genetic trends for weaning and yearling indices and MW were also estimated. Data from 612,244 Nelore animals born between 1984 and 2010, belonging to different beef cattle evaluation programs from Brazil and Paraguay, were used. The following traits were studied: weaning conformation (WC), weaning precocity (WP), weaning muscling (WM), yearling conformation (YC), yearling precocity (YP), yearling muscling (YM), weaning and yearling indices, BW gain from birth to weaning (BWG), postweaning BW gain (PWG), scrotal circumference (SC), and MW. The variance and covariance components were estimated by Bayesian inference in a multitrait analysis, including all traits in the same analysis, using a nonlinear (threshold) animal model for visual scores and a linear animal model for the other traits. The mean direct heritabilities were 0.21±0.007 (WC), 0.22±0.007 (WP), 0.20±0.007 (WM), 0.43±0.005 (YC), 0.40±0.005 (YP), 0.40±0.005 (YM), 0.17±0.003 (BWG), 0.21±0.004 (PWG), 0.32±0.001 (SC), and 0.44±0.018 (MW). The genetic correlations between MW and weaning and yearling indices were positive and of medium magnitude (0.30±0.01 and 0.31±0.01, respectively). The genetic changes in weaning index, yearling index, and MW, expressed as units of genetic SD per year, were 0.26, 0.27, and 0.01, respectively. The genetic trend for MW was nonsignificant, suggesting no negative correlated response. The selection practice based on the use of sires with high final index giving preference for those better ranked for yearling precocity and muscling than for conformation generates only a minimal correlated response in MW.

Relationship between systemic inflammation and delayed-type hypersensitivity response to Candida antigen in older adults.

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Brandt D Pence

Full Text Available Research has shown that aging is associated with increased systemic inflammation as well as a reduction in the strength of immune responses. However, little evidence exists linking the decrease in cell-mediated immunity in older adults with other health parameters. We sought to examine the relationship between cell-mediated immunity as measured in vivo by the delayed-type hypersensitivity (DTH response to candida antigen and demographic and physiological variables in older (65-80 y.o. adults. Candida antigen response was not related to gender or obesity, or to a number of other physiological variables including fitness and body composition. However, positive responders had significantly lower serum C-reactive protein levels (CRP, p4.75 mg•L(-1. Therefore, positive responses to candida antigen in older adults appears to be related to lower levels of systemic inflammation.

Integrating environmental and genetic effects to predict responses of tree populations to climate.

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Wang, Tongli; O'Neill, Gregory A; Aitken, Sally N

2010-01-01

Climate is a major environmental factor affecting the phenotype of trees and is also a critical agent of natural selection that has molded among-population genetic variation. Population response functions describe the environmental effect of planting site climates on the performance of a single population, whereas transfer functions describe among-population genetic variation molded by natural selection for climate. Although these approaches are widely used to predict the responses of trees to climate change, both have limitations. We present a novel approach that integrates both genetic and environmental effects into a single "universal response function" (URF) to better predict the influence of climate on phenotypes. Using a large lodgepole pine (Pinus contorta Dougl. ex Loud.) field transplant experiment composed of 140 populations planted on 62 sites to demonstrate the methodology, we show that the URF makes full use of data from provenance trials to: (1) improve predictions of climate change impacts on phenotypes; (2) reduce the size and cost of future provenance trials without compromising predictive power; (3) more fully exploit existing, less comprehensive provenance tests; (4) quantify and compare environmental and genetic effects of climate on population performance; and (5) predict the performance of any population growing in any climate. Finally, we discuss how the last attribute allows the URF to be used as a mechanistic model to predict population and species ranges for the future and to guide assisted migration of seed for reforestation, restoration, or afforestation and genetic conservation in a changing climate.

Examination of a recommended algorithm for eliminating nonsystematic delay discounting response sets.

Science.gov (United States)

White, Thomas J; Redner, Ryan; Skelly, Joan M; Higgins, Stephen T

2015-09-01

To examine (1) whether use of a recommended algorithm (Johnson and Bickel, 2008) improves upon conventional statistical model fit (R(2)) for identifying nonsystematic response sets in delay discounting (DD) data, (2) whether removing such data meaningfully effects research outcomes, and (3) to identify participant characteristics associated with nonsystematic response sets. Discounting of hypothetical monetary rewards was assessed among 349 pregnant women (231 smokers and 118 recent quitters) via a computerized task comparing $1000 at seven future time points with smaller values available immediately. Nonsystematic response sets were identified using the algorithm and conventional statistical model fit (R(2)). The association between DD and quitting was analyzed with and without nonsystematic response sets to examine whether the inclusion or exclusion impacts this relationship. Logistic regression was used to examine whether participant sociodemographics were associated with nonsystematic response sets. The algorithm excluded fewer cases than the R(2) method (14% vs. 16%), and was not correlated with logk as is R(2). The relationship between logk and the clinical outcome (spontaneous quitting) was unaffected by exclusion methods; however, other variables in the model were affected. Lower educational attainment and younger age were associated with nonsystematic response sets. The algorithm eliminated data that were inconsistent with the nature of discounting and retained data that were orderly. Neither method impacted the smoking/DD relationship in this data set. Nonsystematic response sets are more likely among younger and less educated participants, who may need extra training or support in DD studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Delay Estimator and Improved Proportionate Multi-Delay Adaptive Filtering Algorithm

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E. Verteletskaya

2012-04-01

Full Text Available This paper pertains to speech and acoustic signal processing, and particularly to a determination of echo path delay and operation of echo cancellers. To cancel long echoes, the number of weights in a conventional adaptive filter must be large. The length of the adaptive filter will directly affect both the degree of accuracy and the convergence speed of the adaptation process. We present a new adaptive structure which is capable to deal with multiple dispersive echo paths. An adaptive filter according to the present invention includes means for storing an impulse response in a memory, the impulse response being indicative of the characteristics of a transmission line. It also includes a delay estimator for detecting ranges of samples within the impulse response having relatively large distribution of echo energy. These ranges of samples are being indicative of echoes on the transmission line. An adaptive filter has a plurality of weighted taps, each of the weighted taps having an associated tap weight value. A tap allocation/control circuit establishes the tap weight values in response to said detecting means so that only taps within the regions of relatively large distributions of echo energy are turned on. Thus, the convergence speed and the degree of estimation in the adaptation process can be improved.

Autologous neural progenitor cell transplantation into newborn mice modeling for E200K genetic prion disease delays disease progression.

Science.gov (United States)

Frid, Kati; Binyamin, Orli; Fainstein, Nina; Keller, Guy; Ben-Hur, Tamir; Gabizon, Ruth

2018-05-01

TgMHu2ME199K mice, a transgenic line mimicking genetic prion disease, are born healthy and gradually deteriorate to a terminal neurological condition concomitant with the accumulation of disease-related PrP. To investigate whether transplantation of neural progenitor cells (NPCs) to these mice can delay disease aggravation, we first tested the properties of mutant PrP in homogenates and enriched NPCs from TgMHu2ME199K embryos, as compared to PrP in sick TgMHu2ME199K brains. Next, we tested the clinical effect of NPCs transplantation into newborn TgMHu2ME199K mice. We show that mutant PrP does not convert into a disease-related isoform while in progenitor cells. Most important, transplantation of both wild type and transgenic NPCs significantly delayed the progression of spontaneous prion disease in TgMHu2ME199K mice. While the strong clinical effect was not accompanied by a reduced accumulation of disease-related PrP, treated mouse brains presented a significant reduction in amyloid glycosaminoglycans and preservation of neurogenesis levels, indicating a strong neuroprotective effect. These results may encourage the investigation of new pathways for treatment in these terrible diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Testing for a genetic response to sexual selection in a wild Drosophila population.

Science.gov (United States)

Gosden, T P; Thomson, J R; Blows, M W; Schaul, A; Chenoweth, S F

2016-06-01

In accordance with the consensus that sexual selection is responsible for the rapid evolution of display traits on macroevolutionary scales, microevolutionary studies suggest sexual selection is a widespread and often strong form of directional selection in nature. However, empirical evidence for the contemporary evolution of sexually selected traits via sexual rather than natural selection remains weak. In this study, we used a novel application of quantitative genetic breeding designs to test for a genetic response to sexual selection on eight chemical display traits from a field population of the fly, Drosophila serrata. Using our quantitative genetic approach, we were able to detect a genetically based difference in means between groups of males descended from fathers who had either successfully sired offspring or were randomly collected from the same wild population for one of these display traits, the diene (Z,Z)-5,9-C27 : 2 . Our experimental results, in combination with previous laboratory studies on this system, suggest that both natural and sexual selection may be influencing the evolutionary trajectories of these traits in nature, limiting the capacity for a contemporary evolutionary response. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes — A Meta-Analysis

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Li-Shiun Chen

2016-09-01

Conclusion: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7 years for those who develop it. These results: 1 underscore the potential value of smoking cessation for all smokers, 2 suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3 have potential value for framing preventive interventions for those who smoke.

Response of predatory mites to a herbivore-induced plant volatile: genetic variation for context-dependent behaviour.

Science.gov (United States)

Sznajder, Beata; Sabelis, Maurice W; Egas, Martijn

2010-07-01

Plants infested with herbivores release specific volatile compounds that are known to recruit natural enemies. The response of natural enemies to these volatiles may be either learned or genetically determined. We asked whether there is genetic variation in the response of the predatory mite Phytoseiulus persimilis to methyl salicylate (MeSa). MeSa is a volatile compound consistently produced by plants being attacked by the two-spotted spider mite, the prey of P. persimilis. We predicted that predators express genetically determined responses during long-distance migration where previously learned associations may have less value. Additionally, we asked whether these responses depend on odors from uninfested plants as a background to MeSa. To infer a genetic basis, we analyzed the variation in response to MeSa among iso-female lines of P. persimilis by using choice-tests that involved either (1) MeSa presented as a single compound or (2) MeSa with background-odor from uninfested lima bean plants. These tests were conducted for starved and satiated predators, i.e., two physiological states, one that approximates migration and another that mimics local patch exploration. We found variation among iso-female lines in the responses to MeSa, thus showing genetic variation for this behavior. The variation was more pronounced in the starved predators, thus indicating that P. persimilis relies on innate preferences when migrating. Background volatiles of uninfested plants changed the predators' responses to MeSa in a manner that depended on physiological state and iso-female line. Thus, it is possible to select for context-dependent behavioral responses of natural enemies to plant volatiles.

Exponential Antisynchronization Control of Stochastic Memristive Neural Networks with Mixed Time-Varying Delays Based on Novel Delay-Dependent or Delay-Independent Adaptive Controller

Directory of Open Access Journals (Sweden)

Minghui Yu

2017-01-01

Full Text Available The global exponential antisynchronization in mean square of memristive neural networks with stochastic perturbation and mixed time-varying delays is studied in this paper. Then, two kinds of novel delay-dependent and delay-independent adaptive controllers are designed. With the ability of adapting to environment changes, the proposed controllers can modify their behaviors to achieve the best performance. In particular, on the basis of the differential inclusions theory, inequality theory, and stochastic analysis techniques, several sufficient conditions are obtained to guarantee the exponential antisynchronization between the drive system and response system. Furthermore, two numerical simulation examples are provided to the validity of the derived criteria.

A genetically encoded biosensor for visualising hypoxia responses in vivo

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Tvisha Misra

2017-02-01

Full Text Available Cells experience different oxygen concentrations depending on location, organismal developmental stage, and physiological or pathological conditions. Responses to reduced oxygen levels (hypoxia rely on the conserved hypoxia-inducible factor 1 (HIF-1. Understanding the developmental and tissue-specific responses to changing oxygen levels has been limited by the lack of adequate tools for monitoring HIF-1 in vivo. To visualise and analyse HIF-1 dynamics in Drosophila, we used a hypoxia biosensor consisting of GFP fused to the oxygen-dependent degradation domain (ODD of the HIF-1 homologue Sima. GFP-ODD responds to changing oxygen levels and to genetic manipulations of the hypoxia pathway, reflecting oxygen-dependent regulation of HIF-1 at the single-cell level. Ratiometric imaging of GFP-ODD and a red-fluorescent reference protein reveals tissue-specific differences in the cellular hypoxic status at ambient normoxia. Strikingly, cells in the larval brain show distinct hypoxic states that correlate with the distribution and relative densities of respiratory tubes. We present a set of genetic and image analysis tools that enable new approaches to map hypoxic microenvironments, to probe effects of perturbations on hypoxic signalling, and to identify new regulators of the hypoxia response.

Clinical profile, diagnostic delay, and genetic make-up of cystic fibrosis in Kashmir, India

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Tasaduq Ahmad Mir

2011-01-01

Full Text Available Objectives: This observational study was done to describe the clinical profile, and delays in diagnosing cystic fibrosis (CF disease in Kashmir, India. Materials and Methods : A total of 6758 patients between the ages of 0 and 19 years were registered over a period of 1 year. Out of these, 150 patients suspected of having CF, on clinical grounds, were subjected to pilocarpine iontophoresis, and later on genetic evaluation. Apart from these specific tests, these patients were subjected to laboratory tests like blood counts, blood sugar, KFT, LFT, pancreatic function test, serum electrolytes, and chloride, urine, throat swab, blood culture, ABG analysis, chest and paranasal X-rays. In addition, sonographic evaluation of abdominal organs was carried out to know the status of internal organs. A polymerase chain reaction (PCR-based test was used for the identification of CF mutation. Results: CF was diagnosed in three (0.8% patients. Median age of presentation of CF was 78 months. Family history suggestive of CF was present in one (33.3% and consanguinity in three (100% patients. Common clinical manifestations at the time of presentation included recurrent pneumonia in three (100%, failure to thrive in three (100%, recurrent diarrhea in one (33.3% patients. General physical examination showed pallor in three (100%, malnutrition in three (100%, and clubbing in two (66.7% patients. Examination of respiratory tract revealed hyperinflation in two (66.7%, rhinitis in two (66.7%, and creptations in two (66.7% patients. Sonography of abdominal organs revealed pancreatic cysts in one (33.3%, hyperechoeic and increased liver span in two (66.7%, and small gallbladder in one (33.3%. Staphylococcus aureus was cultured from sputum in one (33.3%, pseudomonas aeruginosa in one (33.3% patients. Delta F508 mutation was present in one (33.3% patient. Conclusion: CF may be more common in Kashmir and other parts of Asia, than indicated by our study; diagnosis is often

Experience of Comamonas acidovorans keratitis with delayed onset and treatment response in immunocompromised cornea.

Science.gov (United States)

Lee, Sang Mok; Kim, Mee Kum; Lee, Jae Lim; Wee, Won Ryang; Lee, Jin Hak

2008-03-01

To report 2 cases of Comamonas acidovorans keratitis in immunocompromised cornea. A complete review of the medical records of the two cases of Comamonas acidovorans keratitis. We found some similarities in clinical courses of two cases. Both of them showed development of keratitis during the management with corticosteroids, delayed onset, slow response to antibiotics, and relatively less affected corneal epithelium. Comamonas acidovorans is known as a less virulent organism. However it can cause an indolent infection that responds slowly even to adequate antibiotics therapy in immunocompromised corneas.

Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis.

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Rosario Lopez-Rodriguez

Full Text Available Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA, given their variable response to TNF inhibitors (TNFi. However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.

Effects of the network structure and coupling strength on the noise-induced response delay of a neuronal network

International Nuclear Information System (INIS)

Ozer, Mahmut; Uzuntarla, Muhammet

2008-01-01

The Hodgkin-Huxley (H-H) neuron model driven by stimuli just above threshold shows a noise-induced response delay with respect to time to the first spike for a certain range of noise strengths, an effect called 'noise delayed decay' (NDD). We study the response time of a network of coupled H-H neurons, and investigate how the NDD can be affected by the connection topology of the network and the coupling strength. We show that the NDD effect exists for weak and intermediate coupling strengths, whereas it disappears for strong coupling strength regardless of the connection topology. We also show that although the network structure has very little effect on the NDD for a weak coupling strength, the network structure plays a key role for an intermediate coupling strength by decreasing the NDD effect with the increasing number of random shortcuts, and thus provides an additional operating regime, that is absent in the regular network, in which the neurons may also exploit a spike time code

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

Science.gov (United States)

Auld, Stuart K J R; Edel, Kai H; Little, Tom J

2012-10-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

The effects of reinforcement and response-cost on a delayed response task in children with attention deficit hyperactivity disorder: a research note.

Science.gov (United States)

Solanto, M V

1990-07-01

Children with attention deficit hyperactivity disorder are more inattentive, active, and impulsive than normal children. Some researchers have postulated that these symptoms can all be explained as a result of reduced sensitivity to reinforcement. In order to evaluate this hypothesis, we tested 20 ADD-H children and 18 matched normal controls, 4 1/2-11 years of age, on a delayed response task, a measure of impulsiveness, under conditions of positive reinforcement, and punishment in the form of response-cost. The contingencies each improved performance compared to baseline but did not differ significantly from each other. Neither contingency affected the groups differentially, thus failing to provide support for the reinforcement hypothesis.

Nutrigenetics: links between genetic background and response to Mediterranean-type diets.

Science.gov (United States)

Lairon, Denis; Defoort, Catherine; Martin, Jean-Charles; Amiot-Carlin, Marie-Jo; Gastaldi, Marguerite; Planells, Richard

2009-09-01

It has been substantiated that the onset of most major diseases (CVD, diabetes, obesity, cancers, etc.) is modulated by the interaction between genetic traits (susceptibility) and environmental factors, especially diet. We aim to report more specific observations relating the effects of Mediterranean-type diets on cardiovascular risk factors and the genetic background of subjects. In the first part, general concepts about nutrigenetics are briefly presented. Human genome has, overall, only marginally changed since its origin but it is thought that minor changes (polymorphisms) of common genes that occurred during evolution are now widespread in human populations, and can alter metabolic pathways and response to diets. In the second part, we report the data obtained during the Medi-RIVAGE intervention study performed in the South-East of France. Data obtained in 169 subjects at moderate cardiovascular risk after a 3-month dietary intervention indicate that some of the twenty-three single nucleotide polymorphisms (SNP) studied exhibit interactions with diets regarding changes of particular parameters after 3-month regimens. Detailed examples are presented, such as interactions between SNP in genes coding for microsomial transfer protein (MTTP) or intestinal fatty acid binding protein (FABP2) and triglyceride, LDL-cholesterol or Framigham score lowering in responses to Mediterranean-type diets. The data provided add further evidence of the interaction between particular SNP and metabolic responses to diets. Finally, improvement in dietary recommendations by taking into account known genetic variability has been discussed.

Genetic analysis of superovulatory response of Holstein cows in Canada.

Science.gov (United States)

Jaton, C; Koeck, A; Sargolzaei, M; Malchiodi, F; Price, C A; Schenkel, F S; Miglior, F

2016-05-01

Superovulation of dairy cattle is frequently used in Canada. The cost of this protocol is high, and so is the variability of the outcome. Knowing the superovulatory potential of a donor cow could influence the breeder's decision to superovulate it or not. The main objective of this study was to perform a genetic analysis for superovulatory response of Holstein cows in Canada using data recorded by Holstein Canada, and to investigate if these data could be used for genetic evaluation. Data contained the total number of embryos and the number of viable embryos from every successful flushing performed across Canada. After editing, 137,446 records of superovulation performed between 1992 and 2014 were analyzed. A univariate repeatability animal model analysis was performed for both total number of embryos and number of viable embryos. Because both data and residuals did not follow a normal distribution, records were subject to either logarithmic or Anscombe transformation. Using logarithmic transformation, heritability estimates (SE) of 0.15 (0.01) and 0.14 (0.01) were found for total number of embryos and number of viable embryos, respectively. Using Anscombe transformation, heritability estimates (SE) of 0.17 (0.01) and 0.14 (0.01) were found for total number of embryos and number of viable embryos, respectively. The genetic correlation between the 2 traits was estimated at 0.97 using logarithmic transformation and 0.95 using Anscombe transformation. Breeding values were estimated for 54,463 cows, and 3,513 sires. Only estimated breeding values of sires having a reliability higher than 40% were considered for estimated breeding values correlations with other routinely evaluated traits. The results showed that selection for a higher response to superovulation would lead to a slight decrease in milk production, but an improvement for functional traits, including all reproduction traits. In all cases, the estimated correlations are either low or modest. We conclude that

Identity recognition in response to different levels of genetic relatedness in commercial soya bean

Science.gov (United States)

Van Acker, Rene; Rajcan, Istvan; Swanton, Clarence J.

2017-01-01

Identity recognition systems allow plants to tailor competitive phenotypes in response to the genetic relatedness of neighbours. There is limited evidence for the existence of recognition systems in crop species and whether they operate at a level that would allow for identification of different degrees of relatedness. Here, we test the responses of commercial soya bean cultivars to neighbours of varying genetic relatedness consisting of other commercial cultivars (intraspecific), its wild progenitor Glycine soja, and another leguminous species Phaseolus vulgaris (interspecific). We found, for the first time to our knowledge, that a commercial soya bean cultivar, OAC Wallace, showed identity recognition responses to neighbours at different levels of genetic relatedness. OAC Wallace showed no response when grown with other commercial soya bean cultivars (intra-specific neighbours), showed increased allocation to leaves compared with stems with wild soya beans (highly related wild progenitor species), and increased allocation to leaves compared with stems and roots with white beans (interspecific neighbours). Wild soya bean also responded to identity recognition but these responses involved changes in biomass allocation towards stems instead of leaves suggesting that identity recognition responses are species-specific and consistent with the ecology of the species. In conclusion, elucidating identity recognition in crops may provide further knowledge into mechanisms of crop competition and the relationship between crop density and yield. PMID:28280587

Timing Analysis of Genetic Logic Circuits using D-VASim

DEFF Research Database (Denmark)

Baig, Hasan; Madsen, Jan

and propagation delay analysis of single as well as cascaded geneticlogic circuits can be performed. D-VASim allows user to change the circuit parameters during runtime simulation to observe its effectson circuit’s timing behavior. The results obtained from D-VASim can be used not only to characterize the timing...... delay analysis may play a very significant role in the designing of genetic logic circuits. In thisdemonstration, we present the capability of D-VASim (Dynamic Virtual Analyzer and Simulator) to perform the timing and propagationdelay analysis of genetic logic circuits. Using D-VASim, the timing...... behavior of geneticlogic circuits but also to analyze the timing constraints of cascaded genetic logic circuits....

Engineering Values Into Genetic Engineering: A Proposed Analytic Framework for Scientific Social Responsibility.

Science.gov (United States)

Sankar, Pamela L; Cho, Mildred K

2015-01-01

Recent experiments have been used to "edit" genomes of various plant, animal and other species, including humans, with unprecedented precision. Furthermore, editing the Cas9 endonuclease gene with a gene encoding the desired guide RNA into an organism, adjacent to an altered gene, could create a "gene drive" that could spread a trait through an entire population of organisms. These experiments represent advances along a spectrum of technological abilities that genetic engineers have been working on since the advent of recombinant DNA techniques. The scientific and bioethics communities have built substantial literatures about the ethical and policy implications of genetic engineering, especially in the age of bioterrorism. However, recent CRISPr/Cas experiments have triggered a rehashing of previous policy discussions, suggesting that the scientific community requires guidance on how to think about social responsibility. We propose a framework to enable analysis of social responsibility, using two examples of genetic engineering experiments.

Effect of caffeine on radiation-induced mitotic delay: delayed expression of G2 arrest

International Nuclear Information System (INIS)

Rowley, R.; Zorch, M.; Leeper, D.B.

1984-01-01

In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G 2 cells progressed to mitosis in register and without arrest in G 2 . Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G 2 arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G 2 phases

The effects of genetic polymorphism on treatment response of recombinant human growth hormone.

Science.gov (United States)

Chen, Shi; You, Hanxiao; Pan, Hui; Zhu, Huijuan; Yang, Hongbo; Gong, Fengying; Wang, Linjie; Jiang, Yu; Yan, Chengsheng

2017-12-06

Recombinant human growth hormone (rhGH) has been widely used in clinical treatment of growth hormone deficiency (GHD) or non GHD since 1985 and technology have achieved a great development in different long-acting formulations. Although the mathematical models for predicting the growth hormone response could help clinicians get to an individual personalized growth dose, many patients just can't reach the target height and the growth hormone responses differed.Genetic polymorphisms may play a role in the varies of individual responses in this treatment process.This article gives an overview of the genetic polymorphisms research of growth hormone in recent years, in order to give some potential suggestion and guide for the dose titration during treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

CGI delay compensation. [Computer Generated Image

Science.gov (United States)

Mcfarland, R. E.

1986-01-01

Computer-generated graphics in real-time helicopter simulation produces objectionable scene-presentation time delays. In the flight simulation laboratory at Ames Research Center, it has been determined that these delays have an adverse influence on pilot performance during agressive tasks such as nap of the earth (NOE) maneuvers. Using contemporary equipment, computer generated image (CGI) time delays are an unavoidable consequence of the operations required for scene generation. However, providing that magnitude distortions at higher frequencies are tolerable, delay compensation is possible over a restricted frequency range. This range, assumed to have an upper limit of perhaps 10 or 15 rad/sec, conforms approximately to the bandwidth associated with helicopter handling qualities research. A compensation algorithm is introduced here and evaluated in terms of tradeoffs in frequency responses. The algorithm has a discrete basis and accommodates both a large, constant transport delay interval and a periodic delay interval, as associated with asynchronous operations.

Genetic Dissection of Anopheles gambiae Gut Epithelial Responses to Serratia marcescens

Science.gov (United States)

Stathopoulos, Stavros; Neafsey, Daniel E.; Lawniczak, Mara K. N.; Muskavitch, Marc A. T.; Christophides, George K.

2014-01-01

Genetic variation in the mosquito Anopheles gambiae profoundly influences its ability to transmit malaria. Mosquito gut bacteria are shown to influence the outcome of infections with Plasmodium parasites and are also thought to exert a strong drive on genetic variation through natural selection; however, a link between antibacterial effects and genetic variation is yet to emerge. Here, we combined SNP genotyping and expression profiling with phenotypic analyses of candidate genes by RNAi-mediated silencing and 454 pyrosequencing to investigate this intricate biological system. We identified 138 An. gambiae genes to be genetically associated with the outcome of Serratia marcescens infection, including the peptidoglycan recognition receptor PGRPLC that triggers activation of the antibacterial IMD/REL2 pathway and the epidermal growth factor receptor EGFR. Silencing of three genes encoding type III fibronectin domain proteins (FN3Ds) increased the Serratia load and altered the gut microbiota composition in favor of Enterobacteriaceae. These data suggest that natural genetic variation in immune-related genes can shape the bacterial population structure of the mosquito gut with high specificity. Importantly, FN3D2 encodes a homolog of the hypervariable pattern recognition receptor Dscam, suggesting that pathogen-specific recognition may involve a broader family of immune factors. Additionally, we showed that silencing the gene encoding the gustatory receptor Gr9 that is also associated with the Serratia infection phenotype drastically increased Serratia levels. The Gr9 antibacterial activity appears to be related to mosquito feeding behavior and to mostly rely on changes of neuropeptide F expression, together suggesting a behavioral immune response following Serratia infection. Our findings reveal that the mosquito response to oral Serratia infection comprises both an epithelial and a behavioral immune component. PMID:24603764

Voicing the lifeworld: Parental accounts of responsibility in genetic consultations for polycystic kidney disease

DEFF Research Database (Denmark)

Clarke, Angus; Sarangi, Srikant; Verrier-Jones, Kate

2011-01-01

decision making, parents nevertheless account for their actions and decisions in an attempt to display parental responsibility. In this paper we explore the accounting practices of parents in genetic consultations, focusing on how they articulate their responsibility with regard to testing their at......When parents, who are carriers of or are affected by a genetic disorder, make decisions about the health risks faced by their children, there may be multiple factors to consider. These may include the medical benefits, the parents’ own experiences of learning about their genetic status...... suggest that (i) parents tend to foreground their practical ‘lifeworld’ considerations to justify their decisional actions; and (ii) there is considerable variation in the ways in which parents respond to information and advice offered by the professionals. The affected parent often presents...

Long-term response to genomic selection: effects of estimation method and reference population structure for different genetic architectures.

Science.gov (United States)

Bastiaansen, John W M; Coster, Albart; Calus, Mario P L; van Arendonk, Johan A M; Bovenhuis, Henk

2012-01-24

Genomic selection has become an important tool in the genetic improvement of animals and plants. The objective of this study was to investigate the impacts of breeding value estimation method, reference population structure, and trait genetic architecture, on long-term response to genomic selection without updating marker effects. Three methods were used to estimate genomic breeding values: a BLUP method with relationships estimated from genome-wide markers (GBLUP), a Bayesian method, and a partial least squares regression method (PLSR). A shallow (individuals from one generation) or deep reference population (individuals from five generations) was used with each method. The effects of the different selection approaches were compared under four different genetic architectures for the trait under selection. Selection was based on one of the three genomic breeding values, on pedigree BLUP breeding values, or performed at random. Selection continued for ten generations. Differences in long-term selection response were small. For a genetic architecture with a very small number of three to four quantitative trait loci (QTL), the Bayesian method achieved a response that was 0.05 to 0.1 genetic standard deviation higher than other methods in generation 10. For genetic architectures with approximately 30 to 300 QTL, PLSR (shallow reference) or GBLUP (deep reference) had an average advantage of 0.2 genetic standard deviation over the Bayesian method in generation 10. GBLUP resulted in 0.6% and 0.9% less inbreeding than PLSR and BM and on average a one third smaller reduction of genetic variance. Responses in early generations were greater with the shallow reference population while long-term response was not affected by reference population structure. The ranking of estimation methods was different with than without selection. Under selection, applying GBLUP led to lower inbreeding and a smaller reduction of genetic variance while a similar response to selection was

Dataset on genetic and physiological adults׳ responses to social distress.

Science.gov (United States)

Bonassi, Andrea; Ghilardi, Tommaso; Truzzi, Anna; Cataldo, Ilaria; Azhari, Atiqah; Setoh, Peipei; Shinohara, Kazuyuki; Esposito, Gianluca

2017-08-01

Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR) and serotonin transporter (5-HTTLPR) polymorphisms), and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos) we assessed participants׳ ( N = 42 males) heart rate (HR) and peripheral nose temperature, which index state of arousal and readiness to action. Self-reported questionnaires were used to evaluate participants' interactional patterns towards peers (Attachment Style Questionnaire, Feeney et al., 1994[1]), and the quality of bond with intimate partners (Experiences in Close Relationships Scale, Fraley et al., 2000 [2]). To assess participants׳ genetic predispositions, the OXTR gene (regions rs53576, and rs2254298) and the 5-HTTLPR gene (region SLC6A4) were genotyped. The data set is made publicly available to enable critical or extended analyzes.

Dataset on genetic and physiological adults׳ responses to social distress

Directory of Open Access Journals (Sweden)

Andrea Bonassi

2017-08-01

Full Text Available Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR and serotonin transporter (5-HTTLPR polymorphisms, and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos we assessed participants׳ (N = 42 males heart rate (HR and peripheral nose temperature, which index state of arousal and readiness to action. Self-reported questionnaires were used to evaluate participants’ interactional patterns towards peers (Attachment Style Questionnaire, Feeney et al., 1994 [1], and the quality of bond with intimate partners (Experiences in Close Relationships Scale, Fraley et al., 2000 [2]. To assess participants׳ genetic predispositions, the OXTR gene (regions rs53576, and rs2254298 and the 5-HTTLPR gene (region SLC6A4 were genotyped. The data set is made publicly available to enable critical or extended analyzes.

Genetic polymorphism and immune response to tuberculosis in indigenous populations: a brief review

Directory of Open Access Journals (Sweden)

Renata Maronna Praça Longhi

Full Text Available We systematically reviewed studies of the immune response to tuberculosis and the genetic polymorphisms associated with Th1-or Th2-mediated cytokine expression in indigenous populations. A bibliographic search was performed on the Medline and ISI databases and included studies published between January 1980 and October 2011. The search terms were tuberculosis, American Indians, Amerindian, indigenous, Indians, native people, aboriginal, immun*, host immune, immune response, cytokine*, polymorphism*, and gene. Regardless of their design, studies that evaluated immunoglobulin, cytokine levels and genetic polymorphisms that altered cytokine expression were included. Thirteen studies met the inclusion criteria. The majority of studies were performed in Latin America, and five investigated the Warao ethnic group of Venezuela. Most of the investigations indirectly evaluated the immune response. Higher anergy to the tuberculin skin test, higher IgG4 and IgM levels, higher IL-5 production and lower TNF-a, IL-12p40 and IFN-I production were found in the indigenous populations. The studies also reported a predominantly Th2-type response in these populations and a possibly higher susceptibility to tuberculosis. A better understanding of the relevant genetic polymorphisms and their role in immune regulation would help to clarify the immunogenetic mechanisms of TB infection in these populations. This information would be useful for identifying new treatments and preventing infection and progression to active disease.

Species loss, delayed numerical responses, and functional compensation in an antbird guild.

Science.gov (United States)

Touchton, Janeene M; Smith, James N M

2011-05-01

When a community loses species through fragmentation, its total food consumption may drop. Compensatory responses of remaining species, whereby survivors assume roles of extinct competitors, may reduce the impact of species loss through numerical or functional responses. We measured compensatory responses in two remaining antbird species on Barro Colorado Island, Panama, four decades after the loss of their dominant competitor, the Ocellated Antbird, Phaenostictus mcleannani. We compared current abundances and behavior of these two species on Barro Colorado to those reported before the island lost Ocellated Antbirds, and to those in a nearby mainland population where all three species still exist as a space-for-time substitution. The smaller, more subordinate Spotted Antbird, Hylophylax naevioides, responded far more strongly than the larger Bicolored Antbird, Gymnopithys leucaspis, which is functionally more like the Ocellated Antbird. Islandwide density of Spotted Antbirds has more than doubled since the loss of Ocellated Antbirds. Moreover, Spotted Antbirds now spend so much more of their time following ant swarms that their metabolic biomass at these swarms has more than tripled since Ocellated Antbirds disappeared. These responses in Spotted Antbirds were apparently delayed by >20 years. Bicolored Antbirds have not increased substantially in islandwide density or metabolic biomass at ant swarms. We hypothesize that behavioral flexibility, as shown by Spotted Antbirds on Barro Colorado Island, is a major factor governing the extent to which fragmented ecosystems can buffer the impacts of species loss.

Shared genetic influences among childhood shyness, social competences, and cortical responses to emotions.

Science.gov (United States)

Battaglia, Marco; Michelini, Giorgia; Pezzica, Elettra; Ogliari, Anna; Fagnani, Corrado; Stazi, Maria-Antonietta; Bertoletti, Eleonora; Scaini, Simona

2017-08-01

Visual event-related potentials (ERPs) evoked by facial expressions are useful to map socioemotional responses among shy children and to predict transition into social phobia. We investigated the sources of covariation among childhood shyness, social competences, and ERPs to other children's happy, neutral, and angry expressions. Electrophysiological and twin analyses examined the phenotypic and etiological association among an index of childhood shyness, an index of social competences, and ERP responses to facial expressions in 200 twins (mean age=9.23years). Multivariate twin analyses showed that the covariation among shyness, social competences, and a composite of a frontal late negative component occurring around 200-400ms in response to happy, neutral, and angry expressions could be entirely explained by shared genetic factors. A coherent causal structure links childhood shyness, social competences, and the cortical responses to facial emotions. A common genetic substrate can explain the interrelatedness of individual differences for childhood shyness, social competences, and some associated electrophysiological responses to socioemotional signals. Copyright © 2017 Elsevier Inc. All rights reserved.

What would you say? Genetic counseling graduate students' and counselors' hypothetical responses to patient requested self-disclosure.

Science.gov (United States)

Redlinger-Grosse, Krista; Veach, Patricia McCarthy; MacFarlane, Ian M

2013-08-01

Genetic counselor self-disclosure is a complex behavior that lacks extensive characterization. In particular, data are limited about genetic counselors' responses when patients ask them to self-disclose. Accordingly, this study investigated genetic counseling students' (n = 114) and practicing genetic counselors' (n = 123) responses to two hypothetical scenarios in which a female prenatal patient requests self-disclosure. Scenarios were identical except for a final patient question: "Have you ever had an amniocentesis?" or "What would you do if you were me?" Imagining themselves as the counselor, participants wrote a response for each scenario and then explained their response. Differences in disclosure frequency for students vs. counselors and disclosure question were assessed, and themes in participant responses and explanations were extracted via content and thematic analysis methods. Chi-square analyses indicated no significant differences in frequency of student versus counselor disclosure. Self-disclosure was significantly higher for, "Have you ever had an amniocentesis?" (78.5 %) than for, "What would you do if you were me?" (53.2 %) (p self-disclosures included personal, professional, and mixed disclosures. Prevalent explanations for disclosure and non-disclosure responses included: remain patient focused and support/empower the patient. Additional findings, practice and training implications, and research recommendations are presented.

When the topic is you: genetic counselor responses to prenatal patients' requests for self-disclosure.

Science.gov (United States)

Balcom, Jessica R; Veach, Patricia McCarthy; Bemmels, Heather; Redlinger-Grosse, Krista; LeRoy, Bonnie S

2013-06-01

A limited amount of research indicates patient requests play a major role in genetic counselors' self-disclosure decisions and that disclosure and non-disclosure responses to patient requests may differentially affect genetic counseling processes. Studies further suggest patient requests may be more common in prenatal settings, particularly when counselors are pregnant. Empirical evidence is limited however, concerning the nature of patient requests. This study explored genetic counselors' experiences of prenatal patients' requests for self-disclosure. Four major research questions were: (1) What types of questions do prenatal patients ask that invite self-disclosure?; (2) Do pregnant genetic counselors have unique experiences with prenatal patient disclosure requests?; (3) How do genetic counselors typically respond to disclosure requests?; and (4) What strategies are effective and ineffective in responding to disclosure requests? One hundred seventy-six genetic counselors completed an online survey and 40 also participated in telephone interviews. Inductive analysis of 21 interviews revealed patient questions vary, although questions about counselor demographics are most common, and patients are more likely to ask pregnant counselors questions about their personal pregnancy decisions. Participants reported greater discomfort with self-disclosure requests during pregnancy, yet also disclosing more frequently during pregnancy. Counselor responses included personal self-disclosure, professional self-disclosure, redirection, and declining to disclose. Factors perceived as influencing disclosure included: topic, patient motivations, timing of request, quality of counseling relationship, patient characteristics, and ethical/legal responsibilities. Disclosure practices changed over time for most counselors. Additional findings, practice implications, and research recommendations are discussed.

Good and bad protons: genetic aspects of acidity stress responses in plants.

Science.gov (United States)

Shavrukov, Yuri; Hirai, Yoshihiko

2016-01-01

Physiological aspects of acidity stress in plants (synonymous with H(+) rhizotoxicity or low-pH stress) have long been a focus of research, in particular with respect to acidic soils where aluminium and H(+) rhizotoxicities often co-occur. However, toxic H(+) and Al(3+) elicit different response mechanisms in plants, and it is important to consider their effects separately. The primary aim of this review was to provide the current state of knowledge regarding the genetics of the specific reactions to low-pH stress in growing plants. A comparison of the results gleaned from quantitative trait loci analysis and global transcriptome profiling of plants in response to high proton concentrations revealed a two-stage genetic response: (i) in the short-term, proton pump H(+)-ATPases present the first barrier in root cells, allocating an excess of H(+) into either the apoplast or vacuole; the ensuing defence signaling system involves auxin, salicylic acid, and methyl jasmonate, which subsequently initiate expression of STOP and DREB transcription factors as well as chaperone ROF; (2) the long-term response includes other genes, such as alternative oxidase and type II NAD(P)H dehydrogenase, which act to detoxify dangerous reactive oxygen species in mitochondria, and help plants better manage the stress. A range of transporter genes including those for nitrate (NTR1), malate (ALMT1), and heavy metals are often up-regulated by H(+) rhizotoxicity. Expansins, cell-wall-related genes, the γ-aminobutyric acid shunt and biochemical pH-stat genes also reflect changes in cell metabolism and biochemistry in acidic conditions. However, the genetics underlying the acidity stress response of plants is complicated and only fragmentally understood. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Home; Journals; Journal of Genetics. IOANNA ALEXANDROU. Articles written in Journal of Genetics. Volume 95 Issue 3 September 2016 pp 621-624 Regular Articles. Deletion of SNURF / SNRPN U1B and U1B* upstream exons in a child with developmental delay and excessive weight · COSTAS KOUFARIS ANGELOS ...

Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

OpenAIRE

Mutiso,Joshua M.; Macharia,John C.; Taracha,Evans; Wafula,Kellern; Rikoi,Hitler; Gicheru,Michael M.

2012-01-01

In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels ...

Response of a Habitat-Forming Marine Plant to a Simulated Warming Event Is Delayed, Genotype Specific, and Varies with Phenology.

Directory of Open Access Journals (Sweden)

Laura K Reynolds

Full Text Available Growing evidence shows that increasing global temperature causes population declines and latitudinal shifts in geographical distribution for plants living near their thermal limits. Yet, even populations living well within established thermal limits of a species may suffer as the frequency and intensity of warming events increase with climate change. Adaptive response to this stress at the population level depends on the presence of genetic variation in thermal tolerance in the populations in question, yet few data exist to evaluate this. In this study, we examined the immediate effects of a moderate warming event of 4.5°C lasting 5 weeks and the legacy effects after a 5 week recovery on different genotypes of the marine plant Zostera marina (eelgrass. We conducted the experiment in Bodega Bay, CA USA, where average summer water temperatures are 14-15°C, but extended warming periods of 17-18°C occur episodically. Experimental warming increased shoot production by 14% compared to controls held at ambient temperature. However, after returning temperature to ambient levels, we found strongly negative, delayed effects of warming on production: shoot production declined by 27% and total biomass decreased by 50% relative to individuals that had not been warmed. While all genotypes' production decreased in the recovery phase, genotypes that grew the most rapidly under benign thermal conditions (control were the most susceptible to the detrimental effects of warming. This suggests a potential tradeoff in relative performance at normal vs. elevated temperatures. Modest short-term increases in water temperature have potentially prolonged negative effects within the species' thermal envelope, but genetic variation within these populations may allow for population persistence and adaptation. Further, intraspecific variation in phenology can result in maintenance of population diversity and lead to enhanced production in diverse stands given sufficient

Risks for communication delays and disorders in infants in an urban ...

African Journals Online (AJOL)

may result in conditions such as fetal alcohol spectrum disorder. (FASD).[4,5] South ... communication delays or disorders in infants aged 0 12 months in an urban PHC ..... Results from the CHARGE (Childhood Autism Risks from Genetics and ...

Humans Optimize Decision-Making by Delaying Decision Onset

Science.gov (United States)

Teichert, Tobias; Ferrera, Vincent P.; Grinband, Jack

2014-01-01

Why do humans make errors on seemingly trivial perceptual decisions? It has been shown that such errors occur in part because the decision process (evidence accumulation) is initiated before selective attention has isolated the relevant sensory information from salient distractors. Nevertheless, it is typically assumed that subjects increase accuracy by prolonging the decision process rather than delaying decision onset. To date it has not been tested whether humans can strategically delay decision onset to increase response accuracy. To address this question we measured the time course of selective attention in a motion interference task using a novel variant of the response signal paradigm. Based on these measurements we estimated time-dependent drift rate and showed that subjects should in principle be able trade speed for accuracy very effectively by delaying decision onset. Using the time-dependent estimate of drift rate we show that subjects indeed delay decision onset in addition to raising response threshold when asked to stress accuracy over speed in a free reaction version of the same motion-interference task. These findings show that decision onset is a critical aspect of the decision process that can be adjusted to effectively improve decision accuracy. PMID:24599295

Non-targeted and delayed effects of exposure to ionizing radiation

International Nuclear Information System (INIS)

Zuo Yahui; Tong Jian

2007-01-01

Non-targeted and delayed effects are relative phenomena in cellular responses to ionizing radiation. These effects (bystander effects, genomic instability and adaptive responses) have been studied most extensively for radiation exposures. It is clear that adaptive responses, bystander effects and genomic instability will play an important role in the low dose-response to radiation. This review will provide a synthesis of the known, and proposed interrelationships amongst low-dose cellular responses to radiation, It also will examine the potential biological significance of non-targeted and delayed effects of exposure to ionizing radiation. (authors)

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Science.gov (United States)

Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.

2015-01-01

Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039

Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

Energy Technology Data Exchange (ETDEWEB)

Sharkey, Leslie C., E-mail: shark009@umn.edu [Veterinary Clinical Sciences Department, University of Minnesota, 1352 Boyd Ave, St. Paul, MN 55108 (United States); Radin, M. Judith, E-mail: radin.1@osu.edu [Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210 (United States); Heller, Lois, E-mail: lheller@d.umn.edu [Department of Biomedical Sciences, University of Minnesota Medical School—Duluth, 1035 University Drive, Duluth, MN 55812-3031 (United States); Rogers, Lynette K., E-mail: Lynette.Rogers@nationwidechildrens.org [Center for Perinatal Research, The Research Institute at Nationwide Children' s Hospital, 700 Childrens Drive, Columbus, OH 43205 (United States); Tobias, Anthony [Veterinary Clinical Sciences Department, University of Minnesota, 1352 Boyd Ave, St. Paul, MN 55108 (United States); Matise, Ilze, E-mail: imatise.vh@gmail.com [Veterinary Population Medicine Department, University of Minnesota, 1365 Gortner Ave, St Paul, MN (United States); Wang, Qi, E-mail: wangx890@umn.edu [Clinical and Translational Science Institute (CTSI), University of Minnesota, 717 Delaware St SE, Minneapolis, MN (United States); Apple, Fred S., E-mail: apple004@umn.edu [Department of Laboratory Medicine and Pathology, Hennepin County Medical Center and University of Minnesota, 701 Park Ave S, Minneapolis, MN USA (United States); McCune, Sylvia A., E-mail: sylvia.mccune@skybeam.com [Department of Integrative Physiology, University of Colorado at Boulder, 354 UCB, Clare Small 114, Boulder, CO 80309 (United States)

2013-11-15

Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic acids

Genetic variation in the response of the weed Ruellia nudiflora (Acanthaceae) to arbuscular mycorrhizal fungi.

Science.gov (United States)

Ramos-Zapata, José Alberto; Campos-Navarrete, María José; Parra-Tabla, Víctor; Abdala-Roberts, Luis; Navarro-Alberto, Jorge

2010-04-01

The main goal of this work was to test for plant genetic variation in the phenotypic plasticity response of the weed Ruellia nudiflora to arbuscular mycorrhizal (AM) fungi inoculation. We collected plants in the field, kept them under homogeneous conditions inside a nursery, and then collected seeds from these parent plants to generate five inbred lines (i.e., genetic families). Half of the plants of each inbred line were inoculated with AM fungi while the other half were not (controls); a fully crossed experimental design was then used to test for the effects of treatment (with or without AM fungi inoculation) and inbred line (genetic family). For each plant, we recorded the number of leaves produced and the number of days it survived during a 2-month period. Results showed a strong positive treatment effect (plastic response to AM fungi inoculation) for leaf production and survival. Moreover, in terms of survival, the treatment effect differed between genetic families (significant genetic family by treatment interaction). These findings indicate that the positive effect of AM fungi on plant survival (and potentially also growth) differs across plant genotypes and that such condition may contribute to R. nudiflora's capacity to colonize new environments.

Direct/Delayed Response Project: Soil-characterization comparison

International Nuclear Information System (INIS)

Fenstermaker, L.K.; Byers, G.E.; Starks, T.H.; Miah, M.J.; Palmer, C.J.

1992-01-01

A large amount of soil characterization data has been collected as a component of the Direct/Delayed Response Project (DDRP) in the acid rain Aquatic Effects Research Program. An interlaboratory comparison study was undertaken to identify the comparability of the data to that obtained from representative soil characterization laboratories. Participating laboratories were selected at random from four regions of the U.S. and two regions of Canada. Two original DDRP contract laboratories also participated. Duplicate samples of six soil audit materials and two liquid soil extracts were sent to each of the laboratories in two separate batches. Laboratories used their own protocols to perform the analyses requested except for the contract laboratories which followed the DDRP protocol. Liquid audits were used in an effort to identify if interlaboratory differences were due to extraction procedures or chemical measurements. A component of the variability in the results was attributed to differences in the methods used such as soil/solution ratios, extractants or extraction procedures. The largest number of different methods used was for the measurement of cation exchange capacity. The results between the DDRP soil survey data and the study's results were compared using Youden-pair plots. In addition, standard statistical tests were performed. Overall, the DDRP data were comparable to the data from the study. However, out of the total 141 comparisons involving results from six or more laboratories, the results from the two contract laboratories did not meet the comparison criteria in 19 cases. Since there was never a case in which both contract laboratories failed, it would appear that the 19 cases which were not comparable were due to random analytical errors, incorrectly reported results, or misapplication of DDRP protocol

Diagnosis delay in tuberculosis and its consequences

International Nuclear Information System (INIS)

Habibullah, S.; Sheikh, M.A.; Sadiq, A.; Anwar, T.

2004-01-01

Objective: To find out the average duration from onset of symptoms to the diagnosis and treatment of tuberculosis, reasons for diagnostic delay, its consequences, association of variables and formulation of recommendations. Results: In this study it was found that average time from onset of initial symptoms to diagnosis and treatment of tuberculosis was 120 days. In 64% of the patients medical practitioners were responsible for delaying the diagnosis of tuberculosis. Loss of weight in 40% and haemoptysis is 21% were the consequences of diagnostic delay of tuberculosis. Delay in the diagnosis of tuberculosis was statistically significant in those patients who consulted private practitioners, and consequences of tuberculosis were severe in those patients who consulted late. (author)

Analysis of an Nth-order nonlinear differential-delay equation

Science.gov (United States)

Vallée, Réal; Marriott, Christopher

1989-01-01

The problem of a nonlinear dynamical system with delay and an overall response time which is distributed among N individual components is analyzed. Such a system can generally be modeled by an Nth-order nonlinear differential delay equation. A linear-stability analysis as well as a numerical simulation of that equation are performed and a comparison is made with the experimental results. Finally, a parallel is established between the first-order differential equation with delay and the Nth-order differential equation without delay.

A fortran programme for determining frequency responses for linear systems with time delays

International Nuclear Information System (INIS)

Milsom, P.R.

1966-11-01

In this report a digital computer programme for evaluating frequency responses is described. In its standard form the programme is capable of determining the gain and phase of up to 35 variables over a range of up to 30 frequencies for a system described by up to 65 equations. The equations must be either first order differential or algebraic and either type may include time delayed terms. Up to 50 such terms are permissible throughout the equation set. Provision is made for up to 10 inputs and up to 50 differentiated input terms are permitted throughout the equation set. However, it is possible for the user to increase a maximum dimension, albeit at the expense of another array dimension. In punching the data from the equations the user has no sorting or arranging of coefficients to do, and the equations may be in any order. The specifying of other input information, such as frequency range, the inputs to be perturbed and the variables for which frequency responses are required, is also very straightforward. (author)

Two galactose-α-1,3-galactose carrying peptidases from pork kidney mediate anaphylactogenic responses in delayed meat allergy

DEFF Research Database (Denmark)

Hilger, Christiane; Fischer, Jörg; Swiontek, Kyra

2016-01-01

BACKGROUND: Serum IgE-antibodies directed at galactose-α-1,3-galactose (α-Gal) are associated with a novel form of delayed anaphylaxis occuring upon consumption of red meat or innards. Pork kidney is known as the most potent trigger of this syndrome, but the culprit allergens have not yet been...... resistent to heat denaturation. Pork kidney extract, isolated ACE I and AP-N were able to activate patient basophils and elicit positive responses in skin prick tests. CONCLUSION: Two cell-membrane proteins carrying α-Gal epitopes were identified in pork kidney. For the first time, isolated meat proteins...... were shown to induce basophil activation in patients with delayed anaphylaxis to red meat providing further confirmation for the clinical relevance of these α-Gal-carrying proteins. This article is protected by copyright. All rights reserved....

Genetic and Genomic Response to Selection for Food Consumption in Drosophila melanogaster

Science.gov (United States)

Garlapow, Megan E.; Everett, Logan J.; Zhou, Shanshan; Gearhart, Alexander W.; Fay, Kairsten A.; Huang, Wen; Morozova, Tatiana V.; Arya, Gunjan H.; Turlapati, Lavanya; Armour, Genevieve St.; Hussain, Yasmeen N.; McAdams, Sarah E.; Fochler, Sophia; Mackay, Trudy F. C.

2016-01-01

Food consumption is an essential component of animal fitness; however, excessive food intake in humans increases risk for many diseases. The roles of neuroendocrine feedback loops, food sensing modalities, and physiological state in regulating food intake are well understood, but not the genetic basis underlying variation in food consumption. Here, we applied ten generations of artificial selection for high and low food consumption in replicate populations of Drosophila melanogaster. The phenotypic response to selection was highly asymmetric, with significant responses only for increased food consumption and minimal correlated responses in body mass and composition. We assessed the molecular correlates of selection responses by DNA and RNA sequencing of the selection lines. The high and low selection lines had variants with significantly divergent allele frequencies within or near 2,081 genes and 3,526 differentially expressed genes in one or both sexes. A total of 519 genes were both genetically divergent and differentially expressed between the divergent selection lines. We performed functional analyses of the effects of RNAi suppression of gene expression and induced mutations for 27 of these candidate genes that have human orthologs and the strongest statistical support, and confirmed that 25 (93%) affected the mean and/or variance of food consumption. PMID:27704301

Artificial Selection Response due to Polygenic Adaptation from a Multilocus, Multiallelic Genetic Architecture.

Science.gov (United States)

Zan, Yanjun; Sheng, Zheya; Lillie, Mette; Rönnegård, Lars; Honaker, Christa F; Siegel, Paul B; Carlborg, Örjan

2017-10-01

The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a 9-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained >60% of the additive genetic variance for the selected trait. We focused particularly on fine-mapping seven major QTL that replicated in this population and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of the range of different genome-wide mechanisms that have been involved in these long-term selection responses. The results illustrate that the genetic architecture of a highly polygenic trait can involve a broad range of genetic mechanisms, and that this can be the case even in a small population bred from founders with limited genetic diversity. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

International Nuclear Information System (INIS)

Sun, Zhongkui; Fu, Jin; Xu, Wei; Xiao, Yuzhu

2015-01-01

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 stochastic 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

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

Energy Technology Data Exchange (ETDEWEB)

Sun, Zhongkui, E-mail: sunzk@nwpu.edu.cn; Fu, Jin; Xu, Wei [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an 710072 (China); Xiao, Yuzhu [Department of Mathematics and Information Science, Chang' an University, Xi' an 710086 (China)

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 stochastic 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.

Mechanisms of motor recovery after subtotal spinal cord injury: insights from the study of mice carrying a mutation (WldS) that delays cellular responses to injury.

Science.gov (United States)

Zhang, Z; Guth, L; Steward, O

1998-01-01

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.

Aging, Genetic Variations, and Ethnopharmacology: Building Cultural Competence Through Awareness of Drug Responses in Ethnic Minority Elders.

Science.gov (United States)

Woods, Diana Lynn; Mentes, Janet C; Cadogan, Mary; Phillips, Linda R

2017-01-01

Unique drug responses that may result in adverse events are among the ethnocultural differences described by the Agency for Healthcare Research and Quality. These differences, often attributed to a lack of adherence on the part of the older adult, may be linked to genetic variations that influence drug responses in different ethnic groups. The paucity of research coupled with a lack of knowledge among health care providers compound the problem, contributing to further disparities, especially in this era of personalized medicine and pharmacogenomics. This article examines how age-related changes and genetic differences influence variations in drug responses among older adults in unique ethnocultural groups. The article starts with an overview of age-related changes and ethnopharmacology, moves to describing genetic differences that affect drug responses, with a focus on medications commonly prescribed for older adults, and ends with application of these issues to culturally congruent health care. © The Author(s) 2015.

Genetic predictors of response to antidepressants in the GENDEP project

DEFF Research Database (Denmark)

Uher, Rudolf; Huezo-Diaz, Patricia; Perroud, Nader

2009-01-01

-reuptake-inhibiting and norepinephrine-reuptake-inhibiting antidepressants. A total of 116 single nucleotide polymorphisms in 10 candidate genes were genotyped in 760 adult patients with moderate-to-severe depression, treated with escitalopram (a serotonin reuptake inhibitor) or nortriptyline (a norepinephrine reuptake inhibitor......) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models. Several variants in a serotonin receptor gene (HTR2A) predicted response to escitalopram with one marker (rs9316233) explaining 1...... to the serotonin-reuptake-inhibiting escitalopram, genes encoding proteins in norepinephrine signaling influencing response to the norepinephrine-reuptake-inhibiting nortriptyline and a common pathway gene influencing response to both antidepressants. The single marker associations explained only a small...

Genetic Influences on Physiological and Subjective Responses to an Aerobic Exercise Session among Sedentary Adults

International Nuclear Information System (INIS)

Karoly, H. C.; Stevens, C.; Harlaar, N.; Hutchison, K. E.; Bryan, A. D.; Magnan, R. E.

2012-01-01

To determine whether genetic variants suggested by the literature to be associated with physiology and fitness phenotypes predicted differential physiological and subjective responses to a bout of aerobic exercise among inactive but otherwise healthy adults. Method. Participants completed a 30-minute submaximal aerobic exercise session. Measures of physiological and subjective responding were taken before, during, and after exercise. 14 single nucleotide polymorphisms (SNPs) that have been previously associated with various exercise phenotypes were tested for associations with physiological and subjective response to exercise phenotypes. Results. We found that two SNPs in the FTO gene (rs8044769 and rs3751812) were related to positive affect change during exercise. Two SNPs in the CREB1 gene (rs2253206 and 2360969) were related to change in temperature during exercise and with maximal oxygen capacity (VO 2 max). The SLIT2 SNP rs1379659 and the FAM5C SNP rs1935881 were associated with norepinephrine change during exercise. Finally, the OPRM1 SNP rs1799971 was related to changes in norepinephrine, lactate, and rate of perceived exertion (RPE) during exercise. Conclusion. Genetic factors influence both physiological and subjective responses to exercise. A better understanding of genetic factors underlying physiological and subjective responses to aerobic exercise has implications for development and potential tailoring of exercise interventions.

Delayed and transient increase of adult hippocampal neurogenesis by physical exercise in DBA/2 mice.

Directory of Open Access Journals (Sweden)

Rupert W Overall

Full Text Available This study builds on the findings that physical activity, such as wheel running in mice, enhances cell proliferation and neurogenesis in the adult hippocampus of the common mouse strain C57BL/6, and that the baseline level of neurogenesis varies by strain, being considerably lower in DBA/2. Because C57BL/6 and DBA/2 are important as the parental strains of the BXD recombinant inbred cross which allows the detection of genetic loci regulating phenotypes such as adult neurogenesis, we performed the current study to investigate the gene x environment interactions regulating neurogenesis. At equal distances and times run DBA/2J mice lacked the acute increase in precursor cell proliferation known from C57BL/6. In DBA/2J proliferation even negatively correlated with the distance run. This was neither due to a stress response (to running itself or single housing nor differences in estrous cycle. DBA/2 animals exhibited a delayed and weaker pro-neurogenic response with a significant increase in numbers of proliferating cells first detectable after more than a week of wheel running. The proliferative response to running was transient in both strains, the effect being undetectable by 6 weeks. There was also a small transient increase in the production of new neurons in DBA/2J, although these extra cells did not survive. These findings indicate that the comparison between C57BL/6 and DBA/2, and by extension the BXD genetic reference population derived from these strains, should provide a powerful tool for uncovering the complex network of modifier genes affecting the activity-dependent regulation of adult hippocampal neurogenesis. More generally, our findings also describe how the external physical environment interacts with the internal genetic environment to produce different responses to the same behavioral stimuli.

Noise-sustained fluctuations in stochastic dynamics with a delay.

Science.gov (United States)

D'Odorico, Paolo; Laio, Francesco; Ridolfi, Luca

2012-04-01

Delayed responses to external drivers are ubiquitous in environmental, social, and biological processes. Delays may induce oscillations, Hopf bifurcations, and instabilities in deterministic systems even in the absence of nonlinearities. Despite recent advances in the study of delayed stochastic differential equations, the interaction of random drivers with delays remains poorly understood. In particular, it is unclear whether noise-induced behaviors may emerge from these interactions. Here we show that noise may enhance and sustain transient periodic oscillations inherent to deterministic delayed systems. We investigate the conditions conducive to the emergence and disappearance of these dynamics in a linear system in the presence of both additive and multiplicative noise.

Exploring the Role of Genetic Variability and Lifestyle in Oxidative Stress Response for Healthy Aging and Longevity

Directory of Open Access Journals (Sweden)

Giuseppe Passarino

2013-08-01

Full Text Available Oxidative stress is both the cause and consequence of impaired functional homeostasis characterizing human aging. The worsening efficiency of stress response with age represents a health risk and leads to the onset and accrual of major age-related diseases. In contrast, centenarians seem to have evolved conservative stress response mechanisms, probably derived from a combination of a diet rich in natural antioxidants, an active lifestyle and a favorable genetic background, particularly rich in genetic variants able to counteract the stress overload at the level of both nuclear and mitochondrial DNA. The integration of these factors could allow centenarians to maintain moderate levels of free radicals that exert beneficial signaling and modulator effects on cellular metabolism. Considering the hot debate on the efficacy of antioxidant supplementation in promoting healthy aging, in this review we gathered the existing information regarding genetic variability and lifestyle factors which potentially modulate the stress response at old age. Evidence reported here suggests that the integration of lifestyle factors (moderate physical activity and healthy nutrition and genetic background could shift the balance in favor of the antioxidant cellular machinery by activating appropriate defense mechanisms in response to exceeding external and internal stress levels, and thus possibly achieving the prospect of living a longer life.

Piloted simulator study of allowable time delays in large-airplane response

Science.gov (United States)

Grantham, William D.; Bert T.?aetingas, Stephen A.dings with ran; Bert T.?aetingas, Stephen A.dings with ran

1987-01-01

A piloted simulation was performed to determine the permissible time delay and phase shift in the flight control system of a specific large transport-type airplane. The study was conducted with a six degree of freedom ground-based simulator and a math model similar to an advanced wide-body jet transport. Time delays in discrete and lagged form were incorporated into the longitudinal, lateral, and directional control systems of the airplane. Three experienced pilots flew simulated approaches and landings with random localizer and glide slope offsets during instrument tracking as their principal evaluation task. Results of the present study suggest a level 1 (satisfactory) handling qualities limit for the effective time delay of 0.15 sec in both the pitch and roll axes, as opposed to a 0.10-sec limit of the present specification (MIL-F-8785C) for both axes. Also, the present results suggest a level 2 (acceptable but unsatisfactory) handling qualities limit for an effective time delay of 0.82 sec and 0.57 sec for the pitch and roll axes, respectively, as opposed to 0.20 sec of the present specifications for both axes. In the area of phase shift between cockpit input and control surface deflection,the results of this study, flown in turbulent air, suggest less severe phase shift limitations for the approach and landing task-approximately 50 deg. in pitch and 40 deg. in roll - as opposed to 15 deg. of the present specifications for both axes.

Greater efficiency of water use in poplar clones having a delayed response of mesophyll conductance to drought.

Science.gov (United States)

Théroux Rancourt, Guillaume; Éthier, Gilbert; Pepin, Steeve

2015-02-01

Improvement of water use efficiency is a key objective to improve the sustainability of cultivated plants, especially fast growing species with high water consumption like poplar. It is well known that water use efficiency (WUE) varies considerably among poplar genotypes, and it was recently suggested that the use of the mesophyll-to-stomatal conductance ratio (gm/gs) would be an appropriate trait to improve WUE. The responses of 7-week-old cuttings of four hybrid poplar clones and one native Balsam poplar (Populus balsamifera L.) to a water stress-recovery cycle were examined to evaluate the relation between the gm/gs ratio and transpiration efficiency (TE), a leaf-level component of WUE. A contrasting gs response to water stress was observed among the five clones, from stomatal closure early on during soil drying up to limited closure in Balsam poplar. However in the hybrids, the decline in gm was consistently delayed by a few days compared with gs. Moreover, in the most water use-efficient hybrids, the recovery following rehydration occurred faster for gm than for gs. Thus, the delay in the response of gm to drought and its faster recovery upon rewatering increased the gm/gs of the hybrids and this ratio scaled positively with TE. Our results support the use of the gm/gs ratio to select genotypes with improved WUE, and the notion that breeding strategies focusing mainly on stomatal responses to soil drying should also look for a strong curvilinearity between net carbon assimilation rate and gs, the indication of a significant increase in gm/gs in the earlier stages of stomatal closure. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Linear time delay methods and stability analyses of the human spine. Effects of neuromuscular reflex response.

Science.gov (United States)

Franklin, Timothy C; Granata, Kevin P; Madigan, Michael L; Hendricks, Scott L

2008-08-01

Linear stability methods were applied to a biomechanical model of the human musculoskeletal spine to investigate effects of reflex gain and reflex delay on stability. Equations of motion represented a dynamic 18 degrees-of-freedom rigid-body model with time-delayed reflexes. Optimal muscle activation levels were identified by minimizing metabolic power with the constraints of equilibrium and stability with zero reflex time delay. Muscle activation levels and associated muscle forces were used to find the delay margin, i.e., the maximum reflex delay for which the system was stable. Results demonstrated that stiffness due to antagonistic co-contraction necessary for stability declined with increased proportional reflex gain. Reflex delay limited the maximum acceptable proportional reflex gain, i.e., long reflex delay required smaller maximum reflex gain to avoid instability. As differential reflex gain increased, there was a small increase in acceptable reflex delay. However, differential reflex gain with values near intrinsic damping caused the delay margin to approach zero. Forward-dynamic simulations of the fully nonlinear time-delayed system verified the linear results. The linear methods accurately found the delay margin below which the nonlinear system was asymptotically stable. These methods may aid future investigations in the role of reflexes in musculoskeletal stability.

Fundamental and Subharmonic Resonances of Harmonically Oscillation with Time Delay State Feedback

Directory of Open Access Journals (Sweden)

A.F. EL-Bassiouny

2006-01-01

Full Text Available Time delays occur in many physical systems. In particular, when automatic control is used with structural or mechanical systems, there exists a delay between measurement of the system state and corrective action. The concept of an equivalent damping related to the delay feedback is proposed and the appropriate choice of the feedback gains and the time delay is discussed from the viewpoint of vibration control. We investigate the fundamental resonance and subharmonic resonance of order one-half of a harmonically oscillation under state feedback control with a time delay. By using the multiple scale perturbation technique, the first order approximation of the resonances are derived and the effect of time delay on the resonances is investigated. The fixed points correspond to a periodic motion for the starting system and we show the external excitation-response and frequency-response curves. We analyze the effect of time delay and the other different parameters on these oscillations.

Genetic basis for childhood interstitial lung disease among Japanese infants and children.

Science.gov (United States)

Hayasaka, Itaru; Cho, Kazutoshi; Akimoto, Takuma; Ikeda, Masahiko; Uzuki, Yutaka; Yamada, Masafumi; Nakata, Koh; Furuta, Itsuko; Ariga, Tadashi; Minakami, Hisanori

2018-02-01

BackgroundGenetic variants responsible for childhood interstitial lung disease (chILD) have not been studied extensively in Japanese patients.MethodsThe study population consisted of 62 Japanese chILD patients. Twenty-one and four patients had pulmonary hypertension resistant to treatment (PH) and hypothyroidism, respectively. Analyses of genetic variants were performed in all 62 patients for SFTPC and ABCA3, in all 21 PH patients for FOXF1, and in a limited number of patients for NKX2.1.ResultsCausative genetic variants for chILD were identified in 11 (18%) patients: SFTPC variants in six, NKX2.1 variants in three, and FOXF1 variants in two patients. No patients had ABCA3 variants. All three and two patients with NKX2.1 variants had hypothyroidism and developmental delay, respectively. We found six novel variants in this study.ConclusionMutations in SFTPC, NKX2.1, and FOXF1 were identified among Japanese infants and children with chILD, whereas ABCA3 mutations were rare.

Comparison of dynamic compensation methods for delayed self-powered neutron detector

International Nuclear Information System (INIS)

In, Wang Kee; Kim, Joon Sung; Auh, Geun Sun; Yoon, Tae Young

1993-01-01

Dynamic compensation methods for rhodium self-powered neutron detector have been developed by Banda and Hoppe to compensate for the time delay associated with detector signals. The time delay is due to the decay of the neutron-activated rhodium and results in delayed detector response. Two digital dynamic compensation methods, were compared for step change of neutron flux in this paper. The inverse kinetics method gave slightly better response time and noise gain. However, the inverse kinetics method also showed overshooting of neutron flux for the step change. (Author)

Delayed speech development in children: Introduction to terminology

Directory of Open Access Journals (Sweden)

M. Yu. Bobylova

2017-01-01

Full Text Available There has been recently an increase in the number of children diagnosed with delayed speech development. There is delay compensation with age, but mild deficiency often remains for life. Delayed speech development is more common in boys than in girls. Its etiology is unknown in most cases, so a child should be followed up to make an accurate diagnosis. Genetic predisposition or environmental factors frequently influence speech development. The course of its delays is various. In the history of a number of disorders (childhood disintegrative disorder, Landau–Kleffner syndrome, there is evidence for the normal development of speech to a certain period and then stops or even regresses. By way of comparison, there are generally speech developmental changes in autism even during the preverbal stage (a complex of revival fails to form; babbling is poor, low emotional, gibberish; at the same time, the baby recipes whole phrases without using them to communicate. These speech disorders are considered not only as a delay, but also as a developmental abnormality. Speech disorders in children should be diagnosed as early as possible in order to initiative corrective measures in time. In this case, a physician makes a diagnosis and a special education teacher does corrective work. The successful collaboration and mutual understanding of the specialists in these areas will determine quality of life for a child in the future. This paper focusses on the terminology and classification of delays, which are necessary for physicians and teachers to speak the same language.

Plant responses to UV and blue light: biochemical and genetic approaches

International Nuclear Information System (INIS)

Jenkins, G.I.; Christie, J.M.; Fuglevand, G.; Long, J.C.; Jackson, J.A.

1995-01-01

UV and blue light control many aspects of plant growth and development. It is evident that several different photoreceptors mediate responses to UV and blue light, and there are reports of the functional and biochemical characterisation of a putative photoreceptor for phototropism and of the functional and molecular characterisation of the CRY1 photoreceptor, encoded by the Arabidopsis HY4 gene. The CRY1 photoreceptor mediates extension growth and gene expression responses to UV-A/blue light presumably through different or branching signal transduction pathways. Progress has been made in cell physiological and biochemical studies of UV/blue light signal transduction, but much remains to be done to relate candidate UV/blue signal transduction events to particular photoreceptors and responses. The application of a genetic approach in Arabidopsis has been responsible for many advances in understanding UV/blue responses, but further UV-B, UV-A and blue light response mutants need to be isolated. (author)

Effects of dynamic synapses on noise-delayed response latency of a single neuron

Science.gov (United States)

Uzuntarla, M.; Ozer, M.; Ileri, U.; Calim, A.; Torres, J. J.

2015-12-01

The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f . This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron.

Soups increase satiety through delayed gastric emptying yet increased glycaemic response.

Science.gov (United States)

Clegg, M E; Ranawana, V; Shafat, A; Henry, C J

2013-01-01

Previous studies have demonstrated the satiating properties of soups compared with solids; however, the mechanisms controlling soup-induced satiety are unknown. This study aimed to understand the physiological mechanisms causing soup to be more satiating. A total of 12 volunteers were tested on three occasions after a solid meal, chunky soup or smooth soup test meal for gastric emptying (GE) using the sodium [1-¹³C] acetate breath test, satiety using visual analog scales (VAS) and glycaemic response (GR) using finger prick blood samples. There was a significant difference in GE half-time (P=0.022) and GE ascension time (P=0.018), with the longest GE times for the smooth soup and the shortest for the solid meal. The GR area under the curve was significantly different between meals (P=0.040). The smooth soup had the greatest GR (87.0 ± 49.5 mmol/l/min), followed by the chunky soup (65.4 ± 48.0 mmol/l/min), with the solid meal having the lowest GR (61.6 ± 36.8 mmol/l/min). Volunteers were fuller after the smooth soup compared with solid meal (P=0.034). The smooth soup induced greater fullness compared with the solid meal because of a combination of delayed GE leading to feelings of gastric distension and rapid accessibility of nutrients causing a greater glycaemic response.

Children with autism spectrum disorders show abnormal conditioned response timing on delay, but not trace, eyeblink conditioning

Science.gov (United States)

Oristaglio, Jeff; West, Susan Hyman; Ghaffari, Manely; Lech, Melissa S.; Verma, Beeta R.; Harvey, John A.; Welsh, John P.; Malone, Richard P.

2013-01-01

Children with autism spectrum disorder (ASD) and age-matched typically-developing (TD) peers were tested on two forms of eyeblink conditioning (EBC), a Pavlovian associative learning paradigm where subjects learn to execute an appropriately-timed eyeblink in response to a previously neutral conditioning stimulus (CS). One version of the task, trace EBC, interposes a stimulus-free interval between the presentation of the CS and the unconditioned stimulus (US), a puff of air to the eye which causes subjects to blink. In delay EBC, the CS overlaps in time with the delivery of the US, usually with both stimuli terminating simultaneously. ASD children performed normally during trace EBC, exhibiting no differences from typically-developing (TD) subjects with regard to learning rate or the timing of the CR. However, when subsequently tested on delay EBC, subjects with ASD displayed abnormally-timed conditioned eye blinks that began earlier and peaked sooner than those of TD subjects, consistent with previous findings. The results suggest an impaired ability of children with ASD to properly time conditioned eye blinks which appears to be specific to delay EBC. We suggest that this deficit may reflect a dysfunction of cerebellar cortex in which increases in the intensity or duration of sensory input can temporarily disrupt the accuracy of motor timing over short temporal intervals. PMID:23769889

Delays due to gas diffusion in flash boiling nucleation

International Nuclear Information System (INIS)

Hanbury, W.T.; McCartney, W.S.

1976-01-01

A theoretical model to account for the time delay between decompression and nucleation in flash boiling is presented and analyzed. It shows that gas diffusion can be responsible for delayed nucleation when the critical radius for nucleation and the suspended particle size are of the same order of magnitude

Controllability and stability of primary frequency control from thermostatic loads with delays

DEFF Research Database (Denmark)

Ziras, Charalampos; Vrettos, Evangelos; You, Shi

2017-01-01

There is an increasing interest in exploiting the flexibility of loads to provide ancillary services to the grid. In this paper we study how response delays and lockout constraints affect the controllability of an aggregation of refrigerators offering primary frequency control (PFC). First we...... examine the effect of delays in PFC provision from an aggregation of refrigerators, using a two-area power system. We propose a framework to systematically address frequency measurement and response delays and we determine safe values for the total delays via simulations. We introduce a controllability...... index to evaluate PFC provision under lockout constraints of refrigerators compressors. We conduct extensive simulations to study the effects of measurement delay, ramping times, lockout durations and rotational inertia on the controllability of the aggregation and system stability. Finally, we discuss...

[Genetically modified organisms in food--production, detection and risks].

Science.gov (United States)

Zeljezić, Davor

2004-11-01

The first genetically modified plant (GMP) was a tobacco resistant to antibiotics in 1983. In 1996, the first genetically altered crop, a delayed-ripening tomato was commercially released. In the year 2003, the estimated global area of GM crops for was 67.7 million hectares. To produce such a plant a gene of interest has to be isolated from the donor. Together with a promoter, terminator sequence and marker gene it has to be introduced into the plant cell which is then stimulated to generate a whole GMP expressing new characteristics (herbicide/insect resistance, delayed ripening). The last few months have seen a strong public debate over genetically modified organisms which has raised scientific, economic, political, and ethical issues. Some questions concerning the safety of GMPs are still to be answered, and decisions about their future should be based on scientifically validated information.

Variable delay-to-signal: a fast paradigm for assessment of aspects of impulsivity in rats

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Hugo eLeite-Almeida

2013-10-01

Full Text Available Testing impulsive behavior in rodents is challenging and labor-intensive. We developed a new behavioral paradigm – the Variable Delay-to-Signal (VDS test – that provides rapid and simultaneous assessment of response and decision impulsivity in rodents. Presentation of a light at variable delays signals the permission for action (nose poke contingent with a reward. Two blocks of 25 trials at 3s delay flank a block of 70 trials in which light is presented with randomly selected 6s or 12s delays. Exposure to such large delays boosts the rate of premature responses when the delay drops to 3s in the final block, an effect that is blunted by an acute methamphetamine challenge and that correlates with the delay-discounting paradigm (choice impulsivity. Finally, as expected, treatment with the NMDA antagonist MK-801 caused a generalized response increase in all VDS blocks. The pharmacological validation, particularly with methamphetamine which has a well established dual effect on response and decision impulsivity, and the correlations between the impulsive behavior in the delay-discounting and VDS paradigms, suggests that the later is able to provide, in a single session, a multi-dimensional assessment of impulsive behavior.

Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile

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Luz María Medrano

2015-01-01

Full Text Available Substantial proportion of Crohn’s disease (CD patients shows no response or a limited response to treatment with infliximab (IFX and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11 reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350 who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276*G/rs3014866*C/rs724781*C/rs3006488*A; P=0.05; G0S2 (rs4844486*A/rs1473683*T; P=0.15; TNFAIP6 (rs11677200*C/rs2342910*A/rs3755480*G/rs10432475*A; P=0.10; and IL11 (rs1126760*C/rs1042506*G; P=0.07. These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway.

The influence of emotion regulation, attribution prompts, and delay, on response aggressiveness in antisocial boys. [IF 1.3

OpenAIRE

Orobio de Castro, B.; Bosch, J.D.; Veerman, J.W.; Koops, W.

2003-01-01

Boys with aggressive behavior problems are frequently taught to "stop and think" before they act. In provocative situations, pausing to monitor their own feelings, to consider the feelings of others, or to delay their response is believed to reduce aggressive behavior. This study aimed to test these assumptions. Thirty-two highly aggressive boys in special education and 31 normal comparison boys were presented vignettes concerning provocation by a peer and given specific cognitive assignments...

SPEECH DELAY IN THE PRACTICE OF A PAEDIATRICIAN AND CHILD’S NEUROLOGIST

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N. N. Zavadenko

2015-01-01

Full Text Available The article describes the main clinical forms and causes of speech delay in children. It presents modern data on the role of neurobiological factors in the speech delay pathogenesis, including early organic damage to the central nervous system due to the pregnancy and childbirth pathology, as well as genetic mechanisms. For early and accurate diagnosis of speech disorders in children, you need to consider normal patterns of speech development. The article presents indicators of pre-speech and speech development in children and describes the screening method for determining the speech delay. The main areas of complex correction are speech therapy, psycho-pedagogical and psychotherapeutic assistance, as well as pharmaceutical treatment. The capabilities of drug therapy for dysphasia (alalia are shown. 

Genetic analysis of the SOS response of Escherichia coli

International Nuclear Information System (INIS)

Mount, D.W.; Wertman, K.F.; Ennis, D.G.; Peterson, K.R.; Fisher, B.L.; Lyons, G.

1983-01-01

In the SOS response, a large number of E. coli genes having different functions are derepressed when the cellular DNA is damaged. This derepression occurs through inactivation of a repressor, the product of the lexA gene, by a protease activity of the recA gene product. The protease is thought to be activated in response to changes in DNA metabolism which follow the damage. After the SOS functions have acted, the protease activity declines and repression is again established. Because the DNA sequence of both lexA and recA have been determined, it is possible to induce many mutations in their regulatory and structural regions in order to analyze further the control of the SOS response. We are studying the effects of mutations in both the lexA and recA regulatory regions, and mutations which affect the protease activity or the sensitivity of repressor to the protease. Finally, we are using genetic methods to analyze a newly identified requirement for recA protein, induced mutagenesis in cells lacking repressor. 16 references, 3 figures

Mixed Modeling of a SAW Delay Line Using VHDL-AMS

Science.gov (United States)

Wilson, William C.; Atkinson, Gary M.

2006-01-01

To aid in the development of SAW sensors for aerospace applications we have created a model of a SAW Delay line using VHDL. The model implements the Impulse Response method to calculate the frequency response, impedance, and insertion loss. The model includes optimization for the number of finger pairs in the IDTs and for the aperture height. This paper presents the model and the results from the model for a SAW delay line design.

Analog Group Delay Equalizers Design Based on Evolutionary Algorithm

Directory of Open Access Journals (Sweden)

M. Laipert

2006-04-01

Full Text Available This paper deals with a design method of the analog all-pass filter designated for equalization of the group delay frequency response of the analog filter. This method is based on usage of evolutionary algorithm, the Differential Evolution algorithm in particular. We are able to design such equalizers to be obtained equal-ripple group delay frequency response in the pass-band of the low-pass filter. The procedure works automatically without an input estimation. The method is presented on solving practical examples.

Genetic variation in the cellular response of Daphnia magna (Crustacea: Cladocera) to its bacterial parasite.

Science.gov (United States)

Auld, Stuart K J R; Scholefield, Jennifer A; Little, Tom J

2010-11-07

Linking measures of immune function with infection, and ultimately, host and parasite fitness is a major goal in the field of ecological immunology. In this study, we tested for the presence and timing of a cellular immune response in the crustacean Daphnia magna following exposure to its sterilizing endoparasite Pasteuria ramosa. We found that D. magna possesses two cell types circulating in the haemolymph: a spherical one, which we call a granulocyte and an irregular-shaped amoeboid cell first described by Metchnikoff over 125 years ago. Daphnia magna mounts a strong cellular response (of the amoeboid cells) just a few hours after parasite exposure. We further tested for, and found, considerable genetic variation for the magnitude of this cellular response. These data fostered a heuristic model of resistance in this naturally coevolving host-parasite interaction. Specifically, the strongest cellular responses were found in the most susceptible hosts, indicating resistance is not always borne from a response that destroys invading parasites, but rather stems from mechanisms that prevent their initial entry. Thus, D. magna may have a two-stage defence--a genetically determined barrier to parasite establishment and a cellular response once establishment has begun.

Classical genetic analyses of responses to nicotine and ethanol in crosses derived from long- and short-sleep mice.

Science.gov (United States)

de Fiebre, C M; Collins, A C

1992-04-01

A classical (Mendelian) genetic analysis of responses to ethanol and nicotine was conducted in crosses derived from mouse lines which were selectively bred for differential duration of loss of the righting response (sleep-time) after ethanol. Dose-response curves for these mice, the long- and short-sleep mouse lines, as well as the derived F1, F2 and backcross (F1 x long-sleep and F1 x short-sleep) generations were generated for several measures of nicotine and ethanol sensitivity. Ethanol sensitivity was assessed using the sleep-time measure. Nicotine sensitivity was tested using a battery of behavioral and physiological tests which included measures of seizure activity, respiration rate, acoustic startle response, Y-maze activities (both crossing and rearing activities), heart rate and body temperature. The inheritance of sensitivities to both of these agents appears to be polygenic and inheritance can be explained primarily by additive genetic effects with some epistasis. Sensitivity to the ethanol sleep-time measure was genetically correlated with sensitivity to both nicotine-induced hypothermia and seizures; the correlation was greater between sleep-time and hypothermia. These data indicate that there is overlap in the genetic regulation of sensitivity to both ethanol and nicotine as measured by some, but not all, tests.

IN SITU COMPARISON OF TREE-RING RESPONSES TO CLIMATE AND POPULATION GENETICS: THE NEED TO CONTROL FOR LOCAL CLIMATE AND SITE VARIABLES

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Johann Mathias Housset

2016-10-01

Full Text Available Tree species responses to climate change will be greatly influenced by their evolutionary potential and their phenotypic plasticity. Investigating tree-rings responses to climate and population genetics at the regional scale is therefore crucial in assessing the tree behaviour to climate change. This study combined in situ dendroclimatology and population genetics over a latitudinal gradient and compared the variations between the two at the intra- and inter-population levels. This approach was applied on the northern marginal populations of Thuja occidentalis (eastern white-cedar in the Canadian boreal forest. We aimed first to assess the radial growth variability (response functional trait within populations across the gradient and to compare it with the genetic diversity (microsatellites. Second, we investigated the variability in the growth response to climate at the regional scale through the radial growth-climate relationships, and tested its correlation with environmental variables and population genetic structure. Model selection based on the Akaike Information Criteria revealed that the growth synchronicity between pairs of trees of a population covariates with both the genetic diversity of this population and the amount of precipitation (inverse correlation, although these variables only explained a small fraction of the observed variance. At the regional scale, variance partitioning and partial redundancy analysis indicate that the growth response to climate was greatly modulated by stand environmental variables, suggesting predominant plastic variations in growth-response to climate. Combining in situ dendroclimatology and population genetics is a promising way to investigate species’ response capacity to climate change in natural stands. We stress the need to control for local climate and site conditions effects on dendroclimatic response to climate to avoid misleading conclusions regarding the associations with genetic variables.

Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study.

Science.gov (United States)

Goetz, Elena L; Hariri, Ahmad R; Pizzagalli, Diego A; Strauman, Timothy J

2013-02-01

Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue responsiveness. Healthy Caucasians (N=59) completed a measure of chronic regulatory focus and a probabilistic reward task. A common functional genetic polymorphism impacting prefrontal dopamine signaling (COMT rs4680) was evaluated. Response bias, the participants' propensity to modulate behavior as a function of reward, was predicted by an interaction of regulatory focus and COMT genotype. Specifically, self-perceived success at achieving promotion goals predicted total response bias, but only for individuals with the COMT genotype (Val/Val) associated with relatively increased phasic dopamine signaling and cognitive flexibility. The combination of success in promotion goal pursuit and Val/Val genotype appears to facilitate responding to reward opportunities in the environment. This study is among the first to integrate an assessment of self-regulatory style with an examination of genetic variability that underlies responsiveness to positive outcomes in goal pursuit.

Reaction time inhibition, working memory and 'delay aversion' performance : genetic influences and their interpretation

NARCIS (Netherlands)

Kuntsi, Jonna; Rogers, Hannah; Swinard, Greer; Börger, Norbert; van der Meere, Jaap; Rijsdijk, Fruhling; Asherson, Philip

2006-01-01

Background. For candidate endophenotypes to be useful for psychiatric genetic research, they first of all need to show significant genetic influences. To address the relative lack of previous data, we set to investigate the extent of genetic and environmental influences on performance in a set of

Genetic correlations between behavioural responses and performance traits in laying hens

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Iwona Rozempolska-Rucińska

2017-12-01

Full Text Available Objective The aim of the study was to evaluate genetic correlations between the behavioural profile and performance in laying hens as an indirect answer to the question whether the observed behavioural responses are associated with increased levels of stress in these birds. Methods The assessment of birds’ temperament was carried out using the novel objects test. The behavioural test was conducted in two successive generations comprising 9,483 Rhode Island White (RIW birds (approx. 4,700 individuals per generation and 4,326 Rhode Island Red (RIR birds (approx. 2,100 individuals per generation. Based on the recorded responses, the birds were divided into two groups: a fearful profile (1,418 RIW hens and 580 RIR hens and a brave/curious profile (8,065 RIW hens and 3,746 RIR hens. The birds were subjected to standard assessment of their performance traits, including SM, age at sexual maturity; ST, shell thickness; SG, egg specific gravity; EW, mean egg weight; IP, initial egg production; and HC, number of hatched chicks. The pedigree was three generations deep (including two behaviour-recorded generations. Estimation of the (covariance components was performed with the Gibbs sampling method, which accounts for the discrete character of the behavioural profile denotation. Results The analyses revealed negative correlations between the performance traits of the laying hens and the behavioural profile defined as fearful. In the group of fearful RIW birds, delayed sexual maturation (0.22 as well as a decrease in the initial egg production (−0.30, egg weight (−0.54, egg specific gravity (−0.331, shell thickness (−0.11, and the number of hatched chicks (−0.24 could be expected. These correlations were less pronounced in the RIR breed, in which the fearful birds exhibited a decline in hatchability (−0.37, egg specific gravity (−0.11, and the number of hatched chicks (−0.18. There were no correlations in the case of the other traits or

Atmospheric Phase Delay in Sentinel SAR Interferometry

Science.gov (United States)

Krishnakumar, V.; Monserrat, O.; Crosetto, M.; Crippa, B.

2018-04-01

The repeat-pass Synthetic Aperture Radio Detection and Ranging (RADAR) Interferometry (InSAR) has been a widely used geodetic technique for observing the Earth's surface, especially for mapping the Earth's topography and deformations. However, InSAR measurements are prone to atmospheric errors. RADAR waves traverse the Earth's atmosphere twice and experience a delay due to atmospheric refraction. The two major layers of the atmosphere (troposphere and ionosphere) are mainly responsible for this delay in the propagating RADAR wave. Previous studies have shown that water vapour and clouds present in the troposphere and the Total Electron Content (TEC) of the ionosphere are responsible for the additional path delay in the RADAR wave. The tropospheric refractivity is mainly dependent on pressure, temperature and partial pressure of water vapour. The tropospheric refractivity leads to an increase in the observed range. These induced propagation delays affect the quality of phase measurement and introduce errors in the topography and deformation fields. The effect of this delay was studied on a differential interferogram (DInSAR). To calculate the amount of tropospheric delay occurred, the meteorological data collected from the Spanish Agencia Estatal de Meteorología (AEMET) and MODIS were used. The interferograms generated from Sentinel-1 carrying C-band Synthetic Aperture RADAR Single Look Complex (SLC) images acquired on the study area are used. The study area consists of different types of scatterers exhibiting different coherence. The existing Saastamoinen model was used to perform a quantitative evaluation of the phase changes caused by pressure, temperature and humidity of the troposphere during the study. Unless the phase values due to atmospheric disturbances are not corrected, it is difficult to obtain accurate measurements. Thus, the atmospheric error correction is essential for all practical applications of DInSAR to avoid inaccurate height and deformation

ATMOSPHERIC PHASE DELAY IN SENTINEL SAR INTERFEROMETRY

Directory of Open Access Journals (Sweden)

V. Krishnakumar

2018-04-01

Full Text Available The repeat-pass Synthetic Aperture Radio Detection and Ranging (RADAR Interferometry (InSAR has been a widely used geodetic technique for observing the Earth’s surface, especially for mapping the Earth’s topography and deformations. However, InSAR measurements are prone to atmospheric errors. RADAR waves traverse the Earth’s atmosphere twice and experience a delay due to atmospheric refraction. The two major layers of the atmosphere (troposphere and ionosphere are mainly responsible for this delay in the propagating RADAR wave. Previous studies have shown that water vapour and clouds present in the troposphere and the Total Electron Content (TEC of the ionosphere are responsible for the additional path delay in the RADAR wave. The tropospheric refractivity is mainly dependent on pressure, temperature and partial pressure of water vapour. The tropospheric refractivity leads to an increase in the observed range. These induced propagation delays affect the quality of phase measurement and introduce errors in the topography and deformation fields. The effect of this delay was studied on a differential interferogram (DInSAR. To calculate the amount of tropospheric delay occurred, the meteorological data collected from the Spanish Agencia Estatal de Meteorología (AEMET and MODIS were used. The interferograms generated from Sentinel-1 carrying C-band Synthetic Aperture RADAR Single Look Complex (SLC images acquired on the study area are used. The study area consists of different types of scatterers exhibiting different coherence. The existing Saastamoinen model was used to perform a quantitative evaluation of the phase changes caused by pressure, temperature and humidity of the troposphere during the study. Unless the phase values due to atmospheric disturbances are not corrected, it is difficult to obtain accurate measurements. Thus, the atmospheric error correction is essential for all practical applications of DInSAR to avoid inaccurate

Hopf bifurcation for tumor-immune competition systems with delay

Directory of Open Access Journals (Sweden)

Ping Bi

2014-01-01

Full Text Available In this article, a immune response system with delay is considered, which consists of two-dimensional nonlinear differential equations. The main purpose of this paper is to explore the Hopf bifurcation of a immune response system with delay. The general formula of the direction, the estimation formula of period and stability of bifurcated periodic solution are also given. Especially, the conditions of the global existence of periodic solutions bifurcating from Hopf bifurcations are given. Numerical simulations are carried out to illustrate the the theoretical analysis and the obtained results.

Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

NARCIS (Netherlands)

Moes, Dirk Jan A. R.; Press, Rogier R.; Ackaert, Oliver; Ploeger, Bart A.; Bemelman, Frederike J.; Diack, Cheikh; Wessels, Judith A. M.; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F.; Homan van der Heide, Jaap J.; Guchelaar, Henk Jan; de Fijter, Johan W.

2016-01-01

This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). Adult renal transplant recipients (n = 361) on cyclosporine-based

Urban sprawl and delayed ambulance arrival in the U.S.

Science.gov (United States)

Trowbridge, Matthew J; Gurka, Matthew J; O'Connor, Robert E

2009-11-01

Minimizing emergency medical service (EMS) response time is a central objective of prehospital care, yet the potential influence of built environment features such as urban sprawl on EMS system performance is often not considered. This study measures the association between urban sprawl and EMS response time to test the hypothesis that features of sprawling development increase the probability of delayed ambulance arrival. In 2008, EMS response times for 43,424 motor-vehicle crashes were obtained from the Fatal Analysis Reporting System, a national census of crashes involving > or =1 fatality. Sprawl at each crash location was measured using a continuous county-level index previously developed by Ewing et al. The association between sprawl and the probability of a delayed ambulance arrival (> or =8 minutes) was then measured using generalized linear mixed modeling to account for correlation among crashes from the same county. Urban sprawl is significantly associated with increased EMS response time and a higher probability of delayed ambulance arrival (p=0.03). This probability increases quadratically as the severity of sprawl increases while controlling for nighttime crash occurrence, road conditions, and presence of construction. For example, in sprawling counties (e.g., Fayette County GA), the probability of a delayed ambulance arrival for daytime crashes in dry conditions without construction was 69% (95% CI=66%, 72%) compared with 31% (95% CI=28%, 35%) in counties with prominent smart-growth characteristics (e.g., Delaware County PA). Urban sprawl is significantly associated with increased EMS response time and a higher probability of delayed ambulance arrival following motor-vehicle crashes in the U.S. The results of this study suggest that promotion of community design and development that follows smart-growth principles and regulates urban sprawl may improve EMS performance and reliability.

Evaluation of Optimum Genetic Contribution Theory to Control Inbreeding While Maximizing Genetic Response

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S.-H. Oh

2012-03-01

Full Text Available Inbreeding is the mating of relatives that produce progeny having more homozygous alleles than non-inbred animals. Inbreeding increases numbers of recessive alleles, which is often associated with decreased performance known as inbreeding depression. The magnitude of inbreeding depression depends on the level of inbreeding in the animal. Level of inbreeding is expressed by the inbreeding coefficient. One breeding goal in livestock is uniform productivity while maintaining acceptable inbreeding levels, especially keeping inbreeding less than 20%. However, in closed herds without the introduction of new genetic sources high levels of inbreeding over time are unavoidable. One method that increases selection response and minimizes inbreeding is selection of individuals by weighting estimated breeding values with average relationships among individuals. Optimum genetic contribution theory (OGC uses relationships among individuals as weighting factors. The algorithm is as follows: i Identify the individual having the best EBV; ii Calculate average relationships ( r j ¯ between selected and candidates; iii Select the individual having the best EBV adjusted for average relationships using the weighting factor k, E B V * = E B V j ( 1 - k r j ¯ . iv Repeat process until the number of individuals selected equals number required. The objective of this study was to compare simulated results based on OGC selection under different conditions over 30 generations. Individuals (n = 110 were generated for the base population with pseudo random numbers of N~ (0, 3, ten were assumed male, and the remainder female. Each male was mated to ten females, and every female was assumed to have 5 progeny resulting in 500 individuals in the following generation. Results showed the OGC algorithm effectively controlled inbreeding and maintained consistent increases in selection response. Difference in breeding values between selection with OGC algorithm and by EBV only was 8

Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

NARCIS (Netherlands)

Moes, Dirk Jan A. R.; Press, Rogier R.; Ackaert, Oliver; Ploeger, Bart A.; Bemelman, Frederike J.; Diack, Cheikh; Wessels, Judith A. M.; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F.; van der Heide, Jaap J. Homan; Guchelaar, Henk Jan; de Fijter, Johan W.

AIMS This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). METHODS Adult renal transplant recipients (n = 361) on cyclosporine-based

Identifying time-delayed gene regulatory networks via an evolvable hierarchical recurrent neural network.

Science.gov (United States)

Kordmahalleh, Mina Moradi; Sefidmazgi, Mohammad Gorji; Harrison, Scott H; Homaifar, Abdollah

2017-01-01

The modeling of genetic interactions within a cell is crucial for a basic understanding of physiology and for applied areas such as drug design. Interactions in gene regulatory networks (GRNs) include effects of transcription factors, repressors, small metabolites, and microRNA species. In addition, the effects of regulatory interactions are not always simultaneous, but can occur after a finite time delay, or as a combined outcome of simultaneous and time delayed interactions. Powerful biotechnologies have been rapidly and successfully measuring levels of genetic expression to illuminate different states of biological systems. This has led to an ensuing challenge to improve the identification of specific regulatory mechanisms through regulatory network reconstructions. Solutions to this challenge will ultimately help to spur forward efforts based on the usage of regulatory network reconstructions in systems biology applications. We have developed a hierarchical recurrent neural network (HRNN) that identifies time-delayed gene interactions using time-course data. A customized genetic algorithm (GA) was used to optimize hierarchical connectivity of regulatory genes and a target gene. The proposed design provides a non-fully connected network with the flexibility of using recurrent connections inside the network. These features and the non-linearity of the HRNN facilitate the process of identifying temporal patterns of a GRN. Our HRNN method was implemented with the Python language. It was first evaluated on simulated data representing linear and nonlinear time-delayed gene-gene interaction models across a range of network sizes and variances of noise. We then further demonstrated the capability of our method in reconstructing GRNs of the Saccharomyces cerevisiae synthetic network for in vivo benchmarking of reverse-engineering and modeling approaches (IRMA). We compared the performance of our method to TD-ARACNE, HCC-CLINDE, TSNI and ebdbNet across different network

Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.

Directory of Open Access Journals (Sweden)

Edwin Choy

2008-11-01

Full Text Available Lymphoblastoid cell lines (LCLs, originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance--i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding.

Climate change : Behavioral responses from extreme events and delayed damages

NARCIS (Netherlands)

Ghidoni, Riccardo; Calzolari, Giacomo; Casari, Marco

2017-01-01

Understanding how to sustain cooperation in the climate change global dilemma is crucial to mitigate its harmful consequences. Damages from climate change typically occur after long delays and can take the form of more frequent realizations of extreme and random events. These features generate a

Climate Change : Behavioral Responses from Extreme Events and Delayed Damages

NARCIS (Netherlands)

Ghidoni, Riccardo; Calzolari, G.; Casari, Marco

2017-01-01

Understanding how to sustain cooperation in the climate change global dilemma is crucial to mitigate its harmful consequences. Damages from climate change typically occurs after long delays and can take the form of more frequent realizations of extreme and random events. These features generate a

Genetic privacy.

Science.gov (United States)

Sankar, Pamela

2003-01-01

During the past 10 years, the number of genetic tests performed more than tripled, and public concern about genetic privacy emerged. The majority of states and the U.S. government have passed regulations protecting genetic information. However, research has shown that concerns about genetic privacy are disproportionate to known instances of information misuse. Beliefs in genetic determinacy explain some of the heightened concern about genetic privacy. Discussion of the debate over genetic testing within families illustrates the most recent response to genetic privacy concerns.

Effects of drugs of abuse and cholinergic agents on delayed matching-to-sample responding in the squirrel monkey.

Science.gov (United States)

Hudzik, T J; Wenger, G R

1993-04-01

To study how drugs may disrupt short-term memory function, squirrel monkeys were trained to respond under a titrating delayed matching-to-sample schedule of reinforcement. Monkeys could respond on each of three keys in an operant chamber. At the start of each trial, the 30th response on the center key illuminated each of the side keys, one of which matched the stimulus presented on the center key (simultaneous matching). A response to the correct (matching) side key turned off all stimuli and initiated a delay, the length of which varied as a function of ongoing performance. After the delay, stimuli were randomly presented on two of the three keys. A response to the key which matched the color on the center key before the delay resulted in delivery of a food pellet (delayed matching). Incorrect simultaneous or delayed matching responses initiated a timeout. Under this procedure, diazepam and scopolamine decreased delayed matching accuracy at one or more doses that did not significantly decrease mean delay values, but only scopolamine decreased matching accuracy at a dose that did not significantly decrease response rates. Cocaine decreased mean delay values after the highest dose without affecting matching accuracy. Pentobarbital and methylscopolamine decreased matching accuracy and mean and maximum delay values after the highest doses. Nicotine and phencyclidine produced small decreases in delayed matching accuracy without affecting mean and maximum delay values. Caffeine, morphine, physostigmine and neostigmine did not alter matching performance even after doses that markedly decreased rates of responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained and transient oscillations and chaos induced by delayed antiviral immune response in an immunosuppressive infection model.

Science.gov (United States)

Shu, Hongying; Wang, Lin; Watmough, James

2014-01-01

Sustained and transient oscillations are frequently observed in clinical data for immune responses in viral infections such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. To account for these oscillations, we incorporate the time lag needed for the expansion of immune cells into an immunosuppressive infection model. It is shown that the delayed antiviral immune response can induce sustained periodic oscillations, transient oscillations and even sustained aperiodic oscillations (chaos). Both local and global Hopf bifurcation theorems are applied to show the existence of periodic solutions, which are illustrated by bifurcation diagrams and numerical simulations. Two types of bistability are shown to be possible: (i) a stable equilibrium can coexist with another stable equilibrium, and (ii) a stable equilibrium can coexist with a stable periodic solution.

Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum.

Science.gov (United States)

Fejzo, Marlena S; Magtira, Aromalyn; Schoenberg, Frederic Paik; Macgibbon, Kimber; Mullin, Patrick M

2015-06-01

The purpose of this study is to determine the frequency of emotional, behavioral, and learning disorders in children exposed in utero to hyperemesis gravidarum (HG) and to identify prognostic factors for these disorders. Neurodevelopmental outcomes of 312 children from 203 mothers with HG were compared to neurodevelopmental outcomes from 169 children from 89 unaffected mothers. Then the clinical profiles of patients with HG and a normal child outcome were compared to the clinical profiles of patients with HG and a child with neurodevelopmental delay to identify prognostic factors. Binary responses were analyzed using either a Chi-square or Fisher Exact test and continuous responses were analyzed using a t-test. Children exposed in utero to HG have a 3.28-fold increase in odds of a neurodevelopmental diagnosis including attention disorders, learning delay, sensory disorders, and speech and language delay (Pneurodevelopmental delay. We found no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder. However, the study was not sufficiently powered to detect rare conditions. Medications, treatments, and preterm birth were not associated with an increased risk for neurodevelopmental delay. Women with HG are at a significantly increased risk of having a child with neurodevelopmental delay. Common antiemetic treatments were not linked to neurodevelopmental delay, but early symptoms may play a role. There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea of pregnancy decreases the risk of neurodevelopmental delay. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of Behavioral Genetic Evidence on Perceptions of Criminal Responsibility and Appropriate Punishment

Science.gov (United States)

Appelbaum, Paul S.; Scurich, Nicholas; Raad, Raymond

2015-01-01

Demonstrations of a link between genetic variants and criminal behavior have stimulated increasing use of genetic evidence to reduce perceptions of defendants’ responsibility for criminal behavior and to mitigate punishment. However, because only limited data exist regarding the impact of such evidence on decision makers and the public at large, we recruited a representative sample of the U.S. adult population (n=960) for a web-based survey. Participants were presented with descriptions of three legal cases and were asked to: determine the length of incarceration for a convicted murderer; adjudicate an insanity defense; and decide whether a defendant should receive the death penalty. A fully crossed, between-participants, factorial design was used, varying the type of evidence (none, genetic, neuroimaging, both), heinousness of the crime, and past criminal record, with sentence or verdict as the primary outcome. Also assessed were participants’ apprehension of the defendant, belief in free will, political ideology, and genetic knowledge. Across all three cases, genetic evidence had no significant effects on outcomes. Neuroimaging data showed an inconsistent effect in one of the two cases in which it was introduced. In contrast, heinousness of the offense and past criminal record were strongly related to participants’ decisions. Moreover, participants’ beliefs about the controllability of criminal behavior and political orientations were significantly associated with their choices. Our findings suggest that neither hopes that genetic evidence will modify judgments of culpability and punishment nor fears about the impact of genetic evidence on decision makers are likely to come to fruition. PMID:26240516

Effects of Behavioral Genetic Evidence on Perceptions of Criminal Responsibility and Appropriate Punishment.

Science.gov (United States)

Appelbaum, Paul S; Scurich, Nicholas; Raad, Raymond

2015-05-01

Demonstrations of a link between genetic variants and criminal behavior have stimulated increasing use of genetic evidence to reduce perceptions of defendants' responsibility for criminal behavior and to mitigate punishment. However, because only limited data exist regarding the impact of such evidence on decision makers and the public at large, we recruited a representative sample of the U.S. adult population (n=960) for a web-based survey. Participants were presented with descriptions of three legal cases and were asked to: determine the length of incarceration for a convicted murderer; adjudicate an insanity defense; and decide whether a defendant should receive the death penalty. A fully crossed, between-participants, factorial design was used, varying the type of evidence (none, genetic, neuroimaging, both), heinousness of the crime, and past criminal record, with sentence or verdict as the primary outcome. Also assessed were participants' apprehension of the defendant, belief in free will, political ideology, and genetic knowledge. Across all three cases, genetic evidence had no significant effects on outcomes. Neuroimaging data showed an inconsistent effect in one of the two cases in which it was introduced. In contrast, heinousness of the offense and past criminal record were strongly related to participants' decisions. Moreover, participants' beliefs about the controllability of criminal behavior and political orientations were significantly associated with their choices. Our findings suggest that neither hopes that genetic evidence will modify judgments of culpability and punishment nor fears about the impact of genetic evidence on decision makers are likely to come to fruition.

Optimal Joint Expected Delay Forwarding in Delay Tolerant Networks

OpenAIRE

Jia Xu; Xin Feng; Wen Jun Yang; Ru Chuan Wang; Bing Qing Han

2013-01-01

Multicopy forwarding schemes have been employed in delay tolerant network (DTN) to improve the delivery delay and delivery rate. Much effort has been focused on reducing the routing cost while retaining high performance. This paper aims to provide an optimal joint expected delay forwarding (OJEDF) protocol which minimizes the expected delay while satisfying a certain constant on the number of forwardings per message. We propose a comprehensive forwarding metric called joint expected delay (JE...

Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer.

Science.gov (United States)

Kurian, Allison W; Li, Yun; Hamilton, Ann S; Ward, Kevin C; Hawley, Sarah T; Morrow, Monica; McLeod, M Chandler; Jagsi, Reshma; Katz, Steven J

2017-07-10

Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing use of multiple-gene panels that can yield uncertain results. However, little is known about the context of such testing or its impact on treatment. Methods A population-based sample of patients with breast cancer diagnosed in 2014 to 2015 and identified by two SEER registries (Georgia and Los Angeles) were surveyed about genetic testing experiences (N = 3,672; response rate, 68%). Responses were merged with SEER data. A patient subgroup at higher pretest risk of pathogenic mutation carriage was defined according to genetic testing guidelines. Patients' attending surgeons were surveyed about genetic testing and results management. We examined patterns and correlates of genetic counseling and testing and the impact of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six patients reported genetic testing. Although two thirds of patients were tested before surgical treatment, patients without private insurance more often experienced delays. Approximately half of patients (57% at higher pretest risk, 42% at average risk) discussed results with a genetic counselor. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication

Genetic and Computational Approaches for Studying Plant Development and Abiotic Stress Responses Using Image-Based Phenotyping

Science.gov (United States)

Campbell, M. T.; Walia, H.; Grondin, A.; Knecht, A.

2017-12-01

The development of abiotic stress tolerant crops (i.e. drought, salinity, or heat stress) requires the discovery of DNA sequence variants associated with stress tolerance-related traits. However, many traits underlying adaptation to abiotic stress involve a suite of physiological pathways that may be induced at different times throughout the duration of stress. Conventional single-point phenotyping approaches fail to fully capture these temporal responses, and thus downstream genetic analysis may only identify a subset of the genetic variants that are important for adaptation to sub-optimal environments. Although genomic resources for crops have advanced tremendously, the collection of phenotypic data for morphological and physiological traits is laborious and remains a significant bottleneck in bridging the phenotype-genotype gap. In recent years, the availability of automated, image-based phenotyping platforms has provided researchers with an opportunity to collect morphological and physiological traits non-destructively in a highly controlled environment. Moreover, these platforms allow abiotic stress responses to be recorded throughout the duration of the experiment, and have facilitated the use of function-valued traits for genetic analyses in major crops. We will present our approaches for addressing abiotic stress tolerance in cereals. This talk will focus on novel open-source software to process and extract biological meaningful data from images generated from these phenomics platforms. In addition, we will discuss the statistical approaches to model longitudinal phenotypes and dissect the genetic basis of dynamic responses to these abiotic stresses throughout development.

Delayed recovery from anesthesia: A postgraduate educational review

OpenAIRE

Misal, Ullhas Sudhakarrao; Joshi, Suchita Annasaheb; Shaikh, Mudassir Mohd

2016-01-01

Delayed awakening from anesthesia remains one of the biggest challenges that involve an anesthesiologist. With the general use of fast-acting anesthetic agents, patients usually awaken quickly in the postoperative period. The time to emerge from anesthesia is affected by patient factors, anesthetic factors, duration of surgery, and painful stimulation. The principal factors responsible for delayed awakening following anesthesia are anesthetic agents and medications used in the perioperative p...

Increasing the response rate of text messaging data collection: a delayed randomized controlled trial

Science.gov (United States)

Li, Ye; Wang, Wei; Wu, Qiong; van Velthoven, Michelle Helena; Chen, Li; Du, Xiaozhen; Zhang, Yanfeng; Rudan, Igor; Car, Josip

2015-01-01

Objective To test the effectiveness of multiple interventions on increasing the response rate of text messaging for longitudinal data collection. Methods Our cohort included 283 caregivers of children aged 6–12 months who were participating in an anemia program in rural China. Using text messages to collect data on anemia medication adherence, we conducted a delayed randomized controlled trial to test multiple interventions (an additional four reminders; a ¥5.0 (US$0.79) credit reward for replying; and a feedback text message). After a 6-week pilot study with week 7 as the baseline measurement, we randomly allocated all participants into two groups: group 1 (n = 142) and group 2 (n = 141). During weeks 8–11, we introduced the interventions to group 1, and in weeks 12–15 the intervention was introduced to both groups. We compared the response rates between groups and explored factors affecting the response rate. Results During weeks 8–11, the response rates in group 1 increased and were significantly higher than in group 2 (p0.05) and slightly decreased in group 1. Younger participants or participants who had children with lower hemoglobin concentration were more likely to reply (p = 0.02). Sending four reminders on the second day contributed to only 286 (11.7%) extra text messages. Discussion Our study showed that multiple interventions were effective in increasing response rate of text messaging data collection in rural China. Conclusions Larger multi-site studies are needed to find the most effective way of using these interventions to allow usage of text messaging data collection for health research. PMID:25332355

Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.

Science.gov (United States)

Joslyn, Geoff; Brush, Gerry; Robertson, Margaret; Smith, Tom L; Kalmijn, Jelger; Schuckit, Marc; White, Raymond L

2008-12-23

As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

Regulation of the Th1 immune response : the role of IL-23 and the influence of genetic variations

NARCIS (Netherlands)

Wetering, Diederik van de

2010-01-01

Part 1: The role of IL-23 in inducing IFN-g production and in the initiation of a Th1 response. Part 2: Genetic variations in the type-1 cytokine pathway. Part 3: Treatment options for a genetic deficiency in the type-1 cytokine pathway

Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection

NARCIS (Netherlands)

Anche, M.T.

2016-01-01

Mahlet Teka Anche. (2016). Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection. PhD thesis, Wageningen University, the Netherlands

Genetic approaches aiming to reduce the prevalence of an infection in a

A novel perspective to calibrate temporal delays in cerebrovascular reactivity using hypercapnic and hyperoxic respiratory challenges.

Science.gov (United States)

Champagne, Allen A; Bhogal, Alex A; Coverdale, Nicole S; Mark, Clarisse I; Cook, Douglas J

2017-12-05

Redistribution of blood flow across different brain regions, arising from the vasoactive nature of hypercapnia, can introduce errors when examining cerebrovascular reactivity (CVR) response delays. In this study, we propose a novel analysis method to characterize hemodynamic delays in the blood oxygen level dependent (BOLD) response to hypercapnia, and hyperoxia, as a way to provide insight into transient differences in vascular reactivity between cortical regions, and across tissue depths. A pseudo-continuous arterial spin labeling sequence was used to acquire BOLD and cerebral blood flow simultaneously in 19 healthy adults (12 F; 20 ± 2 years) during boxcar CO 2 and O 2 gas inhalation paradigms. Despite showing distinct differences in hypercapnia-induced response delay times (P  0.05) once calibrated for bolus arrival time derived using non-vasoactive hyperoxic gas challenges. Longer hypercapnic temporal delays were observed as the depth of the white matter tissue increased, although no significant differences in response lag were found during hyperoxia across tissue depth, or between grey and white matter. Furthermore, calibration of hypercapnic delays using hyperoxia revealed that deeper white matter layers may be more prone to dynamic redistribution of blood flow, which introduces response lag times ranging between 1 and 3 s in healthy subjects. These findings suggest that the combination of hypercapnic and hyperoxic gas-inhalation MRI can be used to distinguish between differences in CVR that arise as a result of delayed stimulus arrival time (due to the local architecture of the cerebrovasculature), or preferential blood flow distribution. Calibrated response delays to hypercapnia provide important insights into cerebrovascular physiology, and may be used to correct response delays associated with vascular impairment. Copyright © 2017. Published by Elsevier Inc.

Genetics and Treatment Response in Parkinson's Disease: An Update on Pharmacogenetic Studies.

Science.gov (United States)

Politi, Cristina; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

2018-03-01

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopamine neurons of the central nervous system. The disease determines a significant disability due to a combination of motor symptoms such as bradykinesia, rigidity and rest tremor and non-motor symptoms such as sleep disorders, hallucinations, psychosis and compulsive behaviors. The current therapies consist in combination of drugs acting to control only the symptoms of the illness by the replacement of the dopamine lost. Although patients generally receive benefits from this symptomatic pharmacological management, they also show great variability in drug response in terms of both efficacy and adverse effects. Pharmacogenetic studies highlighted that genetic factors play a relevant influence in this drug response variability. In this review, we tried to give an overview of the recent progresses in the pharmacogenetics of PD, reporting the major genetic factors identified as involved in the response to drugs and highlighting the potential use of some of these genomic variants in the clinical practice. Many genes have been investigated and several associations have been reported especially with adverse drug reactions. However, only polymorphisms in few genes, including DRD2, COMT and SLC6A3, have been confirmed as associated in different populations and in large cohorts. The identification of genomic biomarkers involved in drug response variability represents an important step in PD treatment, opening the prospective of more personalized therapies in order to identify, for each person, the better therapy in terms of efficacy and toxicity and to improve the PD patients' quality of life.

A possibilistic approach for transient identification with 'don't know' response capability optimized by genetic algorithm

International Nuclear Information System (INIS)

Almeida, Jose Carlos S. de; Schirru, Roberto; Pereira, Claudio M.N.A.; Universidade Federal, Rio de Janeiro, RJ

2002-01-01

This work describes a possibilistic approach for transient identification based on the minimum centroids set method, proposed in previous work, optimized by genetic algorithm. The idea behind this method is to split the complex classification problem into small and simple ones, so that the performance in the classification can be increased. In order to accomplish that, a genetic algorithm is used to learn, from realistic simulated data, the optimized time partitions, which the robustness and correctness in the classification are maximized. The use of a possibilistic classification approach propitiates natural and consistent classification rules, leading naturally to a good heuristic to handle the 'don't know 'response, in case of unrecognized transient, which is fairly desirable in transient classification systems where safety is critical. Application of the proposed approach to a nuclear transient indentification problem reveals good capability of the genetic algorithm in learning optimized possibilistic classification rules for efficient diagnosis including 'don't know' response. Obtained results are shown and commented. (author)

Delayed cell death, giant cell formation and chromosome instability induced by X-irradiation in human embryo cells

International Nuclear Information System (INIS)

Roy, K.; Kodama, Seiji; Suzuki, Keiji; Watanabe, Masami

1999-01-01

We studied X-ray-induced delayed cell death, delayed giant cell formation and delayed chromosome aberrations in normal human embryo cells to explore the relationship between initial radiation damage and delayed effect appeared at 14 to 55 population doubling numbers (PDNs) after X-irradiation. The delayed effect was induced in the progeny of X-ray survivors in a dose-dependent manner and recovered with increasing PDNs after X-irradiation. Delayed plating for 24 h post-irradiation reduced both acute and delayed lethal damage, suggesting that potentially lethal damage repair (PLDR) can be effective for relieving the delayed cell death. The chromosome analysis revealed that most of the dicentrics (more than 90%) observed in the progeny of X-ray survivors were not accompanied with fragments, in contrast with those observed in the first mitosis after X-irradiation. The present results indicate that the potentiality of genetic instability is determined during the repair process of initial radiation damage and suggest that the mechanism for formation of delayed chromosome aberrations by radiation might be different from that of direct radiation-induced chromosome aberrations. (author)

Analysis and improvement measures of flight delay in China

Science.gov (United States)

Zang, Yuhang

2017-03-01

Firstly, this paper establishes the principal component regression model to analyze the data quantitatively, based on principal component analysis to get the three principal component factors of flight delays. Then the least square method is used to analyze the factors and obtained the regression equation expression by substitution, and then found that the main reason for flight delays is airlines, followed by weather and traffic. Aiming at the above problems, this paper improves the controllable aspects of traffic flow control. For reasons of traffic flow control, an adaptive genetic queuing model is established for the runway terminal area. This paper, establish optimization method that fifteen planes landed simultaneously on the three runway based on Beijing capital international airport, comparing the results with the existing FCFS algorithm, the superiority of the model is proved.

Genetic variants in the apoptosis gene BCL2L1 improve response to interferon-based treatment of hepatitis C virus genotype 3 infection

DEFF Research Database (Denmark)

Clausen, Louise Nygaard; Weis, Nina; Ladelund, Steen

2015-01-01

Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon-α and ribav......Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon...

Construction delays causing risks on time and cost - a critical review

Directory of Open Access Journals (Sweden)

Chidambaram Ramanathan

2012-02-01

Full Text Available There is an increase in the number of construction projects experiencing extensive delays leading to exceeding initial time and cost budget.  This paper reviews 41 studies around the world which surveyed the delay factors and classified them into Groups.  The main purpose of this paper is to review literature, each of which have categorized the causes that are responsible for time delays and cost overrun in projects. The collected list has 113 causes for delays categorized in to 18 different groups.  Most of the researches have analysed the responses from the Questionnaire survey.    The collected data are used to rank the problem.  The data are further used to investigate and analyse Important Index, Frequency Index, Severity Index, Relative Important Index, Relative Importance Weight, Weighted Average, Mean, Standard Deviation and Variance.  The collective comparison has revealed that the ranking given by all the researchers is not the same.  Further each and every study has different rank ratings for the different group of the delays.  This review paper attempts to provide an updated compilation of the earlier studies on ranking of the delay causers, which are never similar and constant for universal projects.  It is concluded that a separate study is required for identifying the factors causing delay for projects operated in Sabah, East Malaysia.

Break-before-make CMOS inverter for power-efficient delay implementation.

Science.gov (United States)

Puhan, Janez; Raič, Dušan; Tuma, Tadej; Bűrmen, Árpád

2014-01-01

A modified static CMOS inverter with two inputs and two outputs is proposed to reduce short-circuit current in order to increment delay and reduce power overhead where slow operation is required. The circuit is based on bidirectional delay element connected in series with the PMOS and NMOS switching transistors. It provides differences in the dynamic response so that the direct-path current in the next stage is reduced. The switching transistors are never ON at the same time. Characteristics of various delay element implementations are presented and verified by circuit simulations. Global optimization procedure is used to obtain the most power-efficient transistor sizing. The performance of the modified CMOS inverter chain is compared to standard implementation for various delays. The energy (charge) per delay is reduced up to 40%. The use of the proposed delay element is demonstrated by implementing a low-power delay line and a leading-edge detector cell.

Task Difficulty Differentially Affects Two Measures of Processing Load: The Pupil Response during Sentence Processing and Delayed Cued Recall of the Sentences

Science.gov (United States)

Zekveld, Adriana A.; Festen, Joost M.; Kramer, Kramera

2013-01-01

Purpose: In this study, the authors assessed the influence of masking level (29% or 71% sentence perception) and test modality on the processing load during language perception as reflected by the pupil response. In addition, the authors administered a delayed cued stimulus recall test to examine whether processing load affected the encoding of…

Genetic determinants of heart failure: facts and numbers.

Science.gov (United States)

Czepluch, Frauke S; Wollnik, Bernd; Hasenfuß, Gerd

2018-06-01

The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so-called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next-generation sequencing - NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing. Due to this development, genetic testing has become increasingly accessible and NGS-based sequencing is now applied in clinical routine diagnostics. One of the most common reasons of heart failure are cardiomyopathies such as the dilated or the hypertrophic cardiomyopathy. Nearly 100 disease-associated genes have been identified for cardiomyopathies. The knowledge of a pathogenic mutation can be used for genetic counselling, risk and prognosis determination, therapy guidance and hence for a more effective treatment. Besides, family cascade screening for a known familial, pathogenic mutation can lead to an early diagnosis in affected individuals. At that timepoint, a preventative intervention could be used to avoid or delay disease onset or delay disease progression. Understanding the cellular basis of genetic heart failure syndromes in more detail may provide new insights into the molecular biology of physiological and impaired cardiac (cell) function. As our understanding of the molecular and genetic pathophysiology of heart failure will increase, this might help to identify novel therapeutic targets and may lead to the development of new and specific treatment options in patients with heart failure. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European

Interaural delay sensitivity and the classification of low best-frequency binaural responses in the inferior colliculus of the guinea pig.

Science.gov (United States)

McAlpine, D; Jiang, D; Palmer, A R

1996-08-01

Monaural and binaural response properties of single units in the inferior colliculus (IC) of the guinea pig were investigated. Neurones were classified according to the effect of monaural stimulation of either ear alone and the effect of binaural stimulation. The majority (309/334) of IC units were excited (E) by stimulation of the contralateral ear, of which 41% (127/309) were also excited by monaural ipsilateral stimulation (EE), and the remainder (182/309) were unresponsive to monaural ipsilateral stimulation (EO). For units with best frequencies (BF) up to 3 kHz, similar proportions of EE and EO units were observed. Above 3 kHz, however, significantly more EO than EE units were observed. Units were also classified as either facilitated (F), suppressed (S), or unaffected (O) by binaural stimulation. More EO than EE units were suppressed or unaffected by binaural stimulation, and more EE than EO units were facilitated. There were more EO/S units above 1.5 kHz than below. Binaural beats were used to examine the interaural delay sensitivity of low-BF (BF binaural facilitation, whilst those with larger BPs generally showed binaural suppression. The classification of units based upon binaural stimulation with BF tones was consistent with their interaural-delay sensitivity. Characteristic delays (CD) were examined for 96 low-BF units. A clear relationship between BF and CD was observed. CDs of units with very low BFs (binaural processing in the guinea pig at low frequencies is similar to that reported in all other species studied. However, the dependence of CD on BF would suggest that the delay line system that sets up the interaural-delay sensitivity in the lower brainstem varies across frequency as well as within each frequency band.

Use of physiological and genetic algal tests for the hygienic evaluation of pollutants in waters. Part I

International Nuclear Information System (INIS)

Havlik, B.; Necas, J.

1981-01-01

After exposure for several days of intensively growing algal cultures to a radium concentration of 10 -6 g.l -1 the physiological and genetic responses of Chlorella kessleri and Scenedesmus obliquus cells could clearly be demonstrated. Of physiological characteristics, the frequency of cells with a reduced number of autospores, the length of the lag phase and cell survival were recorded. Of genetic responses, the frequencies of delayed lethal and sublethal effects, the frequencies of minute colonies, colonies with big cells and scabby colonies, and the frequencies of pigmentation changes were followed. The above concentration produced no toxic effect. No clear-cut correlation was found between the responses recorded and the amount of accumulated radium in algal cells. For the interpretation of the mutagenic effect a homogeneous irradiation of the mixed cell suspension had to be assumed. The participation of repair systems of algae with regard to their survival or manifestation of mutagenic changes in individuals in which mutagenesis had been induced had also to be taken into consideration. (author)

Topological Acoustic Delay Line

Science.gov (United States)

Zhang, Zhiwang; Tian, Ye; Cheng, Ying; Wei, Qi; Liu, Xiaojun; Christensen, Johan

2018-03-01

Topological protected wave engineering in artificially structured media is at the frontier of ongoing metamaterials research that is inspired by quantum mechanics. Acoustic analogues of electronic topological insulators have recently led to a wealth of new opportunities in manipulating sound propagation with strikingly unconventional acoustic edge modes immune to backscattering. Earlier fabrications of topological insulators are characterized by an unreconfigurable geometry and a very narrow frequency response, which severely hinders the exploration and design of useful devices. Here we establish topologically protected sound in reconfigurable phononic crystals that can be switched on and off simply by rotating its three-legged "atoms" without altering the lattice structure. In particular, we engineer robust phase delay defects that take advantage of the ultrabroadband reflection-free sound propagation. Such topological delay lines serve as a paradigm in compact acoustic devices, interconnects, and electroacoustic integrated circuits.

TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

Directory of Open Access Journals (Sweden)

Lee Adam Wheeler

2016-05-01

Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to autoantigens in mice.

Directory of Open Access Journals (Sweden)

Rajwahrdhan Yadav

2010-08-01

Full Text Available Pertussis toxin (PTX, an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU and experimental autoimmune encephalomyelitis (EAE in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens.We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180, encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55 or ovalbumin (OVA. PTX injection of mice immunized to IRBP peptide161-180 led to (i the development of EAU as shown by histopathology of the retina, (ii pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA.The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are diverted away from ectopic sites that received the autoantigen and towards

Effects of delayed nonlinear response on wave packet dynamics in one-dimensional generalized Fibonacci chains

International Nuclear Information System (INIS)

Zhang, Jianxin; Zhang, Zhenjun; Tong, Peiqing

2013-01-01

We investigate the spreading of an initially localized wave packet in one-dimensional generalized Fibonacci (GF) lattices by solving numerically the discrete nonlinear Schrödinger equation (DNLSE) with a delayed cubic nonlinear term. It is found that for short delay time, the wave packet is self-trapping in first class of GF lattices, that is, the second moment grows with time, but the corresponding participation number does not grow. However, both the second moment and the participation number grow with time for large delay time. This illuminates that the wave packet is delocalized. For the second class of GF lattices, the dynamic behaviors of wave packet depend on the strength of on-site potential. For a weak on-site potential, the results are similar to the case of the first class. For a strong on-site potential, both the second moment and the participation number does not grow with time in the regime of short delay time. In the regime of large delay time, both the second moment and the participation number exhibit stair-like growth

Effects of delayed nonlinear response on wave packet dynamics in one-dimensional generalized Fibonacci chains

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jianxin; Zhang, Zhenjun [Department of Physics and Institute of Theoretical Physics, Nanjing Normal University, Nanjing 210023 (China); Tong, Peiqing, E-mail: pqtong@njnu.edu.cn [Department of Physics and Institute of Theoretical Physics, Nanjing Normal University, Nanjing 210023 (China); Jiangsu Key Laboratory for Numerical Simulation of Large Scale Complex Systems, Nanjing Normal University, Nanjing 210023 (China)

2013-07-15

We investigate the spreading of an initially localized wave packet in one-dimensional generalized Fibonacci (GF) lattices by solving numerically the discrete nonlinear Schrödinger equation (DNLSE) with a delayed cubic nonlinear term. It is found that for short delay time, the wave packet is self-trapping in first class of GF lattices, that is, the second moment grows with time, but the corresponding participation number does not grow. However, both the second moment and the participation number grow with time for large delay time. This illuminates that the wave packet is delocalized. For the second class of GF lattices, the dynamic behaviors of wave packet depend on the strength of on-site potential. For a weak on-site potential, the results are similar to the case of the first class. For a strong on-site potential, both the second moment and the participation number does not grow with time in the regime of short delay time. In the regime of large delay time, both the second moment and the participation number exhibit stair-like growth.

Preliminary evidence for genetic overlap between body mass index and striatal reward response.

Science.gov (United States)

Lancaster, T M; Ihssen, I; Brindley, L M; Linden, D E

2018-01-10

The reward-processing network is implicated in the aetiology of obesity. Several lines of evidence suggest obesity-linked genetic risk loci (such as DRD2 and FTO) may influence individual variation in body mass index (BMI) through neuropsychological processes reflected in alterations in activation of the striatum during reward processing. However, no study has tested the broader hypotheses that (a) the relationship between BMI and reward-related brain activation (measured through the blood oxygenation-dependent (BOLD) signal) may be observed in a large population study and (b) the overall genetic architecture of these phenotypes overlap, an assumption critical for the progression of imaging genetic studies in obesity research. Using data from the Human Connectome Project (N = 1055 healthy, young individuals: average BMI = 26.4), we first establish a phenotypic relationship between BMI and ventral striatal (VS) BOLD during the processing of rewarding (monetary) stimuli (β = 0.44, P = 0.013), accounting for potential confounds. BMI and VS BOLD were both significantly influenced by additive genetic factors (H2r = 0.57; 0.12, respectively). Further decomposition of this variance suggested that the relationship was driven by shared genetic (ρ g  = 0.47, P = 0.011), but not environmental (ρ E  = -0.07, P = 0.29) factors. To validate the assumption of genetic pleiotropy between BMI and VS BOLD, we further show that polygenic risk for higher BMI is also associated with increased VS BOLD response to appetitive stimuli (calorically high food images), in an independent sample (N = 81; P FWE-ROI  < 0.005). Together, these observations suggest that the genetic factors link risk to obesity to alterations within key nodes of the brain's reward circuity. These observations provide a basis for future work exploring the mechanistic role of genetic loci that confer risk for obesity using the imaging genetics approach.

A hybrid niched-island genetic algorithm applied to a nuclear core optimization problem

International Nuclear Information System (INIS)

Pereira, Claudio M.N.A.

2005-01-01

Diversity maintenance is a key-feature in most genetic-based optimization processes. The quest for such characteristic, has been motivating improvements in the original genetic algorithm (GA). The use of multiple populations (called islands) has demonstrating to increase diversity, delaying the genetic drift. Island Genetic Algorithms (IGA) lead to better results, however, the drift is only delayed, but not avoided. An important advantage of this approach is the simplicity and efficiency for parallel processing. Diversity can also be improved by the use of niching techniques. Niched Genetic Algorithms (NGA) are able to avoid the genetic drift, by containing evolution in niches of a single-population GA, however computational cost is increased. In this work it is investigated the use of a hybrid Niched-Island Genetic Algorithm (NIGA) in a nuclear core optimization problem found in literature. Computational experiments demonstrate that it is possible to take advantage of both, performance enhancement due to the parallelism and drift avoidance due to the use of niches. Comparative results shown that the proposed NIGA demonstrated to be more efficient and robust than an IGA and a NGA for solving the proposed optimization problem. (author)

Delays in using chromatic and luminance information to correct rapid reaches.

Science.gov (United States)

Kane, Adam; Wade, Alex; Ma-Wyatt, Anna

2011-09-07

People can use feedback to make online corrections to movements but only if there is sufficient time to integrate the new information and make the correction. A key variable in this process is therefore the speed at which the new information about the target location is coded. Conduction velocities for chromatic signals are lower than for achromatic signals so it may take longer to correct reaches to chromatic stimuli. In addition to this delay, the sensorimotor system may prefer achromatic information over the chromatic information as delayed information may be less valuable when movements are made under time pressure. A down-weighting of chromatic information may result in additional latencies for chromatically directed reaches. In our study, participants made online corrections to reaches to achromatic, (L-M)-cone, and S-cone stimuli. Our chromatic stimuli were carefully adjusted to minimize stimulation of achromatic pathways, and we equated stimuli both in terms of detection thresholds and also by their estimated neural responses. Similar stimuli were used throughout the subjective adjustments and final reaching experiment. Using this paradigm, we found that responses to achromatic stimuli were only slightly faster than responses to (L-M)-cone and S-cone stimuli. We conclude that the sensorimotor system treats chromatic and achromatic information similarly and that the delayed chromatic responses primarily reflect early conduction delays.

Dynamics of electron wave packet in a disordered chain with delayed nonlinear response

International Nuclear Information System (INIS)

Zhu Hongjun; Xiong Shijie

2010-01-01

We investigate the dynamics of one electron wave packet in a linear chain with random on-site energies and a nonadiabatic electron-phonon interaction which is described by a delayed cubic nonlinear term in the time-dependent Schroedinger equation. We show that in the regime where the wave packet is delocalized in the case with only the delayed nonlinearity, the wave packet becomes localized when the disorder is added and the localization is enhanced by increasing the disorder. In the regime where the self-trapping phenomenon occurs in the case with only the delayed nonlinearity, by adding the disorder the general dynamical features of the wave packet do not change if the nonlinearity parameter is small, but the dynamics shows the subdiffusive behavior if the nonlinearity parameter is large. The numerical results demonstrate complicated wave packet dynamics of systems with both the disorder and nonlinearity.

Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity ...

African Journals Online (AJOL)

Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity Reaction and Cellular Immune Responses. ... The tuberculin skin test (TST) and peripheral blood mono-nuclear cells (PBMCs) culture were conducted using PPD. The cytokines were measured using commercial kits. Results: The mean TST was 24.6 ±8.0 ...

Stability and delay sensitivity of neutral fractional-delay systems.

Science.gov (United States)

Xu, Qi; Shi, Min; Wang, Zaihua

2016-08-01

This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

Bone response to fluoride exposure is influenced by genetics.

Directory of Open Access Journals (Sweden)

Cláudia A N Kobayashi

Full Text Available Genetic factors influence the effects of fluoride (F on amelogenesis and bone homeostasis but the underlying molecular mechanisms remain undefined. A label-free proteomics approach was employed to identify and evaluate changes in bone protein expression in two mouse strains having different susceptibilities to develop dental fluorosis and to alter bone quality. In vivo bone formation and histomorphometry after F intake were also evaluated and related to the proteome. Resistant 129P3/J and susceptible A/J mice were assigned to three groups given low-F food and water containing 0, 10 or 50 ppmF for 8 weeks. Plasma was evaluated for alkaline phosphatase activity. Femurs, tibiae and lumbar vertebrae were evaluated using micro-CT analysis and mineral apposition rate (MAR was measured in cortical bone. For quantitative proteomic analysis, bone proteins were extracted and analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS, followed by label-free semi-quantitative differential expression analysis. Alterations in several bone proteins were found among the F treatment groups within each mouse strain and between the strains for each F treatment group (ratio ≥1.5 or ≤0.5; p<0.05. Although F treatment had no significant effects on BMD or bone histomorphometry in either strain, MAR was higher in the 50 ppmF 129P3/J mice than in the 50 ppmF A/J mice treated with 50 ppmF showing that F increased bone formation in a strain-specific manner. Also, F exposure was associated with dose-specific and strain-specific alterations in expression of proteins involved in osteogenesis and osteoclastogenesis. In conclusion, our findings confirm a genetic influence in bone response to F exposure and point to several proteins that may act as targets for the differential F responses in this tissue.

Chemosensory responsiveness to ethanol and its individual sensory components in alcohol-preferring, -nonpreferring and genetically heterogeneous rats

Science.gov (United States)

Brasser, Susan M.; Silbaugh, Bryant C.; Ketchum, Myles J.; Olney, Jeffrey J.; Lemon, Christian H.

2011-01-01

Alcohol activates orosensory circuits that project to motivationally relevant limbic forebrain areas that control appetite, feeding and drinking. To date, limited data exists regarding the contribution of chemosensory-derived ethanol reinforcement to ethanol preference and consumption. Measures of taste reactivity to intra-orally infused ethanol have not found differences in initial orofacial responses to alcohol between alcohol-preferring (P) and – nonpreferring (NP) genetically selected rat lines. Yet, in voluntary intake tests P rats prefer highly-concentrated ethanol upon initial exposure, suggesting an early sensory-mediated attraction. Here, we directly compared self-initiated chemosensory responding for alcohol and prototypic sweet, bitter, and oral trigeminal stimuli among selectively bred P, NP, and non-selected Wistar (WI) outbred lines to determine whether differential sensory responsiveness to ethanol and its putative sensory components are phenotypically associated with genetically-influenced alcohol preference. Rats were tested for immediate short-term lick responses to alcohol (3–40%), sucrose (0.01–1 M), quinine (0.01–3 mM) and capsaicin (0.003–1 mM) in a brief-access assay designed to index orosensory-guided behavior. P rats exhibited elevated short-term lick responses to both alcohol and sucrose relative to NP and WI lines across a broad range of concentrations of each stimulus and in the absence of blood alcohol levels that would produce significant postabsorptive effects. There was no consistent relationship between genetically-mediated alcohol preference and orosensory avoidance of quinine or capsaicin. These data indicate that enhanced initial chemosensory attraction to ethanol and sweet stimuli are phenotypes associated with genetic alcohol preference and are considered within the framework of downstream activation of oral appetitive reward circuits. PMID:22129513

Estimation of nonlinearities from pseudodynamic and dynamic responses of bridge structures using the Delay Vector Variance method

Science.gov (United States)

Jaksic, Vesna; Mandic, Danilo P.; Karoumi, Raid; Basu, Bidroha; Pakrashi, Vikram

2016-01-01

Analysis of the variability in the responses of large structural systems and quantification of their linearity or nonlinearity as a potential non-invasive means of structural system assessment from output-only condition remains a challenging problem. In this study, the Delay Vector Variance (DVV) method is used for full scale testing of both pseudo-dynamic and dynamic responses of two bridges, in order to study the degree of nonlinearity of their measured response signals. The DVV detects the presence of determinism and nonlinearity in a time series and is based upon the examination of local predictability of a signal. The pseudo-dynamic data is obtained from a concrete bridge during repair while the dynamic data is obtained from a steel railway bridge traversed by a train. We show that DVV is promising as a marker in establishing the degree to which a change in the signal nonlinearity reflects the change in the real behaviour of a structure. It is also useful in establishing the sensitivity of instruments or sensors deployed to monitor such changes.

Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: functional and mechanistic implications.

Directory of Open Access Journals (Sweden)

Aaron R Wolen

Full Text Available Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain across a highly diverse family of 27 isogenic mouse strains (BXD panel before and after treatment with ethanol.Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2.The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol

Delayed child-bearing.

Science.gov (United States)

Johnson, Jo-Ann; Tough, Suzanne

2012-01-01

compensate for age-related decline in fertility. (II-2A) 2. A fertility evaluation should be initiated after 6 months of unprotected intercourse without conception in women 35 to 37 years of age, and earlier in women > 37 years of age. (II-2A) 3. Prospective parents should be informed that semen quality and male fertility deteriorate with advancing age and that the risk of genetic disorders in offspring increases. (II-2A) 4. Women ≥ 35 years of age should be offered screening for fetal aneuploidy and undergo a detailed second trimester ultrasound examination to look for significant fetal birth defects (particularly cardiac defects). (II-1A) 5. Delayed child-bearing is associated with increased obstetrical and perinatal complications. Care providers need to be aware of these complications and adjust obstetrical management protocols to ensure optimal maternal and perinatal outcomes. (II-2A) 6. All adults of reproductive age should be aware of the obstetrical and perinatal risks of advanced maternal age so they can make informed decisions about the timing of child-bearing. (II-2A) 7. Strategies to improve informed decision-making by prospective parents should be designed, implemented, and evaluated. These strategies should provide opportunity for adults to understand the potential medical, social, and economic consequences of child-bearing throughout the reproductive years. (III-B) 8. Barriers to healthy reproduction, including workplace policies, should be reviewed to optimize the likelihood of healthy pregnancies. (III-C).

Optimization of broadband semiconductor chirped mirrors with genetic algorithm

OpenAIRE

Dems, M.; Wnuk, P.; Wasylczyk, P.; Zinkiewicz, L.; Wojcik-Jedlinska, A.; Reginski, K.; Hejduk, K.; Jasik, A.

2016-01-01

Genetic algorithm was applied for optimization of dispersion properties in semiconductor Bragg reflectors for applications in femtosecond lasers. Broadband, large negative group-delay dispersion was achieved in the optimized design: The group-delay dispersion (GDD) as large as −3500 fs2 was theoretically obtained over a 10-nm bandwidth. The designed structure was manufactured and tested, providing GDD −3320 fs2 over a 7-nm bandwidth. The mirror performance was ...

Persistent Memory in Single Node Delay-Coupled Reservoir Computing.

Science.gov (United States)

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.

Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases.

Science.gov (United States)

Zhou, Yan; Proudnikov, Dmitri; Yuferov, Vadim; Kreek, Mary Jeanne

2010-02-16

From the earliest work in our laboratory, we hypothesized, and with studies conducted in both clinical research and animal models, we have shown that drugs of abuse, administered or self-administered, on a chronic basis, profoundly alter stress-responsive systems. Alterations of expression of specific genes involved in stress responsivity, with increases or decreases in mRNA levels, receptor, and neuropeptide levels, and resultant changes in hormone levels, have been documented to occur after chronic intermittent exposure to heroin, morphine, other opiates, cocaine, other stimulants, and alcohol in animal models and in human molecular genetics. The best studied of the stress-responsive systems in humans and mammalian species in general is undoubtedly the HPA axis. In addition, there are stress-responsive systems in other parts in the brain itself, and some of these include components of the HPA axis, such as CRF and CRF receptors, along with POMC gene and gene products. Several other stress-responsive systems are known to influence the HPA axis, such as the vasopressin-vasopressin receptor system. Orexin-hypocretin, acting at its receptors, may effect changes which suggest that it should be properly categorized as a stress-responsive system. However, less is known about the interactions and connectivity of some of these different neuropeptide and receptor systems, and in particular, about the possible connectivity of fast-acting (e.g., glutamate and GABA) and slow-acting (including dopamine, serotonin, and norepinephrine) neurotransmitters with each of these stress-responsive components and the resultant impact, especially in the setting of chronic exposure to drugs of abuse. Several of these stress-responsive systems and components, primarily based on our laboratory-based and human molecular genetics research of addictive diseases, will be briefly discussed in this review. Copyright 2009 Elsevier B.V. All rights reserved.

Measuring and Modelling Delays in Robot Manipulators for Temporally Precise Control using Machine Learning

DEFF Research Database (Denmark)

Andersen, Thomas Timm; Amor, Heni Ben; Andersen, Nils Axel

2015-01-01

and separate. In this paper, we present a data-driven methodology for separating and modelling inherent delays during robot control. We show how both actuation and response delays can be modelled using modern machine learning methods. The resulting models can be used to predict the delays as well...

Ranking of Delay Factors for Makkah’s Construction Industry

Directory of Open Access Journals (Sweden)

Al-Emad Nashwan

2017-01-01

Full Text Available This paper presents identification of significant delay factors encountered by Makkah’s construction industry using quantitative approach. A structured questionnaire developed based on literature review was verified through pilot study involved selected construction experts. Questionnaire survey was conducted amongst Makkah construction practitioners include contractors, consultants and project management consultancy. The survey managed to collect 100 valid responses which were used to rank the factors using average index approach. Results of the analysis for 10 most significant factors causing construction delay in Makkah construction industry are Difficulties in financing project by contractor, Poor coordination between parties, Shortage of manpower, Delays in producing design documents, Improper planning and scheduling of the project, Delay in progress payments, Low productivity level of labour, Poor communication between parties, Unqualified workforce and Poor contract management. This finding is helpful to Makkah construction’s community particularly projects’ stakeholders in avoiding potential delay for their future projects.

In search of genetic constraints limiting the evolution of egg size: direct and correlated responses to artificial selection on a prenatal maternal effector.

Science.gov (United States)

Pick, J L; Hutter, P; Tschirren, B

2016-06-01

Maternal effects are an important force in nature, but the evolutionary dynamics of the traits that cause them are not well understood. Egg size is known to be a key mediator of prenatal maternal effects with an established genetic basis. In contrast to theoretical expectations for fitness-related traits, there is a large amount of additive genetic variation in egg size observed in natural populations. One possible mechanism for the maintenance of this variation is through genetic constraints caused by a shared genetic basis among traits. Here we created replicated, divergent selection lines for maternal egg investment in Japanese quail (Coturnix japonica) to quantify the role of genetic constraints in the evolution of egg size. We found that egg size responds rapidly to selection, accompanied by a strong response in all egg components. Initially, we observed a correlated response in body size, but this response declined over time, showing that egg size and body size can evolve independently. Furthermore, no correlated response in fecundity (measured as the proportion of days on which a female laid an egg) was observed. However, the response to selection was asymmetrical, with egg size plateauing after one generation of selection in the high but not the low investment lines. We attribute this pattern to the presence of genetic asymmetries, caused by directional dominance or unequal allele frequencies. Such asymmetries may contribute to the evolutionary stasis in egg size observed in natural populations, despite a positive association between egg size and fitness.

Dose response behaviour of water scarcity towards genetical and morphological traits in spring wheat

International Nuclear Information System (INIS)

Noorkha, I.R.; Tabasum, S.

2015-01-01

Combining ability was studied in a Line * Tester mating fashion in wheat (Tricticum aestivum L.). Significant differences were observed for all the yield and yield contributing traits. GCA and SCA components of variation were found significant for most of the traits. Under water stressed conditions among lines the genotype Kohistan-97 revealed significant GCA effects for all the traits except spike length. Among testers, the genotype V08172 showed significant effects for the traits spike length, 1000-grain weight and flag leaf area. Based on desirable SCA effects and mean performance the cross combinations Kohistan-97 * V08172, Chakwal-86 * Punjab-81, Fsd-2008 * Punjab-81, Sehar-2006 * V08172 and Chakwal-86 * V08172 behaved best combiner to tolerate the water stress. Results of genetic analysis offered over dominance type of gene action that remained unchanged with the change in water provision for the traits like 1000 grain weight and economic yield. Similarly additive gene action was observed for the trait plant height under both normal irrigation and water stress conditions. However the cumulative genetic effects to control the expression of yield and yield components was shifted due to the changed environments. The study was concluded that due to presence of additive variance, selection could be practiced in early generation whereas in the presence of recessiveness the selection may be delayed up to the later generations. Plant traits associated with water stress tolerance having high heritability and with additive gene action may be used as indirect selection criteria for early selection of water stress tolerant genotypes. The information generated as a result of this study on genetic analysis of important economic traits of wheat under contrasting water availability positions will be of great value to the wheat breeders to design future breeding programmes. (author)

Genetic disorders of thyroid metabolism and brain development

Science.gov (United States)

Kurian, Manju A; Jungbluth, Heinz

2014-01-01

Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

Behavioral genetics and criminal responsibility at the courtroom.

Science.gov (United States)

Tatarelli, Roberto; Del Casale, Antonio; Tatarelli, Caterina; Serata, Daniele; Rapinesi, Chiara; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

2014-04-01

Several questions arise from the recent use of behavioral genetic research data in the courtroom. Ethical issues concerning the influence of biological factors on human free will, must be considered when specific gene patterns are advocated to constrain court's judgment, especially regarding violent crimes. Aggression genetics studies are both difficult to interpret and inconsistent, hence, in the absence of a psychiatric diagnosis, genetic data are currently difficult to prioritize in the courtroom. The judge's probabilistic considerations in formulating a sentence must take into account causality, and the latter cannot be currently ensured by genetic data. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Array CGH Analysis and Developmental Delay: A Diagnostic Tool for Neurologists.

Science.gov (United States)

Cameron, F; Xu, J; Jung, J; Prasad, C

2013-11-01

Developmental delay occurs in 1-3% of the population, with unknown etiology in approximately 50% of cases. Initial genetic work up for developmental delay previously included chromosome analysis and subtelomeric FISH (fluorescent in situ hybridization). Array Comparative Genomic Hybridization (aCGH) has emerged as a tool to detect genetic copy number changes and uniparental disomy and is the most sensitive test in providing etiological diagnosis in developmental delay. aCGH allows for the provision of prognosis and recurrence risks, improves access to resources, helps limit further investigations and may alter medical management in many cases. aCGH has led to the delineation of novel genetic syndromes associated with developmental delay. An illustrative case of a 31-year-old man with long standing global developmental delay and recently diagnosed 4q21 deletion syndrome with a deletion of 20.8 Mb genomic interval is provided. aCGH is now recommended as a first line test in children and adults with undiagnosed developmental delay and congenital anomalies. Puce d'hybridation génomique comparative et retard de développement : un outil diagnostic pour les neurologues. Le retard de développement survient chez 1 à 3% de la population et son étiologie est inconnue chez à peu près 50% des cas. L'évaluation génétique initiale pour un retard de développement incluait antérieurement une analyse chromosomique et une analyse par FISH (hybridation in situ en fluorescence) de régions subtélomériques. La puce d'hybridation génomique comparative (CGHa) est devenue un outil de détection des changements du nombre de copies géniques ainsi que de la disomie uniparentale et elle est le test le plus sensible pour fournir un diagnostic étiologique dans le retard de développement. Le CGHa permet d'offrir un pronostic et un risque de récurrence, améliore l'accès aux ressources, aide à limiter les évaluations et peut modifier le traitement médical dans bien des cas

Echocardiographic estimation of acute haemodynamic response during optimization of multisite pace-maker using different pacing modalities and atrioventricular delays

Directory of Open Access Journals (Sweden)

Šalinger-Martinović Sonja

2009-01-01

Full Text Available Background/Aim. Cardiac resynchronization therapy (CRT improves ventricular dyssynchrony and is associated with an improvement in symptoms, quality of life and prognosis in patients with severe heart failure and intraventricular conduction delay. Different pacing modalities produce variable activation patterns and may be a cause of different haemodynamic changes. The aim of our study was to investigate acute haemodynamic changes with different CRT configurations during optimization procedure. Methods. This study included 30 patients with severe left ventricular systolic dysfunction and left bundle branch block with wide QRS (EF 24.33 ± 3.7%, QRS 159 ± 17.3 ms, New York Heart Association III/IV 25/5 with implanted CRT device. The whole group of patients had severe mitral regurgitation in order to measure dP/dt. After implantation and before discharge all the patients underwent optimization procedure guided by Doppler echocardiography. Left and right ventricular pre-ejection intervals (LVPEI and RVPEI, interventricular mechanical delay (IVD and the maximal rate of ventricular pressure rise during early systole (max dP/dt were measured during left and biventricular pacing with three different atrioventricular (AV delays. Results. After CRT device optimization, optimal AV delay and CRT mode were defined. Left ventricular pre-ejection intervals changed from 170.5 ± 24.6 to 145.9 ± 9.5 (p < 0.001, RVPEI from 102.4 ± 15.9 to 119.8 ± 10.9 (p < 0.001, IVD from 68.1 ± 18.3 to 26.5 ± 8.2 (p < 0.001 and dP/dt from 524.2 ± 67 to 678.2 ± 88.5 (p < 0.01. Conclusion. In patients receiving CRT echocardiographic assessment of the acute haemodynamic response to CRT is a useful tool in optimization procedure. The variability of Doppler parameters with different CRT modalities emphasizes the necessity of individualized approach in optimization procedure.

Third delay of maternal mortality in a tertiary hospital

International Nuclear Information System (INIS)

Shah, N.; Khan, N.H.

2007-01-01

To assess the magnitude, causes and substandard care factors responsible for the third delay of maternal mortality seen in our unit III, Department of Obstetrics and Gynecology, Civil Hospital, Karachi. This Cross-sectional, retrospective study was carried out on 152 mothers who died over a period of eight years from 1997 to 2004 at Civil Hospital Karachi. Death summaries of all maternal deaths were reviewed from death registers and were studied for substandard care factors which could have been responsible for the third delay of maternal mortality. The frequency of maternal mortality was 1.3 per 100 deliveries. The mean age was 29+-6.49 years and mean parity was 3.24+-3.25. The main causes of death were hypertensive disorders in 52/152 (34.21%), hemorrhage in 40/152 (26.31%), unsafe abortion in 16/152 (10.52%), puerperal sepsis in 14/152 (9.21%) and obstructed labor in 11/152 (7.2%) cases. Substandard care factors were present in 76.7% of patients, which included inappropriate management of pulmonary edema, delay in arranging blood for hemorrhaging patients and delay in surgical intervention. Substandard care factors were present in majority of cases of maternal deaths. Improvement of maternity care services in Civil Hospital Karachi is needed on an urgent basis. (author)

Molecular genetics of growth hormone deficient children: correlation with auxology and response to first year of growth hormone therapy.

Science.gov (United States)

Khadilkar, Vaman; Phadke, Nikhil; Khatod, Kavita; Ekbote, Veena; Gupte, Supriya Phanse; Nadar, Ruchi; Khadilkar, Anuradha

2017-05-24

With the paucity of available literature correlating genetic mutation and response to treatment, we aimed to study the genetic makeup of children with growth hormone (GH) deficiency in Western India and correlate the mutation with auxology and response to GH treatment at end of 1 year. Fifty-three (31 boys and 22 girls) children with severe short stature (height for age z-score imaging (MRI) brain scan was done in all. Genetic mutations were tested for in GH1, GHRH, LHX3, LHX4 and PROP1, POU1F1 and HESX1 genes. Mean age at presentation was 9.7±5.1 years. Thirty-seven children (Group A) had no genetic mutation detected. Six children (Group B) had mutations in the GH releasing hormone receptor (GHRHR) gene, while eight children (Group C) had mutation in the GH1 gene. In two children, one each had a mutation in PROP1 and LHX3. There was no statistically significant difference in baseline height, weight and BMI for age z-score and height velocity for age z-score (HVZ). HVZ was significantly lower, post 1 year GH treatment in the group with homozygous GH1 deletion than in children with no genetic defect. Response to GH at the end of 1 year was poor in children with the homozygous GH1 deletion as compared to those with GHRHR mutation or without a known mutation.

The role for decorin in delayed-type hypersensitivity

Science.gov (United States)

Seidler, Daniela G.; Mohamed, Negia A.; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V.; Zarbock, Alexander; Götte, Martin

2016-01-01

Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling and cell growth. As decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity, DTH) in decorin-deficient (Dcn−/−) and wild-type mice. Dcn−/− mice showed a reduced ear swelling 24 hours after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism as determined by 18FDG uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn−/− blood vessels were significantly increased, accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy, flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn−/− leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn−/− mice 24 hours after DTH elicitation, but only moderately increased in wild-type mice. Expression of the pro-inflammatory cytokine TNF-α was reduced, while syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn−/− mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn−/− mice. Collectively, these results implicate a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two non-mutually exclusive mechanisms that involve a direct anti-adhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID:22043007

Delayed diagnosis of a patient with Usher syndrome 1C in a Louisiana Acadian family highlights the necessity of timely genetic testing for the diagnosis and management of congenital hearing loss.

Science.gov (United States)

Umrigar, Ayesha; Musso, Amanda; Mercer, Danielle; Hurley, Annette; Glausier, Cassondra; Bakeer, Mona; Marble, Michael; Hicks, Chindo; Tsien, Fern

2017-01-01

Advances in sequencing technologies and increased understanding of the contribution of genetics to congenital sensorineural hearing loss have led to vastly improved outcomes for patients and their families. Next-generation sequencing and diagnostic panels have become increasingly reliable and less expensive for clinical use. Despite these developments, the diagnosis of genetic sensorineural hearing loss still presents challenges for healthcare providers. Inherited sensorineural hearing loss has high levels of genetic heterogeneity and variable expressivity. Additionally, syndromic hearing loss (hearing loss and additional clinical abnormalities) should be distinguished from non-syndromic (hearing loss is the only clinical symptom). Although the diagnosis of genetic sensorineural hearing loss can be challenging, the patient's family history and ethnicity may provide critical information, as certain genetic mutations are more common in specific ethnic populations. The early identification of the cause of deafness can benefit patients and their families by estimating recurrence risks for future family planning and offering the proper interventions to improve their quality of life. Collaboration between pediatricians, audiologists, otolaryngologists, geneticists, and other specialists are essential in the diagnosis and management of patients with hearing disorders. An early diagnosis is vital for proper management and care, as some clinical manifestations of syndromic sensorineural hearing loss are not apparent at birth and have a delayed age of onset. We present a case of Usher syndrome (congenital deafness and childhood-onset blindness) illustrating the challenges encountered in the diagnosis and management of children presenting with congenital genetic sensorineural hearing loss, along with helpful resources for clinicians and families.

A Cucker--Smale Model with Noise and Delay

KAUST Repository

Erban, Radek

2016-08-09

A generalization of the Cucker-Smale model for collective animal behavior is investigated. The model is formulated as a system of delayed stochastic differential equations. It incorporates two additional processes which are present in animal decision making, but are often neglected in modeling: (i) stochasticity (imperfections) of individual behavior and (ii) delayed responses of individuals to signals in their environment. Sufficient conditions for flocking for the generalized Cucker-Smale model are derived by using a suitable Lyapunov functional. As a by-product, a new result regarding the asymptotic behavior of delayed geometric Brownian motion is obtained. In the second part of the paper, results of systematic numerical simulations are presented. They not only illustrate the analytical results, but hint at a somehow surprising behavior

A Cucker--Smale Model with Noise and Delay

KAUST Repository

Erban, Radek; Haskovec, Jan; Sun, Yongzheng

2016-01-01

A generalization of the Cucker-Smale model for collective animal behavior is investigated. The model is formulated as a system of delayed stochastic differential equations. It incorporates two additional processes which are present in animal decision making, but are often neglected in modeling: (i) stochasticity (imperfections) of individual behavior and (ii) delayed responses of individuals to signals in their environment. Sufficient conditions for flocking for the generalized Cucker-Smale model are derived by using a suitable Lyapunov functional. As a by-product, a new result regarding the asymptotic behavior of delayed geometric Brownian motion is obtained. In the second part of the paper, results of systematic numerical simulations are presented. They not only illustrate the analytical results, but hint at a somehow surprising behavior

Delayed Face Recognition in Children and Adolescents with Autism Spectrum Disorders

Directory of Open Access Journals (Sweden)

Zahra Shahrivar

2012-06-01

Full Text Available Objective: Children with autism spectrum disorders (ASDs have great problems in social interactions including face recognition. There are many studies reporting deficits in face memory in individuals with ASDs. On the other hand, some studies indicate that this kind of memory is intact in this group. In the present study, delayed face recognition has been investigated in children and adolescents with ASDs compared to the age and sex matched typically developing group.Methods: In two sessions, Benton Facial Recognition Test was administered to 15 children and adolescents with ASDs (high functioning autism and Asperger syndrome and to 15 normal participants, ages 8-17 years. In the first condition, the long form of Benton Facial Recognition Test was used without any delay. In the second session, this test was administered with 15 seconds delay after one week. The reaction times and correct responses were measured in both conditions as the dependent variables.Results: Comparison of the reaction times and correct responses in the two groups revealed no significant difference in delayed and non-delayed conditions. Furthermore, no significant difference was observed between the two conditions in ASDs patients when comparing the variables. Although a significant correlation (p<0.05 was found between delayed and non-delayed conditions, it was not significant in the normal group. Moreover, data analysis revealed no significant difference between the two groups in the two conditions when the IQ was considered as covariate. Conclusion: In this study, it was found that the ability to recognize faces in simultaneous and delayed conditions is similar between adolescents with ASDs and their normal counterparts.

Delay-area trade-off for MPRM circuits based on hybrid discrete particle swarm optimization

International Nuclear Information System (INIS)

Jiang Zhidi; Wang Zhenhai; Wang Pengjun

2013-01-01

Polarity optimization for mixed polarity Reed—Muller (MPRM) circuits is a combinatorial issue. Based on the study on discrete particle swarm optimization (DPSO) and mixed polarity, the corresponding relation between particle and mixed polarity is established, and the delay-area trade-off of large-scale MPRM circuits is proposed. Firstly, mutation operation and elitist strategy in genetic algorithm are incorporated into DPSO to further develop a hybrid DPSO (HDPSO). Then the best polarity for delay and area trade-off is searched for large-scale MPRM circuits by combining the HDPSO and a delay estimation model. Finally, the proposed algorithm is testified by MCNC Benchmarks. Experimental results show that HDPSO achieves a better convergence than DPSO in terms of search capability for large-scale MPRM circuits. (semiconductor integrated circuits)

Mapping genetic variants associated with beta-adrenergic responses in inbred mice.

Directory of Open Access Journals (Sweden)

Micha Hersch

Full Text Available β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS addressing the values and susceptibility of cardiovascular-related traits to a selective β(1-blocker, Atenolol (ate, and a β-agonist, Isoproterenol (iso. The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA, a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8. An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6. Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD. Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.

The WNT2 Gene Polymorphism Associated with Speech Delay Inherent to Autism

Science.gov (United States)

Lin, Ping-I; Chien, Yi-Ling; Wu, Yu-Yu; Chen, Chia-Hsiang; Gau, Susan Shur-Fen; Huang, Yu-Shu; Liu, Shih-Kai; Tsai, Wen-Che; Chiu, Yen-Nan

2012-01-01

Previous evidence suggests that language function is modulated by genetic variants on chromosome 7q31-36. However, it is unclear whether this region harbors loci that contribute to speech delay in autism. We previously reported that the WNT2 gene located on 7q31 was associated with the risk of autism. Additionally, two other genes on 7q31-36,…

Temporal-contextual processing in working memory: evidence from delayed cued recall and delayed free recall tests.

Science.gov (United States)

Loaiza, Vanessa M; McCabe, David P

2012-02-01

Three experiments are reported that addressed the nature of processing in working memory by investigating patterns of delayed cued recall and free recall of items initially studied during complex and simple span tasks. In Experiment 1, items initially studied during a complex span task (i.e., operation span) were more likely to be recalled after a delay in response to temporal-contextual cues, relative to items from subspan and supraspan list lengths in a simple span task (i.e., word span). In Experiment 2, items initially studied during operation span were more likely to be recalled from neighboring serial positions during delayed free recall than were items studied during word span trials. Experiment 3 demonstrated that the number of attentional refreshing opportunities strongly predicts episodic memory performance, regardless of whether the information is presented in a spaced or massed format in a modified operation span task. The results indicate that the content-context bindings created during complex span trials reflect attentional refreshing opportunities that are used to maintain items in working memory.

Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders

Science.gov (United States)

Coleman, Jonathan R. I.; Roberts, Susanna; Keers, Robert; Breen, Gerome; Bögels, Susan; Creswell, Cathy; Hudson, Jennifer L.; McKinnon, Anna; Nauta, Maaike; Rapee, Ronald M.; Schneider, Silvia; Silverman, Wendy K.; Thastum, Mikael; Waite, Polly; Wergeland, Gro Janne H.; Eley, Thalia C.

2016-01-01

Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re‐emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre‐ and post‐treatment and during the follow‐up period in the full sample and a subset with fear‐based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P < 0.05) with two SNPs. During the follow‐up period, five SNPs were nominally associated with a poorer treatment response (rs806365 [CNR1]; rs2501431 [CNR2]; rs2070956 [CNR2]; rs7769940 [CNR1]; rs2209172 [FAAH]) and one with a more favorable response (rs6928813 [CNR1]). Within the fear‐based subset, the effect of rs806365 survived multiple testing corrections (P < 0.0016). We found very limited evidence for an association between variants in endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27346075

Regulation-Structured Dynamic Metabolic Model Provides a Potential Mechanism for Delayed Enzyme Response in Denitrification Process

Energy Technology Data Exchange (ETDEWEB)

Song, Hyun-Seob; Thomas, Dennis G.; Stegen, James C.; Li, Minjing; Liu, Chongxuan; Song, Xuehang; Chen, Xingyuan; Fredrickson, Jim K.; Zachara, John M.; Scheibe, Timothy D.

2017-09-29

In a recent study of denitrification dynamics in hyporheic zone sediments, we observed a significant time lag (up to several days) in enzymatic response to the changes in substrate concentration. To explore an underlying mechanism and understand the interactive dynamics between enzymes and nutrients, we developed a trait-based model that associates a community’s traits with functional enzymes, instead of typically used species guilds (or functional guilds). This enzyme-based formulation allows to collectively describe biogeochemical functions of microbial communities without directly parameterizing the dynamics of species guilds, therefore being scalable to complex communities. As a key component of modeling, we accounted for microbial regulation occurring through transcriptional and translational processes, the dynamics of which was parameterized based on the temporal profiles of enzyme concentrations measured using a new signature peptide-based method. The simulation results using the resulting model showed several days of a time lag in enzymatic responses as observed in experiments. Further, the model showed that the delayed enzymatic reactions could be primarily controlled by transcriptional responses and that the dynamics of transcripts and enzymes are closely correlated. The developed model can serve as a useful tool for predicting biogeochemical processes in natural environments, either independently or through integration with hydrologic flow simulators.

Delayed Match Retrieval: A Novel Anticipation-Based Visual Working Memory Paradigm

Science.gov (United States)

Kaldy, Zsuzsa; Guillory, Sylvia B.; Blaser, Erik

2016-01-01

We tested 8- and 10-month-old infants' visual working memory (VWM) for object-location bindings--"what is where"--with a novel paradigm, Delayed Match Retrieval, that measured infants' anticipatory gaze responses (using a Tobii T120 eye tracker). In an inversion of Delayed-Match-to-Sample tasks and with inspiration from the game…

A model for integrating elementary neural functions into delayed-response behavior.

Directory of Open Access Journals (Sweden)

Thomas Gisiger

2006-04-01

Full Text Available It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning, and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task, or recalling from this image another one that has been associated with it during training (delayed-pair association task. The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

A model for integrating elementary neural functions into delayed-response behavior.

Science.gov (United States)

Gisiger, Thomas; Kerszberg, Michel

2006-04-01

It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

Clinical and genetic assessment of pediatric patients with Gaucherâ ...

African Journals Online (AJOL)

Tahia H. Saleem

2016-09-24

Sep 24, 2016 ... were squint, seizures and delayed mental development. Five different .... or miscarriages or genetically affected siblings with GD was also included. ..... with Gaucher disease and relation to disease phenotypes. World J.

Persistent Memory in Single Node Delay-Coupled Reservoir Computing.

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André David Kovac

Full Text Available 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.

Fuzzy delay model based fault simulator for crosstalk delay fault test ...

Indian Academy of Sciences (India)

In this paper, a fuzzy delay model based crosstalk delay fault simulator is proposed. As design trends move towards nanometer technologies, more number of new parameters affects the delay of the component. Fuzzy delay models are ideal for modelling the uncertainty found in the design and manufacturing steps.

Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia

DEFF Research Database (Denmark)

Nordentoft, Merete; Tidselbak Larsen, Janne; Pedersen, Carsten Bøcker

2015-01-01

for this association. Therefore, we investigated whether the increased risk can be explained by other risk factors for schizophrenia. METHODS: A case-control design was applied. A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register. One control was selected for each case......BACKGROUND: The Danish Neonatal Screening Biobank, containing dried blood spot samples from all newborn in Denmark, is a unique source of data that can be utilized for analyses of genetic and environmental exposures related to schizophrenia and other mental disorders. In previous analyses, we have...... found that early and late blood sampling, compared to sampling at day 5, was associated with increased risk of schizophrenia. As delay in sampling of blood for neonatal screening cannot in itself influence the risk of schizophrenia, it must be seen as a proxy for unknown underlying causes responsible...

Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

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Joshua M. Mutiso

2012-02-01

Full Text Available In this study, we report on the safety and skin delayed-type hypersensitivity (DTH, responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG, Montanide ISA 720 (MISA or Monophosphoryl lipid A (MPLA in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α and interferon gamma (IFN-γ levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001. The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001. Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.

Crenelated fast oscillatory outputs of a two-delay electro-optic oscillator.

Science.gov (United States)

Weicker, Lionel; Erneux, Thomas; Jacquot, Maxime; Chembo, Yanne; Larger, Laurent

2012-02-01

An electro-optic oscillator subject to two distinct delayed feedbacks has been designed to develop pronounced broadband chaotic output. Its route to chaos starts with regular pulsating gigahertz oscillations that we investigate both experimentally and theoretically. Of particular physical interest are the transitions to various crenelated fast time-periodic oscillations, prior to the onset of chaotic regimes. The two-delay problem is described mathematically by two coupled delay-differential equations, which we analyze by using multiple-time-scale methods. We show that the interplay of a large delay and a relatively small delay is responsible for the onset of fast oscillations modulated by a slowly varying square-wave envelope. As the bifurcation parameter progressively increases, this envelope undergoes a sequence of bifurcations that corresponds to successive fixed points of a sine map.

Coping with persistent environmental problems: systemic delays in reducing eutrophication of the Baltic Sea

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Riku Varjopuro

2014-12-01

Full Text Available In this paper we focus on systemic delays in the Baltic Sea that cause the problem of eutrophication to persist. These problems are demonstrated in our study by addressing three types of delays: (1 decision delay: the time it takes for an idea or perceived need to be launched as a policy; (2 implementation delay: the time from the launch of a policy to the actual implementation; (3 ecosystem delay: the time difference between the implementation and an actual measurable effects. A policy process is one characterized by delays. It may take years from problem identification to a decision to taking action and several years further for actual implementation. Ecosystem responses to measures illustrate that feedback can keep the ecosystem in a certain state and cause a delay in ecosystem response. These delays can operate on decadal scales. Our aim in this paper is to analyze these systemic delays and especially to discuss how the critical delays can be better addressed in marine protection policies by strengthening the adaptive capacity of marine protection. We conclude that the development of monitoring systems and reflexive, participatory analysis of dynamics involved in the implementation are keys to improve understanding of the systemic delays. The improved understanding is necessary for the adaptive management of a persistent environmental problem. In addition to the state of the environment, the monitoring and analysis should be targeted also at the implementation of policies to ensure that the societies are investing in the right measures.

Investigation of a delayed feedback controller of MEMS resonators

KAUST Repository

Masri, Karim M.

2013-08-04

Controlling mechanical systems is an important branch of mechanical engineering. Several techniques have been used to control Microelectromechanical systems (MEMS) resonators. In this paper, we study the effect of a delayed feedback controller on stabilizing MEMS resonators. A delayed feedback velocity controller is implemented through modifying the parallel plate electrostatic force used to excite the resonator into motion. A nonlinear single degree of freedom model is used to simulate the resonator response. Long time integration is used first. Then, a finite deference technique to capture periodic motion combined with the Floquet theory is used to capture the stable and unstable periodic responses. We show that applying a suitable positive gain can stabilize the MEMS resonator near or inside the instability dynamic pull in band. We also study the stability of the resonator by tracking its basins of attraction while sweeping the controller gain and the frequency of excitations. For positive delayed gains, we notice significant enhancement in the safe area of the basins of attraction. Copyright © 2013 by ASME.

Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

Science.gov (United States)

Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

2016-05-01

Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

Attributions of Responsibility and Blame for Procrastination Behavior.

Science.gov (United States)

Rahimi, Sonia; Hall, Nathan C; Pychyl, Timothy A

2016-01-01

The present study examined the relationship between procrastination, delay, blameworthiness, and moral responsibility. Undergraduate students (N = 240) were provided two scenarios in which the reason for inaction (procrastination, delay), the target (self, other), and the outcome (positive, negative) were manipulated, and students were asked to rate the moral responsibility and blameworthiness of the agent. Results indicated that individuals who procrastinated were seen as more morally responsible and blameworthy than those who experienced delay. More specifically, after a negative outcome, procrastination was associated with more moral responsibility, whereas delay was associated with less moral responsibility. After a positive outcome, individuals perceived procrastination as deserving of less moral responsibility, and delays as associated with more moral responsibility. Finally, a three-way interaction showed that participants rated procrastination that resulted in failure as deserving of responsibility when engaged in by others as opposed to oneself.

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity.

Directory of Open Access Journals (Sweden)

Stephen R Doyle

2017-07-01

Full Text Available Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR and sub-optimal responder (SOR parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs, with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Science.gov (United States)

Nana-Djeunga, Hugues C.; Kengne-Ouafo, Jonas A.; Pion, Sébastien D. S.; Bopda, Jean; Kamgno, Joseph; Wanji, Samuel; Che, Hua; Kuesel, Annette C.; Walker, Martin; Basáñez, Maria-Gloria; Boakye, Daniel A.; Osei-Atweneboana, Mike Y.; Boussinesq, Michel; Prichard, Roger K.; Grant, Warwick N.

2017-01-01

Background Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana—exposed to more than a decade of regular ivermectin treatment—have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. Methodology/Principal findings Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR. Conclusions/Significance This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different

Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

Science.gov (United States)

Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

2016-11-01

Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response

Weight Stigma Reduction and Genetic Determinism.

Science.gov (United States)

Hilbert, Anja

2016-01-01

One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of-and responsibility for-obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention's gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity.

Weight Stigma Reduction and Genetic Determinism.

Directory of Open Access Journals (Sweden)

Anja Hilbert

Full Text Available One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of-and responsibility for-obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1 develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2 evaluate this intervention in the general population (N = 128 and determine mechanisms of change. The results showed (1 decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2 decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention's gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity.

On the cost/delay tradeoff of wireless delay tolerant geographic routing

OpenAIRE

Tasiopoulos, Argyrios; Tsiaras, Christos; Toumpis, Stavros

2012-01-01

In Delay Tolerant Networks (DTNs), there is a fundamental tradeoff between the aggregate transport cost of a packet and the delay in its delivery. We study this tradeoff in the context of geographical routing in wireless DTNs.We ?rst specify the optimal cost/delay tradeoff, i.e., the tradeoff under optimal network operation, using a dynamic network construction termed the Cost/Delay Evolving Graph (C/DEG) and the Optimal Cost/Delay Curve (OC/DC), a function that gives the minimum possible agg...

Genetic predispositions and parental bonding interact to shape adults’ physiological responses to social distress

Science.gov (United States)

Esposito, Gianluca; Truzzi, Anna; Setoh, Peipei; Putnick, Diane L.; Shinohara, Kazuyuki; Bornstein, Marc H.

2018-01-01

Parental bonding and oxytocin receptor (OXTR) gene genotype each influences social abilities in adulthood. Here, we hypothesized an interaction between the two – environmental experience (parental bonding history) and genetic factors (OXTR gene genotype) – in shaping adults’ social sensitivity (physiological response to distress). We assessed heart rate and peripheral temperature (tip of the nose) in 42 male adults during presentation of distress vocalizations (distress cries belonging to female human infants and adults as well as bonobo). The two physiological responses index, respectively, state of arousal and readiness to action. Participants’ parental bonding in childhood was assessed through the self-report Parental Bonding Instrument. To assess participants’ genetic predispositions, buccal mucosa cell samples were collected, and region rs2254298 of the oxytocin receptor gene was analyzed: previous OXTR gene findings point to associations between the G allele and better sociality (protective factor) and the A allele and poorer sociality (risk factor). We found a gene * environment interaction for susceptibility to social distress: Participants with a genetic risk factor (A carriers) with a history of high paternal overprotection showed higher heart rate increase than those without this risk factor (G/G genotype) to social distress. Also, a significant effect of the interaction between paternal care and genotype on nose temperature changes was found. This susceptibility appears to represent an indirect pathway through which genes and experiences interact to shape mature social sensitivity in males. PMID:27343933

New Therapeutic Approaches to Prevent or Delay Beta-Cell Failure in Diabetes

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Ionica Floriana Elvira

2015-09-01

Full Text Available Background and aims: The most recent estimates of International Diabetes Federation indicate that 382 million people have diabetes, and the incidence of this disease is increasing. While in type 1 diabetes mellitus (T1DM beta-cell death is autoimmunemediated, type 2 diabetes mellitus (T2DM results from an interaction between genetic and environmental factors that impair beta-cell function and insulin action. Many people with T2DM remain unaware of their illness for a long time because symptoms may take years to appear or be recognized, while the body is affected by excess blood glucose. These patients are often diagnosed only when diabetes complications have already developed. The aim of this article was to perform a review based on literature data on therapeutic modalities to prevent/delay beta cell function decline. Material and Methods: We searched MEDLINE from 2000 to the present to identify the therapeutic approaches to prevent or delay beta-cell failure in patients with T2DM. Results and conclusions: Several common polymorphisms in genes linked to monogenic forms of diabetes appear to influence the response to T2DM pharmacotherapy. Recent studies report the role of the G protein coupled receptor 40 (GPR40, also known as Free Fatty Acids Receptor 1 (FFAR1 in the regulation of beta-cell function- CNX-011-67 (a GPR40 agonist has the potential to provide good and durable glycemic control in T2DM patients.

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

Science.gov (United States)

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

2018-03-15

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.

Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

Science.gov (United States)

Dempsey, D A; St Helen, G; Jacob, P; Tyndale, R F; Benowitz, N L

2013-12-01

The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never-smokers. Sixty never-smokers, balanced for gender and race (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

Genetic Spot Optimization for Peak Power Estimation in Large VLSI Circuits

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Michael S. Hsiao

2002-01-01

Full Text Available Estimating peak power involves optimization of the circuit's switching function. The switching of a given gate is not only dependent on the output capacitance of the node, but also heavily dependent on the gate delays in the circuit, since multiple switching events can result from uneven circuit delay paths in the circuit. Genetic spot expansion and optimization are proposed in this paper to estimate tight peak power bounds for large sequential circuits. The optimization spot shifts and expands dynamically based on the maximum power potential (MPP of the nodes under optimization. Four genetic spot optimization heuristics are studied for sequential circuits. Experimental results showed an average of 70.7% tighter peak power bounds for large sequential benchmark circuits was achieved in short execution times.

Improving Genetics Education in Graduate and Continuing Health Professional Education: Workshop Summary

Science.gov (United States)

Berger, Adam C.; Johnson, Samuel G.; Beachy, Sarah H.; Olson, Steve

2015-01-01

Many health care providers do not have either the knowledge or the tools they need in order to apply genetic information in their day-to-day practices. This lack of support is contributing to a substantial delay in the translation of genetic research findings, when appropriate, into improvement in patient outcomes within the health care system.…

Improved AODV route recovery in mobile ad-hoc networks using a genetic algorithm

Directory of Open Access Journals (Sweden)

Ahmad Maleki

2014-09-01

Full Text Available An important issue in ad-hoc on-demand distance vector (AODV routing protocols is route failure caused by node mobility in the MANETs. The AODV requires a new route discovery procedure whenever a route breaks and these frequent route discoveries increase transmission delays and routing overhead. The present study proposes a new method for AODVs using a genetic algorithm to improve the route recovery mechanism. When failure occurs in a route, the proposed method (GAAODV makes decisions regarding the QOS parameter to select source or local repair. The task of the genetic algorithm is to find an appropriate combination of weights to optimize end-to-end delay. This paper evaluates the metrics of routing overhead, average end-to-end delay, and packet delivery ratio. Comparison of the new algorithm and AODV (RFC 3561 using a NS-2 simulator shows that GAAODV obtains better results for the QOS parameters.

Genetic progress in multistage dairy cattle breeding schemes using genetic markers.

Science.gov (United States)

Schrooten, C; Bovenhuis, H; van Arendonk, J A M; Bijma, P

2005-04-01

The aim of this paper was to explore general characteristics of multistage breeding schemes and to evaluate multistage dairy cattle breeding schemes that use information on quantitative trait loci (QTL). Evaluation was either for additional genetic response or for reduction in number of progeny-tested bulls while maintaining the same response. The reduction in response in multistage breeding schemes relative to comparable single-stage breeding schemes (i.e., with the same overall selection intensity and the same amount of information in the final stage of selection) depended on the overall selection intensity, the selection intensity in the various stages of the breeding scheme, and the ratio of the accuracies of selection in the various stages of the breeding scheme. When overall selection intensity was constant, reduction in response increased with increasing selection intensity in the first stage. The decrease in response was highest in schemes with lower overall selection intensity. Reduction in response was limited in schemes with low to average emphasis on first-stage selection, especially if the accuracy of selection in the first stage was relatively high compared with the accuracy in the final stage. Closed nucleus breeding schemes in dairy cattle that use information on QTL were evaluated by deterministic simulation. In the base scheme, the selection index consisted of pedigree information and own performance (dams), or pedigree information and performance of 100 daughters (sires). In alternative breeding schemes, information on a QTL was accounted for by simulating an additional index trait. The fraction of the variance explained by the QTL determined the correlation between the additional index trait and the breeding goal trait. Response in progeny test schemes relative to a base breeding scheme without QTL information ranged from +4.5% (QTL explaining 5% of the additive genetic variance) to +21.2% (QTL explaining 50% of the additive genetic variance). A

Elite athletes and pubertal delay.

Science.gov (United States)

Kapczuk, Karina

2017-10-01

Intensive physical training and participation in competitive sports during childhood and early adolescence may affect athletes' pubertal development. On the other hand, pubertal timing, early or late, may impact on an athlete selection for a particular sport. Genetic predisposition, training load, nutritional status and psychological stress determine athletes' pubertal timing. Athletes that practice esthetic sports, especially gymnasts, are predisposed to a delay in pubertal development. The growing evidence indicates that energy deficiency, not a systemic training per se, plays a crucial role in the pathogenesis of functional hypothalamic hypogonadism in female athletes. Metabolic and psychologic stress activate hypothalamic-pituitary-adrenal axis and suppress hypothalamic-pituitary-ovarian axis. Female athletes who do not begin secondary sexual development by the age of 14 or menstruation by the age of 16 warrant a comprehensive evaluation and a targeted treatment. Somatic growth and sexual maturation of elite female athletes are largely sport-specific since each sport favors a particular somatotype and requires a specific training. Chronic negative energy balance resulting from a systemic physical training and inadequate energy intake may delay pubertal development in elite athletes. Youth athletes, especially those engaged in competitive sports that emphasize prepubertal or lean appearance, are at risk of developing relative energy deficiency in sport associated with disordered eating or eating disorders. Management strategies should address the complex conditions underlying functional hypothalamic hypogonadism.

Delayed appearance of tracer lead in facial hair

International Nuclear Information System (INIS)

Rabinowitz, M.; Wetherill, G.; Kopple, J.

1976-01-01

Three adult men were fed 204 Pb--a rare, stable isotope of lead--daily for about 100 days. Simultaneous blood and facial hair measurements of this tracer and of total lead concentrations were made by mass spectrometric isotope dilution analysis. Although the blood showed an immediate response to the intake of the tracer, the facial hair showed a more gradual response and a delay of approximately 35 days. Since the pattern of appearance of lead in hair does not appear to represent a simple time delay of blood lead concentration, the existence of a physiological pool of lead fed by the blood and giving rise to the content in hair is suggested. Hair lead values should therefore, be interpreted as the integral of the blood lead values over the mean life of this intermediate pool--about 100 days

Novel technologies emerging for preimplantation genetic diagnosis and preimplantation genetic testing for aneuploidy.

Science.gov (United States)

Sermon, Karen

2017-01-01

Preimplantation genetic diagnosis (PGD) was introduced as an alternative to prenatal diagnosis: embryos cultured in vitro were analysed for a monogenic disease and only disease-free embryos were transferred to the mother, to avoid the termination of pregnancy with an affected foetus. It soon transpired that human embryos show a great deal of acquired chromosomal abnormalities, thought to explain the low success rate of IVF - hence preimplantation genetic testing for aneuploidy (PGT-A) was developed to select euploid embryos for transfer. Areas covered: PGD has followed the tremendous evolution in genetic analysis, with only a slight delay due to adaptations for diagnosis on small samples. Currently, next generation sequencing combining chromosome with single-base pair analysis is on the verge of becoming the golden standard in PGD and PGT-A. Papers highlighting the different steps in the evolution of PGD/PGT-A were selected. Expert commentary: Different methodologies used in PGD/PGT-A with their pros and cons are discussed.

[Genetic counseling and testing for families with Alzheimer's disease].

Science.gov (United States)

Kowalska, Anna

2004-01-01

With the identification of the genes responsible for autosomal dominant early-onset familial Alzheimer's disease (FAD genes), there is a considerable interest in the application of this genetic information in medical practice through genetic testing and counseling. Pathogenic mutations in the PSEN1 and PSEN2 genes encoding presenilin-1 and -2, and the APP gene encoding amyloid b precursor protein, account for 18-50% of familial EOAD cases with autosomal dominant pattern of inheritance. A clinical algorithm of genetic testing and counseling proposed for families with AD has been presented here. A screening for mutations in the APP, PSEN1, and PSEN2 genes is available to individuals with AD symptoms and at-risk children or siblings of patients with early-onset disease determined by a known mutation. In an early-onset family, a known mutation in an affected patient puts the siblings and children at a 50% risk of inheriting the same mutation. The goal of genetic testing is to identify at-risk individuals in order to facilitate early and effective treatments in the symptomatic person based on an individual's genotype and strategies to delay the onset of disease in the presymptomatic mutation carriers. However, there are several arguments against the use of genetic testing both presymptomatically (unpredictable psychological consequences of information about a genetic defect for family members) and as a diagnostic tool for the differential diagnosis of dementia in general practice (a risk of errors in an interpretation of mutation penetrance and its secondary effects on family members, especially for novel mutations; the possibility of coexistence of another form of dementia at the presence of a mutation). Currently, APOE genotyping for presymptomatic individuals with a family history of late-onset disease is not recommended. The APOE4 allele may only confer greater risk for disease, but its presence is not conclusive for the development of AD.

Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces.

Science.gov (United States)

Taylor, Marcus K; Carpenter, Jennifer; Stone, Michael; Hernandez, Lisa M; Rauh, Mitchell J; Laurent, Heidemarie K; Granger, Douglas A

2015-11-01

The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings. Copyright © 2015. Published by Elsevier Inc.

Attributions of Responsibility and Blame for Procrastination Behavior

Directory of Open Access Journals (Sweden)

Sonia Rahimi

2016-08-01

Full Text Available The present study examined the relationship between procrastination, delay, blameworthiness, and moral responsibility. Undergraduate students (N = 240 were provided two scenarios in which the reason for inaction (procrastination, delay, the target (self, other, and the outcome (positive, negative were manipulated, and students were asked to rate the moral responsibility and blameworthiness of the agent. Results indicated that individuals who procrastinated were seen as more morally responsible and blameworthy than those who otherwise experienced delay. More specifically, after a negative outcome, procrastination was associated with more moral responsibility, whereas delay was associated with less moral responsibility. After a positive outcome, individuals perceived procrastination as deserving of less moral responsibility, and delays as associated with more moral responsibility. Finally, a three-way interaction showed that participants rated procrastination that resulted in failure as deserving of responsibility when engaged in by others as opposed to oneself.

Gene pathways that delay Caenorhabditis elegans reproductive senescence.

Directory of Open Access Journals (Sweden)

Meng C Wang

2014-12-01

Full Text Available Reproductive senescence is a hallmark of aging. The molecular mechanisms regulating reproductive senescence and its association with the aging of somatic cells remain poorly understood. From a full genome RNA interference (RNAi screen, we identified 32 Caenorhabditis elegans gene inactivations that delay reproductive senescence and extend reproductive lifespan. We found that many of these gene inactivations interact with insulin/IGF-1 and/or TGF-β endocrine signaling pathways to regulate reproductive senescence, except nhx-2 and sgk-1 that modulate sodium reabsorption. Of these 32 gene inactivations, we also found that 19 increase reproductive lifespan through their effects on oocyte activities, 8 of them coordinate oocyte and sperm functions to extend reproductive lifespan, and 5 of them can induce sperm humoral response to promote reproductive longevity. Furthermore, we examined the effects of these reproductive aging regulators on somatic aging. We found that 5 of these gene inactivations prolong organismal lifespan, and 20 of them increase healthy life expectancy of an organism without altering total life span. These studies provide a systemic view on the genetic regulation of reproductive senescence and its intersection with organism longevity. The majority of these newly identified genes are conserved, and may provide new insights into age-associated reproductive senescence during human aging.

Representing delayed force feedback as a combination of current and delayed states.

Science.gov (United States)

Avraham, Guy; Mawase, Firas; Karniel, Amir; Shmuelof, Lior; Donchin, Opher; Mussa-Ivaldi, Ferdinando A; Nisky, Ilana

2017-10-01

To adapt to deterministic force perturbations that depend on the current state of the hand, internal representations are formed to capture the relationships between forces experienced and motion. However, information from multiple modalities travels at different rates, resulting in intermodal delays that require compensation for these internal representations to develop. To understand how these delays are represented by the brain, we presented participants with delayed velocity-dependent force fields, i.e., forces that depend on hand velocity either 70 or 100 ms beforehand. We probed the internal representation of these delayed forces by examining the forces the participants applied to cope with the perturbations. The findings showed that for both delayed forces, the best model of internal representation consisted of a delayed velocity and current position and velocity. We show that participants relied initially on the current state, but with adaptation, the contribution of the delayed representation to adaptation increased. After adaptation, when the participants were asked to make movements with a higher velocity for which they had not previously experienced with the delayed force field, they applied forces that were consistent with current position and velocity as well as delayed velocity representations. This suggests that the sensorimotor system represents delayed force feedback using current and delayed state information and that it uses this representation when generalizing to faster movements. NEW & NOTEWORTHY The brain compensates for forces in the body and the environment to control movements, but it is unclear how it does so given the inherent delays in information transmission and processing. We examined how participants cope with delayed forces that depend on their arm velocity 70 or 100 ms beforehand. After adaptation, participants applied opposing forces that revealed a partially correct representation of the perturbation using the current and the

Chemosensory responsiveness to ethanol and its individual sensory components in alcohol-preferring, alcohol-nonpreferring and genetically heterogeneous rats.

Science.gov (United States)

Brasser, Susan M; Silbaugh, Bryant C; Ketchum, Myles J; Olney, Jeffrey J; Lemon, Christian H

2012-03-01

Alcohol activates orosensory circuits that project to motivationally relevant limbic forebrain areas that control appetite, feeding and drinking. To date, limited data exists regarding the contribution of chemosensory-derived ethanol reinforcement to ethanol preference and consumption. Measures of taste reactivity to intra-orally infused ethanol have not found differences in initial orofacial responses to alcohol between alcohol-preferring (P) and alcohol-non-preferring (NP) genetically selected rat lines. Yet, in voluntary intake tests, P rats prefer highly concentrated ethanol upon initial exposure, suggesting an early sensory-mediated attraction. Here, we directly compared self-initiated chemosensory responding for alcohol and prototypic sweet, bitter and oral trigeminal stimuli among selectively bred P, NP and non-selected Wistar (WI) outbred lines to determine whether differential sensory responsiveness to ethanol and its putative sensory components are phenotypically associated with genetically influenced alcohol preference. Rats were tested for immediate short-term lick responses to alcohol (3-40%), sucrose (0.01-1 M), quinine (0.01-3 mM) and capsaicin (0.003-1 mM) in a brief-access assay designed to index orosensory-guided behavior. P rats exhibited elevated short-term lick responses to both alcohol and sucrose relative to NP and WI lines across a broad range of concentrations of each stimulus and in the absence of blood alcohol levels that would produce significant post-absorptive effects. There was no consistent relationship between genetically mediated alcohol preference and orosensory avoidance of quinine or capsaicin. These data indicate that enhanced initial chemosensory attraction to ethanol and sweet stimuli are phenotypes associated with genetic alcohol preference and are considered within the framework of downstream activation of oral appetitive reward circuits. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of

Meiotic delay of translocation carrying spermatocytes responsible for reduced transmission

International Nuclear Information System (INIS)

Buul, P.P.W. van

1991-01-01

Using in vivo pulse labelling of spermatocytes from mice irradiated with different doses of X-rays (6 and 7 Gy). The authors demonstrated that cells having translocations derived from irradiated stem cells tend to spend longer time at the meiotic prophase than normal cells. At the 2 Gy level this effect is much less pronounced. The recorded delay forms a good explanation for the reduced transmission of translocations to the next generation observed by others. (author)

Delayed response after repeated {sup 177}Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Rahbar, Kambiz; Schaefers, Michael [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Boegeman, Martin [University Hospital Muenster, Department of Urology, Muenster (Germany); Yordanova, Anna; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Eveslage, Maria [University Hospital Muenster, Institute for Biostatistics, Muenster (Germany)

2018-02-15

Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA. Seventy-one patients (median age: 72 years; range 44-87) received 3 cycles of RLT with Lu-PSMA (mean administered activity: 6.016 ± 0.543 GBq) every 8 weeks. Response was evaluated using serum PSA levels and a PSA decline ≥50% was considered as biochemical response. Additionally, any PSA decline after the first cycle was evaluated for further therapy effects after the second and third cycle. A total of 213 cycles were performed in 71 patients. Data for response and adverse events were available for all patients. A PSA decline ≥50% and some PSA decline occurred in 56% and 66% of the patients. Of 30 patients with a PSA response after the first cycle, 28 remained responders and 12/41 of non-responders responded to further therapy cycles. RLT with Lu-177-PSMA-617 shows respectable response rates. In this retrospective analysis, a relevant number of patients showed a delayed response, even if they did not respond to the first cycle of the therapy. (orig.)

Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

Science.gov (United States)

Tansey, Katherine E; Guipponi, Michel; Perroud, Nader; Bondolfi, Guido; Domenici, Enrico; Evans, David; Hall, Stephanie K; Hauser, Joanna; Henigsberg, Neven; Hu, Xiaolan; Jerman, Borut; Maier, Wolfgang; Mors, Ole; O'Donovan, Michael; Peters, Tim J; Placentino, Anna; Rietschel, Marcella; Souery, Daniel; Aitchison, Katherine J; Craig, Ian; Farmer, Anne; Wendland, Jens R; Malafosse, Alain; Holmans, Peter; Lewis, Glyn; Lewis, Cathryn M; Stensbøl, Tine Bryan; Kapur, Shitij; McGuffin, Peter; Uher, Rudolf

2012-01-01

It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way. The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance panalysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D. No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.

Genetic Synthesis of New Reversible/Quantum Ternary Comparator

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DEIBUK, V.

2015-08-01

Full Text Available Methods of quantum/reversible logic synthesis are based on the use of the binary nature of quantum computing. However, multiple-valued logic is a promising choice for future quantum computer technology due to a number of advantages over binary circuits. In this paper we have developed a synthesis of ternary reversible circuits based on Muthukrishnan-Stroud gates using a genetic algorithm. The method of coding chromosome is presented, and well-grounded choice of algorithm parameters allowed obtaining better circuit schemes of one- and n-qutrit ternary comparators compared with other methods. These parameters are quantum cost of received reversible devices, delay time and number of constant input (ancilla lines. Proposed implementation of the genetic algorithm has led to reducing of the device delay time and the number of ancilla qutrits to 1 and 2n-1 for one- and n-qutrits full comparators, respectively. For designing of n-qutrit comparator we have introduced a complementary device which compares output functions of 1-qutrit comparators.

Topology Detection for Output-Coupling Weighted Complex Dynamical Networks with Coupling and Transmission Delays

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Xinwei Wang

2017-01-01

Full Text Available Topology detection for output-coupling weighted complex dynamical networks with two types of time delays is investigated in this paper. Different from existing literatures, coupling delay and transmission delay are simultaneously taken into account in the output-coupling network. Based on the idea of the state observer, we build the drive-response system and apply LaSalle’s invariance principle to the error dynamical system of the drive-response system. Several convergent criteria are deduced in the form of algebraic inequalities. Some numerical simulations for the complex dynamical network, with node dynamics being chaotic, are given to verify the effectiveness of the proposed scheme.

Asymptotic Delay Analysis for Cross-Layer Delay-Based Routing in Ad Hoc Networks

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Philippe Jacquet

2007-01-01

Full Text Available This paper addresses the problem of the evaluation of the delay distribution via analytical means in IEEE 802.11 wireless ad hoc networks. We show that the asymptotic delay distribution can be expressed as a power law. Based on the latter result, we present a cross-layer delay estimation protocol and we derive new delay-distribution-based routing algorithms, which are well adapted to the QoS requirements of real-time multimedia applications. In fact, multimedia services are not sensitive to average delays, but rather to the asymptotic delay distributions. Indeed, video streaming applications drop frames when they are received beyond a delay threshold, determined by the buffer size. Although delay-distribution-based routing is an NP-hard problem, we show that it can be solved in polynomial time when the delay threshold is large, because of the asymptotic power law distribution of the link delays.

Spectrum optimization-based chaotification using time-delay feedback control

International Nuclear Information System (INIS)

Zhou Jiaxi; Xu Daolin; Zhang Jing; Liu Chunrong

2012-01-01

Highlights: ► A time-delay feedback controller is designed for chaotification. ► A spectrum optimization method is proposed to determine chaotification parameters. ► Numerical examples verify the spectrum optimization- based chaotification method. ► Engineering application in line spectrum reconfiguration is demonstrated. - Abstract: In this paper, a spectrum optimization method is developed for chaotification in conjunction with an application in line spectrum reconfiguration. A key performance index (the objective function) based on Fourier spectrum is specially devised with the idea of suppressing spectrum spikes and broadening frequency band. Minimization of the index empowered by a genetic algorithm enables to locate favorable parameters of the time-delay feedback controller, by which a line spectrum of harmonic vibration can be transformed into a broad-band continuous spectrum of chaotic motion. Numerical simulations are carried out to verify the feasibility of the method and to demonstrate its effectiveness of chaotifying a 2-DOFs linear mechanical system.

Selective lesion of septal cholinergic neurons in rats impairs acquisition of a delayed matching to position T-maze task by delaying the shift from a response to a place strategy.

Science.gov (United States)

Fitz, Nicholas F; Gibbs, Robert B; Johnson, David A

2008-12-16

This study tested the hypothesis that septal cholinergic lesions impair acquisition of a delayed matching to position (DMP) T-maze task in male rats by affecting learning strategy. Rats received either the selective cholinergic immunotoxin, 192 IgG-saporin (SAP) or artificial cerebrospinal fluid directly into the medial septum. Two weeks later, animals were trained to acquire the DMP task. SAP-treated rats took significantly longer to acquire the task than corresponding controls. Both SAP-treated and control rats adopted a persistent turn and utilized a response strategy during early periods of training. By the time rats reached criterion the persistent turn was no longer evident, and all rats had shifted to an allocentric strategy, i.e., were relying on extramaze cues to a significant degree. During the acquisition period, SAP-treated rats spent significantly more days showing a persistent turn and using a response strategy than corresponding controls. The added time spent using a response strategy accounted entirely for the added days required to reach criterion among the SAP-treated rats. This suggests that the principal mechanism by which septal cholinergic lesions impair DMP acquisition in male rats is by increasing the predisposition to use a response vs. a place strategy, thereby affecting the ability to switch from one strategy to another.

Stroop Interference in a Delayed Match-to-Sample Task: Evidence for Semantic Competition

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Bradley R. Sturz

2013-11-01

Full Text Available Discussions of the source of the Stroop interference effect continue to pervade the literature. Semantic competition posits that interference results from competing semantic activation of word and color dimensions of the stimulus prior to response selection. Response competition posits that interference results from competing responses for articulating the word dimension versus the color dimension at the time of response selection. We embedded Stroop stimuli into a delayed match-to-sample task in an attempt to test semantic and response competition accounts of the interference effect. Participants viewed a sample color word in black or colored fonts that were congruent or incongruent with respect to the color word itself. After a 5s delay, participants were presented with two targets (i.e., a match and a foil and were instructed to select the correct match. We probed each dimension independently during target presentations via color targets (i.e., two colors or word targets (i.e., two words and manipulated whether the semantic content of the foil was related to the semantic content of the irrelevant sample dimension (e.g., word sample red in blue font with the word red as the match and the word blue as the foil. We provide evidence for Stroop interference such that response times increased for incongruent trials even in the presence of a response option with semantic content unrelated to the semantic content of the irrelevant sample dimension. Accuracy also deteriorated during the related foil trials. A follow-up experiment with a 10s delay between sample and targets replicated the results. Results appear to provide converging evidence for Stroop interference in a delayed match-to-sample task in a manner that is consistent with an explanation based upon semantic competition and inconsistent with an explanation based upon response competition.

Vadose zone processes delay groundwater nitrate reduction response to BMP implementation as observed in paired cultivated vs. uncultivated potato rotation fields

Science.gov (United States)

Jiang, Y.; Nyiraneza, J.; Murray, B. J.; Chapman, S.; Malenica, A.; Parker, B.

2017-12-01

Nitrate leaching from crop production contributes to groundwater contamination and subsequent eutrophication of the receiving surface water. A study was conducted in a 7-ha potato-grain-forages rotation field in Prince Edward Island (PEI), Canada during 2011-2016 to link potato rotation practices and groundwater quality. The field consists of fine sandy loam soil and is underlain by 7-9 m of glacial till, which overlies the regional fractured ;red-bed; sandstone aquifer. The water table is generally located in overburden close to the bedrock interface. Field treatments included one field zone taken out of production in 2011 with the remaining zones kept under a conventional potato rotation. Agronomy data including crop tissue, soil, and tile-drain water quality were collected. Hydrogeology data including multilevel monitoring of groundwater nitrate and hydraulic head and data from rock coring for nitrate distribution in overburden and bedrock matrix were also collected. A significant amount of nitrate leached below the soil profile after potato plant kill (referred to as topkill) in 2011, most of it from fertilizer N. A high level of nitrate was also detected in the till vadose zone through coring in December 2012 and through multilevel groundwater sampling from January to May 2014 in both cultivated and uncultivated field zones. Groundwater nitrate concentrations increased for about 2.5 years after the overlying potato field was removed from production. Pressure-driven uniform flow processes dominate water and nitrate transport in the vadose zone, producing an apparently instant water table response but a delayed groundwater quality response to nitrate leaching events. These data suggest that the uniform flow dominated vadose zone in agricultural landscapes can cause the accumulation of a significant amount of nitrate originated from previous farming activities, and the long travel time of this legacy nitrate in the vadose zone can result in substantially delayed

Steady State Analysis of Stochastic Systems with Multiple Time Delays

Science.gov (United States)

Xu, W.; Sun, C. Y.; Zhang, H. Q.

In this paper, attention is focused on the steady state analysis of a class of nonlinear dynamic systems with multi-delayed feedbacks driven by multiplicative correlated Gaussian white noises. The Fokker-Planck equations for delayed variables are at first derived by Novikov's theorem. Then, under small delay assumption, the approximate stationary solutions are obtained by the probability density approach. As a special case, the effects of multidelay feedbacks and the correlated additive and multiplicative Gaussian white noises on the response of a bistable system are considered. It is shown that the obtained analytical results are in good agreement with experimental results in Monte Carlo simulations.

Global synchronization of general delayed complex networks with stochastic disturbances

International Nuclear Information System (INIS)

Tu Li-Lan

2011-01-01

In this paper, global synchronization of general delayed complex networks with stochastic disturbances, which is a zero-mean real scalar Wiener process, is investigated. The networks under consideration are continuous-time networks with time-varying delay. Based on the stochastic Lyapunov stability theory, Ito's differential rule and the linear matrix inequality (LMI) optimization technique, several delay-dependent synchronous criteria are established, which guarantee the asymptotical mean-square synchronization of drive networks and response networks with stochastic disturbances. The criteria are expressed in terms of LMI, which can be easily solved using the Matlab LMI Control Toolbox. Finally, two examples show the effectiveness and feasibility of the proposed synchronous conditions. (general)

Predicting memory performance under conditions of proactive interference: immediate and delayed judgments of learning.

Science.gov (United States)

Wahlheim, Christopher N

2011-07-01

Four experiments examined the monitoring accuracy of immediate and delayed judgments of learning (JOLs) under conditions of proactive interference (PI). PI was produced using paired-associate learning tasks that conformed to variations of classic A-B, A-D paradigms. Results revealed that the relative monitoring accuracy of interference items was better for delayed than for immediate JOLs. However, delayed JOLs were overconfident for interference items, but not for items devoid of interference. Intrusions retrieved prior to delayed JOLs produced inflated predictions of performance. These results show that delayed JOLs enhance monitoring accuracy in PI situations, except when intrusions are mistaken for target responses.

Genetic architecture of wild soybean (Glycine soja) response to soybean cyst nematode (Heterodera glycines).

Science.gov (United States)

Zhang, Hengyou; Song, Qijian; Griffin, Joshua D; Song, Bao-Hua

2017-12-01

The soybean cyst nematode (SCN) is one of the most destructive pathogens of soybean plants worldwide. Host-plant resistance is an environmentally friendly method to mitigate SCN damage. To date, the resistant soybean cultivars harbor limited genetic variation, and some are losing resistance. Thus, a better understanding of the genetic mechanisms of the SCN resistance, as well as developing diverse resistant soybean cultivars, is urgently needed. In this study, a genome-wide association study (GWAS) was conducted using 1032 wild soybean (Glycine soja) accessions with over 42,000 single-nucleotide polymorphisms (SNPs) to understand the genetic architecture of G. soja resistance to SCN race 1. Ten SNPs were significantly associated with the response to race 1. Three SNPs on chromosome 18 were localized within the previously identified quantitative trait loci (QTLs), and two of which were localized within a strong linkage disequilibrium block encompassing a nucleotide-binding (NB)-ARC disease resistance gene (Glyma.18G102600). Genes encoding methyltransferases, the calcium-dependent signaling protein, the leucine-rich repeat kinase family protein, and the NB-ARC disease resistance protein, were identified as promising candidate genes. The identified SNPs and candidate genes can not only shed light on the molecular mechanisms underlying SCN resistance, but also can facilitate soybean improvement employing wild genetic resources.

Modelling and tuning for a time-delayed vibration absorber with friction

Science.gov (United States)

Zhang, Xiaoxu; Xu, Jian; Ji, Jinchen

2018-06-01

This paper presents an integrated analytical and experimental study to the modelling and tuning of a time-delayed vibration absorber (TDVA) with friction. In system modelling, this paper firstly applies the method of averaging to obtain the frequency response function (FRF), and then uses the derived FRF to evaluate the fitness of different friction models. After the determination of the system model, this paper employs the obtained FRF to evaluate the vibration absorption performance with respect to tunable parameters. A significant feature of the TDVA with friction is that its stability is dependent on the excitation parameters. To ensure the stability of the time-delayed control, this paper defines a sufficient condition for stability estimation. Experimental measurements show that the dynamic response of the TDVA with friction can be accurately predicted and the time-delayed control can be precisely achieved by using the modelling and tuning technique provided in this paper.

Delay of behavioral estrus in hamsters and phenobarbital.

Science.gov (United States)

Alleva, J J

1989-01-01

The onset of behavioral estrus was used as a phase marker of the hamster timing system in SLD 16:8 (dark 20:00-04:00). TZ was injected between 11:00 of cycle day 3 and noon of cycle day 4 when onset of estrus was determined. At no time did injection of TZ cause a phase advance in SLD 16:8. Small delays of estrus resulted from 11:00-16:00 injections but marked delays began with the 17:00 injection. Phenobarbital was injected between noon and 19:30 on cycle day 3. Injections between noon and 16:00 had no effect but all later injections beginning at 17:00 delayed estrus, the 17:30 injection causing the greatest delay. Diazepam also markedly delayed estrus when tested at 17:30. These results with three drugs support results with light pulses that 18:00 in SLD 16:8 marks the same phase of the 24-h hamster timing system as the onset of wheel running does in DD, LL, and WLD. These findings with three GABA potentiators extend to SLD previous evidence based on the onset of wheel running in DD, LL and WLD that GABA may be involved in hamster timekeeping and its responses to light and drugs.

Delayed fission

Energy Technology Data Exchange (ETDEWEB)

Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1997-07-01

Delayed fission is a nuclear decay process that couples {beta} decay and fission. In the delayed fission process, a parent nucleus undergoes {beta} decay and thereby populates excited states in the daughter. If these states are of energies comparable to or greater than the fission barrier of the daughter, then fission may compete with other decay modes of the excited states in the daughter. In this paper, mechanism and some experiments of the delayed fission will be discussed. (author)

Parallel responses of species and genetic diversities of Indonesian butterflies to disturbance in tropical rainforests

NARCIS (Netherlands)

Fauvelot, C.Y.; Cleary, D.F.R.; Menken, S.B.J.

2007-01-01

Cécile Fauvelot1,2, Daniel F.R Cleary2,3, and Steph B.J Menken2. Parallel responses of species and genetic diversities of Indonesian butterflies to disturbance in tropical rainforests. 1Environmental Science, University of Bologna at Ravenna, Via S. Alberto 163, I-48100 Ravenna, Italia; 2Institute

ATM directs DNA damage responses and proteostasis via genetically separable pathways.

Science.gov (United States)

Lee, Ji-Hoon; Mand, Michael R; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W; Richards, Alicia L; Coon, Joshua J; Paull, Tanya T

2018-01-09

The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of a variant ATM incapable of activation by oxidative stress resulted in widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicate ATM in the control of protein homeostasis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Kalman filter analysis of delayed neutron nondestructive assay measurements

International Nuclear Information System (INIS)

Aumeier, S. E.

1998-01-01

The ability to nondestructively determine the presence and quantity of fissile and fertile nuclei in various matrices is important in several nuclear applications including international and domestics safeguards, radioactive waste characterization and nuclear facility operations. Material irradiation followed by delayed neutron counting is a well known and useful nondestructive assay technique used to determine the fissile-effective content of assay samples. Previous studies have demonstrated the feasibility of using Kalman filters to unfold individual isotopic contributions to delayed neutron measurements resulting from the assay of mixes of uranium and plutonium isotopes. However, the studies in question used simulated measurement data and idealized parameters. We present the results of the Kalman filter analysis of several measurements of U/Pu mixes taken using Argonne National Laboratory's delayed neutron nondestructive assay device. The results demonstrate the use of Kalman filters as a signal processing tool to determine the fissile and fertile isotopic content of an assay sample from the aggregate delayed neutron response following neutron irradiation

Genetic and environmental contributions to pro-social attitudes: a twin study of social responsibility.

Science.gov (United States)

Rushton, J Philippe

2004-12-22

Although 51 twin and adoption studies have been performed on the genetic architecture of antisocial behaviour, only four previous studies have examined a genetic contribution to pro-social behaviour. Earlier work by the author with the University of London Institute of Psychiatry Adult Twin Register found that genes contributed approximately half of the variance to measures of self-report altruism, empathy, nurturance and aggression, including acts of violence. The present study extends those results by using a 22-item Social Responsibility Questionnaire with 174 pairs of monozygotic twins and 148 pairs of dizygotic twins. Forty-two per cent of the reliable variance was due to the twins' genes, 23% to the twins' common environment and the remainder to the twins' non-shared environment.

Allowing Brief Delays in Responding Improves Event-Based Prospective Memory for Young Adults Living with HIV Disease

Science.gov (United States)

Loft, Shayne; Doyle, Katie L.; Naar-King, Sylvie; Outlaw, Angulique Y.; Nichols, Sharon L.; Weber, Erica; Blackstone, Kaitlin; Woods, Steven Paul

2014-01-01

Event-based prospective memory (PM) tasks require individuals to remember to perform an action when they encounter a specific cue in the environment, and have clear relevance for daily functioning for individuals with HIV. In many everyday tasks, the individual must not only maintain the intent to perform the PM task, but the PM task response also competes with the alternative and more habitual task response. The current study examined whether event-based PM can be improved by slowing down the pace of the task environment. Fifty-seven young adults living with HIV performed an ongoing lexical decision task while simultaneously performing a PM task of monitoring for a specific word (which was focal to the ongoing task of making lexical decisions) or syllable contained in a word (which was nonfocal). Participants were instructed to refrain from making task responses until after a tone was presented, which occurred at varying onsets (0–1600ms) after each stimulus appeared. Improvements in focal and non-focal PM accuracy were observed with response delays of 600ms. Furthermore, the difference in PM accuracy between the low demand focal PM task and the resource demanding non-focal PM task was reduced by half across increasingly longer delays, falling from 31% at 0ms delay to only 14% at 1600ms delay. The degree of ongoing task response slowing for the PM conditions, relative to a control condition that did not have a PM task and made lexical decisions only, also decreased with increased delay. Overall, the evidence indicates that delaying the task responses of younger HIV-infected adults increased the probability that the PM relevant features of task stimuli were adequately assessed prior to the ongoing task response, and by implication that younger HIV infected adults can more adequately achieve PM goals when the pace of the task environment is slowed down. PMID:25116075

Genetic Evaluation of Children with Global Developmental Delay—Current Status of Network Systems in Taiwan

Directory of Open Access Journals (Sweden)

Yong-Lin Foo

2015-08-01

Full Text Available This review article aims to introduce the screening and referral network of genetic evaluation for children with developmental delay in Taiwan. For these children, integrated systems provide services from the medical, educational, and social welfare sectors. All cities and counties in Taiwan have established a network for screening, detection, referral, evaluation, and intervention services. Increased awareness improves early detection and intervention. There remains a gap between supply and demand, especially with regard to financial resources and professional manpower. Genetic etiology has a major role in prenatal causes of developmental delay. A summary of reports on some related genetic disorders in the Taiwanese population is included in this review. Genetic diagnosis allows counseling with regard to recurrence risk and prevention. Networking with neonatal screening, laboratory diagnosis, genetic counseling, and orphan drugs logistics systems can provide effective treatment for patients. In Taiwan, several laboratories provide genetic tests for clinical diagnosis. Accessibility to advanced expensive tests such as gene chips or whole exome sequencing is limited because of funding problems; however, the service system in Taiwan can still operate in a relatively cost-effective manner. This experience in Taiwan may serve as a reference for other countries.

Stimulus-specific variability in color working memory with delayed estimation.

Science.gov (United States)

Bae, Gi-Yeul; Olkkonen, Maria; Allred, Sarah R; Wilson, Colin; Flombaum, Jonathan I

2014-04-08

Working memory for color has been the central focus in an ongoing debate concerning the structure and limits of visual working memory. Within this area, the delayed estimation task has played a key role. An implicit assumption in color working memory research generally, and delayed estimation in particular, is that the fidelity of memory does not depend on color value (and, relatedly, that experimental colors have been sampled homogeneously with respect to discriminability). This assumption is reflected in the common practice of collapsing across trials with different target colors when estimating memory precision and other model parameters. Here we investigated whether or not this assumption is secure. To do so, we conducted delayed estimation experiments following standard practice with a memory load of one. We discovered that different target colors evoked response distributions that differed widely in dispersion and that these stimulus-specific response properties were correlated across observers. Subsequent experiments demonstrated that stimulus-specific responses persist under higher memory loads and that at least part of the specificity arises in perception and is eventually propagated to working memory. Posthoc stimulus measurement revealed that rendered stimuli differed from nominal stimuli in both chromaticity and luminance. We discuss the implications of these deviations for both our results and those from other working memory studies.

Delay-enhanced coherence of spiral waves in noisy Hodgkin-Huxley neuronal networks

International Nuclear Information System (INIS)

Wang Qingyun; Perc, Matjaz; Duan Zhisheng; Chen Guanrong

2008-01-01

We study the spatial dynamics of spiral waves in noisy Hodgkin-Huxley neuronal ensembles evoked by different information transmission delays and network topologies. In classical settings of coherence resonance the intensity of noise is fine-tuned so as to optimize the system's response. Here, we keep the noise intensity constant, and instead, vary the length of information transmission delay amongst coupled neurons. We show that there exists an intermediate transmission delay by which the spiral waves are optimally ordered, hence indicating the existence of delay-enhanced coherence of spatial dynamics in the examined system. Additionally, we examine the robustness of this phenomenon as the diffusive interaction topology changes towards the small-world type, and discover that shortcut links amongst distant neurons hinder the emergence of coherent spiral waves irrespective of transmission delay length. Presented results thus provide insights that could facilitate the understanding of information transmission delay on realistic neuronal networks

The Adenovirus E1A C Terminus Suppresses a Delayed Antiviral Response and Modulates RAS Signaling.

Science.gov (United States)

Zemke, Nathan R; Berk, Arnold J

2017-12-13

The N-terminal half of adenovirus e1a assembles multimeric complexes with host proteins that repress innate immune responses and force host cells into S-phase. In contrast, the functions of e1a's C-terminal interactions with FOXK, DCAF7, and CtBP are unknown. We found that these interactions modulate RAS signaling, and that a single e1a molecule must bind all three of these host proteins to suppress activation of a subset of IFN-stimulated genes (ISGs). These ISGs were otherwise induced in primary respiratory epithelial cells at 12 hr p.i. This delayed activation of ISGs required IRF3 and coincided with an ∼10-fold increase in IRF3 from protein stabilization. The induced IRF3 bound to chromatin and localized to the promoters of activated ISGs. While IRF3, STAT1/2, and IRF9 all greatly increased in concentration, there were no corresponding mRNA increases, suggesting that e1a regulates the stabilities of these key activators of innate immune responses, as shown directly for IRF3. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetics and genomics of susceptibility and immune response to necrotic enteritis in chicken: a review.

Science.gov (United States)

Zahoor, Imran; Ghayas, Abdul; Basheer, Atia

2018-02-01

Global poultry production is facing many challenges and is currently under pressure due to the presence of several diseases like Necrotic Enteritis (NE). It is estimated that NE-caused global economic losses has increased from 2 billion to 6 billion US$ in 2015 because it is not easy to diagnose and control disease at the earlier stage of occurrence. Additionally, ban on the in-feed antibiotics and some other genetic and non-genetic predisposing factors affect the occurrence of the disease. Though the incidence of the disease can be reduced by minimizing the predisposing factors and through immunization of birds but there is no single remedy to control the disease. Therefore, we suggest that there is need to find out the genetic variants that could help to select the birds resistant to NE. The current review details the pertinent features about the genetic and genomics of susceptibility and immune response of birds to Necrotic Enteritis. We report here the list of candidate gene reported for their involvement with the susceptibility and/or resistance to the disease. However, most of these genes are involved in immune-related functions. For better understanding of the role of Clostridium perfringens and its toxins in the pathogenesis of disease there is need to unveil the association between any specific genetic variation and clinical status of NE. However, the presence of substantial genetic variations among different breeds/strains of chicken shows that it is possible to develop broiler strain with genetic resistant against NE. It would help in the cost-effective and sustainable production of safe broiler meat.

A Delay Time Measurement of ULTRAS (Ultra-high Temperature Ultrasonic Response Analysis System) for a High Temperature Experiment

International Nuclear Information System (INIS)

Koo, Kil Mo; Kim, Sang Baik

2010-01-01

The temperature measurement of very high temperature core melt is of importance in a high temperature as the molten pool experiment in which gap formation between core melt and the reactor lower head, and the effect of the gap on thermal behavior are to be measured. The existing temperature measurement techniques have some problems, which the thermocouple, one of the contact methods, is restricted to under 2000 .deg. C, and the infrared thermometry, one of the non-contact methods, is unable to measure an internal temperature and very sensitive to the interference from reacted gases. In order to solve these problems, the delay time technique of ultrasonic wavelets due to high temperature has two sorts of stage. As a first stage, a delay time measurement of ULTRAS (Ultra-high Temperature Ultrasonic Response Analysis System) is suggested. As a second stage, a molten material temperature was measured up to 2300 .deg. C. Also, the optimization design of the UTS (ultrasonic temperature sensor) with persistence at the high temperature was suggested in this paper. And the utilization of the theory suggested in this paper and the efficiency of the developed system are performed by special equipment and some experiments supported by KRISS (Korea Research Institute of Standard and Science)

CD14-159C/T polymorphism in the development of delayed skin hypersensitivity to tuberculin.

Directory of Open Access Journals (Sweden)

Magdalena Druszczynska

Full Text Available The skin tuberculin test (TST, an example of a delayed-type hypersensitivity (DTH reaction, is based on measuring the extent of skin induration to mycobacterial tuberculin (PPD. Little is known about the genetic basis of TST reactivity, widely used for diagnosing TB infection. The study investigated the relationship of the single base change polymorphic variants in CD14 gene (CD14(-159C/T with the development of DTH to PPD in BCG-vaccinated Polish Caucasian individuals. We found persistent lack of TST reactivity in about 40% of healthy subjects despite receiving more than one dose of BCG. The TST size was negatively correlated with the number of BCG inoculations. The distribution of C/T genotype was significantly more frequent among TST-negative compared with TST-positive individuals. The concentration of serum sCD14 was positively associated with mCD14 expression, but not with the TST status or CD14(-159C/T polymorphism. A significant increase in mCD14 expression and serum sCD14 levels was found in TB group. We hypothesize that CD14(-159C/T polymorphic variants might be one of genetic components in the response to attenuated M. bovis BCG bacilli.

Fuzzy delay model based fault simulator for crosstalk delay fault test ...

Indian Academy of Sciences (India)

In this paper, a fuzzy delay model based crosstalk delay fault simulator is proposed. As design .... To find the quality of non-robust tests, a fuzzy delay ..... Dubois D and Prade H 1989 Processing Fuzzy temporal knowledge. IEEE Transactions ...

Evaluation of the innate immune response of Angus heifers with genetic marker variation for intramuscular fat deposition following a lipopolysaccharide challenge

Science.gov (United States)

This study evaluated the effect of genetic selection for markers related to marbling deposition in Angus heifers on the immune response following a lipopolysaccharide (LPS) challenge. Fall-born heifers (n = 19; ~7 months of age, 274 +/- 24 kg) with genetic variation for marbling were utilized inclu...

[Application of single nucleotide polymorphism-microarray and target gene sequencing in the study of genetic etiology of children with unexplained intellectual disability or developmental delay].

Science.gov (United States)

Gao, Z J; Jiang, Q; Cheng, D Z; Yan, X X; Chen, Q; Xu, K M

2016-10-02

Objective: To evaluate the application of single nucleotide polymorphism (SNP)-microarray and target gene sequencing technology in the clinical molecular genetic diagnosis of unexplained intellectual disability(ID) or developmental delay (DD). Method: Patients with ID or DD were recruited in the Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics between September 2015 and February 2016. The intellectual assessment of the patients was performed using 0-6-year-old pediatric examination table of neuropsychological development or Wechsler intelligence scale (>6 years). Patients with a DQ less than 49 or IQ less than 51 were included in this study. The patients were scanned by SNP-array for detection of genomic copy number variations (CNV), and the revealed genomic imbalance was confirmed by quantitative real time-PCR. Candidate gene mutation screening was carried out by target gene sequencing technology.Causal mutations or likely pathogenic variants were verified by polymerase chain reaction and direct sequencing. Result: There were 15 children with ID or DD enrolled, 9 males and 6 females. The age of these patients was 7 months-16 years and 9 months. SNP-array revealed that two of the 15 patients had genomic CNV. Both CNV were de novo micro deletions, one involved 11q24.1q25 and the other micro deletion located on 21q22.2q22.3. Both micro deletions were proved to have a clinical significance due to their association with ID, brain DD, unusual faces etc. by querying Decipher database. Thirteen patients with negative findings in SNP-array were consequently examined with target gene sequencing technology, genotype-phenotype correlation analysis and genetic analysis. Five patients were diagnosed with monogenic disorder, two were diagnosed with suspected genetic disorder and six were still negative. Conclusion: Sequential use of SNP-array and target gene sequencing technology can significantly increase the molecular genetic etiologic

Delayed power analysis

International Nuclear Information System (INIS)

Adamovich, L.A.; Azarov, V.V.

1999-01-01

Time dependent core power behavior in a nuclear reactor is described with well-known neutron kinetics equations. At the same time, two portions are distinguished in energy released from uranium nuclei fission; one released directly at fission and another delayed (residual) portion produced during radioactive decay of fission products. While prompt power is definitely described with kinetics equations, the delayed power presentation still remains outstanding. Since in operation the delayed power part is relatively small (about 6%) operation, it can be neglected for small reactivity disturbances assuming that entire power obeys neutron kinetics equations. In case of a high negative reactivity rapidly inserted in core (e.g. reactor scram initiation) the prompt and delayed components can be calculated separately with practically no impact on each other, employing kinetics equations for prompt power and known approximation formulas for delayed portion, named residual in this specific case. Under substantial disturbances the prompt component in the dynamic process becomes commensurable with delayed portion, thus making necessary to take into account their cross impact. A system of differential equations to describe time-dependent behavior of delayed power is presented. Specific NPP analysis shows a way to significantly simplify the task formulation. (author)

Genetic determinants of P wave duration and PR segment

NARCIS (Netherlands)

Verweij, Niek; Mateo Leach, Irene; van den Boogaard, Malou; van Veldhuisen, Dirk J.; Christoffels, Vincent M.; Hillege, Hans L.; van Gilst, Wiek H.; Barnett, Phil; de Boer, Rudolf A.; van der Harst, Pim

2014-01-01

The PR interval on the ECG reflects atrial depolarization and atrioventricular nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. Genome-wide association studies have identified several genetic loci for PR interval, but it remains to be determined

Genetic Determinants of P Wave Duration and PR Segment

NARCIS (Netherlands)

Verweij, Niek; Mateo Leach, Irene; van den Boogaard, Malou; van Veldhuisen, Dirk J.; Christoffels, Vincent M.; Hillege, Hans L.; van Gilst, Wiek H.; Barnett, Phil; de Boer, Rudolf A.; van der Harst, Pim

Background-The PR interval on the ECG reflects atrial depolarization and atrioventricular nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. Genome-wide association studies have identified several genetic loci for PR interval, but it remains to be

Anti-synchronization control of BAM memristive neural networks with multiple proportional delays and stochastic perturbations

Science.gov (United States)

Wang, Weiping; Yuan, Manman; Luo, Xiong; Liu, Linlin; Zhang, Yao

2018-01-01

Proportional delay is a class of unbounded time-varying delay. A class of bidirectional associative memory (BAM) memristive neural networks with multiple proportional delays is concerned in this paper. First, we propose the model of BAM memristive neural networks with multiple proportional delays and stochastic perturbations. Furthermore, by choosing suitable nonlinear variable transformations, the BAM memristive neural networks with multiple proportional delays can be transformed into the BAM memristive neural networks with constant delays. Based on the drive-response system concept, differential inclusions theory and Lyapunov stability theory, some anti-synchronization criteria are obtained. Finally, the effectiveness of proposed criteria are demonstrated through numerical examples.

Does delaying the first mowing date benefit biodiversity in meadowland?

Directory of Open Access Journals (Sweden)

Humbert Jean-Yves

2012-07-01

Full Text Available Abstract Background Meadows are regularly mown in order to provide fodder or litter for livestock and to prevent vegetation succession. However, the time of year at which meadows should be first mown in order to maximize biological diversity remains controversial and may vary with respect to context and focal taxa. We carried out a systematic review and meta-analysis on the effects of delaying the first mowing date upon plants and invertebrates in European meadowlands. Methods Following a CEE protocol, ISI Web of Science, Science Direct, JSTOR, Google and Google Scholar were searched. We recorded all studies that compared the species richness of plants, or the species richness or abundance of invertebrates, between grassland plots mown at a postponed date (treatment vs plots mown earlier (control. In order to be included in the meta-analysis, compared plots had to be similar in all management respects, except the date of the first cut that was (mostly experimentally manipulated. They were also to be located in the same meadow type. Meta-analyses applying Hedges’d statistic were performed. Results Plant species richness responded differently to the date to which mowing was postponed. Delaying mowing from spring to summer had a positive effect, while delaying either from spring to fall, or from early summer to later in the season had a negative effect. Invertebrates were expected to show a strong response to delayed mowing due to their dependence on sward structure, but only species richness showed a clearly significant positive response. Invertebrate abundance was positively influenced in only a few studies. Conclusions The present meta-analysis shows that in general delaying the first mowing date in European meadowlands has either positive or neutral effects on plant and invertebrate biodiversity (except for plant species richness when delaying from spring to fall or from early summer to later. Overall, there was also strong between

Independence of echo-threshold and echo-delay in the barn owl.

Directory of Open Access Journals (Sweden)

Brian S Nelson

Full Text Available Despite their prevalence in nature, echoes are not perceived as events separate from the sounds arriving directly from an active source, until the echo's delay is long. We measured the head-saccades of barn owls and the responses of neurons in their auditory space-maps while presenting a long duration noise-burst and a simulated echo. Under this paradigm, there were two possible stimulus segments that could potentially signal the location of the echo. One was at the onset of the echo; the other, after the offset of the direct (leading sound, when only the echo was present. By lengthening the echo's duration, independently of its delay, spikes and saccades were evoked by the source of the echo even at delays that normally evoked saccades to only the direct source. An echo's location thus appears to be signaled by the neural response evoked after the offset of the direct sound.

Modelling Compensation Policy for Quality and Delay Deterioration in Rail Transport

Directory of Open Access Journals (Sweden)

Tatiana Molkova

2013-06-01

Full Text Available The contribution deals with the customers’ claims on provided services during train delay in personal railway transport. There is comparison between the situation in the Czech Republic (Brno main station and Austria (Wien Westbahnhof in the contribution. Development of the compensation policy cannot be based only on customer requirements. If the railway company focuses on providing compensation for delays, it must follow its economic balance. However, as the passengers' opinion survey showed, the negative impact of delays can be reduced by providing adequate information to passengers. Based on the passengers' opinion survey, it is necessary to consider the Regulation 1371/2007/ES as the minimum of the possible and on the basis of this reasoning to compile a compensation policy. The costs associated with compensation for the delay should be divided according to the causes of the delay among the individual culprits, so that railway undertakings bear the responsibility even for delays arising from reasons that are beyond the control of the railway undertaking itself. 

Patient Delay, Diagnosis Delay and Treatment Delay for Breast Cancer: Comparison of the Pattern between Patients in Public and Private Health Sectors

Directory of Open Access Journals (Sweden)

Iraj Harirchi

2015-05-01

Full Text Available Background: The purpose of this study was to compare patient delay, diagnosis delay and treatment delay in breast cancer patients of selected public and private health centers in Tehran, Iran.Methods: In this cross-sectional study, female patients with newly diagnosed breast cancer in a public medical complex and a private breast clinic within one year were included. Patient delay was considered positive, if the interval between the detection of the first symptom by the patient and the first visit to a health care provider took longer than one month. Delay in diagnosis was defined as the period of more than one week between the first medical visit for the symptoms and the diagnosis of breast cancer. Following the confirmed diagnosis of breast malignancy, if the medical treatment was initiated later than one week, treatment delay had occurred. The potential reasons for patient, diagnosis and treatment delay according to the patients’ reports were also recorded.Results: Overall, 385 patients were included of whom 52.7% were recruited from the public hospitals and 47.3% from a private clinic. The prevalence of patient delay, diagnosis delay and treatment delay were 31.7%, 17.9% and 28.3%, respectively. Patient delay was significantly more common among patients with lower socio-economic status and those recruited from the public hospitals. All the patients with diagnosis delay were in the group recruited from the public hospitals.Conclusions: Gaps between women of different socio-economic levels of the society need to be addressed in order to decrease patient, diagnosis and treatment delay.

Speech and Language Delay

Science.gov (United States)

... OTC Relief for Diarrhea Home Diseases and Conditions Speech and Language Delay Condition Speech and Language Delay Share Print Table of Contents1. ... Treatment6. Everyday Life7. Questions8. Resources What is a speech and language delay? A speech and language delay ...

Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)

Science.gov (United States)

The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a...

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

Science.gov (United States)

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.

A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay.

Science.gov (United States)

Liang, Liyang; Xie, Yingjun; Shen, Yiping; Yin, Qibin; Yuan, Haiming

2016-01-01

Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments. A de novo 4.5-Mb interstitial duplication at 4p15.2p15.1 was detected by chromosomal microarray analysis. Next-generation sequencing was employed and confirmed the duplication, but revealed no additional pathogenic variants. Several candidate genes in this interval responsible for the complex clinical phenotype were identified, such as RBPJ, STIM2, CCKAR, and LGI2. The results suggest a novel contiguous gene duplication syndrome. © 2016 S. Karger AG, Basel.

Targeted resequencing of the pericentromere of chromosome 2 linked to constitutional delay of growth and puberty.

Directory of Open Access Journals (Sweden)

Diana L Cousminer

Full Text Available Constitutional delay of growth and puberty (CDGP is the most common cause of pubertal delay. CDGP is defined as the proportion of the normal population who experience pubertal onset at least 2 SD later than the population mean, representing 2.3% of all adolescents. While adolescents with CDGP spontaneously enter puberty, they are at risk for short stature, decreased bone mineral density, and psychosocial problems. Genetic factors contribute heavily to the timing of puberty, but the vast majority of CDGP cases remain biologically unexplained, and there is no definitive test to distinguish CDGP from pathological absence of puberty during adolescence. Recently, we published a study identifying significant linkage between a locus at the pericentromeric region of chromosome 2 (chr 2 and CDGP in Finnish families. To investigate this region for causal variation, we sequenced chr 2 between the genomic coordinates of 79-124 Mb (genome build GRCh37 in the proband and affected parent of the 13 families contributing most to this linkage signal. One gene, DNAH6, harbored 6 protein-altering low-frequency variants (< 6% in the Finnish population in 10 of the CDGP probands. We sequenced an additional 135 unrelated Finnish CDGP subjects and utilized the unique Sequencing Initiative Suomi (SISu population reference exome set to show that while 5 of these variants were present in the CDGP set, they were also present in the Finnish population at similar frequencies. Additional variants in the targeted region could not be prioritized for follow-up, possibly due to gaps in sequencing coverage or lack of functional knowledge of non-genic genomic regions. Thus, despite having a well-characterized sample collection from a genetically homogeneous population with a large population-based reference sequence dataset, we were unable to pinpoint variation in the linked region predisposing delayed puberty. This study highlights the difficulties of detecting genetic variants

Biochemical and genetic diagnosis of Smith-Lemli- Opitz syndrome ...

African Journals Online (AJOL)

The clinical spectrum of manifestations is broad, ... delay as well as selfinjurious behaviour and autism are reported. ... recessive disorder that is more common than other defects in cholesterol biosynthesis. ... To perform biochemical and genetic workups in four South African families of European ancestry with suspected ...

Epigenetic and genetic factors in the cellular response to radiations and DNA-damaging chemicals

International Nuclear Information System (INIS)

Williams, J.R.; D'Arpa, P.

1981-01-01

DNA-damaging agents are widely used as therapeutic tools for a variety of disease states. Many such agents are considered to produce detrimental side effects. Thus, it is important to evaluate both therapeutic efficacy and potential risk. DNA-damaging agents can be so evaluated by comparison to agents whose therapeutic benefit and potential hazards are better known. We propose a framework for such comparison, demonstrating that a simple transformation of cytotoxicity-dose response patterns permits a facile comparison of variation between cells exposed to a single DNA-damaging agent or to different cytotoxic agents. Further, by transforming data from experiments which compare responses of 2 cell populations to an effects ratio, different patterns for the changes in cytotoxicity produced by epigenetic and genetic factors were compared. Using these transformations, we found that there is a wide variation (a factor of 4) between laboratories for a single agent (UVC) and only a slightly larger variation (factor of 6) between normal cell response for different types of DNA-damaging agents (x-ray, UVC, alkylating agents, crosslinking agents). Epigenetic factors such as repair and recovery appear to be a factor only at higher dose levels. Comparison in the cytotoxic effect of a spectrum of DNA-damaging agents in xeroderma pigmentosum, ataxia telangiectasia, and Fanconi's anemia cells indicates significantly different patterns, implying that the effect, and perhaps the nature, of these genetic conditions are quite different

Congestion Service Facilities Location Problem with Promise of Response Time

Directory of Open Access Journals (Sweden)

Dandan Hu

2013-01-01

Full Text Available In many services, promise of specific response time is advertised as a commitment by the service providers for the customer satisfaction. Congestion on service facilities could delay the delivery of the services and hurts the overall satisfaction. In this paper, congestion service facilities location problem with promise of response time is studied, and a mixed integer nonlinear programming model is presented with budget constrained. The facilities are modeled as M/M/c queues. The decision variables of the model are the locations of the service facilities and the number of servers at each facility. The objective function is to maximize the demands served within specific response time promised by the service provider. To solve this problem, we propose an algorithm that combines greedy and genetic algorithms. In order to verify the proposed algorithm, a lot of computational experiments are tested. And the results demonstrate that response time has a significant impact on location decision.

Exploring genetic suppression interactions on a global scale.

Science.gov (United States)

van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C; Yamaguchi, Takafumi N; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire E; Cao, Jessica; Cote, Atina; Gebbia, Marinella; Horecka, Gene; Horecka, Ira; Kuzmin, Elena; Legro, Nicole; Liang, Wendy; van Lieshout, Natascha; McNee, Margaret; San Luis, Bryan-Joseph; Shaeri, Fatemeh; Shuteriqi, Ermira; Sun, Song; Yang, Lu; Youn, Ji-Young; Yuen, Michael; Costanzo, Michael; Gingras, Anne-Claude; Aloy, Patrick; Oostenbrink, Chris; Murray, Andrew; Graham, Todd R; Myers, Chad L; Andrews, Brenda J; Roth, Frederick P; Boone, Charles

2016-11-04

Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations,in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population. These findings allow us to formulate and quantify general mechanisms of genetic suppression. Copyright © 2016, American Association for the Advancement of Science.

Genetics Home Reference: proximal 18q deletion syndrome

Science.gov (United States)

... characteristic features. Most cases of proximal 18q deletion syndrome are the result of a new (de novo) deletion and are not inherited from a ... J, Fox PT, Stratton RF, Perry B, Hale DE. Recurrent interstitial deletions of proximal 18q: a new syndrome involving expressive speech delay. Am J Med Genet ...

Adaptation to delayed force perturbations in reaching movements.

Directory of Open Access Journals (Sweden)

Noa Levy

Full Text Available Adaptation to deterministic force perturbations during reaching movements was extensively studied in the last few decades. Here, we use this methodology to explore the ability of the brain to adapt to a delayed velocity-dependent force field. Two groups of subjects preformed a standard reaching experiment under a velocity dependent force field. The force was either immediately proportional to the current velocity (Control or lagged it by 50 ms (Test. The results demonstrate clear adaptation to the delayed force perturbations. Deviations from a straight line during catch trials were shifted in time compared to post-adaptation to a non-delayed velocity dependent field (Control, indicating expectation to the delayed force field. Adaptation to force fields is considered to be a process in which the motor system predicts the forces to be expected based on the state that a limb will assume in response to motor commands. This study demonstrates for the first time that the temporal window of this prediction needs not to be fixed. This is relevant to the ability of the adaptive mechanisms to compensate for variability in the transmission of information across the sensory-motor system.

Genetic relationships between feed efficiency in growing males and beef cow performance.

Science.gov (United States)

Crowley, J J; Evans, R D; Mc Hugh, N; Kenny, D A; McGee, M; Crews, D H; Berry, D P

2011-11-01

Most studies on feed efficiency in beef cattle have focused on performance in young animals despite the contribution of the cow herd to overall profitability of beef production systems. The objective of this study was to quantify, using a large data set, the genetic covariances between feed efficiency in growing animals measured in a performance-test station, and beef cow performance including fertility, survival, calving traits, BW, maternal weaning weight, cow price, and cull cow carcass characteristics in commercial herds. Feed efficiency data were available on 2,605 purebred bulls from 1 test station. Records on cow performance were available on up to 94,936 crossbred beef cows. Genetic covariances were estimated using animal and animal-dam linear mixed models. Results showed that selection for feed efficiency, defined as feed conversion ratio (FCR) or residual BW gain (RG), improved maternal weaning weight as evidenced by the respective genetic correlations of -0.61 and 0.57. Despite residual feed intake (RFI) being phenotypically independent of BW, a negative genetic correlation existed between RFI and cow BW (-0.23; although the SE of 0.31 was large). None of the feed efficiency traits were correlated with fertility, calving difficulty, or perinatal mortality. However, genetic correlations estimated between age at first calving and FCR (-0.55 ± 0.14), Kleiber ratio (0.33 ± 0.15), RFI (-0.29 ± 0.14), residual BW gain (0.36 ± 0.15), and relative growth rate (0.37 ± 0.15) all suggest that selection for improved efficiency may delay the age at first calving, and we speculate, using information from other studies, that this may be due to a delay in the onset of puberty. Results from this study, based on the estimated genetic correlations, suggest that selection for improved feed efficiency will have no deleterious effect on cow performance traits with the exception of delaying the age at first calving.

Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease progression

DEFF Research Database (Denmark)

Tolstrup, Martin; Laursen, Alex Lund; Gerstoft, J.

2006-01-01

on the delayed disease status. However, the results demonstrate a high incidence of a single amino acid polymorphism (cysteine 138) in HIV-1 Nef. The allelic frequency of cysteine 138 between the delayed disease progression group and the progressor group was found to be statistically significant (P = 0.......0139). The phylogeny of isolates was investigated and the variants harbouring the cysteine 138 mutation clustered independently. CONCLUSION: The present study describes a viral genetic polymorphism related to AIDS disease progression. The polymorphism (cysteine 138) has previously been reported to confer decreased...... viral replication (Premkumar DR, et al. AIDS Res Hum Retroviruses 1996; 12(4): 337-45). A sequence database search for comparative mutations revealed a high frequency of cysteine 138 in patients with reported SP AIDS...

Synchronization of delayed systems in the presence of delay time modulation

International Nuclear Information System (INIS)

Kye, Won-Ho; Choi, Muhan; Kim, Myung-Woon; Lee, Soo-Young; Rim, Sunghwan; Kim, Chil-Min; Park, Young-Jai

2004-01-01

We investigate synchronization in the presence of delay time modulation for application to communication. We have observed that the robust synchronization is established by a common delay signal and its threshold is presented using Lyapunov exponents analysis. The influence of the delay time modulation in chaotic oscillators is also discussed

Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

Directory of Open Access Journals (Sweden)

Katherine E Tansey

Full Text Available It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study. After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8. No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8 were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D, with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the

Mechanisms underlying cellular responses of cells from haemopoietic tissue to low

Energy Technology Data Exchange (ETDEWEB)

Kadhim, Munira A

2012-08-22

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.

Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig

International Nuclear Information System (INIS)

Morison, W.L.; Parrish, J.A.; Woehler, M.E.; Krugler, J.I.; Bloch, K.J.

1981-01-01

Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses

Regenerative memory in time-delayed neuromorphic photonic resonators

Science.gov (United States)

Romeira, B.; Avó, R.; Figueiredo, José M. L.; Barland, S.; Javaloyes, J.

2016-01-01

We investigate a photonic regenerative memory based upon a neuromorphic oscillator with a delayed self-feedback (autaptic) connection. We disclose the existence of a unique temporal response characteristic of localized structures enabling an ideal support for bits in an optical buffer memory for storage and reshaping of data information. We link our experimental implementation, based upon a nanoscale nonlinear resonant tunneling diode driving a laser, to the paradigm of neuronal activity, the FitzHugh-Nagumo model with delayed feedback. This proof-of-concept photonic regenerative memory might constitute a building block for a new class of neuron-inspired photonic memories that can handle high bit-rate optical signals.

The TCD50 and regrowth delay assay in human tumor xenografts: Differences and implications

International Nuclear Information System (INIS)

Budach, W.; Budach, V.; Stuschke, M.; Dinges, S.; Sack, H.

1993-01-01

The response to irradiation of five human xenograft cell lines - a malignant paraganglioma, a neurogenic sarcoma, a malignant histiocytoma, a primary lymphoma of the brain, and a squamous cell carcinoma - were tested in nude mice. All mice underwent 5 Gy whole body irradiation prior to xenotransplantation to minimize the residual immune response. The subcutaneous tumors were irradiated at a tumor volume of 120 mm 3 under acutely hypoxic conditions with single doses between 8 Gy and 80 Gy depending on the expected radiation sensitivity of the tumor line. Endpoints of the study were the tumor control dose 50% (TCD 50 ) and the regrowth delay endpoints growth delay, specific growth delay, and the tumor bed effect corrected specific growth delay. Specific growth delay and corrected specific growth delay at 76% of the TCD 50 was used in order to compare the data to previously published data from spheroids. The lowest TCD 50 was found in the lymphoma with 24.9 Gy, whereas the TCD 50 of the soft tissue sarcomas and the squamous cell carcinoma ranged from 57.8 Gy to 65.6 Gy. The isoeffective dose levels for the induction of 30 days growth delay, a specific growth delay of 3, and a corrected specific growth delay of 3 ranged from 15.5 Gy (ECL1) to 37.1 Gy (FADU), from 7.2 Gy (ENE2) to 45.6 Gy (EPG1) and from 9.2 Gy (ENE2) to 37.6 Gy (EPG1), respectively. The corrected specific growth delay at 76% of the TCD 50 was correlated with the number of tumor rescue units per 100 cells in spheroids, which was available for three tumor lines, and with the tumor doubling time in xenografts (n = 5). The TCD 50 values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD 50 and any of the regrowth delay endpoints. This missing correlation was most likely a result of large differences in the number of tumor rescue units in human xenografts of the same size

Chaos synchronization in time-delayed systems with parameter mismatches and variable delay times

International Nuclear Information System (INIS)

Shahverdiev, E.M.; Nuriev, R.A.; Hashimov, R.H.; Shore, K.A.

2004-06-01

We investigate synchronization between two undirectionally linearly coupled chaotic nonidentical time-delayed systems and show that parameter mismatches are of crucial importance to achieve synchronization. We establish that independent of the relation between the delay time in the coupled systems and the coupling delay time, only retarded synchronization with the coupling delay time is obtained. We show that with parameter mismatch or without it neither complete nor anticipating synchronization occurs. We derive existence and stability conditions for the retarded synchronization manifold. We demonstrate our approach using examples of the Ikeda and Mackey Glass models. Also for the first time we investigate chaos synchronization in time-delayed systems with variable delay time and find both existence and sufficient stability conditions for the retarded synchronization manifold with the coupling-delay lag time. (author)

Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice

DEFF Research Database (Denmark)

Jögi, Annika; Rønø, Birgitte; Lund, Ida K

2010-01-01

Proteolytic degradation by plasmin and metalloproteinases is essential for epidermal regeneration in skin wound healing. Plasminogen deficient mice have severely delayed wound closure as have mice simultaneously lacking the two plasminogen activators, urokinase-type plasminogen activator (u......PA) and tissue-type plasminogen activator (tPA). In contrast, individual genetic deficiencies in either uPA or tPA lead to wound healing kinetics with no or only slightly delayed closure of skin wounds....

Delay in an Eating Disorder Diagnosis: The Reason Was a "Shox".

Science.gov (United States)

Reed, Sara; Curran, Kelly A; Middleman, Amy B

2018-04-01

Patients' underlying medical conditions might affect the presentation and progression of an eating disorder. We describe a patient with an undiagnosed, rare, genetic skeletal dysplasia with effects on body mass index that likely led to body image distortion and delayed the diagnosis of an eating disorder. It is critical to fully assess disordered eating in the context of each patient's clinical status. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Role of genetics in the etiopathogenesis of genetic generalized epilepsy: A review of current literature

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S A Balarabe

2016-01-01

Full Text Available Until recently, genetic generalized epilepsy (GGE was believed to be of presumed genetic etiology with no identifiable genetic mutation or demonstrable epigenetic abnormality. A wide range of epileptic disorders has clue for an inherited susceptibility. Monogenic disorders associated with epilepsy mental retardation and structural brain lesion typified by heterotopias, tuberous sclerosis, and progressive myoclonus epilepsies account for about 1% of epilepsies. This review focuses on the role of genetic mutations and epigenetic rearrangements in the pathophysiologic mechanism of GGE. To achieve this; PubMed, EMBASE, and Google Scholar were systematically and comprehensively searched using keywords (“epilepsy” “juvenile myoclonic epilepsy (JME,” “typical absences,” “idiopathic generalized epilepsy,” “JME,” “juvenile absence epilepsy,” “childhood absence epilepsy” “generalized tonic-clonic seizure” “GTCS”. Most GGE has evidence of underlying genetic inheritance. Recent animal studies have shown that early detection and treatment of genetic generalized epilepsies can alter the phenotypic presentation in rodents. These findings suggest a critical period in epileptogenesis, during which spike-and-wave seizures can be suppressed, leading to chronic changes in the brain (epileptogenesis and the preceding dysfunctions may, therefore, be targeted using therapeutic approaches that may either delay or inhibit the transition to active epileptic attack. The interplay between genetic mutations and epigenetic rearrangements play important roles in the development of GCE and that this process, especially at crucial developmental periods, is very susceptible to environmental modulations.

Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

International Nuclear Information System (INIS)

Hoffmann, A.A.; Parsons, P.A.

1989-01-01

Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, 60 Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock

Stochastic resonance in a delayed triple-well potential driven by correlated noises.

Science.gov (United States)

Xu, Pengfei; Jin, Yanfei; Xiao, Shaomin

2017-11-01

In this paper, we investigate stochastic resonance (SR) in a delayed triple-well potential subject to correlated noises and a harmonic signal. The stationary probability density, together with the response amplitude of the system, is obtained by using the small time delay approximation. It is found that the time delay, noise intensities, and the cross-correlation between noises can induce the occurrence of the transition. Moreover, the appropriate choice of noise intensities and time delay can improve the output of the system, enhance the SR effect, and lead to the phenomenon of noise enhanced stability. Especially, the stochastic multi-resonance phenomenon is observed when the multiplicative and additive noises are correlated. Finally, the theoretical results are well verified through numerical simulations.

GENETIC ASPECTS OF AUTISM

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Anastas LAKOSKI

1997-06-01

Full Text Available In the first paper on the syndrome of autism, Kanner described it as innate and inborn. He drew attention to the abnormalities in infancy without evidence of prior normal development and the intellectual, non emotional qualities shown by many of the parents and grandparents. Subsequently, the supposed lack of parental warmth led many clinicians to abandon the notions of constitutional deficit in the child and instead to postulate a psychogenic origin etiology was likely, genetic factors probably did not play a major role. Attention was draw to the low rate of autism in siblings, the lack of chromosome anomalies, and the similarities with syndromes associated with known brain trauma. Although the rate of autism in siblings was indeed low, it was much higher than in the general population rate providing a strong pointer to the genetic factors. The recognition that this was so, associated with the parallel finding of apparently high familiar loading for language delay, stimulated the first, systematic, twin study of autism, which suggested a strong genetic component. Subsequent research has produced findings in the same direction, although many questions remain unanswered. In this paper the evidence that has accumulated on genetic influences on autism is summarized and the remained dilemmas on this field are discussed.

Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

Science.gov (United States)

Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

2017-04-01

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of

The Effects of Delayed Reinforcement on Variability and Repetition of Response Sequences

Science.gov (United States)

Odum, Amy L.; Ward, Ryan D.; Burke, K. Anne; Barnes, Christopher A.

2006-01-01

Four experiments examined the effects of delays to reinforcement on key peck sequences of pigeons maintained under multiple schedules of contingencies that produced variable or repetitive behavior. In Experiments 1, 2, and 4, in the repeat component only the sequence right-right-left-left earned food, and in the vary component four-response…

Using the Genetics Concept Assessment to document persistent conceptual difficulties in undergraduate genetics courses.

Science.gov (United States)

Smith, Michelle K; Knight, Jennifer K

2012-05-01

To help genetics instructors become aware of fundamental concepts that are persistently difficult for students, we have analyzed the evolution of student responses to multiple-choice questions from the Genetics Concept Assessment. In total, we examined pretest (before instruction) and posttest (after instruction) responses from 751 students enrolled in six genetics courses for either majors or nonmajors. Students improved on all 25 questions after instruction, but to varying degrees. Notably, there was a subgroup of nine questions for which a single incorrect answer, called the most common incorrect answer, was chosen by >20% of students on the posttest. To explore response patterns to these nine questions, we tracked individual student answers before and after instruction and found that particular conceptual difficulties about genetics are both more likely to persist and more likely to distract students than other incorrect ideas. Here we present an analysis of the evolution of these incorrect ideas to encourage instructor awareness of these genetics concepts and provide advice on how to address common conceptual difficulties in the classroom.

System Response Analysis and Model Order Reduction, Using Conventional Method, Bond Graph Technique and Genetic Programming

Directory of Open Access Journals (Sweden)

Lubna Moin

2009-04-01

Full Text Available This research paper basically explores and compares the different modeling and analysis techniques and than it also explores the model order reduction approach and significance. The traditional modeling and simulation techniques for dynamic systems are generally adequate for single-domain systems only, but the Bond Graph technique provides new strategies for reliable solutions of multi-domain system. They are also used for analyzing linear and non linear dynamic production system, artificial intelligence, image processing, robotics and industrial automation. This paper describes a unique technique of generating the Genetic design from the tree structured transfer function obtained from Bond Graph. This research work combines bond graphs for model representation with Genetic programming for exploring different ideas on design space tree structured transfer function result from replacing typical bond graph element with their impedance equivalent specifying impedance lows for Bond Graph multiport. This tree structured form thus obtained from Bond Graph is applied for generating the Genetic Tree. Application studies will identify key issues and importance for advancing this approach towards becoming on effective and efficient design tool for synthesizing design for Electrical system. In the first phase, the system is modeled using Bond Graph technique. Its system response and transfer function with conventional and Bond Graph method is analyzed and then a approach towards model order reduction is observed. The suggested algorithm and other known modern model order reduction techniques are applied to a 11th order high pass filter [1], with different approach. The model order reduction technique developed in this paper has least reduction errors and secondly the final model retains structural information. The system response and the stability analysis of the system transfer function taken by conventional and by Bond Graph method is compared and

A note on chaotic synchronization of time-delay secure communication systems

International Nuclear Information System (INIS)

Li Demin; Wang Zidong; Zhou Jie; Fang Jianan; Ni Jinjin

2008-01-01

In a real world, the signals are often transmitted through a hostile environment, and therefore the secure communication system has attracted considerable research interests. In this paper, the observer-based chaotic synchronization problem is studied for a class of time-delay secure communication systems. The system under consideration is subject to delayed state and nonlinear disturbances. The time-delay is allowed to be time-varying, and the nonlinearities are assumed to satisfy global Lipschitz conditions. The problem addressed is the design of a synchronization scheme such that, for the admissible time-delay as well as nonlinear disturbances, the response system can globally synchronize the driving system. An effective algebraic matrix inequality approach is developed to solve the chaotic synchronization problem. A numerical example is presented to show the effectiveness and efficiency of the proposed secure communication scheme

The Influence of Retrieval Practice Versus Delayed Judgments of Learning on Memory: Resolving a Memory-Metamemory Paradox.

Science.gov (United States)

Tauber, Sarah K Uma; Dunlosky, John; Rawson, Katherine A

2015-01-01

The positive effect of delayed retrieval practice on subsequent test performance is robust; by contrast, making delayed judgments of learning (JOLs) encourages covert retrieval but has a minor influence on final test performance. In three experiments, we experimentally established and explored this memory-metamemory paradox. After initial study of paired associates (e.g., husky - ram), participants either were explicitly tested (husky - ?) or made a JOL. In Experiment 1, we adopted the standard JOL method, using a short retention interval, whereas in Experiments 2 and 3, we used a common testing-effect method involving a longer retention interval. Delayed JOLs did not boost test performance, but explicit delayed tests boosted memory after a longer retention interval. As important, participants spent less time to make JOLs than to retrieve responses. These data indicate that differences in the dynamics of retrieval for practice tests versus delayed JOLs are responsible for the paradox.

Pro-inflammatory Cytokine Response and Genetic Diversity in Merozoite Surface Protein 2 of Plasmodium falciparum Isolates from Nigeria.

Science.gov (United States)

Ajibaye, Olusola; Osuntoki, Akinniyi A; Ebuehi, Albert Ot; Iwalokun, Bamidele A; Balogun, Emmanuel O; Egbuna, Kathleen N

2017-01-01

Polymorphisms in Plasmodium falciparum merozoite surface protein-2 ( msp -2) and associated parasite genetic diversity which varies between malaria-endemic regions remain a limitation in malaria vaccine development. Pro-inflammatory cytokines are important in immunity against malaria, understanding the influence of genetic diversity on cytokine response is important for effective vaccine design. P. falciparum isolates obtained from 300 Nigerians with uncomplicated falciparum malaria at Ijede General Hospital, Ijede (IJE), General Hospital Ajeromi, Ajeromi (AJE) and Saint Kizito Mission Hospital, Lekki, were genotyped by nested polymerase chain reaction of msp -2 block 3 while ELISA was used to determine the pro-inflammatory cytokine response to describe the genetic diversity of P. falciparum . Eighteen alleles were observed for msp -2 loci. Of the 195 isolates, 61 (31.0%) had only FC27-type alleles, 38 (19.7%) had only 3D7-type alleles, and 49.3% had multiple parasite lines with both alleles. Band sizes were 275-625 bp for FC27 and 150-425 bp for 3D7. Four alleles were observed from LEK, 2 (375-425 bp) and 2 (275-325 bp) of FC27-and 3D7-types, respectively; 12 alleles from AJE, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively; while IJE had a total of 12 alleles, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively. Mean multiplicity of infection (MOI) was 1.54. Heterozygosity ( H E ) ranged from 0.77 to 0.87 and was highest for IJE (0.87). Cytokine response was higher among 0.05) but with neither parasite density nor infection type. P. falciparum genetic diversity is extensive in Nigeria, protection via pro-inflammatory cytokines have little or no interplay with infection multiplicity.

Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

Science.gov (United States)

Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

2016-10-01

Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

Dynamics of a delayed intraguild predation model with harvesting

Science.gov (United States)

Collera, Juancho A.; Balilo, Aldrin T.

2018-03-01

In [1], a delayed three-species intraguild predation (IGP) model was considered. This particular tri-trophic community module includes a predator and its prey which share a common basal resource for their sustenance [3]. Here, it is assumed that in the absence of predation, the growth of the basal resource follows the delayed logistic equation. Without delay time, the IGP model in [1] reduces to the system considered in [7] where it was shown that IGP may induce chaos even if the functional responses are linear. Meanwhile, in [2] the delayed IGP model in [1] was generalized to include harvesting. Under the assumption that the basal resource has some economic value, a constant harvesting term on the basal resource was incorporated. However, both models in [1] and [2] use the delay time as the main parameter. In this research, we studied the delayed IGP model in [1] with the addition of linear harvesting term on each of the three species. The dynamical behavior of this system is examined using the harvesting rates as main parameter. In particular, we give conditions on the existence, stability, and bifurcations of equilibrium solutions of this system. This allows us to better understand the effects of harvesting in terms of the survival or extinction of one or more species in our system. Numerical simulations are carried out to illustrate our results. In fact, we show that the chaotic behavior in [7] unfolds when the harvesting rate parameter is varied.

Expression quantitative trait loci and genetic regulatory network analysis reveals that Gabra2 is involved in stress responses in the mouse.

Science.gov (United States)

Dai, Jiajuan; Wang, Xusheng; Chen, Ying; Wang, Xiaodong; Zhu, Jun; Lu, Lu

2009-11-01

Previous studies have revealed that the subunit alpha 2 (Gabra2) of the gamma-aminobutyric acid receptor plays a critical role in the stress response. However, little is known about the gentetic regulatory network for Gabra2 and the stress response. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Gabra2 expression in the hippocampus of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Gabra2 exhibited much variation in the hippocampus across the BXD RI strains and between the parental strains, C57BL/6J, and DBA/2J. Expression QTL (eQTL) mapping showed three microarray probe sets of Gabra2 to have highly significant linkage likelihood ratio statistic (LRS) scores. Gene co-regulatory network analysis showed that 10 genes, including Gria3, Chka, Drd3, Homer1, Grik2, Odz4, Prkag2, Grm5, Gabrb1, and Nlgn1 are directly or indirectly associated with stress responses. Eleven genes were implicated as Gabra2 downstream genes through mapping joint modulation. The genetical genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to complex traits, such as stress responses.

The Effects of Four-Hour Delay of PUnishment under Two Conditions of Verbal Instruction

Science.gov (United States)

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)

Effects of brief time delays on matching-to-sample abilities in capuchin monkeys (Sapajus spp.).

Science.gov (United States)

Truppa, Valentina; De Simone, Diego Antonio; Piano Mortari, Eva; De Lillo, Carlo

2014-09-01

Traditionally, studies of delayed matching-to-sample (DMTS) tasks in nonhuman species have focused on the assessment of the limits of the retrieval of information stored in short- and long-term memory systems. However, it is still unclear if visual recognition in these tasks is affected by very brief delay intervals, which are typically used to study rapidly decaying types of visual memory. This study aimed at evaluating if tufted capuchin monkeys' ability to recognise visual stimuli in a DMTS task is affected by (i) the disappearance of the sample stimulus and (ii) the introduction of delay intervals (0.5, 1.0, 2.0 and 3.0s) between the disappearance of the sample and the presentation of the comparison stimuli. The results demonstrated that the simple disappearance of the sample and the introduction of a delay of 0.5s did not affect capuchins' performance either in terms of accuracy or response time. A delay interval of 1.0s produced a significant increase in response time but still did not affect recognition accuracy. By contrast, delays of 2.0 and 3.0s determined a significant increase in response time and a reduction in recognition accuracy. These findings indicate the existence in capuchin monkeys of processes enabling a very accurate retention of stimulus features within time frames comparable to those reported for humans' sensory memory (0.5-1.0s). The extent to which such processes can be considered analogous to the sensory memory processes observed in human visual cognition is discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetics Home Reference: leptin receptor deficiency

Science.gov (United States)

... caused by reduced production of hormones that direct sexual development. Affected individuals experience delayed puberty or do not ... regulating the body's response to hormones that control sexual development, and that this response is affected by LEPR ...

Multi-objective optimization of MOSFETs channel widths and supply voltage in the proposed dual edge-triggered static D flip-flop with minimum average power and delay by using fuzzy non-dominated sorting genetic algorithm-II.

Science.gov (United States)

Keivanian, Farshid; Mehrshad, Nasser; Bijari, Abolfazl

2016-01-01

D Flip-Flop as a digital circuit can be used as a timing element in many sophisticated circuits. Therefore the optimum performance with the lowest power consumption and acceptable delay time will be critical issue in electronics circuits. The newly proposed Dual-Edge Triggered Static D Flip-Flop circuit layout is defined as a multi-objective optimization problem. For this, an optimum fuzzy inference system with fuzzy rules is proposed to enhance the performance and convergence of non-dominated sorting Genetic Algorithm-II by adaptive control of the exploration and exploitation parameters. By using proposed Fuzzy NSGA-II algorithm, the more optimum values for MOSFET channel widths and power supply are discovered in search space than ordinary NSGA types. What is more, the design parameters involving NMOS and PMOS channel widths and power supply voltage and the performance parameters including average power consumption and propagation delay time are linked. To do this, the required mathematical backgrounds are presented in this study. The optimum values for the design parameters of MOSFETs channel widths and power supply are discovered. Based on them the power delay product quantity (PDP) is 6.32 PJ at 125 MHz Clock Frequency, L = 0.18 µm, and T = 27 °C.

Evaluation of performance of distributed delay model for chemotherapy-induced myelosuppression.

Science.gov (United States)

Krzyzanski, Wojciech; Hu, Shuhua; Dunlavey, Michael

2018-04-01

The distributed delay model has been introduced that replaces the transit compartments in the classic model of chemotherapy-induced myelosuppression with a convolution integral. The maturation of granulocyte precursors in the bone marrow is described by the gamma probability density function with the shape parameter (ν). If ν is a positive integer, the distributed delay model coincides with the classic model with ν transit compartments. The purpose of this work was to evaluate performance of the distributed delay model with particular focus on model deterministic identifiability in the presence of the shape parameter. The classic model served as a reference for comparison. Previously published white blood cell (WBC) count data in rats receiving bolus doses of 5-fluorouracil were fitted by both models. The negative two log-likelihood objective function (-2LL) and running times were used as major markers of performance. Local sensitivity analysis was done to evaluate the impact of ν on the pharmacodynamics response WBC. The ν estimate was 1.46 with 16.1% CV% compared to ν = 3 for the classic model. The difference of 6.78 in - 2LL between classic model and the distributed delay model implied that the latter performed significantly better than former according to the log-likelihood ratio test (P = 0.009), although the overall performance was modestly better. The running times were 1 s and 66.2 min, respectively. The long running time of the distributed delay model was attributed to computationally intensive evaluation of the convolution integral. The sensitivity analysis revealed that ν strongly influences the WBC response by controlling cell proliferation and elimination of WBCs from the circulation. In conclusion, the distributed delay model was deterministically identifiable from typical cytotoxic data. Its performance was modestly better than the classic model with significantly longer running time.

Mutations in KPTN Cause Macrocephaly, Neurodevelopmental Delay, and Seizures

Science.gov (United States)

Baple, Emma L.; Maroofian, Reza; Chioza, Barry A.; Izadi, Maryam; Cross, Harold E.; Al-Turki, Saeed; Barwick, Katy; Skrzypiec, Anna; Pawlak, Robert; Wagner, Karin; Coblentz, Roselyn; Zainy, Tala; Patton, Michael A.; Mansour, Sahar; Rich, Phillip; Qualmann, Britta; Hurles, Matt E.; Kessels, Michael M.; Crosby, Andrew H.

2014-01-01

The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. Our immunofluorescence analyses in primary neuronal cell cultures showed that endogenous and GFP-tagged kaptin associates with dynamic actin cytoskeletal structures and that this association is lost upon introduction of the identified mutations. Taken together, our studies have identified kaptin alterations responsible for macrocephaly and neurodevelopmental delay and define kaptin as a molecule crucial for normal human neuromorphogenesis. PMID:24239382

Global synchronization criteria with channel time-delay for chaotic time-delay system

International Nuclear Information System (INIS)

Sun Jitao

2004-01-01

Based on the Lyapunov stabilization theory, matrix measure, and linear matrix inequality (LMIs), this paper studies the chaos synchronization of time-delay system using the unidirectional linear error feedback coupling with time-delay. Some generic conditions of chaos synchronization with time-delay in the transmission channel is established. The chaotic Chua's circuit is used for illustration, where the coupling parameters are determined according to the criteria under which the global chaos synchronization of the time-delay coupled systems is achieved

Delayed minocycline but not delayed mild hypothermia protects against embolic stroke

Directory of Open Access Journals (Sweden)

Noor Raza

2002-04-01

Full Text Available Abstract Background Inflammatory reactions occurring in the brain after ischemia may contribute to secondary damage. In the present study, effects of minocycline, an anti-inflammatory agent, alone or in combination with mild hypothermia on focal embolic cerebral ischemia have been examined. Methods Focal ischemic injury was induced by embolizing a preformed clot into the middle cerebral artery (MCA. Infarction volume was measured at 48 h after the injury. Mortality was also recorded. Results Delayed administration of minocycline alone or delayed minocycline plus delayed mild hypothermia reduced the infarction volume significantly. However, delayed mild hypothermia alone was not protective and delayed mild hypothermia in combination with minocycline did not show any additive effect. Conclusions These results suggest that minocycline is beneficial in focal ischemic brain injury, and the lack of the enhanced neuroprotection may be due to the brief exposure to hypothermia.

A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection.

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Siddle, Katherine J; Deschamps, Matthieu; Tailleux, Ludovic; Nédélec, Yohann; Pothlichet, Julien; Lugo-Villarino, Geanncarlo; Libri, Valentina; Gicquel, Brigitte; Neyrolles, Olivier; Laval, Guillaume; Patin, Etienne; Barreiro, Luis B; Quintana-Murci, Lluís

2014-05-01

MicroRNAs (miRNAs) are critical regulators of gene expression, and their role in a wide variety of biological processes, including host antimicrobial defense, is increasingly well described. Consistent with their diverse functional effects, miRNA expression is highly context dependent and shows marked changes upon cellular activation. However, the genetic control of miRNA expression in response to external stimuli and the impact of such perturbations on miRNA-mediated regulatory networks at the population level remain to be determined. Here we assessed changes in miRNA expression upon Mycobacterium tuberculosis infection and mapped expression quantitative trait loci (eQTL) in dendritic cells from a panel of healthy individuals. Genome-wide expression profiling revealed that ∼40% of miRNAs are differentially expressed upon infection. We find that the expression of 3% of miRNAs is controlled by proximate genetic factors, which are enriched in a promoter-specific histone modification associated with active transcription. Notably, we identify two infection-specific response eQTLs, for miR-326 and miR-1260, providing an initial assessment of the impact of genotype-environment interactions on miRNA molecular phenotypes. Furthermore, we show that infection coincides with a marked remodeling of the genome-wide relationships between miRNA and mRNA expression levels. This observation, supplemented by experimental data using the model of miR-29a, sheds light on the role of a set of miRNAs in cellular responses to infection. Collectively, this study increases our understanding of the genetic architecture of miRNA expression in response to infection, and highlights the wide-reaching impact of altering miRNA expression on the transcriptional landscape of a cell.

APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy.

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