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Sample records for stimulated multiple time-course

  1. Efficacy and Time Course of Theta Burst Stimulation in Healthy Humans

    NARCIS (Netherlands)

    Wischnewski, M.; Schutter, D.J.L.G.

    2015-01-01

    BACKGROUND: In the past decade research has shown that continuous (cTBS) and intermittent theta burst stimulation (iTBS) alter neuronal excitability levels in the primary motor cortex. OBJECTIVE: Quantitatively review the magnitude and time course on cortical excitability of cTBS and iTBS. METHODS:

  2. Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

    Science.gov (United States)

    Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C

    2011-08-15

    Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. Copyright © 2011 Movement Disorder Society.

  3. Skin complications in deep brain stimulation for Parkinson's disease: frequency, time course, and risk factors.

    Science.gov (United States)

    Sixel-Döring, Friederike; Trenkwalder, Claudia; Kappus, Christoph; Hellwig, Dieter

    2010-02-01

    Deep brain stimulation (DBS) has been recognized as an efficacious treatment for movement disorders. Its beneficial effects however may be lost due to skin complications such as erosions or infections over the implanted foreign material. We sought to document skin complications in the entire Parkinson's disease patient population who received a DBS system at the Marburg/Kassel implantation centre since the start of our DBS program in January 2002 to analyze frequency, time course, and possible risk factors. We investigated 85 consecutive patients with Parkinson's disease (PD) from a single center/single surgeon DBS series for the occurrence of skin complications and analyzed localization, time course, and possible risk factors. Mean follow-up was 3 years (range 1-7 years). In total, 21/85 patients (24.7%) suffered a total of 30 single skin complications. Sixty percent of all incidents occurred within the first post-operative year. Forty percent of all incidents occurred later than the first year following primary implantation. Complications involved the burr hole cap in 37%, the course of the cables in 33%, and the impulse generator (IPG) site in 30%. Six of 21 patients suffered recurring skin complications. Eight patients permanently lost their DBS system. Factor analysis for age, gender, disease duration, disease severity, the incidence of hypertension or diabetes as well as a 2-day period with externalized electrodes for continuous test stimulation did not have any statistically significant impact on skin complications. We conclude that (1) PD patients have a risk for skin complications after DBS as long as the system remains in situ and (2) there are at present no identifiable risk factors for skin complications after DBS, other than PD itself.

  4. A permutation-based multiple testing method for time-course microarray experiments

    Directory of Open Access Journals (Sweden)

    George Stephen L

    2009-10-01

    Full Text Available Abstract Background Time-course microarray experiments are widely used to study the temporal profiles of gene expression. Storey et al. (2005 developed a method for analyzing time-course microarray studies that can be applied to discovering genes whose expression trajectories change over time within a single biological group, or those that follow different time trajectories among multiple groups. They estimated the expression trajectories of each gene using natural cubic splines under the null (no time-course and alternative (time-course hypotheses, and used a goodness of fit test statistic to quantify the discrepancy. The null distribution of the statistic was approximated through a bootstrap method. Gene expression levels in microarray data are often complicatedly correlated. An accurate type I error control adjusting for multiple testing requires the joint null distribution of test statistics for a large number of genes. For this purpose, permutation methods have been widely used because of computational ease and their intuitive interpretation. Results In this paper, we propose a permutation-based multiple testing procedure based on the test statistic used by Storey et al. (2005. We also propose an efficient computation algorithm. Extensive simulations are conducted to investigate the performance of the permutation-based multiple testing procedure. The application of the proposed method is illustrated using the Caenorhabditis elegans dauer developmental data. Conclusion Our method is computationally efficient and applicable for identifying genes whose expression levels are time-dependent in a single biological group and for identifying the genes for which the time-profile depends on the group in a multi-group setting.

  5. Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Durand, M.T.; Mota, A.L. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Barale, A.R. [Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG (Brazil); Castania, J.A.; Fazan, R. Jr.; Salgado, H.C. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-16

    The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN). The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR.

  6. Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Durand, M.T.; Mota, A.L.; Barale, A.R.; Castania, J.A.; Fazan, R. Jr.; Salgado, H.C.

    2012-01-01

    The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN). The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR

  7. Time courses of MRI BOLD signals in prolonged visual stimulation. Comparison between colors and orders

    International Nuclear Information System (INIS)

    Kashikura, Kenichi; Fujita, Hideaki; Kershaw, J.B.; Matsuura, Tetsuya; Seki, Chie; Kashikura, Akemi; Ardekani, B.A.; Kanno, Iwao

    1998-01-01

    We investigated: the BOLD signal response during 270 second photic stimulation using an EPI pulse sequence; the BOLD signal response for two different color checkerboards; and the BOLD signal response during six consecutive stimulation series. Ten healthy human subjects (age 25±5.5 years) were studied with a 1.5 T MRI system (Siemens Vision, Erlangen, Germany). Black and white (BW) and red and white (RW) checkerboards alternating at 8 Hz were applied in turns for a total series of six. Stimulation timing was: 30 sec. off, 15 sec. on, 15 sec. off, 270 sec. on, 15 sec. off, 15 sec. on, 15 sec. off. Acquired data were analyzed according to color and/or order: color (without considering the order); color and order (1st BW vs. 1st RW, 2nd BW vs. 2nd RW, 3rd BW vs. 3rd RW); and order (without considering the color). A t-test (p<0.001) was used for obtaining the activated areas, and simple regression and two-way repeated-measures ANOVA were used for testing the statistical significance of the BOLD response. Results were: the BOLD signal responses during sustained photic stimulation maintained a constant level for the full duration and all series, suggesting stable levels of oxygen extraction and metabolism during cortical activation; the BOLD signal responses in two colors showed no significant difference in time response, suggesting that the neuronal populations perceiving black and red give a similar time response; and the effect of habituation or fatigue as observed by a signal decrease was not obtained, although the S.D. for each subject greatly increased with time and might be an indicator for evaluation fatigue or attention. (author)

  8. Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data

    Directory of Open Access Journals (Sweden)

    Tomasz Dzida

    2017-09-01

    Full Text Available We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα, RNA polymerase (Pol II and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ERα binding. We use the method to identify a genome-wide confident set of ERα target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ERα binding proximity alone.

  9. The time-course of feature interference in agreement comprehension: Multiple mechanisms and asymmetrical attraction.

    Science.gov (United States)

    Tanner, Darren; Nicol, Janet; Brehm, Laurel

    2014-10-01

    Attraction interference in language comprehension and production may be as a result of common or different processes. In the present paper, we investigate attraction interference during language comprehension, focusing on the contexts in which interference arises and the time-course of these effects. Using evidence from event-related brain potentials (ERPs) and sentence judgment times, we show that agreement attraction in comprehension is best explained as morphosyntactic interference during memory retrieval. This stands in contrast to attraction as a message-level process involving the representation of the subject NP's number features, which is a strong contributor to attraction in production. We thus argue that the cognitive antecedents of agreement attraction in comprehension are non-identical with those of attraction in production, and moreover, that attraction in comprehension is primarily a consequence of similarity-based interference in cue-based memory retrieval processes. We suggest that mechanisms responsible for attraction during language comprehension are a subset of those involved in language production.

  10. Reliability of Autonomic Responses and Malaise Across Multiple Motion Sickness Stimulation Tests

    Science.gov (United States)

    Stout, Cynthia S.; Toscano, William B.; Cowings, Patricia S.

    1993-01-01

    There is general agreement that a high degree of variability exists between subjects in their autonomic nervous system responses to motion sickness stimulation. Additionally, a paucity of data exists that examines the variability within an individual across repeated motion sickness tests. Investigators have also examined the relationship of autonomic responses to motion sickness development. These investigations have used analyses at discrete points in time to describe this relationship. This approach fails to address the time course of autonomic responses and malaise development throughout the motion sickness test. Our objectives were to examine the reliability of autonomic responses and malaise using the final minute of the motion sickness test across five testing occasions, to examine the reliability of the change in autonomic responses and the change in malaise across five testing occasions, and to examine the relationship between changes in autonomic responses and changes in malaise level across the entire motion sickness test. Our results indicate that, based on the final minute of testing, the autonomic responses of heart rate, blood volume pulse, and respiration rate are moderately stable across multiple tests. Changes in heart rate, blood volume pulse, respiration rate, and malaise throughout the test duration were less stable across the tests. We attribute this instability to variations in individual susceptibility and the error associated with estimating a measure of autonomic gain.

  11. Reconstructing biochemical pathways from time course data.

    Science.gov (United States)

    Srividhya, Jeyaraman; Crampin, Edmund J; McSharry, Patrick E; Schnell, Santiago

    2007-03-01

    Time series data on biochemical reactions reveal transient behavior, away from chemical equilibrium, and contain information on the dynamic interactions among reacting components. However, this information can be difficult to extract using conventional analysis techniques. We present a new method to infer biochemical pathway mechanisms from time course data using a global nonlinear modeling technique to identify the elementary reaction steps which constitute the pathway. The method involves the generation of a complete dictionary of polynomial basis functions based on the law of mass action. Using these basis functions, there are two approaches to model construction, namely the general to specific and the specific to general approach. We demonstrate that our new methodology reconstructs the chemical reaction steps and connectivity of the glycolytic pathway of Lactococcus lactis from time course experimental data.

  12. Time course of clinical change following neurofeedback.

    Science.gov (United States)

    Rance, Mariela; Walsh, Christopher; Sukhodolsky, Denis G; Pittman, Brian; Qiu, Maolin; Kichuk, Stephen A; Wasylink, Suzanne; Koller, William N; Bloch, Michael; Gruner, Patricia; Scheinost, Dustin; Pittenger, Christopher; Hampson, Michelle

    2018-05-02

    Neurofeedback - learning to modulate brain function through real-time monitoring of current brain state - is both a powerful method to perturb and probe brain function and an exciting potential clinical tool. For neurofeedback effects to be useful clinically, they must persist. Here we examine the time course of symptom change following neurofeedback in two clinical populations, combining data from two ongoing neurofeedback studies. This analysis reveals a shared pattern of symptom change, in which symptoms continue to improve for weeks after neurofeedback. This time course has several implications for future neurofeedback studies. Most neurofeedback studies are not designed to test an intervention with this temporal pattern of response. We recommend that new studies incorporate regular follow-up of subjects for weeks or months after the intervention to ensure that the time point of greatest effect is sampled. Furthermore, this time course of continuing clinical change has implications for crossover designs, which may attribute long-term, ongoing effects of real neurofeedback to the control intervention that follows. Finally, interleaving neurofeedback sessions with assessments and examining when clinical improvement peaks may not be an appropriate approach to determine the optimal number of sessions for an application. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Reliability of psychophysiological responses across multiple motion sickness stimulation tests

    Science.gov (United States)

    Stout, C. S.; Toscano, W. B.; Cowings, P. S.

    1995-01-01

    Although there is general agreement that a high degree of variability exists between subjects in their autonomic nervous system responses to motion sickness stimulation, very little evidence exists that examines the reproducibility of autonomic responses within subjects during motion sickness stimulation. Our objectives were to examine the reliability of autonomic responses and symptom levels across five testing occasions using the (1) final minute of testing, (2) change in autonomic response and the change in symptom level, and (3) strength of the relationship between the change in symptom level and the change in autonomic responses across the entire motion sickness test. The results indicate that, based on the final minute of testing, the autonomic responses of heart rate, blood volume pulse, and respiration rate are moderately stable across multiple tests. Changes in heart rate, blood volume pulse, respiration rate, and symptoms throughout the test duration are less stable across the tests. Finally, autonomic responses and symptom levels are significantly related across the entire motion sickness test.

  14. Smoothing dynamic positron emission tomography time courses using functional principal components

    OpenAIRE

    Jiang, Ci-Ren; Aston, John A. D.; Wang, Jane-Ling

    2009-01-01

    A functional smoothing approach to the analysis of PET time course data is presented. By borrowing information across space and accounting for this pooling through the use of a non-parametric covariate adjustment, it is possible to smooth the PET time course data thus reducing the noise. A new model for functional data analysis, the Multiplicative Nonparametric Random Effects Model, is introduced to more accurately account for the variation in the data. A locally adaptive bandwidth choice hel...

  15. Bisensory stimulation increases gamma-responses over multiple cortical regions.

    Science.gov (United States)

    Sakowitz, O W; Quiroga, R Q; Schürmann, M; Başar, E

    2001-04-01

    In the framework of the discussion about gamma (approx. 40 Hz) oscillations as information carriers in the brain, we investigated the relationship between gamma responses in the EEG and intersensory association. Auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) were compared with bisensory evoked potentials (BEPs; simultaneous auditory and visual stimulation) in 15 subjects. Gamma responses in AEPs, VEPs and BEPs were assessed by means of wavelet decomposition. Overall maximum gamma-components post-stimulus were highest in BEPs (P < 0.01). Bisensory evoked gamma-responses also showed significant central, parietal and occipital amplitude-increases (P < 0.001, P < 0.01, P < 0.05, respectively; prestimulus interval as baseline). These were of greater magnitude when compared with the unisensory responses. As a correlate of the marked gamma responses to bimodal stimulation we suggest a process of 'intersensory association', i.e. one of the steps between sensory transmission and perception. Our data may be interpreted as a further example of function-related gamma responses in the EEG.

  16. Comparative Time Course Profiles of Phthalate Stereoisomers in Mice

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    ABSTRACT More efficient models are needed to assess potential carcinogenicity hazard of environmental chemicals. Here we evaluated time course profiles for two reference phthalates, di(2-ethylhexyl) phthalate (DEHP) and its stereoisomer di-n-octyl phthalate (DNOP), to identify...

  17. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    NARCIS (Netherlands)

    Hanken, K.; Bosse, M.; Möhrke, K.; Eling, P.A.T.M.; Kastrup, A.; Antal, A.; Hildebrandt, H.

    2016-01-01

    Background: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation

  18. Clinical implications of ST segment time-course recovery patterns ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    Journal home page: http://www.akspublication.com/ijmu. Original Work. 3. Copyrighted © by Dr. ... KEY WORDS: Exercise stress test; ST segment time course patterns. INTRODUCTIONᴪ .... using simple descriptive statistics (mean ± SD) and contingency .... two patients who had the recovery time of less than. 3 minutes, had ...

  19. Modeling Fan Effects on the Time Course of Associative Recognition

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    Schneider, Darryl W.; Anderson, John R.

    2012-01-01

    We investigated the time course of associative recognition using the response signal procedure, whereby a stimulus is presented and followed after a variable lag by a signal indicating that an immediate response is required. More specifically, we examined the effects of associative fan (the number of associations that an item has with other items…

  20. Effect of rhythmic auditory stimulation on gait kinematic parameters of patients with multiple sclerosis.

    Science.gov (United States)

    Shahraki, M; Sohrabi, M; Taheri Torbati, H R; Nikkhah, K; NaeimiKia, M

    2017-01-01

    Purpose: This study aimed to examine the effect of rhythmic auditory stimulation on gait kinematic parameters of patients with multiple sclerosis. Subjects and Methods: In this study, 18 subjects, comprising 4 males and 14 females with Multiple Sclerosis with expanded disability status scale of 3 to 6 were chosen. Subjects were selected by available and targeted sampling and were randomly divided into two experimental (n = 9) and control (n = 9) groups. Exercises were gait with rhythmic auditory stimulation by a metronome device, in addition to gait without stimulation for the experimental and control groups, respectively. Training was carried out for 3 weeks, with 30 min duration for each session 3 times a week. Stride length, stride time, double support time, cadence and gait speed were measured by motion analysis device. Results: There was a significant difference between stride length, stride time, double support time, cadence and gait speed in the experimental group, before and after the training. Furthermore, there was a significant difference between the experimental and control groups in the enhancement of stride length, stride time, cadence and gait speed in favor of the experimental group. While this difference was not significant for double support time. Conclusion: The results of this study showed that rhythmic auditory stimulation is an effective rehabilitation method to improve gait kinematic parameters in patients with multiple sclerosis.

  1. Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor

    Directory of Open Access Journals (Sweden)

    Natalya V. Shneyder

    2012-04-01

    Full Text Available Background: Both hypothyroidism and Hashimoto's thyroiditis (HT can rarely be associated with cerebellar ataxia. Severe essential tremor (ET as well as bilateral thalamic deep brain stimulation (DBS may lead to subtle cerebellar signs. Case Report: We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers confirming the diagnosis of HT. Discussion: Our case demonstrates multiple possible causes of cerebellar ataxia in a patient, including hypothyroidism, HT, chronic ET, and bilateral thalamic DBS. Counseling of patients may be appropriate when multiple risk factors for cerebellar ataxia coexist in one individual.

  2. Self-stimulating rats combine subjective reward magnitude and subjective reward rate multiplicatively.

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    Leon, M I; Gallistel, C R

    1998-07-01

    For rats that bar pressed for intracranial electrical stimulation in a 2-lever matching paradigm with concurrent variable interval schedules of reward, the authors found that the time allocation ratio is based on a multiplicative combination of the ratio of subjective reward magnitudes and the ratio of the rates of reward. Multiplicative combining was observed in a range covering approximately 2 orders of magnitude in the ratio of the rates of reward from about 1:10 to 10:1) and an order of magnitude change in the size of rewards. After determining the relation between the pulse frequency of stimulation and subjective reward magnitude, the authors were able to predict from knowledge of the subjective magnitudes of the rewards and the obtained relative rates of reward the subject's time allocation ratio over a range in which it varied by more than 3 orders of magnitude.

  3. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    OpenAIRE

    Katrin Hanken; Katrin Hanken; Mona Bosse; Kim Möhrke; Paul Eling; Andreas Kastrup; Andrea Antal; Helmut Hildebrandt; Helmut Hildebrandt

    2016-01-01

    Background: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anoda...

  4. Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation

    OpenAIRE

    Hanken, Katrin; Bosse, Mona; M?hrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

    2016-01-01

    BACKGROUND: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. OBJECTIVES: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. METHODS: In study I, a randomized double-blind placebo-controll...

  5. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    Directory of Open Access Journals (Sweden)

    Katrin Hanken

    2016-09-01

    Full Text Available Background: Fatigue in multiple sclerosis (MS patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1,5mA was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20min of a 40min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5mA over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. TDCS was delivered for 20min before patients performed a 20min lasting visual vigilance task.Results: Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in reaction time associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation.Conclusions: Anodal tDCS over the right parietal cortex can counteract the increase in reaction times during vigilance performance but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

  6. Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Hanken, Katrin; Bosse, Mona; Möhrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

    2016-01-01

    Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20 min of a 40-min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS was delivered for 20 min before patients performed a 20-min lasting visual vigilance task. Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in RT associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Anodal tDCS over the right parietal cortex can counteract the increase in RTs during vigilance performance, but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

  7. Time course of dynamic range adaptation in the auditory nerve

    Science.gov (United States)

    Wang, Grace I.; Dean, Isabel; Delgutte, Bertrand

    2012-01-01

    Auditory adaptation to sound-level statistics occurs as early as in the auditory nerve (AN), the first stage of neural auditory processing. In addition to firing rate adaptation characterized by a rate decrement dependent on previous spike activity, AN fibers show dynamic range adaptation, which is characterized by a shift of the rate-level function or dynamic range toward the most frequently occurring levels in a dynamic stimulus, thereby improving the precision of coding of the most common sound levels (Wen B, Wang GI, Dean I, Delgutte B. J Neurosci 29: 13797–13808, 2009). We investigated the time course of dynamic range adaptation by recording from AN fibers with a stimulus in which the sound levels periodically switch from one nonuniform level distribution to another (Dean I, Robinson BL, Harper NS, McAlpine D. J Neurosci 28: 6430–6438, 2008). Dynamic range adaptation occurred rapidly, but its exact time course was difficult to determine directly from the data because of the concomitant firing rate adaptation. To characterize the time course of dynamic range adaptation without the confound of firing rate adaptation, we developed a phenomenological “dual adaptation” model that accounts for both forms of AN adaptation. When fitted to the data, the model predicts that dynamic range adaptation occurs as rapidly as firing rate adaptation, over 100–400 ms, and the time constants of the two forms of adaptation are correlated. These findings suggest that adaptive processing in the auditory periphery in response to changes in mean sound level occurs rapidly enough to have significant impact on the coding of natural sounds. PMID:22457465

  8. The time course of attention modulation elicited by spatial uncertainty.

    Science.gov (United States)

    Huang, Dan; Liang, Huilou; Xue, Linyan; Wang, Meijian; Hu, Qiyi; Chen, Yao

    2017-09-01

    Uncertainty regarding the target location is an influential factor for spatial attention. Modulation in spatial uncertainty can lead to adjustments in attention scope and variations in attention effects. Hence, investigating spatial uncertainty modulation is important for understanding the underlying mechanism of spatial attention. However, the temporal dynamics of this modulation remains unclear. To evaluate the time course of spatial uncertainty modulation, we adopted a Posner-like attention orienting paradigm with central or peripheral cues. Different numbers of cues were used to indicate the potential locations of the target and thereby manipulate the spatial uncertainty level. The time interval between the onsets of the cue and the target (stimulus onset asynchrony, SOA) varied from 50 to 2000ms. We found that under central cueing, the effect of spatial uncertainty modulation could be detected from 200 to 2000ms after the presence of the cues. Under peripheral cueing, the effect of spatial uncertainty modulation was observed from 50 to 2000ms after cueing. Our results demonstrate that spatial uncertainty modulation produces robust and sustained effects on target detection speed. The time course of this modulation is influenced by the cueing method, which suggests that discrepant processing procedures are involved under different cueing conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Time course of brain activation elicited by basic emotions.

    Science.gov (United States)

    Hot, Pascal; Sequeira, Henrique

    2013-11-13

    Whereas facial emotion recognition protocols have shown that each discrete emotion has a specific time course of brain activation, there is no electrophysiological evidence to support these findings for emotional induction by complex pictures. Our objective was to specify the differences between the time courses of brain activation elicited by feelings of happiness and, with unpleasant pictures, by feelings of disgust and sadness. We compared event-related potentials (ERPs) elicited by the watching of high-arousing pictures from the International Affective Picture System, selected to induce specific emotions. In addition to a classical arousal effect on late positive components, we found specific ERP patterns for each emotion in early temporal windows (emotion to be associated with different brain processing after 140 ms, whereas happiness and sadness differed in ERPs elicited at the frontal and central sites after 160 ms. Our findings highlight the limits of the classical averaging of ERPs elicited by different emotions inside the same valence and suggest that each emotion could elicit a specific temporal pattern of brain activation, similar to those observed with emotional face recognition.

  10. Binding Isotherms and Time Courses Readily from Magnetic Resonance.

    Science.gov (United States)

    Xu, Jia; Van Doren, Steven R

    2016-08-16

    Evidence is presented that binding isotherms, simple or biphasic, can be extracted directly from noninterpreted, complex 2D NMR spectra using principal component analysis (PCA) to reveal the largest trend(s) across the series. This approach renders peak picking unnecessary for tracking population changes. In 1:1 binding, the first principal component captures the binding isotherm from NMR-detected titrations in fast, slow, and even intermediate and mixed exchange regimes, as illustrated for phospholigand associations with proteins. Although the sigmoidal shifts and line broadening of intermediate exchange distorts binding isotherms constructed conventionally, applying PCA directly to these spectra along with Pareto scaling overcomes the distortion. Applying PCA to time-domain NMR data also yields binding isotherms from titrations in fast or slow exchange. The algorithm readily extracts from magnetic resonance imaging movie time courses such as breathing and heart rate in chest imaging. Similarly, two-step binding processes detected by NMR are easily captured by principal components 1 and 2. PCA obviates the customary focus on specific peaks or regions of images. Applying it directly to a series of complex data will easily delineate binding isotherms, equilibrium shifts, and time courses of reactions or fluctuations.

  11. The time course of ethanol tolerance: associative learning

    Directory of Open Access Journals (Sweden)

    J.L.O. Bueno

    2007-11-01

    Full Text Available The effect of different contextual stimuli on different ethanol-induced internal states was investigated during the time course of both the hypothermic effect of the drug and of drug tolerance. Minimitters were surgically implanted in 16 Wistar rats to assess changes in their body temperature under the effect of ethanol. Rat groups were submitted to ethanol or saline trials every other day. The animals were divided into two groups, one receiving a constant dose (CD of ethanol injected intraperitoneally, and the other receiving increasing doses (ID during the 10 training sessions. During the ethanol training sessions, conditioned stimuli A (tone and B (buzzer were presented at "state +" (35 min after drug injection and "state -" (170 min after drug injection, respectively. Conditioned stimuli C (bip and D (white noise were presented at moments equivalent to stimuli A and B, respectively, but during the saline training sessions. All stimuli lasted 15 min. The CD group, but not the ID group, developed tolerance to the hypothermic effect of ethanol. Stimulus A (associated with drug "state +" induced hyperthermia with saline injection in the ID group. Stimulus B (associated with drug "state -" reduced ethanol tolerance in the CD group and modulated the hypothermic effect of the drug in the ID group. These results indicate that contextual stimuli acquire modulatory conditioned properties that are associated with the time course of both the action of the drug and the development of drug tolerance.

  12. Illusory conjunctions reflect the time course of the attentional blink.

    Science.gov (United States)

    Botella, Juan; Privado, Jesús; de Liaño, Beatriz Gil-Gómez; Suero, Manuel

    2011-07-01

    Illusory conjunctions in the time domain are binding errors for features from stimuli presented sequentially but in the same spatial position. A similar experimental paradigm is employed for the attentional blink (AB), an impairment of performance for the second of two targets when it is presented 200-500 msec after the first target. The analysis of errors along the time course of the AB allows the testing of models of illusory conjunctions. In an experiment, observers identified one (control condition) or two (experimental condition) letters in a specified color, so that illusory conjunctions in each response could be linked to specific positions in the series. Two items in the target colors (red and white, embedded in distractors of different colors) were employed in four conditions defined according to whether both targets were in the same or different colors. Besides the U-shaped function for hits, the errors were analyzed by calculating several response parameters reflecting characteristics such as the average position of the responses or the attentional suppression during the blink. The several error parameters cluster in two time courses, as would be expected from prevailing models of the AB. Furthermore, the results match the predictions from Botella, Barriopedro, and Suero's (Journal of Experimental Psychology: Human Perception and Performance, 27, 1452-1467, 2001) model for illusory conjunctions.

  13. Binding of Multiple Rap1 Proteins Stimulates Chromosome Breakage Induction during DNA Replication.

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    Greicy H Goto

    2015-08-01

    Full Text Available Telomeres, the ends of linear eukaryotic chromosomes, have a specialized chromatin structure that provides a stable chromosomal terminus. In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomere length. Here we show that binding of multiple Rap1 proteins stimulates DNA double-stranded break (DSB induction at both telomeric and non-telomeric regions. Consistent with the role of DSB induction, Rap1 stimulates nearby recombination events in a dosage-dependent manner. Rap1 recruits Rif1 and Rif2 to telomeres, but neither Rif1 nor Rif2 is required for DSB induction. Rap1-mediated DSB induction involves replication fork progression but inactivation of checkpoint kinase Mec1 does not affect DSB induction. Rap1 tethering shortens artificially elongated telomeres in parallel with telomerase inhibition, and this telomere shortening does not require homologous recombination. These results suggest that Rap1 contributes to telomere homeostasis by promoting chromosome breakage.

  14. Transcranial magnetic stimulation primes the effects of exercise therapy in multiple sclerosis.

    Science.gov (United States)

    Mori, Francesco; Ljoka, Concetta; Magni, Elisabetta; Codecà, Claudia; Kusayanagi, Hajime; Monteleone, Fabrizia; Sancesario, Andrea; Bernardi, Giorgio; Koch, Giacomo; Foti, Calogero; Centonze, Diego

    2011-07-01

    Exercise therapy (ET) can be beneficial in disabled multiple sclerosis (MS) patients. Intermittent transcranial magnetic theta burst stimulation (iTBS) induces long-term excitability changes of the cerebral cortex and may ameliorate spasticity in MS. We investigated whether the combination of iTBS and a program of ET can improve motor disability in MS patients. In a double-blind, sham-controlled trial, 30 participants were randomized to three different interventions: iTBS plus ET, sham stimulation plus ET, and iTBS alone. Before and after 2 weeks of treatment, measures of spasticity through the modified Ashworth scale (MAS) and the 88 items Multiple Sclerosis Spasticity Score questionnaire (MSSS-88), fatigue through the Fatigue Severity Scale (FSS), daily living activities (ADL) through the Barthel index and health-related quality of life (HRQoL) through the 54 items Multiple Sclerosis Quality of life inventory (MSQoL-54) were collected. iTBS plus ET reduced MAS, MSSS-88, FSS scores, while in the Barthel index and MSQoL-54, physical composite scores were increased. iTBS alone caused a reduction of the MAS score, while none of the measured scales showed significant changes after sham iTBS plus ET. iTBS associated with ET is a promising tool for motor rehabilitation of MS patients.

  15. The time course of attentional modulation on emotional conflict processing.

    Science.gov (United States)

    Zhou, Pingyan; Yang, Guochun; Nan, Weizhi; Liu, Xun

    2016-01-01

    Cognitive conflict resolution is critical to human survival in a rapidly changing environment. However, emotional conflict processing seems to be particularly important for human interactions. This study examined whether the time course of attentional modulation on emotional conflict processing was different from cognitive conflict processing during a flanker task. Results showed that emotional N200 and P300 effects, similar to colour conflict processing, appeared only during the relevant task. However, the emotional N200 effect preceded the colour N200 effect, indicating that emotional conflict can be identified earlier than cognitive conflict. Additionally, a significant emotional N100 effect revealed that emotional valence differences could be perceived during early processing based on rough aspects of input. The present data suggest that emotional conflict processing is modulated by top-down attention, similar to cognitive conflict processing (reflected by N200 and P300 effects). However, emotional conflict processing seems to have more time advantages during two different processing stages.

  16. The time course of explicit and implicit categorization.

    Science.gov (United States)

    Smith, J David; Zakrzewski, Alexandria C; Herberger, Eric R; Boomer, Joseph; Roeder, Jessica L; Ashby, F Gregory; Church, Barbara A

    2015-10-01

    Contemporary theory in cognitive neuroscience distinguishes, among the processes and utilities that serve categorization, explicit and implicit systems of category learning that learn, respectively, category rules by active hypothesis testing or adaptive behaviors by association and reinforcement. Little is known about the time course of categorization within these systems. Accordingly, the present experiments contrasted tasks that fostered explicit categorization (because they had a one-dimensional, rule-based solution) or implicit categorization (because they had a two-dimensional, information-integration solution). In Experiment 1, participants learned categories under unspeeded or speeded conditions. In Experiment 2, they applied previously trained category knowledge under unspeeded or speeded conditions. Speeded conditions selectively impaired implicit category learning and implicit mature categorization. These results illuminate the processing dynamics of explicit/implicit categorization.

  17. On the Time Course of Vocal Emotion Recognition

    Science.gov (United States)

    Pell, Marc D.; Kotz, Sonja A.

    2011-01-01

    How quickly do listeners recognize emotions from a speaker's voice, and does the time course for recognition vary by emotion type? To address these questions, we adapted the auditory gating paradigm to estimate how much vocal information is needed for listeners to categorize five basic emotions (anger, disgust, fear, sadness, happiness) and neutral utterances produced by male and female speakers of English. Semantically-anomalous pseudo-utterances (e.g., The rivix jolled the silling) conveying each emotion were divided into seven gate intervals according to the number of syllables that listeners heard from sentence onset. Participants (n = 48) judged the emotional meaning of stimuli presented at each gate duration interval, in a successive, blocked presentation format. Analyses looked at how recognition of each emotion evolves as an utterance unfolds and estimated the “identification point” for each emotion. Results showed that anger, sadness, fear, and neutral expressions are recognized more accurately at short gate intervals than happiness, and particularly disgust; however, as speech unfolds, recognition of happiness improves significantly towards the end of the utterance (and fear is recognized more accurately than other emotions). When the gate associated with the emotion identification point of each stimulus was calculated, data indicated that fear (M = 517 ms), sadness (M = 576 ms), and neutral (M = 510 ms) expressions were identified from shorter acoustic events than the other emotions. These data reveal differences in the underlying time course for conscious recognition of basic emotions from vocal expressions, which should be accounted for in studies of emotional speech processing. PMID:22087275

  18. Time course of recovery of idiopathic vocal fold paralysis.

    Science.gov (United States)

    Husain, Solomon; Sadoughi, Babak; Mor, Niv; Levin, Ariana M; Sulica, Lucian

    2018-01-01

    To clarify the time course of recovery in patients with idiopathic vocal fold paralysis. Retrospective chart review. Medical records for all patients with idiopathic vocal fold paralysis over a 10-year period were reviewed to obtain demographic and clinical information, including onset of disease and recovery of vocal function. Stroboscopic exams of patients who recovered voice were reviewed blindly to assess return of vocal fold motion. Thirty-eight of 55 patients (69%) recovered vocal function. Time course of recovery could be assessed in 34 patients who did not undergo injection augmentation. The mean time to recovery was 152.8 ± 109.3 days (left, 179.8 ± 111.3 days; right, 105.3 ± 93.7 days; P = .088). Two-thirds of patients recovered within 6 months. Probability of recovery declined over time. Five of 22 patients who recovered voice had return of vocal fold motion; 17 did not. The mean time to recovery did not differ between these groups (return of motion, 127.4 ± 132.3 days; no return of motion, 160.1 ± 105.1 days; P = .290). Sixty-nine percent of patients with idiopathic vocal fold paralysis recovered vocal function, two-thirds doing so within 6 months of onset. Age, gender, laterality, use of injection augmentation did not influence recovery rate. Declining probability of recovery over time leads us to consider framework surgery after 6 months in patients with idiopathic paralysis. 4. Laryngoscope, 128:148-152, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  19. Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation.

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    Guoshi Li

    2017-10-01

    Full Text Available The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh and norepinephrine (NE and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.

  20. Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) Trial: Baseline Characteristics

    Science.gov (United States)

    Diamond, Michael P.; Legro, Richard S.; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D.; Casson, Peter; Christman, Gregory M.; Ager, Joel; Huang, Hao; Hansen, Karl R.; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G. Wright; Rosen, R. Mitchell; Haisonleder, Daniell; Krawetz, Stephen A.; Barnhart, Kurt; Trussell, J.C.; Jin, Yufeng; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

    2015-01-01

    Objective To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. Design Randomized, prospective clinical trial Patients 900 couples with unexplained infertility Interventions: Ovarian stimulation with gonadotropins, clomiphene citrate, or letrozole in conjunction with intrauterine insemination. Setting Multicenter University based clinical practices. Main Outcome Measures Demographic, laboratory, imaging, and survey characteristics. Interventions Collection of baseline demographics, blood samples, and ultrasonographic assessments. Results Demographic characteristics of women receiving clomiphene citrate, letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7± 25.7 months, with 59% primary infertility. More than 1/3 of the women were current or past smokers. The mean BMI was 27 and mean AMH level was 2.6; only 11 women (1.3%) had antral follicle counts of less than 5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. Conclusion The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, AMH levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment subgroups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and clomiphene citrate treatment. PMID:25707331

  1. Angiogenesis interactome and time course microarray data reveal the distinct activation patterns in endothelial cells.

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    Liang-Hui Chu

    Full Text Available Angiogenesis involves stimulation of endothelial cells (EC by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the "angiome" could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A. We used the Short Time-series Expression Miner (STEM to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC and human microvascular EC (MEC. The results show that VEGFR1-VEGFR2 levels are more closely coupled than VEGFR1-VEGFR3 or VEGFR2-VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle.

  2. Comparison of peripheral nerve stimulator versus ultrasonography guided axillary block using multiple injection technique.

    Science.gov (United States)

    Kumar, Alok; Sharma, Dk; Sibi, Maj E; Datta, Barun; Gogoi, Biraj

    2014-01-01

    The established methods of nerve location were based on either proper motor response on nerve stimulation (NS) or ultrasound guidance. In this prospective, randomised, observer-blinded study, we compared ultrasound guidance with NS for axillary brachial plexus block using 0.5% bupivacaine with the multiple injection techniques. A total of 120 patients receiving axillary brachial plexus block with 0.5% bupivacaine, using a multiple injection technique, were randomly allocated to receive either NS (group NS, n = 60), or ultrasound guidance (group US, n = 60) for nerve location. A blinded observer recorded the onset of sensory and motor blocks, skin punctures, needle redirections, procedure-related pain and patient satisfaction. The median (range) number of skin punctures were 2 (2-4) in group US and 3 (2-5) in group NS (P =0.27). Insufficient block was observed in three patient (5%) of group US and four patients (6.67%) of group NS (P > =0.35). Patient acceptance was similarly good in the two groups. Multiple injection axillary blocks with ultrasound guidance provided similar success rates and comparable incidence of complications as compared with NS guidance with 20 ml 0.5% bupivacaine.

  3. Comparison of peripheral nerve stimulator versus ultrasonography guided axillary block using multiple injection technique

    Directory of Open Access Journals (Sweden)

    Alok Kumar

    2014-01-01

    Full Text Available Background: The established methods of nerve location were based on either proper motor response on nerve stimulation (NS or ultrasound guidance. In this prospective, randomised, observer-blinded study, we compared ultrasound guidance with NS for axillary brachial plexus block using 0.5% bupivacaine with the multiple injection techniques. Methods : A total of 120 patients receiving axillary brachial plexus block with 0.5% bupivacaine, using a multiple injection technique, were randomly allocated to receive either NS (group NS, n = 60, or ultrasound guidance (group US, n = 60 for nerve location. A blinded observer recorded the onset of sensory and motor blocks, skin punctures, needle redirections, procedure-related pain and patient satisfaction. Results: The median (range number of skin punctures were 2 (2-4 in group US and 3 (2-5 in group NS (P =0.27. Insufficient block was observed in three patient (5% of group US and four patients (6.67% of group NS (P > =0.35. Patient acceptance was similarly good in the two groups. Conclusion: Multiple injection axillary blocks with ultrasound guidance provided similar success rates and comparable incidence of complications as compared with NS guidance with 20 ml 0.5% bupivacaine.

  4. Time-course of attention biases in social phobia.

    Science.gov (United States)

    Schofield, Casey A; Inhoff, Albrecht W; Coles, Meredith E

    2013-10-01

    Theoretical models of social phobia implicate preferential attention to social threat in the maintenance of anxiety symptoms, though there has been limited work characterizing the nature of these biases over time. The current study utilized eye-movement data to examine the time-course of visual attention over 1500ms trials of a probe detection task. Nineteen participants with a primary diagnosis of social phobia based on DSM-IV criteria and 20 non-clinical controls completed this task with angry, fearful, and happy face trials. Overt visual attention to the emotional and neutral faces was measured in 50ms segments across the trial. Over time, participants with social phobia attend less to emotional faces and specifically less to happy faces compared to controls. Further, attention to emotional relative to neutral expressions did not vary notably by emotion for participants with social phobia, but control participants showed a pattern after 1000ms in which over time they preferentially attended to happy expressions and avoided negative expressions. Findings highlight the importance of considering attention biases to positive stimuli as well as the pattern of attention between groups. These results suggest that attention "bias" in social phobia may be driven by a relative lack of the biases seen in non-anxious participants. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. The time course of attentional deployment in contextual cueing.

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    Jiang, Yuhong V; Sigstad, Heather M; Swallow, Khena M

    2013-04-01

    The time course of attention is a major characteristic on which different types of attention diverge. In addition to explicit goals and salient stimuli, spatial attention is influenced by past experience. In contextual cueing, behaviorally relevant stimuli are more quickly found when they appear in a spatial context that has previously been encountered than when they appear in a new context. In this study, we investigated the time that it takes for contextual cueing to develop following the onset of search layout cues. In three experiments, participants searched for a T target in an array of Ls. Each array was consistently associated with a single target location. In a testing phase, we manipulated the stimulus onset asynchrony (SOA) between the repeated spatial layout and the search display. Contextual cueing was equivalent for a wide range of SOAs between 0 and 1,000 ms. The lack of an increase in contextual cueing with increasing cue durations suggests that as an implicit learning mechanism, contextual cueing cannot be effectively used until search begins.

  6. Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis.

    Science.gov (United States)

    Fiene, Marina; Rufener, Katharina S; Kuehne, Maria; Matzke, Mike; Heinze, Hans-Jochen; Zaehle, Tino

    2018-03-01

    Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient's ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.

  7. Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors

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    Wang Cheng-Li

    2012-08-01

    Full Text Available Abstract Background The fungus of Ganoderma is a traditional medicine in Asia with a variety of pharmacological functions including anti-cancer activities. We have purified an extracellular heteropolysaccharide fraction, PS-F2, from the submerged mycelia culture of G. formosanum and shown that PS-F2 exhibits immunostimulatory activities. In this study, we investigated the molecular mechanisms of immunostimulation by PS-F2. Results PS-F2-stimulated TNF-α production in macrophages was significantly reduced in the presence of blocking antibodies for Dectin-1 and complement receptor 3 (CR3, laminarin, or piceatannol (a spleen tyrosine kinase inhibitor, suggesting that PS-F2 recognition by macrophages is mediated by Dectin-1 and CR3 receptors. In addition, the stimulatory effect of PS-F2 was attenuated in the bone marrow-derived macrophages from C3H/HeJ mice which lack functional Toll-like receptor 4 (TLR4. PS-F2 stimulation triggered the phosphorylation of mitogen-activated protein kinases JNK, p38, and ERK, as well as the nuclear translocation of NF-κB, which all played essential roles in activating TNF-α expression. Conclusions Our results indicate that the extracellular polysaccharides produced by G. formosanum stimulate macrophages via the engagement of multiple pattern-recognition receptors including Dectin-1, CR3 and TLR4, resulting in the activation of Syk, JNK, p38, ERK, and NK-κB and the production of TNF-α.

  8. Fatigue in multiple sclerosis: neural correlates and the role of non-invasive brain stimulation

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    Moussa A. Chalah

    2015-11-01

    Full Text Available Multiple sclerosis (MS is a chronic progressive inflammatory disease of the central nervous system and the major cause of non-traumatic disability in young adults. Fatigue is a frequent symptom reported by the majority of MS patients during their disease course and drastically af-fects their quality of life. Despite its significant prevalence and impact, the underlying patho-physiological mechanisms are not well elucidated. MS fatigue is still considered the result of multifactorial and complex constellations, and is commonly classified into primary fatigue related to the pathological changes of the disease itself, and secondary fatigue attributed to mimicking symptoms, comorbid sleep and mood disorders, and medications side effects. Data from neuroimaging, neurophysiology, neuroendocrine and neuroimmune studies have raised hypotheses regarding the origin of this symptom, some of which have succeeded in identifying an association between MS fatigue and structural or functional abnormalities within various brain networks. Hence, the aim of this work is to reappraise the neural correlates of MS fatigue and to discuss the rationale for the emergent use of noninvasive brain stimulation (NIBS techniques as potential treatments. This will include a presentation of the various NIBS modalities and a proposition of their potential mechanisms of action in this context. Specific issues related to the value of transcranial direct current stimulation will be addressed.

  9. Generalized Correlation Coefficient for Non-Parametric Analysis of Microarray Time-Course Data.

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    Tan, Qihua; Thomassen, Mads; Burton, Mark; Mose, Kristian Fredløv; Andersen, Klaus Ejner; Hjelmborg, Jacob; Kruse, Torben

    2017-06-06

    Modeling complex time-course patterns is a challenging issue in microarray study due to complex gene expression patterns in response to the time-course experiment. We introduce the generalized correlation coefficient and propose a combinatory approach for detecting, testing and clustering the heterogeneous time-course gene expression patterns. Application of the method identified nonlinear time-course patterns in high agreement with parametric analysis. We conclude that the non-parametric nature in the generalized correlation analysis could be an useful and efficient tool for analyzing microarray time-course data and for exploring the complex relationships in the omics data for studying their association with disease and health.

  10. The time course from gender categorization to gender-stereotype activation.

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    Zhang, Xiaobin; Li, Qiong; Sun, Shan; Zuo, Bin

    2018-02-01

    Social categorization is the foundation of stereotype activation, and the process from social categorization to stereotype activation is rapid. However, the time from social categorization to stereotype activation is unknown. This study involves a real-time measurement of the time course of gender-stereotype activation beginning with gender categorization using event-related potential technology with a face as the priming stimulus. We found that 195 ms after a face stimulus was presented, brain waves stimulated by male or female gender categorization showed a clear separation, with male faces stimulating larger N200 waves. In addition, 475 ms after a face stimulus appeared or 280 ms after the gendercategorization process occurred, gender-stereotype-consistent and gender-stereotype-inconsistent stimuli were distinct, with gender-stereotype-inconsistent stimuli inducing larger N400 waves. These results indicate that during gender-stereotype activation by face perception, gender categorization occurs approximately 195 ms after seeing a face stimulus and a gender stereotype is activated at approximately 475 ms.

  11. Tracing the time course of picture--word processing.

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    Smith, M C; Magee, L E

    1980-12-01

    A number of independent lines of research have suggested that semantic and articulatory information become available differentially from pictures and words. The first of the experiments reported here sought to clarify the time course by which information about pictures and words becomes available by considering the pattern of interference generated when incongruent pictures and words are presented simultaneously in a Stroop-like situation. Previous investigators report that picture naming is easily disrupted by the presence of a distracting word but that word naming is relatively immune to interference from an incongruent picture. Under the assumption that information available from a completed process may disrupt an ongoing process, these results suggest that words access articulatory information more rapidly than do pictures. Experiment 1 extended this paradigm by requiring subjects to verify the category of the target stimulus. In accordance with the hypothesis that picture access the semantic code more rapidly than words, there was a reversal in the interference pattern: Word categorization suffered considerable disruption, whereas picture categorization was minimally affected by the presence of an incongruent word. Experiment 2 sought to further test the hypothesis that access to semantic and articulatory codes is different for pictures and words by examining memory for those items following naming or categorization. Categorized words were better recognized than named words, whereas the reverse was true for pictures, a result which suggests that picture naming involves more extensive processing than picture categorization. Experiment 3 replicated this result under conditions in which viewing time was held constant. The last experiment extended the investigation of memory differences to a situation in which subjects were required to generate the superordinate category name. Here, memory for categorized pictures was as good as memory for named pictures. Category

  12. Response variability of different anodal transcranial direct current stimulation intensities across multiple sessions.

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    Ammann, Claudia; Lindquist, Martin A; Celnik, Pablo A

    It is well known that transcranial direct current stimulation (tDCS) is capable of modulating corticomotor excitability. However, a source of growing concern has been the observed inter- and intra-individual variability of tDCS-responses. Recent studies have assessed whether individuals respond in a predictable manner across repeated sessions of anodal tDCS (atDCS). The findings of these investigations have been inconsistent, and their methods have some limitations (i.e. lack of sham condition or testing only one tDCS intensity). To study inter- and intra-individual variability of atDCS effects at two different intensities on primary motor cortex (M1) excitability. Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in three separate conditions (2 mA, 1 mA, sham) each repeated three times separated by 48 h. Motor evoked potentials were recorded before and after stimulation (up to 30min). Time of testing was maintained consistent within participants. To estimate the reliability of tDCS effects across sessions, we calculated the Intra-class Correlation Coefficient (ICC). AtDCS at 2 mA, but not 1 mA, significantly increased cortical excitability at the group level in all sessions. The overall ICC revealed fair to high reliability of tDCS effects for multiple sessions. Given that the distribution of responses showed important variability in the sham condition, we established a Sham Variability-Based Threshold to classify responses and to track individual changes across sessions. Using this threshold an intra-individual consistent response pattern was then observed only for the 2 mA condition. 2 mA anodal tDCS results in consistent intra- and inter-individual increases of M1 excitability. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Transcranial direct current stimulation over multiple days enhances motor performance of a grip task.

    Science.gov (United States)

    Fan, Julie; Voisin, Julien; Milot, Marie-Hélène; Higgins, Johanne; Boudrias, Marie-Hélène

    2017-09-01

    Recovery of handgrip is critical after stroke since it is positively related to upper limb function. To boost motor recovery, transcranial direct current stimulation (tDCS) is a promising, non-invasive brain stimulation technique for the rehabilitation of persons with stroke. When applied over the primary motor cortex (M1), tDCS has been shown to modulate neural processes involved in motor learning. However, no studies have looked at the impact of tDCS on the learning of a grip task in both stroke and healthy individuals. To assess the use of tDCS over multiple days to promote motor learning of a grip task using a learning paradigm involving a speed-accuracy tradeoff in healthy individuals. In a double-blinded experiment, 30 right-handed subjects (mean age: 22.1±3.3 years) participated in the study and were randomly assigned to an anodal (n=15) or sham (n=15) stimulation group. First, subjects performed the grip task with their dominant hand while following the pace of a metronome. Afterwards, subjects trained on the task, at their own pace, over 5 consecutive days while receiving sham or anodal tDCS over M1. After training, subjects performed de novo the metronome-assisted task. The change in performance between the pre and post metronome-assisted task was used to assess the impact of the grip task and tDCS on learning. Anodal tDCS over M1 had a significant effect on the speed-accuracy tradeoff function. The anodal tDCS group showed significantly greater improvement in performance (39.28±15.92%) than the sham tDCS group (24.06±16.35%) on the metronome-assisted task, t(28)=2.583, P=0.015 (effect size d=0.94). Anodal tDCS is effective in promoting grip motor learning in healthy individuals. Further studies are warranted to test its potential use for the rehabilitation of fine motor skills in stroke patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Novel risk stratification with time course assessment of in-hospital mortality in patients with acute heart failure.

    Directory of Open Access Journals (Sweden)

    Takeshi Yagyu

    Full Text Available Patients with acute heart failure (AHF show various clinical courses during hospitalization. We aimed to identify time course predictors of in-hospital mortality and to establish a sequentially assessable risk model.We enrolled 1,035 consecutive AHF patients into derivation (n = 597 and validation (n = 438 cohorts. For risk assessments at admission, we utilized Get With the Guidelines-Heart Failure (GWTG-HF risk scores. We examined significant predictors of in-hospital mortality from 11 variables obtained during hospitalization and developed a risk stratification model using multiple logistic regression analysis. Across both cohorts, 86 patients (8.3% died during hospitalization. Using backward stepwise selection, we identified five time-course predictors: catecholamine administration, minimum platelet concentration, maximum blood urea nitrogen, total bilirubin, and C-reactive protein levels; and established a time course risk score that could sequentially assess a patient's risk status. The addition of a time course risk score improved the discriminative ability of the GWTG-HF risk score (c-statistics in derivation and validation cohorts: 0.776 to 0.888 [p = 0.002] and 0.806 to 0.902 [p<0.001], respectively. A calibration plot revealed a good relationship between observed and predicted in-hospital mortalities in both cohorts (Hosmer-Lemeshow chi-square statistics: 6.049 [p = 0.642] and 5.993 [p = 0.648], respectively. In each group of initial low-intermediate risk (GWTG-HF risk score <47 and initial high risk (GWTG-HF risk score ≥47, in-hospital mortality was about 6- to 9-fold higher in the high time course risk score group than in the low-intermediate time course risk score group (initial low-intermediate risk group: 20.3% versus 2.2% [p<0.001], initial high risk group: 57.6% versus 8.5% [p<0.001].A time course assessment related to in-hospital mortality during the hospitalization of AHF patients can clearly categorize a patient's on

  15. Stimulated Emission Depletion Nanoscopy Reveals Time-Course of Human Immunodeficiency Virus Proteolytic Maturation

    Czech Academy of Sciences Publication Activity Database

    Hanne, J.; Göttfert, F.; Schimer, Jiří; Anders-Össwein, M.; Konvalinka, Jan; Engelhardt, J.; Müller, B.; Hell, S. W.; Kräusslich, H. G.

    2016-01-01

    Roč. 10, č. 9 (2016), s. 8215-8222 ISSN 1936-0851 R&D Projects: GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388963 Keywords : HIV-1 maturation * STED nanoscopy * super-resolution microscopy * native virus imaging Subject RIV: CE - Biochemistry Impact factor: 13.942, year: 2016

  16. Assisting People with Multiple Disabilities Actively Correct Abnormal Standing Posture with a Nintendo Wii Balance Board through Controlling Environmental Stimulation

    Science.gov (United States)

    Shih, Ching-Hsiang; Shih, Ching-Tien; Chu, Chiung-Ling

    2010-01-01

    The latest researches adopted software technology turning the Nintendo Wii Balance Board into a high performance change of standing posture (CSP) detector, and assessed whether two persons with multiple disabilities would be able to control environmental stimulation using body swing (changing standing posture). This study extends Wii Balance Board…

  17. Clinical analysis of electroacupuncture and multiple acupoint stimulation in relieving cancer pain in patients with advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Lili Xu

    2018-01-01

    Conclusion: Cancer pain in patients with advanced hepatocellular carcinoma can be alleviated with electroacupuncture and multiple acupoint stimulation, but the onset pain relief was slow. To improve the analgesic effects of this technique, the combination of various analgesic methods should be necessary in early stage of the treatment.

  18. Generalized Correlation Coefficient for Non-Parametric Analysis of Microarray Time-Course Data

    DEFF Research Database (Denmark)

    Tan, Qihua; Thomassen, Mads; Burton, Mark

    2017-01-01

    the heterogeneous time-course gene expression patterns. Application of the method identified nonlinear time-course patterns in high agreement with parametric analysis. We conclude that the non-parametric nature in the generalized correlation analysis could be an useful and efficient tool for analyzing microarray...... time-course data and for exploring the complex relationships in the omics data for studying their association with disease and health....

  19. Suppression of Stimulated Brillouin Scattering in multiple-ion species inertial confinement fusion Hohlraum Plasmas

    International Nuclear Information System (INIS)

    Neumayer, P

    2007-01-01

    A long-standing problem in the field of laser-plasma interactions is to successfully employ multiple-ion species plasmas to reduce stimulated Brillouin scattering (SBS) in inertial confinement fusion (ICF) hohlraum conditions. Multiple-ion species increase significantly the linear Landau damping for acoustic waves. Consequently, recent hohlraum designs for indirect-drive ignition on the National Ignition Facility investigate wall liner material options so that the liner gain for parametric instabilities will be below threshold for the onset SBS. Although the effect of two-ion species plasmas on Landau damping has been directly observed with Thomson scattering, early experiments on SBS in these plasmas have suffered from competing non-linear effects or laser beam filamentation. In this study, a reduction of SBS scattering to below the percent level has been observed in hohlraums at Omega that emulate the plasma conditions in an indirect drive ICF experiments. These experiments have measured the laser-plasma interaction processes in ignition-relevant high-electron temperature regime demonstrating Landau damping as a controlling process for SBS. The hohlraums have been filled with various fractions of CO 2 and C 3 H 8 varying the ratio of the light (H) to heavy (C and O) ion density from 0 to 2.6. They have been heated by 14.5 kJ of 351-nm light, thus increasing progressively Landau damping by an order of magnitude at constant electron density and temperature. A delayed 351-nm interaction beam, spatially smoothed to produce a 200-(micro)m laser spot at best focus, has propagated along the axis of the hohlraum. The backscattered light, both into the lens and outside, the transmitted light through the hohlraum plasma and the radiation temperature of the hohlraum has been measured. For ignition relevant laser intensities (3-9 10 14 Wcm -2 ), we find that the SBS reflectivity scales as predicted with Landau damping from >30% to <1%. Simultaneously, the hohlraum radiation

  20. Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

    Directory of Open Access Journals (Sweden)

    Boris P Hejblum

    2015-06-01

    Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.

  1. The time course of individual face recognition: A pattern analysis of ERP signals.

    Science.gov (United States)

    Nemrodov, Dan; Niemeier, Matthias; Mok, Jenkin Ngo Yin; Nestor, Adrian

    2016-05-15

    An extensive body of work documents the time course of neural face processing in the human visual cortex. However, the majority of this work has focused on specific temporal landmarks, such as N170 and N250 components, derived through univariate analyses of EEG data. Here, we take on a broader evaluation of ERP signals related to individual face recognition as we attempt to move beyond the leading theoretical and methodological framework through the application of pattern analysis to ERP data. Specifically, we investigate the spatiotemporal profile of identity recognition across variation in emotional expression. To this end, we apply pattern classification to ERP signals both in time, for any single electrode, and in space, across multiple electrodes. Our results confirm the significance of traditional ERP components in face processing. At the same time though, they support the idea that the temporal profile of face recognition is incompletely described by such components. First, we show that signals associated with different facial identities can be discriminated from each other outside the scope of these components, as early as 70ms following stimulus presentation. Next, electrodes associated with traditional ERP components as well as, critically, those not associated with such components are shown to contribute information to stimulus discriminability. And last, the levels of ERP-based pattern discrimination are found to correlate with recognition accuracy across subjects confirming the relevance of these methods for bridging brain and behavior data. Altogether, the current results shed new light on the fine-grained time course of neural face processing and showcase the value of novel methods for pattern analysis to investigating fundamental aspects of visual recognition. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. THE INCREASING OF PRESCHOOL MULTIPLE INTELLIGENCES BY EDUCATIVE PLAYING INSTRUMENT STIMULATION

    Directory of Open Access Journals (Sweden)

    Yuni Sufyanti Arief

    2017-04-01

    Full Text Available Introduction: Multiple Intelligences can be incresed by playing stimulation with educative playing instrument. Educative playing is the activity that uses educate ways and instrument. Educative playing very important to increase speech development, cognitive, socialisation with the environment and also increse the streght and skill of child’s body. Method: Design used in this study was quasy experiment design. The population was preschool children 4–5 years old in working area of Mojo Public Health Centre of Surabaya. The sample was preschool children 4–5 years old that spesific in inclution criteria of this study. Data were analyzed by wilcoxon signed rank test to compare the ordinal data pre and post intervention and mann withney u-test that compare between intervention group and control  group with level of signifi cance of α ≤ 0.05. Result: The result of speech development that analyzed by Wilcoxon signed rank test showed that controlled group had p = 0.157 and intervention group had p = 0.005 and the result of mann whitney test was p = 0.03. The result of kinesthetic development by wilcoxon signed rank test showed that controlled group has p = 0.317 and intervention group has p = 0.005, and analyzed by mann whitney test in kinesthetic development showed the result of p = 0.02. Discussion: Educative playing instrument (picture cards, play dough, origami and meronce increased speech and fine motoric development of preschool children 4–5 years old in Mojo Indah Kindergarten of Surabaya. Educative playing instrument is the activity that makes the playing function optimally in child development and this activity can increase the child development such as physical, speech, cognitive and social adaptation.

  3. Evidence of impaired brain activity balance after passive sensorimotor stimulation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Nikolaos Petsas

    Full Text Available OBJECTIVES: Examination of sensorimotor activation alone in multiple sclerosis (MS patients may not yield a comprehensive view of cerebral response to task stimulation. Additional information may be obtained by examining the negative BOLD response (deactivation. Aim of this work was to characterize activation and deactivation patterns during passive hand movements in MS patients. METHODS: 13 relapsing remitting-MS patients (RRMS, 18 secondary progressive-MS patients (SPMS and 15 healthy controls (HC underwent an fMRI study during passive right-hand movements. Activation and deactivation contrasts in the three groups were entered into ANOVA, age and gender corrected. Post-hoc analysis was performed with one-sample and two-sample t-tests. For each patient we obtained lesion volume (LV from both T1- and T2-weighted images. RESULTS: Activations showed a progressive extension to the ipsilateral brain hemisphere according to the group and the clinical form (HC

  4. Involvement of Subcortical Brain Structures During Olfactory Stimulation in Multiple Chemical Sensitivity.

    Science.gov (United States)

    Alessandrini, Marco; Micarelli, Alessandro; Chiaravalloti, Agostino; Bruno, Ernesto; Danieli, Roberta; Pierantozzi, Mariangela; Genovesi, Giuseppe; Öberg, Johanna; Pagani, Marco; Schillaci, Orazio

    2016-03-01

    Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated (18)F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects' bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints.

  5. Time course of arterial vascular adaptations to inactivity and paralyses in humans.

    NARCIS (Netherlands)

    Groot, P.C.E. de; Kuppevelt, D. van; Pons, C.; Snoek, G.V.E.; Woude, L.H.V. van der; Hopman, M.T.E.

    2003-01-01

    PURPOSE: The aim of the present study was to assess the time course of vascular adaptations to inactivity and paralyses in humans. The spinal cord-injured (SCI) population offers a unique "human model of nature" to assess peripheral vascular adaptations and its time course to extreme inactivity and

  6. Identification of driving network of cellular differentiation from single sample time course gene expression data

    Science.gov (United States)

    Chen, Ye; Wolanyk, Nathaniel; Ilker, Tunc; Gao, Shouguo; Wang, Xujing

    Methods developed based on bifurcation theory have demonstrated their potential in driving network identification for complex human diseases, including the work by Chen, et al. Recently bifurcation theory has been successfully applied to model cellular differentiation. However, there one often faces a technical challenge in driving network prediction: time course cellular differentiation study often only contains one sample at each time point, while driving network prediction typically require multiple samples at each time point to infer the variation and interaction structures of candidate genes for the driving network. In this study, we investigate several methods to identify both the critical time point and the driving network through examination of how each time point affects the autocorrelation and phase locking. We apply these methods to a high-throughput sequencing (RNA-Seq) dataset of 42 subsets of thymocytes and mature peripheral T cells at multiple time points during their differentiation (GSE48138 from GEO). We compare the predicted driving genes with known transcription regulators of cellular differentiation. We will discuss the advantages and limitations of our proposed methods, as well as potential further improvements of our methods.

  7. Mathematical Modeling of Loop Heat Pipes with Multiple Capillary Pumps and Multiple Condensers. Part 1; Stead State Stimulations

    Science.gov (United States)

    Hoang, Triem T.; OConnell, Tamara; Ku, Jentung

    2004-01-01

    Loop Heat Pipes (LHPs) have proven themselves as reliable and robust heat transport devices for spacecraft thermal control systems. So far, the LHPs in earth-orbit satellites perform very well as expected. Conventional LHPs usually consist of a single capillary pump for heat acquisition and a single condenser for heat rejection. Multiple pump/multiple condenser LHPs have shown to function very well in ground testing. Nevertheless, the test results of a dual pump/condenser LHP also revealed that the dual LHP behaved in a complicated manner due to the interaction between the pumps and condensers. Thus it is redundant to say that more research is needed before they are ready for 0-g deployment. One research area that perhaps compels immediate attention is the analytical modeling of LHPs, particularly the transient phenomena. Modeling a single pump/single condenser LHP is difficult enough. Only a handful of computer codes are available for both steady state and transient simulations of conventional LHPs. No previous effort was made to develop an analytical model (or even a complete theory) to predict the operational behavior of the multiple pump/multiple condenser LHP systems. The current research project offered a basic theory of the multiple pump/multiple condenser LHP operation. From it, a computer code was developed to predict the LHP saturation temperature in accordance with the system operating and environmental conditions.

  8. Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor

    OpenAIRE

    Shneyder, Natalya; Lyons, Mark K.; Driver-dunckley, Erika; Evidente, Virgilio Gerald H.

    2012-01-01

    Background: Both hypothyroidism and Hashimoto's thyroiditis (HT) can rarely be associated with cerebellar ataxia. Severe essential tremor (ET) as well as bilateral thalamic deep brain stimulation (DBS) may lead to subtle cerebellar signs. Case Report: We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers c...

  9. Time-course of myocardial perfusion and fatty acid metabolism after coronary reperfusion

    International Nuclear Information System (INIS)

    Sochor, H.; Pachinger, O.; Ogris, E.; Probst, P.; Kaindl, F.

    1985-01-01

    To investigate the relationship and time-course of myocardial perfusion and behaviour of fatty acid uptake and clearance following reperfusion, the authors studied 19 patients after successful intracoronary thrombolysis with Tl-201 and I-123 hepta-decanoic acid (HDA) and planar imaging. Pts were studied acute (A: 48 hours), early (E:6-8 days) and late (L:6-12 months). %-defect size and relative tracer uptake were determined for both markers as well as t1/2 of the early clearance phase for HDA. Late Tl was done as stress test study after dipyridamole infusion. As in a previous report acute HDA uptake-defects were larger than Tl (38 +- 10% vs 24 +- 9%, p<0.05) suggesting a larger area of metabolic impairment than outlined by perfusion. HDA and Tl uptake at A correlated significantly (p<0.01, r=0.86) but HDA uptake was 19% lower than Tl and not different at E and L. Tl stress studies exhibited in 74% reversible ischemia in the area of ''metabolic recovery''. The authors conclude that early after reperfusion uptake of HDA is frequently impaired despite improved perfusion suggesting metabolic derangement showing a slow recovery over time. A multiple tracer approach including metabolic markers may improve the characterization of reperfused myocardium

  10. Weekly Time Course of Neuro-Muscular Adaptation to Intensive Strength Training.

    Science.gov (United States)

    Brown, Niklas; Bubeck, Dieter; Haeufle, Daniel F B; Weickenmeier, Johannes; Kuhl, Ellen; Alt, Wilfried; Schmitt, Syn

    2017-01-01

    Detailed description of the time course of muscular adaptation is rarely found in literature. Thus, models of muscular adaptation are difficult to validate since no detailed data of adaptation are available. In this article, as an initial step toward a detailed description and analysis of muscular adaptation, we provide a case report of 8 weeks of intense strength training with two active, male participants. Muscular adaptations were analyzed on a morphological level with MRI scans of the right quadriceps muscle and the calculation of muscle volume, on a voluntary strength level by isometric voluntary contractions with doublet stimulation (interpolated twitch technique) and on a non-voluntary level by resting twitch torques. Further, training volume and isokinetic power were closely monitored during the training phase. Data were analyzed weekly for 1 week prior to training, pre-training, 8 weeks of training and 2 weeks of detraining (no strength training). Results show a very individual adaptation to the intense strength training protocol. While training volume and isokinetic power increased linearly during the training phase, resting twitch parameters decreased for both participants after the first week of training and stayed below baseline until de-training. Voluntary activation level showed an increase in the first 4 weeks of training, while maximum voluntary contraction showed only little increase compared to baseline. Muscle volume increased for both subjects. Especially training status seemed to influence the acute reaction to intense strength training. Fatigue had a major influence on performance and could only be overcome by one participant. The results give a first detailed insight into muscular adaptation to intense strength training on various levels, providing a basis of data for a validation of muscle fatigue and adaptation models.

  11. Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study

    NARCIS (Netherlands)

    van de Heijning, B. J.; Stolk, M. F.; van Erpecum, K. J.; Renooij, W.; Groen, A. K.; vanBerge-Henegouwen, G. P.

    1994-01-01

    Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid

  12. Face-to-Face or Telematic Cognitive Stimulation in Patients with Multiple Sclerosis and Cognitive Impairment: Why Not Both?

    Directory of Open Access Journals (Sweden)

    C. Guijarro-Castro

    2017-01-01

    Full Text Available Introduction. Cognitive impairment (CI affects 40–65% of patients with multiple sclerosis (MS. Few studies address telematic cognitive stimulation (TCS in MS. The objective of this study is to evaluate the efficacy and impact of telestimulation or distance cognitive stimulation (TCS, with and without the support of face-to-face cognitive stimulation (FCS in cognitive impairment in MS. Methods. Multicentre, prospective, randomised, controlled study. We will include 98 MS patients with EDSS ≤ 6, symbol digit modality test (SDMT ≤ Pc 25, and Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ > 26 points. Patients will be randomised into 3 groups, a TCS group, a mixed TCS/FCS group, and a control group. CS is performed 3 days a week for 3 months. Processing speed, memory, attention, and executive functions will be rehabilitated. FCS will include ecological exercises and strategies. EDSS and a cognitive evaluation (SDMT, CTMT, PASAT, and TAVEC, MSNQ, psychological impact scales (MSIS, and depression (BDI will be carried out, baseline, postrehabilitation, and also 6 and 12 months later, to evaluate the effect of CS in the longer term. Conclusion. This study could help to establish the usefulness of TCS or, in its absence, TCS with face-to-face help for CI in MS. The interest lies in the clear benefits of remote rehabilitation in the daily life of patients.

  13. Boosting Cognition : Effects of Multiple-Session Transcranial Direct Current Stimulation on Working Memory

    NARCIS (Netherlands)

    Talsma, L.J.; Kroese, H.A.; Slagter, H.A.

    Transcranial direct current stimulation (tDCS) is a promising tool for neurocognitive enhancement. Several studies have shown that just a single session of tDCS over the left dorsolateral pFC (lDLPFC) can improve the core cognitive function of working memory (WM) in healthy adults. Yet, recent

  14. Red-IR stimulated luminescence in K-feldspar: Single or multiple trap origin?

    DEFF Research Database (Denmark)

    Andersen, Martin Thalbitzer; Jain, Mayank; Tidemand-Lichtenberg, Peter

    2012-01-01

    We investigate on the origins of the infra-red stimulated luminescence (IRSL) signals in 3 potassium feldspars based on IR-red spectroscopy (700–1050 nm) using a fiber-coupled tunable Ti:Sapphire laser, in combination with different thermal and optical (pre)treatments of the samples. We also...

  15. Cortical activity during olfactory stimulation in multiple chemical sensitivity: a 18F-FDG PET/CT study

    International Nuclear Information System (INIS)

    Chiaravalloti, Agostino; Di Pietro, Barbara; Pagani, Marco; Micarelli, Alessandro; Alessandrini, Marco; Genovesi, Giuseppe; Schillaci, Orazio

    2015-01-01

    To investigate the differences in brain glucose consumption during olfactory stimulation between subjects affected by multiple chemical sensitivity (MCS) and a group of healthy individuals. Two 18 F-FDG PET/CT scans were performed in 26 subjects (6 men and 20 women; mean age 46.7 ± 11 years) with a clinical diagnosis of MCS and in 11 healthy controls (6 women and 5 men; mean age 45.7 ± 11 years), the first scan after a neutral olfactory stimulation (NS) and the second after a pure olfactory stimulation (OS). Differences in 18 F-FDG uptake were analysed by statistical parametric mapping (SPM2). In controls OS led to an increase in glucose consumption in BA 18 and 19 and a reduction in glucose metabolism in BA 10, 11, 32 and 47. In MCS subjects, OS led to an increase in glucose consumption in BA 20, 23, 18 and 37 and a reduction in glucose metabolism in BA 8, 9 and 10. The results of our study suggest that cortical activity in subjects with MCS differs from that in healthy individuals during olfactory stimulation. (orig.)

  16. Cortical activity during olfactory stimulation in multiple chemical sensitivity: a {sup 18}F-FDG PET/CT study

    Energy Technology Data Exchange (ETDEWEB)

    Chiaravalloti, Agostino; Di Pietro, Barbara [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Department of Nuclear Medicine Karolinska Hospital Stockholm, Stockholm (Sweden); Micarelli, Alessandro; Alessandrini, Marco [University Tor Vergata, Department of Medical Science and Translational Medicine, Rome (Italy); Genovesi, Giuseppe [University La Sapienza, Department of Experimental Medicine, Rome (Italy); University La Sapienza, Regional Center for Diagnosis, Treatment and Prevention of MCS, Rome (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy); IRCCS Neuromed, Pozzilli (Italy)

    2015-04-01

    To investigate the differences in brain glucose consumption during olfactory stimulation between subjects affected by multiple chemical sensitivity (MCS) and a group of healthy individuals. Two {sup 18}F-FDG PET/CT scans were performed in 26 subjects (6 men and 20 women; mean age 46.7 ± 11 years) with a clinical diagnosis of MCS and in 11 healthy controls (6 women and 5 men; mean age 45.7 ± 11 years), the first scan after a neutral olfactory stimulation (NS) and the second after a pure olfactory stimulation (OS). Differences in {sup 18}F-FDG uptake were analysed by statistical parametric mapping (SPM2). In controls OS led to an increase in glucose consumption in BA 18 and 19 and a reduction in glucose metabolism in BA 10, 11, 32 and 47. In MCS subjects, OS led to an increase in glucose consumption in BA 20, 23, 18 and 37 and a reduction in glucose metabolism in BA 8, 9 and 10. The results of our study suggest that cortical activity in subjects with MCS differs from that in healthy individuals during olfactory stimulation. (orig.)

  17. Cortical activity during olfactory stimulation in multiple chemical sensitivity: a (18)F-FDG PET/CT study.

    Science.gov (United States)

    Chiaravalloti, Agostino; Pagani, Marco; Micarelli, Alessandro; Di Pietro, Barbara; Genovesi, Giuseppe; Alessandrini, Marco; Schillaci, Orazio

    2015-04-01

    To investigate the differences in brain glucose consumption during olfactory stimulation between subjects affected by multiple chemical sensitivity (MCS) and a group of healthy individuals. Two (18)F-FDG PET/CT scans were performed in 26 subjects (6 men and 20 women; mean age 46.7 ± 11 years) with a clinical diagnosis of MCS and in 11 healthy controls (6 women and 5 men; mean age 45.7 ± 11 years), the first scan after a neutral olfactory stimulation (NS) and the second after a pure olfactory stimulation (OS). Differences in (18)F-FDG uptake were analysed by statistical parametric mapping (SPM2). In controls OS led to an increase in glucose consumption in BA 18 and 19 and a reduction in glucose metabolism in BA 10, 11, 32 and 47. In MCS subjects, OS led to an increase in glucose consumption in BA 20, 23, 18 and 37 and a reduction in glucose metabolism in BA 8, 9 and 10. The results of our study suggest that cortical activity in subjects with MCS differs from that in healthy individuals during olfactory stimulation.

  18. The time-course of cortico-limbic neural responses to air hunger

    OpenAIRE

    Binks, Andrew P.; Evans, Karleyton C.; Reed, Jeffrey D.; Moosavi, Shakeeb H.; Banzett, Robert B.

    2014-01-01

    Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (~45 mmHg). Subjects rated dyspnea (air hunger) via visual analog scale...

  19. Anxiety and its time courses during radiotherapy for non-metastatic breast cancer: A longitudinal study

    OpenAIRE

    Lewis, Florence; Merckaert, Isabelle; Liénard, Aurore; Libert, Yves; Etienne, Anne-Marie; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Van Houtte, Paul; COUCKE, Philippe; Salamon, Emile; Razavi, Darius

    2014-01-01

    Purpose: To our knowledge, no study has specifically assessed the time course of anxiety during radiotherapy (RT). The objective of this study was to assess anxiety time courses in patients with nonmetastatic breast cancer. Material and methods: This multicenter, descriptive longitudinal study included 213 consecutive patients with breast cancer who completed visual analog scales (VASs) assessing state anxiety before and after the RT simulation and the first and last five RT se...

  20. Time Course of the Soleus M Response and H Reflex after Lidocaine Tibial Nerve Block in the Rat

    Directory of Open Access Journals (Sweden)

    Kévin Buffenoir

    2013-01-01

    Full Text Available Aims. In spastic subjects, lidocaine is often used to induce a block predictive of the result provided by subsequent surgery. Lidocaine has been demonstrated to inhibit the Hoffmann (H reflex to a greater extent than the direct motor (M response induced by electrical stimulation, but the timecourse of these responses has not been investigated. Methods. An animal (rat model of the effects of lidocaine on M and H responses was therefore developed to assess this time course. M and H responses were recorded in 18 adult rats before and after application of lidocaine to the sciatic nerve. Results. Two to five minutes after lidocaine injection, M responses were markedly reduced (mean reduction of 44% and H reflexes were completely abolished. Changes were observed more rapidly for the H reflex. The effects of lidocaine then persisted for 100 minutes. The effect of lidocaine was therefore more prolonged on the H reflex than on the M response. Conclusion. This study confirms that lidocaine blocks not only alpha motoneurons but also Ia afferent fibres responsible for the H reflex. The authors describe, for the first time, the detailed time course of the effect of lidocaine on direct or reflex activation of motoneurons in the rat.

  1. Demonstration of a stimulating effect of natural ionizing radiation and of very low radiation doses on cell multiplication

    International Nuclear Information System (INIS)

    Planel, G.; Soleilhavoup, J.P.; Tixador, R.; Croute, F.; Richoilley, G.

    1976-01-01

    Experiments have been carried out to demonstrate a possible effect of natural ionizing radiation. Using lead shielding devices or an underground laboratory, it was shown that a decrease in background irradiation induces a decrease in cell growth rate (experiments carried out on Paramecia). On the other hand, the recovery of a normal irradiation level in shielding devices induces a quite normal cell proliferation. Moreover, small doses of γ rays from 60 Co exhibit a stimulating effect. Variations in cell radiosensitivity to these low doses are reported. Experiments carried out in the underground laboratory and at high altitude show that both telluric radioactivity and cosmic rays contribute to this stimulating effect on cell multiplication. (author)

  2. Stimulation of Lactic Acid Bacteria by a Micrococcus Isolate: Evidence for Multiple Effects

    Science.gov (United States)

    Nath, K. R.; Wagner, B. J.

    1973-01-01

    Growth of, and rate of acid production by, six cultures of lactic acid bacteria were increased in the presence of Micrococcus isolate F4 or a preparation of its capsular material. Concentrations of hydrogen peroxide found in pure cultures of the lactic acid bacteria were not detectable, or were greatly reduced, in mixed culture with Micrococcus isolate F4. The capsular material was not as effective as whole cells in preventing accumulation of H2O2. Catalase stimulated growth of, and the rate of acid production by, the lactic acid bacteria, but not to the same extent as Micrococcus isolate F4 in some cultures. The existence of two mechanisms for micrococcal stimulation of the lactic acid bacteria is postulated. One mechanism involves removal of H2O2; the other has not been characterized. PMID:4199337

  3. Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Amy T. Mccurley

    2010-01-01

    Full Text Available It is well-established that neurons in the adult mammalian central nervous system (CNS are terminally differentiated and, if injured, will be unable to regenerate their connections. In contrast to mammals, zebrafish and other teleosts display a robust neuroregenerative response. Following optic nerve crush (ONX, retinal ganglion cells (RGC regrow their axons to synapse with topographically correct targets in the optic tectum, such that vision is restored in ~21 days. What accounts for these differences between teleostean and mammalian responses to neural injury is not fully understood. A time course analysis of global gene expression patterns in the zebrafish eye after ONX can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration. To define different phases of regeneration after ONX, alpha tubulin 1 ( tuba1 and growth-associated protein 43 ( gap43 , markers previously shown to correspond to morphophological events, were measured by real time quantitative PCR (qPCR. Microarray analysis was then performed at defined intervals (6 hours, 1, 4, 12, and 21 days post-ONX and compared to SHAM. Results show that optic nerve damage induces multiple, phase-related transcriptional programs, with the maximum number of genes changed and highest fold-change occurring at 4 days. Several functional groups affected by optic nerve regeneration, including cell adhesion, apoptosis, cell cycle, energy metabolism, ion channel activity, and calcium signaling, were identified. Utilizing the whole eye allowed us to identify signaling contributions from the vitreous, immune and glial cells as well as the neural cells of the retina. Comparisons between our dataset and transcriptional profiles from other models of regeneration in zebrafish retina, heart and fin revealed a subset of commonly regulated transcripts, indicating shared mechanisms in different regenerating tissues. Knowledge of gene expression patterns in all

  4. Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response

    Directory of Open Access Journals (Sweden)

    Nasrine Bendjilali

    2017-01-01

    Full Text Available Many cells experience hypoxia, or low oxygen, and respond by dramatically altering gene expression. In the yeast Saccharomyces cerevisiae, genes that respond are required for many oxygen-dependent cellular processes, such as respiration, biosynthesis, and redox regulation. To more fully characterize the global response to hypoxia, we exposed yeast to hypoxic conditions, extracted RNA at different times, and performed RNA sequencing (RNA-seq analysis. Time-course statistical analysis revealed hundreds of genes that changed expression by up to 550-fold. The genes responded with varying kinetics suggesting that multiple regulatory pathways are involved. We identified most known oxygen-regulated genes and also uncovered new regulated genes. Reverse transcription-quantitative PCR (RT-qPCR analysis confirmed that the lysine methyltransferase EFM6 and the recombinase DMC1, both conserved in humans, are indeed oxygen-responsive. Looking more broadly, oxygen-regulated genes participate in expected processes like respiration and lipid metabolism, but also in unexpected processes like amino acid and vitamin metabolism. Using principle component analysis, we discovered that the hypoxic response largely occurs during the first 2 hr and then a new steady-state expression state is achieved. Moreover, we show that the oxygen-dependent genes are not part of the previously described environmental stress response (ESR consisting of genes that respond to diverse types of stress. While hypoxia appears to cause a transient stress, the hypoxic response is mostly characterized by a transition to a new state of gene expression. In summary, our results reveal that hypoxia causes widespread and complex changes in gene expression to prepare the cell to function with little or no oxygen.

  5. Pancreatic cellular injury after cardiac surgery with cardiopulmonary bypass: frequency, time course and risk factors.

    Science.gov (United States)

    Nys, Monique; Venneman, Ingrid; Deby-Dupont, Ginette; Preiser, Jean-Charles; Vanbelle, Sophie; Albert, Adelin; Camus, Gérard; Damas, Pierre; Larbuisson, Robert; Lamy, Maurice

    2007-05-01

    Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation (alpha1-protease inhibitor, alpha2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and alpha1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT >or=40 ng/mL, amylase >or=42 IU/mL, and pancreatic isoamylase >or=20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, alpha1-protease inhibitor, and alpha2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively.

  6. Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response.

    Science.gov (United States)

    Bendjilali, Nasrine; MacLeon, Samuel; Kalra, Gurmannat; Willis, Stephen D; Hossian, A K M Nawshad; Avery, Erica; Wojtowicz, Olivia; Hickman, Mark J

    2017-01-05

    Many cells experience hypoxia, or low oxygen, and respond by dramatically altering gene expression. In the yeast Saccharomyces cerevisiae, genes that respond are required for many oxygen-dependent cellular processes, such as respiration, biosynthesis, and redox regulation. To more fully characterize the global response to hypoxia, we exposed yeast to hypoxic conditions, extracted RNA at different times, and performed RNA sequencing (RNA-seq) analysis. Time-course statistical analysis revealed hundreds of genes that changed expression by up to 550-fold. The genes responded with varying kinetics suggesting that multiple regulatory pathways are involved. We identified most known oxygen-regulated genes and also uncovered new regulated genes. Reverse transcription-quantitative PCR (RT-qPCR) analysis confirmed that the lysine methyltransferase EFM6 and the recombinase DMC1, both conserved in humans, are indeed oxygen-responsive. Looking more broadly, oxygen-regulated genes participate in expected processes like respiration and lipid metabolism, but also in unexpected processes like amino acid and vitamin metabolism. Using principle component analysis, we discovered that the hypoxic response largely occurs during the first 2 hr and then a new steady-state expression state is achieved. Moreover, we show that the oxygen-dependent genes are not part of the previously described environmental stress response (ESR) consisting of genes that respond to diverse types of stress. While hypoxia appears to cause a transient stress, the hypoxic response is mostly characterized by a transition to a new state of gene expression. In summary, our results reveal that hypoxia causes widespread and complex changes in gene expression to prepare the cell to function with little or no oxygen. Copyright © 2017 Bendjilali et al.

  7. Studies on laser beam propagation and stimulated scattering in multiple beam experiments

    International Nuclear Information System (INIS)

    Labaune, C.; Lewis, K.; Bandulet, H.; Lewis, K.; Depierreux, S.; Huller, S.; Masson-Laborde, P.E.; Pesme, D.; Riazuelo, G.

    2006-01-01

    The propagation and stimulated scattering of intense laser beams interacting with underdense plasmas are two important issues for inertial confinement fusion (ICF). The purpose of this work was to perform experiments under well-controlled interaction conditions and confront them with numerical simulations to test the physics included in the codes. Experimental diagnostics include time and space resolved images of incident and SBS light and of SBS-ion acoustic activity. New numerical diagnostics, including similar constraints as the experimental ones and the treatment of the propagation of the light between the emitting area and the detectors, have been developed. Particular care was put to include realistic plasma density and velocity profiles, as well as laser pulse shape in the simulations. In the experiments presented in this paper, the interaction beam was used with a random phase plate (RPP) to produce a statistical distribution of speckles in the focal volume. Stimulated Brillouin Scattering (SBS) was described using a decomposition of the spatial scales which provides a predictive modeling of SBS in an expanding mm-scale plasma. Spatial and temporal behavior of the SBS-ion acoustic waves was found to be in good agreement with the experimental ones for two laser intensities. (authors)

  8. Altered time course of amygdala activation during speech anticipation in social anxiety disorder.

    Science.gov (United States)

    Davies, Carolyn D; Young, Katherine; Torre, Jared B; Burklund, Lisa J; Goldin, Philippe R; Brown, Lily A; Niles, Andrea N; Lieberman, Matthew D; Craske, Michelle G

    2017-02-01

    Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Participants (SAD n=58; HC n=16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Repeated measures multi-level modeling analyses were used to examine group differences in time course activity during speech vs. control anticipation for regions of interest, including bilateral amygdala, insula, ventral striatum, and dorsal anterior cingulate cortex. The time course of amygdala activity was more prolonged and less variable throughout speech anticipation in SAD participants compared to HCs, whereas the overall magnitude of amygdala response did not differ between groups. Magnitude and time course of activity was largely similar between groups across other regions of interest. Analyses were restricted to regions of interest and task order was the same across participants due to the nature of deception instructions. Sustained amygdala time course during anticipation may uniquely reflect heightened detection of threat or deficits in emotion regulation in socially anxious individuals. Findings highlight the importance of examining temporal dynamics of amygdala responding. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia

    DEFF Research Database (Denmark)

    Kimberley, Teresa Jacobson; Borich, Michael R; Arora, Sanjeev

    2013-01-01

    , respectively. Behavioral measures included pen force and velocity during handwriting and subjective report. Results: Multiple-session rTMS strengthened intracortical inhibition causing a prolongation of CSP after 3 days of intervention and pen force was reduced at day 1 and 5, leaving other measures unchanged...

  10. Time course analyses of orthographic and phonological priming effects during word recognition in a transparent orthography.

    Science.gov (United States)

    Zeguers, M H T; Snellings, P; Huizenga, H M; van der Molen, M W

    2014-10-01

    In opaque orthographies, the activation of orthographic and phonological codes follows distinct time courses during visual word recognition. However, it is unclear how orthography and phonology are accessed in more transparent orthographies. Therefore, we conducted time course analyses of masked priming effects in the transparent Dutch orthography. The first study used targets with small phonological differences between phonological and orthographic primes, which are typical in transparent orthographies. Results showed consistent orthographic priming effects, yet phonological priming effects were absent. The second study explicitly manipulated the strength of the phonological difference and revealed that both orthographic and phonological priming effects became identifiable when phonological differences were strong enough. This suggests that, similar to opaque orthographies, strong phonological differences are a prerequisite to separate orthographic and phonological priming effects in transparent orthographies. Orthographic and phonological priming appeared to follow distinct time courses, with orthographic codes being quickly translated into phonological codes and phonology dominating the remainder of the lexical access phase.

  11. Added value of multiple versus single sessions of repetitive transcranial magnetic stimulation in predicting motor cortex stimulation efficacy for refractory neuropathic pain.

    Science.gov (United States)

    Pommier, Benjamin; Quesada, Charles; Fauchon, Camille; Nuti, Christophe; Vassal, François; Peyron, Roland

    2018-05-18

    OBJECTIVE Selection criteria for offering patients motor cortex stimulation (MCS) for refractory neuropathic pain are a critical topic of research. A single session of repetitive transcranial magnetic stimulation (rTMS) has been advocated for selecting MCS candidates, but it has a low negative predictive value. Here the authors investigated whether multiple rTMS sessions would more accurately predict MCS efficacy. METHODS Patients included in this longitudinal study could access MCS after at least four rTMS sessions performed 3-4 weeks apart. The positive (PPV) and negative (NPV) predictive values of the four rTMS sessions and the correlation between the analgesic effects of the two treatments were assessed. RESULTS Twelve MCS patients underwent an average of 15.9 rTMS sessions prior to surgery; nine of the patients were rTMS responders. Postoperative follow-up was 57.8 ± 15.6 months (mean ± standard deviation). Mean percentage of pain relief (%R) was 21% and 40% after the first and fourth rTMS sessions, respectively. The corresponding mean durations of pain relief were respectively 2.4 and 12.9 days. A cumulative effect of the rTMS sessions was observed on both %R and duration of pain relief (p < 0.01). The %R value obtained with MCS was 35% after 6 months and 43% at the last follow-up. Both the PPV and NPV of rTMS were 100% after the fourth rTMS session (p = 0.0045). A significant correlation was found between %R or duration of pain relief after the fourth rTMS session and %R at the last MCS follow-up (R 2 = 0.83, p = 0.0003). CONCLUSIONS Four rTMS sessions predicted MCS efficacy better than a single session in neuropathic pain patients. Taking into account the cumulative effects of rTMS, the authors found a high-level correlation between the analgesic effects of rTMS and MCS.

  12. The Time-Course of Lexical Activation during Sentence Comprehension in People with Aphasia

    Science.gov (United States)

    Ferrill, Michelle; Love, Tracy; Walenski, Matthew; Shapiro, Lewis P.

    2012-01-01

    Purpose: To investigate the time-course of processing of lexical items in auditorily presented canonical (subject-verb-object) constructions in young, neurologically unimpaired control participants and participants with left-hemisphere damage and agrammatic aphasia. Method: A cross modal picture priming (CMPP) paradigm was used to test 114 control…

  13. The time course of working memory effects on visual attention differs depending on memory type

    NARCIS (Netherlands)

    Dombrowe, I.; Olivers, C.N.L.; Donk, M.

    2010-01-01

    Previous work has generated inconsistent results with regard to what extent working memory (WM) content guides visual attention. Some studies found effects of easy to verbalize stimuli, whereas others only found an influence of visual memory content. To resolve this, we compared the time courses of

  14. An Analysis of the Time Course of Lexical Processing during Reading

    Science.gov (United States)

    Sheridan, Heather; Reichle, Erik D.

    2016-01-01

    Reingold, Reichle, Glaholt, and Sheridan (2012) reported a gaze-contingent eye-movement experiment in which survival-curve analyses were used to examine the effects of word frequency, the availability of parafoveal preview, and initial fixation location on the time course of lexical processing. The key results of these analyses suggest that…

  15. Time course of the antiproteinuric and antihypertensive effects of direct renin inhibition in type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, F; Rossing, P; Schjoedt, K J

    2008-01-01

    Inhibition of renin with an active site inhibitor, aliskiren, lowers blood pressure (BP) in diabetic patients. Here, we studied the time course of the antihypertensive and antiproteinuric effect of renin inhibition in 15 patients with type 2 diabetes and elevated urinary albumin/creatinine ratios...

  16. The time course of myonuclear accretion during hypertrophy in young adult and older rat plantaris muscle

    NARCIS (Netherlands)

    van der Meer, S.F.T.; Jaspers, R.T.; Jones, D.A.; Degens, H.

    2011-01-01

    To investigate whether accretion of myonuclei precedes or follows the increase in fibre cross-sectional area and whether this time course is affected by age, left plantaris muscle of 5- and 25-month-old male Wistar rats was overloaded by denervation of its synergists for 1, 2 or 4 weeks.

  17. The time-course of alpha neurofeedback training effects in healthy participants

    NARCIS (Netherlands)

    Dekker, M.K.J.; Sitskoorn, M.M.; Denissen, A.; van Boxtel, G.J.M.

    2014-01-01

    The time-course of alpha neurofeedback training (NFT) was investigated in 18 healthy participants who received 15 sessions of training (eyes open), each consisting of three training periods (data are from Van Boxtel et al., 2012). Here we report on the within- and between-session training effects

  18. The time course of temporal preparation in an applied setting: a study of gaming behavior

    NARCIS (Netherlands)

    Los, S.A.; Hoorn, J.F.; Grin, M.; van den Burg, E.

    2013-01-01

    We examined the time course of temporal preparation in the practice of computer gaming. Participants held an infrared rifle to shoot animated figures ("terrorists") that appeared from an elevator that opened briefly after the sound of a bell. The sound was either loud or soft and the interval

  19. Adverse radiation effect after stereotactic radiosurgery for brain metastases : incidence, time course, and risk factors

    NARCIS (Netherlands)

    Sneed, Penny K.; Mendez, Joe; Vemer-van den Hoek, Johanna; Seymour, Zachary A.; Ma, Lijun; Molinaro, Annette M.; Fogh, Shannon E.; Nakamura, Jean L.; McDermott, Michael W.

    OBJECT The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases. METHODS All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at

  20. The visual-auditory color-word Stroop asymmetry and its time course

    NARCIS (Netherlands)

    Roelofs, A.P.A.

    2005-01-01

    Four experiments examined crossmodal versions of the Stroop task in order (1) to look for Stroop asymmetries in color naming, spoken-word naming, and written-word naming and to evaluate the time course of these asymmetries, and (2) to compare these findings to current models of the Stroop effect.

  1. More powerful significant testing for time course gene expression data using functional principal component analysis approaches.

    Science.gov (United States)

    Wu, Shuang; Wu, Hulin

    2013-01-16

    One of the fundamental problems in time course gene expression data analysis is to identify genes associated with a biological process or a particular stimulus of interest, like a treatment or virus infection. Most of the existing methods for this problem are designed for data with longitudinal replicates. But in reality, many time course gene experiments have no replicates or only have a small number of independent replicates. We focus on the case without replicates and propose a new method for identifying differentially expressed genes by incorporating the functional principal component analysis (FPCA) into a hypothesis testing framework. The data-driven eigenfunctions allow a flexible and parsimonious representation of time course gene expression trajectories, leaving more degrees of freedom for the inference compared to that using a prespecified basis. Moreover, the information of all genes is borrowed for individual gene inferences. The proposed approach turns out to be more powerful in identifying time course differentially expressed genes compared to the existing methods. The improved performance is demonstrated through simulation studies and a real data application to the Saccharomyces cerevisiae cell cycle data.

  2. Elucidation of time-dependent systems biology cell response patterns with time course network enrichment

    DEFF Research Database (Denmark)

    Wiwie, Christian; Rauch, Alexander; Haakonsson, Anders

    2018-01-01

    , no methods exist to integrate time series data with networks, thus preventing the identification of time-dependent systems biology responses. We close this gap with Time Course Network Enrichment (TiCoNE). It combines a new kind of human-augmented clustering with a novel approach to network enrichment...

  3. The Slow Developmental Time Course of Real-Time Spoken Word Recognition

    Science.gov (United States)

    Rigler, Hannah; Farris-Trimble, Ashley; Greiner, Lea; Walker, Jessica; Tomblin, J. Bruce; McMurray, Bob

    2015-01-01

    This study investigated the developmental time course of spoken word recognition in older children using eye tracking to assess how the real-time processing dynamics of word recognition change over development. We found that 9-year-olds were slower to activate the target words and showed more early competition from competitor words than…

  4. The initial time-course of headache in patients with spontaneous subarachnoid hemorrhage

    NARCIS (Netherlands)

    Čomić, Hata; Rinkel, Gabriel J.E.; Vergouwen, Mervyn D.I.

    2017-01-01

    Background If acute severe headache disappears early after its onset, the question arises whether subarachnoid hemorrhage (SAH) should still be ruled out. We studied the initial time-course and minimal duration of headache in a consecutive series of neurologically intact patients with spontaneous

  5. The Magnitude and Time Course of Muscle Cross-section Decrease in Intensive Care Unit Patients

    NARCIS (Netherlands)

    Haaf, D. Ten; Hemmen, B.; Meent, H. van de; Bovend'Eerdt, T.J.H.

    2017-01-01

    OBJECTIVE: Bedriddenness and immobilization of patients at an intensive care unit may result in muscle atrophy and devaluation in quality of life. The exact effect of immobilization on intensive care unit patients is not known. The aim of this study was to investigate the magnitude and time course

  6. TIME-COURSE OF ACTION AND INTUBATING CONDITIONS FOLLOWING VECURONIUM, ROCURONIUM AND MIVACURIUM

    NARCIS (Netherlands)

    WIERDA, JMKH; HOMMES, FDM; NAP, HJA; VANDENBROEK, L

    The purpose of this study was to compare the time course of action and tracheal intubating conditions of vecuronium, rocuronium, and mivacurium in anaesthetised patients. Anaesthesia consisted of thiopentone, fentanyl, N2O/O-2 and isoflurane. After a 2 x ED(50) dose the first attempt at tracheal

  7. Time-course analysis of the accumulation of phenols in tomato ...

    African Journals Online (AJOL)

    i.e. cv. Fukuju No. 2) were mock inoculated with buffer only or singly and doubly with potato Virus X (PVX) and/or an attenuated strain (L11A) of tobacco mosaic virus (TMV-L11A) in greenhouse experiments. Time-course analysis of the ...

  8. Time-course of changes in neuronal activity markers following iTBS-TMS of the rat neocortex.

    Science.gov (United States)

    Hoppenrath, Kathrin; Funke, Klaus

    2013-03-01

    In a rat model of transcranial magnetic stimulation we could recently show that intermittent theta-burst stimulation (iTBS) affects the neocortical expression of the immediate early gene products c-Fos and zif268 as well as that of the two glutamic acid decarboxylase isoforms GAD65 and GAD67 and that of the calcium-binding proteins calbindin (CB) and parvalbumin (PV), known as markers of excitatory and inhibitory activity. We now analyzed in more detail the time course of changes in the expression of these proteins at 10, 20, 40, 80 and 160min following a single block of iTBS consisting of 600 stimuli. Initial increase in c-Fos, zif268 and GAD65 (20min) signals transient activation of excitatory and inhibitory neurons, thereafter first followed by a decrease in markers of activity of inhibitory neurons (GAD67, PV, CB: 20-80min) and then by a late decrease in c-Fos and GAD65 expression (160min). The results demonstrate that one iTBS block may have an after-effect of at least two different phases, an early phase with increased neuronal activity (c-Fos, zif268) but also the likelihood of increased GABA-release (GAD65), followed by a late phase (>40min) of reduced neuronal activity in excitatory and inhibitory systems which may indicate a state of reduced excitability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Time-course gene expression data on the transcriptional effects of Aminaphtone on ECV304 endothelial cells

    Directory of Open Access Journals (Sweden)

    Giulia Salazar

    2016-09-01

    Full Text Available We previously showed that Aminaphtone, a drug used in the treatment of chronic venous insufficiency, modulates several vasoactive factors, such as endothelin-1 and adhesion molecules. Here, we provide data of time-course experiments about the effects of Aminaphtone on gene expression at the genome-wide level in human endothelial cells undergoing cytokine stimulation in vitro. ECV-304 endothelial cells were incubated with interleukin-1β (IL-1β in the presence or absence of Aminaphtone for 1, 3, and 6 h. Gene expression profiles were analyzed by microarray. This article contains complete data on the genes significantly modulated by the drug over time. The data are supplemental to our original research article reporting detailed analysis of the actions of Aminaphtone on IL-1β stimulated endothelial cells at the molecular level, ''Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells'' (Salazar et al., 2016 [1]. Chemical compound studied in this article: Aminaphtone (PubChem CID: 84621, Keywords: Endothelial cells, Transcriptome, Inflammation, Vasoactive drug

  10. Activation of Human Peripheral Blood Eosinophils by Cytokines in a Comparative Time-Course Proteomic/Phosphoproteomic Study.

    Science.gov (United States)

    Soman, Kizhake V; Stafford, Susan J; Pazdrak, Konrad; Wu, Zheng; Luo, Xuemei; White, Wendy I; Wiktorowicz, John E; Calhoun, William J; Kurosky, Alexander

    2017-08-04

    Activated eosinophils contribute to airway dysfunction and tissue remodeling in asthma and thus are considered to be important factors in asthma pathology. We report here comparative proteomic and phosphoproteomic changes upon activation of eosinophils using eight cytokines individually and in selected cytokine combinations in time-course reactions. Differential protein and phosphoprotein expressions were determined by mass spectrometry after 2-dimensional gel electrophoresis (2DGE) and by LC-MS/MS. We found that each cytokine-stimulation produced significantly different changes in the eosinophil proteome and phosphoproteome, with phosphoproteomic changes being more pronounced and having an earlier onset. Furthermore, we observed that IL-5, GM-CSF, and IL-3 showed the greatest change in protein expression and phosphorylation, and this expression differed markedly from those of the other five cytokines evaluated. Comprehensive univariate and multivariate statistical analyses were employed to evaluate the comparative results. We also monitored eosinophil activation using flow cytometry (FC) analysis of CD69. In agreement with our proteomic studies, FC indicated that IL-5, GM-CSF, and IL-3 were more effective than the other five cytokines studied in stimulating a cell surface CD69 increase indicative of eosinophil activation. Moreover, selected combinations of cytokines revealed proteomic patterns with many proteins in common with single cytokine expression patterns but also showed a greater effect of the two cytokines employed, indicating a more complex signaling pathway that was reflective of a more typical inflammatory pathology.

  11. Three-dimensional weight-accumulation algorithm for generating multiple excitation spots in fast optical stimulation

    Science.gov (United States)

    Takiguchi, Yu; Toyoda, Haruyoshi

    2017-11-01

    We report here an algorithm for calculating a hologram to be employed in a high-access speed microscope for observing sensory-driven synaptic activity across all inputs to single living neurons in an intact cerebral cortex. The system is based on holographic multi-beam generation using a two-dimensional phase-only spatial light modulator to excite multiple locations in three dimensions with a single hologram. The hologram was calculated with a three-dimensional weighted iterative Fourier transform method using the Ewald sphere restriction to increase the calculation speed. Our algorithm achieved good uniformity of three dimensionally generated excitation spots; the standard deviation of the spot intensities was reduced by a factor of two compared with a conventional algorithm.

  12. A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS).

    Science.gov (United States)

    Kasschau, Margaret; Sherman, Kathleen; Haider, Lamia; Frontario, Ariana; Shaw, Michael; Datta, Abhishek; Bikson, Marom; Charvet, Leigh

    2015-12-26

    Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access. Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.

  13. Stimulation of Toll-like receptor-1/2 combined with Velcade increases cytotoxicity to human multiple myeloma cells

    International Nuclear Information System (INIS)

    Abdi, J; Mutis, T; Garssen, J; Redegeld, F

    2013-01-01

    An increasing body of evidence supports the important role of adhesion to bone marrow microenvironment components for survival and drug resistance of multiple myeloma (MM) cells. Previous studies suggested that stimulation of Toll-like receptors by endogenous ligands released during inflammation and tissue damage may be pro-tumorigenic, but no studies have been performed in relation to modulation of cell adhesion and drug cytotoxicity. Here, we investigated the effect of TLR1/2 activation on adhesion of human myeloma cells to fibronectin, and their sensitivity to the proteasome inhibitor Velcade. It was found that TLR1/2 activation with Pam3CSK4 increased the cytotoxicity of Velcade in L363, OPM-2 and U266 human myeloma cells. This effect was not related to a decreased adhesion of the cells to fibronectin, but TLR1/2 activation stimulated the caspase-3 activity in Velcade-treated myeloma cells, which may be responsible for the enhanced cell death. Inhibitors of NF-κB and MAPK reduced the stimulatory effect. These findings indicate that TLR activation of MM cells could bypass protective effects of cell adhesion and suggest that TLR signaling may also have antitumorigenic potential

  14. Modulation of the Left Prefrontal Cortex with High Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Gait in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Amer M. Burhan

    2015-01-01

    Full Text Available Multiple Sclerosis (MS is a chronic central nervous system (CNS demyelinating disease. Gait abnormalities are common and disabling in patients with MS with limited treatment options available. Emerging evidence suggests a role of prefrontal attention networks in modulating gait. High-frequency repetitive transcranial magnetic stimulation (rTMS is known to enhance cortical excitability in stimulated cortex and its correlates. We investigated the effect of high-frequency left prefrontal rTMS on gait parameters in a 51-year-old Caucasian male with chronic relapsing/remitting MS with residual disabling attention and gait symptoms. Patient received 6 Hz, rTMS at 90% motor threshold using figure of eight coil centered on F3 location (using 10-20 electroencephalography (EEG lead localization system. GAITRite gait analysis system was used to collect objective gait measures before and after one session and in another occasion three consecutive daily sessions of rTMS. Two-tailed within subject repeated measure t-test showed significant enhancement in ambulation time, gait velocity, and cadence after three consecutive daily sessions of rTMS. Modulating left prefrontal cortex excitability using rTMS resulted in significant change in gait parameters after three sessions. To our knowledge, this is the first report that demonstrates the effect of rTMS applied to the prefrontal cortex on gait in MS patients.

  15. Using Functional Electrical Stimulation Mediated by Iterative Learning Control and Robotics to Improve Arm Movement for People With Multiple Sclerosis.

    Science.gov (United States)

    Sampson, Patrica; Freeman, Chris; Coote, Susan; Demain, Sara; Feys, Peter; Meadmore, Katie; Hughes, Ann-Marie

    2016-02-01

    Few interventions address multiple sclerosis (MS) arm dysfunction but robotics and functional electrical stimulation (FES) appear promising. This paper investigates the feasibility of combining FES with passive robotic support during virtual reality (VR) training tasks to improve upper limb function in people with multiple sclerosis (pwMS). The system assists patients in following a specified trajectory path, employing an advanced model-based paradigm termed iterative learning control (ILC) to adjust the FES to improve accuracy and maximise voluntary effort. Reaching tasks were repeated six times with ILC learning the optimum control action from previous attempts. A convenience sample of five pwMS was recruited from local MS societies, and the intervention comprised 18 one-hour training sessions over 10 weeks. The accuracy of tracking performance without FES and the amount of FES delivered during training were analyzed using regression analysis. Clinical functioning of the arm was documented before and after treatment with standard tests. Statistically significant results following training included: improved accuracy of tracking performance both when assisted and unassisted by FES; reduction in maximum amount of FES needed to assist tracking; and less impairment in the proximal arm that was trained. The system was well tolerated by all participants with no increase in muscle fatigue reported. This study confirms the feasibility of FES combined with passive robot assistance as a potentially effective intervention to improve arm movement and control in pwMS and provides the basis for a follow-up study.

  16. Microbial uptake of radiolabeled substrates: estimates of growth rates from time course measurements

    International Nuclear Information System (INIS)

    Li, W.K.W.

    1984-01-01

    The uptake of [ 3 H]glucose and a mixture of 3 H-labeled amino acids was measured, in time course fashion, in planktonic microbial assemblages of the eastern tropical Pacific Ocean. The average generation times of those portions of the assemblages able to utilize these substrates were estimated from a simple exponential growth model. Other workers have independently used this model in its integrated or differential form. A mathematical verification and an experimental demonstration of the equivalence of the two approaches are presented. A study was made of the size distribution of heterotrophic activity, using time course measurements. It was found that the size distribution and the effect of sample filtration before radiolabeling were dependent on time of incubation. In principle, it was possible to ascribe these time dependences to differences in th specific growth rate and initial standing stock of the microbial assemblages. 33 references

  17. The time course of location-avoidance learning in fear of spiders.

    Science.gov (United States)

    Rinck, Mike; Koene, Marieke; Telli, Sibel; Moerman-van den Brink, Wiltine; Verhoeven, Barbara; Becker, Eni S

    2016-01-01

    Two experiments were designed to study the time course of avoidance learning in spider fearfuls (SFs) under controlled experimental conditions. To achieve this, we employed an immersive virtual environment (IVE): While walking freely through a virtual art museum to search for specific paintings, the participants were exposed to virtual spiders. Unbeknown to the participants, only two of four museum rooms contained spiders, allowing for avoidance learning. Indeed, the more SF the participants were, the faster they learned to avoid the rooms that contained spiders (Experiment. 1), and within the first six trials, high fearfuls already developed a preference for starting their search task in rooms without spiders (Experiment 2). These results illustrate the time course of avoidance learning in SFs, and they speak to the usefulness of IVEs in fundamental anxiety research.

  18. The time-course of cortico-limbic neural responses to air hunger.

    Science.gov (United States)

    Binks, Andrew P; Evans, Karleyton C; Reed, Jeffrey D; Moosavi, Shakeeb H; Banzett, Robert B

    2014-12-01

    Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak 40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The time course of the influence of colour terms on visual processing

    OpenAIRE

    Forder, Lewis

    2016-01-01

    This thesis explores whether colour terms (e.g., “red”, “blue”, “purple”, etc.) influence visual processing of colour, and if so, the time course of any effect. Broadly, this issue relates to debate concerning whether language affects the way we perceive the world (i.e., the theory of linguistic relativity). Three of the experiments conducted used the event-related potential method (ERP), taking electrophysiological measurements of visual processing and visual cognition in human participants....

  20. Time course of Chinese monosyllabic spoken word recognition: evidence from ERP analyses.

    Science.gov (United States)

    Zhao, Jingjing; Guo, Jingjing; Zhou, Fengying; Shu, Hua

    2011-06-01

    Evidence from event-related potential (ERP) analyses of English spoken words suggests that the time course of English word recognition in monosyllables is cumulative. Different types of phonological competitors (i.e., rhymes and cohorts) modulate the temporal grain of ERP components differentially (Desroches, Newman, & Joanisse, 2009). The time course of Chinese monosyllabic spoken word recognition could be different from that of English due to the differences in syllable structure between the two languages (e.g., lexical tones). The present study investigated the time course of Chinese monosyllabic spoken word recognition using ERPs to record brain responses online while subjects listened to spoken words. During the experiment, participants were asked to compare a target picture with a subsequent picture by judging whether or not these two pictures belonged to the same semantic category. The spoken word was presented between the two pictures, and participants were not required to respond during its presentation. We manipulated phonological competition by presenting spoken words that either matched or mismatched the target picture in one of the following four ways: onset mismatch, rime mismatch, tone mismatch, or syllable mismatch. In contrast to the English findings, our findings showed that the three partial mismatches (onset, rime, and tone mismatches) equally modulated the amplitudes and time courses of the N400 (a negative component that peaks about 400ms after the spoken word), whereas, the syllable mismatched words elicited an earlier and stronger N400 than the three partial mismatched words. The results shed light on the important role of syllable-level awareness in Chinese spoken word recognition and also imply that the recognition of Chinese monosyllabic words might rely more on global similarity of the whole syllable structure or syllable-based holistic processing rather than phonemic segment-based processing. We interpret the differences in spoken word

  1. Time-Course Analysis of the Neuroanatomical Correlates of Sexual Arousal Evoked by Erotic Video Stimuli in Healthy Males

    Energy Technology Data Exchange (ETDEWEB)

    Sundaram, Thirunavukkarasu; Jeong, Gwang Woo; Kim, Tae Hoon; Kim, Gwang Won; Baek, Han Su; Kang, Heoung Keun [Chonnam National University Hospital, Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2010-06-15

    To assess the dynamic activations of the key brain areas associated with the time-course of the sexual arousal evoked by visual sexual stimuli in healthy male subjects. Fourteen right-handed heterosexual male volunteers participated in this study. Alternatively combined rest period and erotic video visual stimulation were used according to the standard block design. In order to illustrate and quantify the spatiotemporal activation patterns of the key brain regions, the activation period was divided into three different stages as the EARLY, MID and LATE stages. For the group result (p < 0.05), when comparing the MID stage with the EARLY stage, a significant increase of the brain activation was observed in the areas that included the inferior frontal gyrus, the supplementary motor area, the hippocampus, the head of the caudate nucleus, the midbrain, the superior occipital gyrus and the fusiform gyrus. At the same time, when comparing the EARLY stage with the MID stage, the putamen, the globus pallidus, the pons, the thalamus, the hypothalamus, the lingual gyrus and the cuneus yielded significantly increased activations. When comparing the LATE stage with the MID stage, all the above mentioned brain regions showed elevated activations except the hippocampus. Our results illustrate the spatiotemporal activation patterns of the key brain regions across the three stages of visual sexual arousal.

  2. Time-course analysis of the neuroanatomical correlates of sexual arousal evoked by erotic video stimuli in healthy males.

    Science.gov (United States)

    Sundaram, Thirunavukkarasu; Jeong, Gwang-Woo; Kim, Tae-Hoon; Kim, Gwang-Won; Baek, Han-Su; Kang, Heoung-Keun

    2010-01-01

    To assess the dynamic activations of the key brain areas associated with the time-course of the sexual arousal evoked by visual sexual stimuli in healthy male subjects. Fourteen right-handed heterosexual male volunteers participated in this study. Alternatively combined rest period and erotic video visual stimulation were used according to the standard block design. In order to illustrate and quantify the spatiotemporal activation patterns of the key brain regions, the activation period was divided into three different stages as the EARLY, MID and LATE stages. For the group result (p < 0.05), when comparing the MID stage with the EARLY stage, a significant increase of the brain activation was observed in the areas that included the inferior frontal gyrus, the supplementary motor area, the hippocampus, the head of the caudate nucleus, the midbrain, the superior occipital gyrus and the fusiform gyrus. At the same time, when comparing the EARLY stage with the MID stage, the putamen, the globus pallidus, the pons, the thalamus, the hypothalamus, the lingual gyrus and the cuneus yielded significantly increased activations. When comparing the LATE stage with the MID stage, all the above mentioned brain regions showed elevated activations except the hippocampus. Our results illustrate the spatiotemporal activation patterns of the key brain regions across the three stages of visual sexual arousal.

  3. Time-Course Analysis of the Neuroanatomical Correlates of Sexual Arousal Evoked by Erotic Video Stimuli in Healthy Males

    International Nuclear Information System (INIS)

    Sundaram, Thirunavukkarasu; Jeong, Gwang Woo; Kim, Tae Hoon; Kim, Gwang Won; Baek, Han Su; Kang, Heoung Keun

    2010-01-01

    To assess the dynamic activations of the key brain areas associated with the time-course of the sexual arousal evoked by visual sexual stimuli in healthy male subjects. Fourteen right-handed heterosexual male volunteers participated in this study. Alternatively combined rest period and erotic video visual stimulation were used according to the standard block design. In order to illustrate and quantify the spatiotemporal activation patterns of the key brain regions, the activation period was divided into three different stages as the EARLY, MID and LATE stages. For the group result (p < 0.05), when comparing the MID stage with the EARLY stage, a significant increase of the brain activation was observed in the areas that included the inferior frontal gyrus, the supplementary motor area, the hippocampus, the head of the caudate nucleus, the midbrain, the superior occipital gyrus and the fusiform gyrus. At the same time, when comparing the EARLY stage with the MID stage, the putamen, the globus pallidus, the pons, the thalamus, the hypothalamus, the lingual gyrus and the cuneus yielded significantly increased activations. When comparing the LATE stage with the MID stage, all the above mentioned brain regions showed elevated activations except the hippocampus. Our results illustrate the spatiotemporal activation patterns of the key brain regions across the three stages of visual sexual arousal

  4. Rehabilitation of Motor Function after Stroke: A Multiple Systematic Review Focused on Techniques to Stimulate Upper Extremity Recovery

    Science.gov (United States)

    Hatem, Samar M.; Saussez, Geoffroy; della Faille, Margaux; Prist, Vincent; Zhang, Xue; Dispa, Delphine; Bleyenheuft, Yannick

    2016-01-01

    Stroke is one of the leading causes for disability worldwide. Motor function deficits due to stroke affect the patients' mobility, their limitation in daily life activities, their participation in society and their odds of returning to professional activities. All of these factors contribute to a low overall quality of life. Rehabilitation training is the most effective way to reduce motor impairments in stroke patients. This multiple systematic review focuses both on standard treatment methods and on innovating rehabilitation techniques used to promote upper extremity motor function in stroke patients. A total number of 5712 publications on stroke rehabilitation was systematically reviewed for relevance and quality with regards to upper extremity motor outcome. This procedure yielded 270 publications corresponding to the inclusion criteria of the systematic review. Recent technology-based interventions in stroke rehabilitation including non-invasive brain stimulation, robot-assisted training, and virtual reality immersion are addressed. Finally, a decisional tree based on evidence from the literature and characteristics of stroke patients is proposed. At present, the stroke rehabilitation field faces the challenge to tailor evidence-based treatment strategies to the needs of the individual stroke patient. Interventions can be combined in order to achieve the maximal motor function recovery for each patient. Though the efficacy of some interventions may be under debate, motor skill learning, and some new technological approaches give promising outcome prognosis in stroke motor rehabilitation. PMID:27679565

  5. Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis.

    Science.gov (United States)

    Tedesco Triccas, L; Burridge, J H; Hughes, A M; Pickering, R M; Desikan, M; Rothwell, J C; Verheyden, G

    2016-01-01

    To systematically review the methodology in particular treatment options and outcomes and the effect of multiple sessions of transcranial direct current stimulation (tDCS) with rehabilitation programmes for upper extremity recovery post stroke. A search was conducted for randomised controlled trials involving tDCS and rehabilitation for the upper extremity in stroke. Quality of included studies was analysed using the Modified Downs and Black form. The extent of, and effect of variation in treatment parameters such as anodal, cathodal and bi-hemispheric tDCS on upper extremity outcome measures of impairment and activity were analysed using meta-analysis. Nine studies (371 participants with acute, sub-acute and chronic stroke) were included. Different methodologies of tDCS and upper extremity intervention, outcome measures and timing of assessments were identified. Real tDCS combined with rehabilitation had a small non-significant effect of +0.11 (p=0.44) and +0.24 (p=0.11) on upper extremity impairments and activities at post-intervention respectively. Various tDCS methods have been used in stroke rehabilitation. The evidence so far is not statistically significant, but is suggestive of, at best, a small beneficial effect on upper extremity impairment. Future research should focus on which patients and rehabilitation programmes are likely to respond to different tDCS regimes. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Rehabilitation of motor function after stroke: a multiple systematic review focused on techniques to stimulate upper extremity recovery

    Directory of Open Access Journals (Sweden)

    Samar M Hatem

    2016-09-01

    Full Text Available Stroke is one of the leading causes for disability worldwide. Motor function deficits due to stroke affect the patients’ mobility, their limitation in daily life activities, their participation in society and their odds of returning to professional activities. All of these factors contribute to a low overall quality of life. Rehabilitation training is the most effective way to reduce motor impairments in stroke patients. This multiple systematic review focuses both on standard treatment methods and on innovating rehabilitation techniques used to promote upper extremity motor function in stroke patients. A total number of 5712 publications on stroke rehabilitation was systematically reviewed for relevance and quality with regards to upper extremity motor outcome. This procedure yielded 270 publications corresponding to the inclusion criteria of the systematic review. Recent technology-based interventions in stroke rehabilitation including non-invasive brain stimulation, robot-assisted training and virtual reality immersion are addressed. Finally, a decisional tree based on evidence from the literature and characteristics of stroke patients is proposed.At present, the stroke rehabilitation field faces the challenge to tailor evidence-based treatment strategies to the needs of the individual stroke patient. Interventions can be combined in order to achieve the maximal motor function recovery for each patient. Though the efficacy of some interventions may be under debate, motor skill learning and some new technological approaches give promising outcome prognosis in stroke motor rehabilitation.

  7. Fluvoxamine stimulates oligodendrogenesis of cultured neural stem cells and attenuates inflammation and demyelination in an animal model of multiple sclerosis.

    Science.gov (United States)

    Ghareghani, Majid; Zibara, Kazem; Sadeghi, Heibatollah; Dokoohaki, Shima; Sadeghi, Hossein; Aryanpour, Roya; Ghanbari, Amir

    2017-07-07

    Multiple Sclerosis (MS) require medications controlling severity of the pathology and depression, affecting more than half of the patients. In this study, the effect of antidepressant drug fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in vitro and in vivo. Nanomolar concentrations of fluvoxamine significantly increased cell viability and proliferation of neural stem cells (NSCs) through increasing mRNA expression of Notch1, Hes1 and Ki-67, and protein levels of NICD. Also, physiological concentrations of fluvoxamine were optimal for NSC differentiation toward oligodendrocytes, astrocytes and neurons. In addition, fluvoxamine attenuated experimental autoimmune encephalomyelitis (EAE) severity, a rat MS model, by significantly decreasing its clinical scores. Moreover, fluvoxamine treated EAE rats showed a decrease in IFN-γ serum levels and an increase in IL-4, pro- and anti-inflammatory cytokines respectively, compared to untreated EAE rats. Furthermore, immune cell infiltration and demyelination plaque significantly decreased in spinal cords of fluvoxamine-treated rats, which was accompanied by an increase in protein expression of MBP and GFAP positive cells and a decrease in lactate serum levels, a new biomarker of MS progression. In summary, besides its antidepressant activity, fluvoxamine stimulates proliferation and differentiation of NSCs particularly toward oligodendrocytes, a producer of CNS myelin.

  8. Current evidence on the potential therapeutic applications of transcranial magnetic stimulation in multiple sclerosis: A systematic review of the literature.

    Science.gov (United States)

    León Ruiz, M; Sospedra, M; Arce Arce, S; Tejeiro-Martínez, J; Benito-León, J

    2018-06-10

    A growing number of studies have evaluated the effects of transcranial magnetic stimulation (TMS) for the symptomatic treatment of multiple sclerosis (MS). We performed a PubMed search for articles, recent books, and recommendations from the most relevant clinical practice guidelines and scientific societies regarding the use of TMS as symptomatic treatment in MS. Excitatory electromagnetic pulses applied to the affected cerebral hemisphere allow us to optimise functional brain activity, including the transmission of nerve impulses through the demyelinated corticospinal pathway. Various studies into TMS have shown statistically significant improvements in spasticity, fatigue, lower urinary tract dysfunction, manual dexterity, gait, and cognitive deficits related to working memory in patients with MS; however, the exact level of evidence has not been defined as the results have not been replicated in a sufficient number of controlled studies. Further well-designed, randomised, controlled clinical trials involving a greater number of patients are warranted to attain a higher level of evidence in order to recommend the appropriate use of TMS in MS patients across the board. TMS acts as an adjuvant with other symptomatic and immunomodulatory treatments. Additional studies should specifically investigate the effect of conventional repetitive TMS on fatigue in these patients, something that has yet to see the light of day. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Onset of surface stimulated emission at 260 nm from AlGaN multiple quantum wells

    International Nuclear Information System (INIS)

    Li, Xiaohang; Xie, Hongen; Ponce, Fernando A.; Ryou, Jae-Hyun; Detchprohm, Theeradetch; Dupuis, Russell D.

    2015-01-01

    We demonstrated onset of deep-ultraviolet (DUV) surface stimulated emission (SE) from c-plane AlGaN multiple-quantum well (MQW) heterostructures grown on a sapphire substrate by optical pumping at room temperature. The onset of SE became observable at a pumping power density of 630 kW/cm 2 . Spectral deconvolution revealed superposition of a linearly amplified spontaneous emission peak at λ ∼ 257.0 nm with a full width at half maximum (FWHM) of ∼12 nm and a superlinearly amplified SE peak at λ ∼ 260 nm with a narrow FWHM of less than 2 nm. In particular, the wavelength of ∼260 nm is the shortest wavelength of surface SE from III-nitride MQW heterostructures to date. Atomic force microscopy and scanning transmission electron microscopy measurements were employed to investigate the material and structural quality of the AlGaN heterostructures, showing smooth surface and sharp layer interfaces. This study offers promising results for AlGaN heterostructures grown on sapphire substrates for the development of DUV vertical cavity surface emitting lasers (VCSELs)

  10. The Development of LinguaBytes : An Interactive Tangible Play and Learning System to Stimulate the Language Development of Toddlers with Multiple Disabilities

    NARCIS (Netherlands)

    Hengeveld, B.; Voort, R.; Hummels, C.; De Moor, J.; Van Balkom, H.; Overbeeke, K.; Van der Helm, A.

    2008-01-01

    Young children with multiple disabilities (e.g., both cognitive and motor disabilities) are confronted with severe limitations in language development from birth and later on. Stimulating the adult-child communication can decrease these limitations. Within LinguaBytes, a three-year research program,

  11. A New Standing Posture Detector to Enable People with Multiple Disabilities to Control Environmental Stimulation by Changing Their Standing Posture through a Commercial Wii Balance Board

    Science.gov (United States)

    Shih, Ching-Hsiang; Shih, Ching-Tien; Chiang, Ming-Shan

    2010-01-01

    This study assessed whether two persons with multiple disabilities would be able to control environmental stimulation using body swing (changing standing posture) and a Wii Balance Board with a newly developed standing posture detection program (i.e. a new software program turns a Wii Balance Board into a precise standing posture detector). The…

  12. A Limb Action Detector Enabling People with Multiple Disabilities to Control Environmental Stimulation through Limb Action with a Nintendo Wii Remote Controller

    Science.gov (United States)

    Shih, Ching-Hsiang; Chang, Man-Ling; Shih, Ching-Tien

    2010-01-01

    This study assessed whether two persons with multiple disabilities would be able to control environmental stimulation using limb action with a Nintendo Wii Remote Controller and a newly developed limb action detection program (LADP, i.e., a new software program that turns a Wii Remote Controller into a precise limb action detector). This study was…

  13. Diabetes patients show different time-course of myocardial perfusion improvement after coronary artery bypass grafting

    International Nuclear Information System (INIS)

    Lee, J. J.; Seok, J. W.; Eo, J. S.

    2005-01-01

    Diabetes mellitus is an independent risk factor of cardiovascular disease. Diabetes is known to cause microangiopathy. The microangiopathy is hardly detectable on the coronary angiography. Myocardial perfusion imaging shows the resultant perfusion status which reflects the microangiopathy. For patients who underwent revascularization, the microangiopathy could affect the myocardial perfusion improvement. Diabetes patients probably experience the different myocardial perfusion improvement as compared to the non-diabetes patients although they have similar angiographic findings. The aim of this study is to find out whether there is a time-course difference of perfusion improvement between the diabetes and non diabetes patients who showed patent angiographic findings after coronary artery grafting surgery (CABG). A total of 129 patients who underwent coronary artery bypass grafting surgery were enrolled in this study. Myocardial SPECTs performed at previous, short-term (3 month), and mid-term (1 year) to CABG. One-year follow up angiography was done 411±121 days after surgery. Graft patency was determined according to the FitzGibbon et al. Segments were assigned to vascular territories using a 20 segment model. The segments of excellent patency were included in this study. Time course differences of concerned segments were analyzed using RMANOVA. The number of segments enrolled was 764 of diabetes and 1083 of non-diabetes. At short-term follow up, reversibility score was 2.8±8.1% in diabetes and 0.3±7.5% in non-diabetes. At long-term follow up, reversibility score was 1.8±8.0% in diabetes and 0.1±7.3% in non-diabetes. The time-course of reversibility score was significantly different between the diabetes and non diabetes (p<0.001) Diabetic segments showed high residual reversibility score than non-diabetic segments after CABG although the angiographic finding was patent in both groups. This result is maybe attributable to microangiopathy induced by diabetes

  14. Time course of cognitive recovery after propofol anaesthesia: a level of processing approach.

    Science.gov (United States)

    N'Kaoua, Bernard; Véron, Anne-Lise H; Lespinet, Véronique C; Claverie, Bernard; Sztark, François

    2002-09-01

    The aim of this study was to investigate the time course of recovery of verbal memory after general anaesthesia, as a function of the level (shallow or deep) of processing induced at the time of encoding. Thirty-one patients anaesthetized with propofol and alfentanil were compared with 28 control patients receiving only alfentanil. Memory functions were assessed the day before and 1, 6 and 24 hr after operation. Results show that for the anaesthetized group, shallow processing was impaired for 6 hr after surgery whereas the deeper processing was not recovered even at 24 hr. In addition, no specific effect of age was found.

  15. Comparative analysis of clustering methods for gene expression time course data

    Directory of Open Access Journals (Sweden)

    Ivan G. Costa

    2004-01-01

    Full Text Available This work performs a data driven comparative study of clustering methods used in the analysis of gene expression time courses (or time series. Five clustering methods found in the literature of gene expression analysis are compared: agglomerative hierarchical clustering, CLICK, dynamical clustering, k-means and self-organizing maps. In order to evaluate the methods, a k-fold cross-validation procedure adapted to unsupervised methods is applied. The accuracy of the results is assessed by the comparison of the partitions obtained in these experiments with gene annotation, such as protein function and series classification.

  16. Elucidating dynamic metabolic physiology through network integration of quantitative time-course metabolomics

    DEFF Research Database (Denmark)

    Bordbar, Aarash; Yurkovich, James T.; Paglia, Giuseppe

    2017-01-01

    The increasing availability of metabolomics data necessitates novel methods for deeper data analysis and interpretation. We present a flux balance analysis method that allows for the computation of dynamic intracellular metabolic changes at the cellular scale through integration of time-course ab......The increasing availability of metabolomics data necessitates novel methods for deeper data analysis and interpretation. We present a flux balance analysis method that allows for the computation of dynamic intracellular metabolic changes at the cellular scale through integration of time...

  17. The Natural Time Course of Membrane Alterations During Peritoneal Dialysis Is Partly Altered by Peritonitis.

    Science.gov (United States)

    van Esch, Sadie; Struijk, Dirk G; Krediet, Raymond T

    2016-01-01

    ♦ The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis ("no-peritonitis group") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes ("peritonitis group") during a follow-up of 4 years. ♦ The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the

  18. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

    Science.gov (United States)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

    2018-02-20

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

  19. Influence of intravenous self-administered psychomotor stimulants on performance of rhesus monkeys in a multiple schedule paradigm.

    Science.gov (United States)

    Hoffmeister, F

    1980-01-01

    Rhesus monkeys were trained to complete three multiple schedules. The schedules consisted of three components: a fixed interval (component 1), a variable interval (component 2), and a fixed ratio (component 3). During components 1 and 2, pressing lever 1 was always reinforced by food delivery. During component 3, pressing lever 2 resulted in either food delivery or intravenous infusions of saline solution, solutions of cocaine, of d-amphetamine, of phenmetrazine, or fenetylline. In schedule I, animals were presented with all three components independent of key-pressing behavior during components 1 and 2. In schedule II the availability of component 2 was dependent on completion of component 1. Component 3 was made available only on completion of component 2. Noncompletion of components 1 or 2 resulted in time-out of 15 and 10 min, respectively. Schedule III was identical with schedule II, except that in schedule III the completion of components was indicated only by a change in the lever lights. The influence of self-administered drugs on behavior in all three components was evaluated. Self-administration of psychomotor stimulants impaired the performance of animals and delayed completion of components 1 and 2 of schedules I, II, and III. The effects on behavior were similar with low drug intake in schedule III, moderate intake in schedule II, and high drug intake in schedule I. These effects were strong with self-administration of phenmetrazine, moderate with self-administration of cocaine and d-amphetamine, and weak with self-administration of fenetylline.

  20. [The application of high-frequency and iTBS transcranial magnetic stimulation for the treatment of spasticity in the patients presenting with secondary progressive multiple sclerosis].

    Science.gov (United States)

    Korzhova, J E; Chervyakov, A V; Poydasheva, A G; Kochergin, I A; Peresedova, A V; Zakharova, M N; Suponeva, N A; Chernikova, L A; Piradov, M A

    Spasticity is considered to be a common manifestation of multiple sclerosis. Muscle relaxants are not sufficiently effective; more than that, some of them often cause a variety of adverse reactions. Transcranial magnetic stimulation (TMS) can be a promising new tool for the treatment of spasticity. The objective of the present study was to compare the effectiveness of the two TMS protocols: rhythmic (high-frequency) TMS (rTMS) and stimulation with the theta bursts (iTBS) in terms of their ability to reduce spasticity in the patients presenting with multiple sclerosis. Twenty two patients with secondary-progressive multiple sclerosis were pseudo-randomized into two groups: those in the first (high-frequency) group received the treatment with the use of rTMS therapy at a frequency of 10 Hz; the patients of the second group, underwent stimulation with the theta bursts (iTBS). All the patients received 10 sessions of either stimulation applied to the primary motor area (M1) of both legs. The effectiveness of TMS protocols was evaluated before therapy and after 10 sessions of stimulation based on the Modified Ashworth scale (MAS), the expanded disability status scale (EDSS), and the Kurtzke functional scale (Kfs). In addition, the patients were interviewed before treatment, after 10 rTMS sessions, immediately after and within 2 and 12 weeks after the completion of the treatment using questionnaires for the evaluation of spasticity (SESS) , fatigue, and dysfunction of the pelvic organs (severity of defecation and urination disorders), fatigue. The study has demonstrated a significant reduction in spasticity in the patients of both groups at the end of the TMS protocol based on the MAS scale. There was no significant difference between the outcomes of the two protocols. Both had positive effect on the concomitant «non-motor» symptoms (fatigue, dysfunction of the pelvic organs). High-frequency transcranial magnetic stimulation (10 sessions of rTMS therapy at a frequency

  1. Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex.

    Science.gov (United States)

    Thimm, Andreas; Funke, Klaus

    2015-02-15

    Theta-burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability. Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex. We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8-18 ms). The effect increased with each of the five iTBS blocks applied. cTBS somewhat reduced the early response component after the first block but had a similar effect as iTBS after four to five blocks. We conclude that iTBS primarly modulates the activity of (inhibitory) cortical interneurons while cTBS may first reduce general neuronal excitability with a single block but reverse to iTBS-like effects with application of several blocks. Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (iTBS diminished the suppression of the second response evoked by paired PW or AW-PW stimulation at 20 ms intervals. The effects

  2. Analysis of anabolic steroids in hair: time courses in guinea pigs.

    Science.gov (United States)

    Shen, Min; Xiang, Ping; Yan, Hui; Shen, Baohua; Wang, Mengye

    2009-09-01

    Sensitive, specific, and reproducible methods for the quantitative determination of eight anabolic steroids in guinea pig hair have been developed using LC/MS/MS and GC/MS/MS. Methyltestosterone, stanozolol, methandienone, nandrolone, trenbolone, boldenone, methenolone and DHEA were administered intraperitoneally in guinea pigs. After the first injection, black hair segments were collected on shaved areas of skin. The analysis of these segments revealed the distribution of anabolic steroids in the guinea pig hair. The major components in hair are the parent anabolic steroids. The time courses of the concentrations of the steroids in hair (except methenolone, which does not deposit in hair) demonstrated that the peak concentrations were reached on days 2-4, except stanozolol, which peaked on day 10 after administration. The concentrations in hair appeared to be related to the physicochemical properties of the drug compound and to the dosage. These studies on the distribution of drugs in the hair shaft and on the time course of their concentration changes provide information relevant to the optimal time and method of collecting hair samples. Such studies also provide basic data that will be useful in the application of hair analysis in the control of doping and in the interpretation of results.

  3. Time course of cortisol loss in hair segments under immersion in hot water.

    Science.gov (United States)

    Li, Jifeng; Xie, Qiaozhen; Gao, Wei; Xu, Youyun; Wang, Shuang; Deng, Huihua; Lu, Zuhong

    2012-02-18

    Hair cortisol is supposed to be a good biomarker of chronic stress. Major loss of hair cortisol in long-term exposure to environmental factors affected strongly its proper assessment of chronic stress in human. However, there was no research on time course of hair cortisol loss during the long-term exposure. Hair samples with longer than 1cm in the posterior vertex region were cut as close as possible to the scalp. The 1-cm hair samples were treated by ultraviolet irradiation or immersion in shampoo solution or water immersion at 40, 65 and 80°C. Hair cortisol content was determined with high performance liquid chromatography tandem mass spectrometry. Ultraviolet irradiation and immersion in shampoo solution and hot water gave rise to the significant cortisol loss in hair. Hair cortisol content was sharply decreased with water immersion duration during initial stage and slowly decreased in the following stage. The 2-stage loss process with water immersion duration modeled to some extent time course of hair cortisol loss in long-term exposure to external environments. Cortisol from hair samples closest to the scalp in the posterior vertex could represent more accurately central hypothalamo-pituitary-adrenal activity. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Difference-based clustering of short time-course microarray data with replicates

    Directory of Open Access Journals (Sweden)

    Kim Jihoon

    2007-07-01

    Full Text Available Abstract Background There are some limitations associated with conventional clustering methods for short time-course gene expression data. The current algorithms require prior domain knowledge and do not incorporate information from replicates. Moreover, the results are not always easy to interpret biologically. Results We propose a novel algorithm for identifying a subset of genes sharing a significant temporal expression pattern when replicates are used. Our algorithm requires no prior knowledge, instead relying on an observed statistic which is based on the first and second order differences between adjacent time-points. Here, a pattern is predefined as the sequence of symbols indicating direction and the rate of change between time-points, and each gene is assigned to a cluster whose members share a similar pattern. We evaluated the performance of our algorithm to those of K-means, Self-Organizing Map and the Short Time-series Expression Miner methods. Conclusions Assessments using simulated and real data show that our method outperformed aforementioned algorithms. Our approach is an appropriate solution for clustering short time-course microarray data with replicates.

  5. Time course influences transfer of visual perceptual learning across spatial location.

    Science.gov (United States)

    Larcombe, S J; Kennard, C; Bridge, H

    2017-06-01

    Visual perceptual learning describes the improvement of visual perception with repeated practice. Previous research has established that the learning effects of perceptual training may be transferable to untrained stimulus attributes such as spatial location under certain circumstances. However, the mechanisms involved in transfer have not yet been fully elucidated. Here, we investigated the effect of altering training time course on the transferability of learning effects. Participants were trained on a motion direction discrimination task or a sinusoidal grating orientation discrimination task in a single visual hemifield. The 4000 training trials were either condensed into one day, or spread evenly across five training days. When participants were trained over a five-day period, there was transfer of learning to both the untrained visual hemifield and the untrained task. In contrast, when the same amount of training was condensed into a single day, participants did not show any transfer of learning. Thus, learning time course may influence the transferability of perceptual learning effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Electrophysiological assessment of the time course of bilingual visual word recognition: Early access to language membership.

    Science.gov (United States)

    Yiu, Loretta K; Pitts, Michael A; Canseco-Gonzalez, Enriqueta

    2015-08-01

    Previous research examining the time course of lexical access during word recognition suggests that phonological processing precedes access to semantic information, which in turn precedes access to syntactic information. Bilingual word recognition likely requires an additional level: knowledge of which language a specific word belongs to. Using the recording of event-related potentials, we investigated the time course of access to language membership information relative to semantic (Experiment 1) and syntactic (Experiment 2) encoding during visual word recognition. In Experiment 1, Spanish-English bilinguals viewed a series of printed words while making dual-choice go/nogo and left/right hand decisions based on semantic (whether the word referred to an animal or an object) and language membership information (whether the word was in English or in Spanish). Experiment 2 used a similar paradigm but with syntactic information (whether the word was a noun or a verb) as one of the response contingencies. The onset and peak latency of the N200, a component related to response inhibition, indicated that language information is accessed earlier than semantic information. Similarly, language information was also accessed earlier than syntactic information (but only based on peak latency). We discuss these findings with respect to models of bilingual word recognition and language comprehension in general. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The time course of perceptual grouping: the role of segregation and shape formation.

    Science.gov (United States)

    Razpurker-Apfeld, Irene; Kimchi, Ruth

    2007-07-01

    The time course of perceptual grouping was examined in two experiments, using a primed matching task. In different conditions, elements were grouped into columns/rows by common lightness, into a shape (triangle/ arrow or square/cross) by common lightness, and into a shape without segregation of elements. The results showed an early and rapid grouping into columns/rows by common lightness and into a shape when no segregation from other elements was involved. Goodness of shape (i.e., triangle/arrow vs. square/cross) had no influence on how early grouping was evident, but the relatively poorer shapes appeared to consolidate with time. In contrast, grouping into a shape that involved segregation and required resolving figure-ground relations between segregated units, as grouping into a shape by common lightness, consumed time, regardless of shape goodness. These results suggest that the time course of grouping varies as a function of the processes involved in it (e.g., segregation and shape formation) and the conditions prevailing for each process.

  8. Anxiety and its time courses during radiotherapy for non-metastatic breast cancer: A longitudinal study

    International Nuclear Information System (INIS)

    Lewis, Florence; Merckaert, Isabelle; Liénard, Aurore; Libert, Yves; Etienne, Anne-Marie; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Paul, Van Houtte; Coucke, Philippe

    2014-01-01

    Purpose: To our knowledge, no study has specifically assessed the time course of anxiety during radiotherapy (RT). The objective of this study was to assess anxiety time courses in patients with non-metastatic breast cancer. Material and methods: This multicenter, descriptive longitudinal study included 213 consecutive patients with breast cancer who completed visual analog scales (VASs) assessing state anxiety before and after the RT simulation and the first and last five RT sessions. Results: Pre- and post-session anxiety mean levels were highest at the RT simulation (respectively, 2.9 ± 2.9 and 1.6 ± 2.5) and first RT session (respectively, 3.4 ± 2.9 and 2.0 ± 2.4), then declined rapidly. Clinically relevant mean differences (⩾1 cm on the VAS) between pre- and post-simulation/session VAS scores were found only for the RT simulation (−1.3 ± 2.7; p < 0.001) and first RT session (−1.4 ± 2.4; p < 0.001). Five percent to 16% of patients presented clinically relevant anxiety (pre- and post-simulation/session VAS scores ⩾ 4 cm) throughout treatment. Conclusions: To optimize care, RT team members should offer all patients appropriate information about treatment at the simulation, check patients’ understanding, and identify patients with clinically relevant anxiety requiring appropriate support throughout RT

  9. Time course for arm and chest muscle thickness changes following bench press training

    Science.gov (United States)

    Ogasawara, Riki; Thiebaud, Robert S.; Loenneke, Jeremy P.; Loftin, Mark

    2012-01-01

    The purpose of this study was to investigate the time course of hypertrophic adaptations in both the upper arm and trunk muscles following high-intensity bench press training. Seven previously untrained young men (aged 25 ± 3 years) performed free-weight bench press training 3 days (Monday, Wednesday and Friday) per week for 24 weeks. Training intensity and volume were set at 75% of one repetition maximum (1-RM) and 30 repetitions (3 sets of 10 repetitions, with 2−3 min of rest between sets), respectively. Muscle thickness (MTH) was measured using B-mode ultrasound at three sites: the biceps and triceps brachii and the pectoralis major. Measurements were taken a week prior to the start of training, before the training session on every Monday and 3 days after the final training session. Pairwise comparisons from baseline revealed that pectoralis major MTH significantly increased after week-1 (p = 0.002), triceps MTH increased after week-5 (p = 0.001) and 1-RM strength increased after week-3 (p = 0.001) while no changes were observed in the biceps MTH from baseline. Significant muscle hypertrophy was observed earlier in the chest compared to that of the triceps. Our results indicate that the time course of the muscle hypertrophic response differs between the upper arm and chest. PMID:24265879

  10. The Impact of Feedback on the Different Time Courses of Multisensory Temporal Recalibration

    Directory of Open Access Journals (Sweden)

    Matthew A. De Niear

    2017-01-01

    Full Text Available The capacity to rapidly adjust perceptual representations confers a fundamental advantage when confronted with a constantly changing world. Unexplored is how feedback regarding sensory judgments (top-down factors interacts with sensory statistics (bottom-up factors to drive long- and short-term recalibration of multisensory perceptual representations. Here, we examined the time course of both cumulative and rapid temporal perceptual recalibration for individuals completing an audiovisual simultaneity judgment task in which they were provided with varying degrees of feedback. We find that in the presence of feedback (as opposed to simple sensory exposure temporal recalibration is more robust. Additionally, differential time courses are seen for cumulative and rapid recalibration dependent upon the nature of the feedback provided. Whereas cumulative recalibration effects relied more heavily on feedback that informs (i.e., negative feedback rather than confirms (i.e., positive feedback the judgment, rapid recalibration shows the opposite tendency. Furthermore, differential effects on rapid and cumulative recalibration were seen when the reliability of feedback was altered. Collectively, our findings illustrate that feedback signals promote and sustain audiovisual recalibration over the course of cumulative learning and enhance rapid trial-to-trial learning. Furthermore, given the differential effects seen for cumulative and rapid recalibration, these processes may function via distinct mechanisms.

  11. Time course of effects of emotion on item memory and source memory for Chinese words.

    Science.gov (United States)

    Wang, Bo; Fu, Xiaolan

    2011-05-01

    Although many studies have investigated the effect of emotion on memory, it is unclear whether the effect of emotion extends to all aspects of an event. In addition, it is poorly understood how effects of emotion on item memory and source memory change over time. This study examined the time course of effects of emotion on item memory and source memory. Participants learned intentionally a list of neutral, positive, and negative Chinese words, which were presented twice, and then took test of free recall, followed by recognition and source memory tests, at one of eight delayed points of time. The main findings are (within the time frame of 2 weeks): (1) Negative emotion enhances free recall, whereas there is only a trend that positive emotion enhances free recall. In addition, negative and positive emotions have different points of time at which their effects on free recall reach the greatest magnitude. (2) Negative emotion reduces recognition, whereas positive emotion has no effect on recognition. (3) Neither positive nor negative emotion has any effect on source memory. The above findings indicate that effect of emotion does not necessarily extend to all aspects of an event and that valence is a critical modulating factor in effect of emotion on item memory. Furthermore, emotion does not affect the time course of item memory and source memory, at least with a time frame of 2 weeks. This study has implications for establishing the theoretical model regarding the effect of emotion on memory. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Illusory conjunctions in the time domain and the resulting time-course of the attentional blink.

    Science.gov (United States)

    Botella, Juan; Arend, Isabel; Suero, Manuel

    2004-05-01

    Illusory conjunctions in the time domain are errors made in binding stimulus features presented In the same spatial position in Rapid Serial Visual Presentation (RSVP) conditions. Botella, Barriopedro, and Suero (2001) devised a model to explain how the distribution of responses originating from stimuli around the target in the series is generated. They proposed two routes consisting of two sequential attempts to make a response. The second attempt (sophisticated guessing) is only employed if the first one (focal attention) fails in producing an integrated perception. This general outline enables specific predictions to be made and tested related to the efficiency of focal attention in generating responses in the first attempt. Participants had to report the single letter in an RSVP stream of letters that was presented in a previously specified color (first target, T1) and then report whether an X (second target, T2) was or was not presented. Performance on T2 showed the typical U-shaped function across the T1-T2 lag that reflects the attentional blink phenomenon. However, as was predicted by Botella, Barriopedro, and Suero's model, the time-course of the interference was shorter for trials with a correct response to T1 than for trials with a T1 error. Furthermore, longer time-courses of interference associated with pre-target and post-target errors to the first target were indistinguishable.

  13. The time course of lexical competition during spoken word recognition in Mandarin Chinese: an event-related potential study.

    Science.gov (United States)

    Huang, Xianjun; Yang, Jin-Chen

    2016-01-20

    The present study investigated the effect of lexical competition on the time course of spoken word recognition in Mandarin Chinese using a unimodal auditory priming paradigm. Two kinds of competitive environments were designed. In one session (session 1), only the unrelated and the identical primes were presented before the target words. In the other session (session 2), besides the two conditions in session 1, the target words were also preceded by the cohort primes that have the same initial syllables as the targets. Behavioral results showed an inhibitory effect of the cohort competitors (primes) on target word recognition. The event-related potential results showed that the spoken word recognition processing in the middle and late latency windows is modulated by whether the phonologically related competitors are presented or not. Specifically, preceding activation of the competitors can induce direct competitions between multiple candidate words and lead to increased processing difficulties, primarily at the word disambiguation and selection stage during Mandarin Chinese spoken word recognition. The current study provided both behavioral and electrophysiological evidences for the lexical competition effect among the candidate words during spoken word recognition.

  14. Time-Course Investigation of Small Molecule Metabolites in MAP-Stored Red Blood Cells Using UPLC-QTOF-MS

    Directory of Open Access Journals (Sweden)

    Yong Zhou

    2018-04-01

    Full Text Available Red blood cells (RBCs are routinely stored for 35 to 42 days in most countries. During storage, RBCs undergo biochemical and biophysical changes known as RBC storage lesion, which is influenced by alternative storage additive solutions (ASs. Metabolomic studies have been completed on RBCs stored in a number of ASs, including SAGM, AS-1, AS-3, AS-5, AS-7, PAGGGM, and MAP. However, the reported metabolome analysis of laboratory-made MAP-stored RBCs was mainly focused on the time-dependent alterations in glycolytic intermediates during storage. In this study, we investigated the time-course of alterations in various small molecule metabolites in RBCs stored in commercially used MAP for 49 days using ultra-high performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS. These alterations indicated that RBC storage lesion is related to multiple pathways including glycolysis, pentose phosphate pathway, glutathione homeostasis, and purine metabolism. Thus, our findings might be useful for understanding the complexity of metabolic mechanisms of RBCs in vitro aging and encourage the deployment of systems biology methods to blood products in transfusion medicine.

  15. Dissociated time course between peak torque and total work recovery following bench press training in resistance trained men.

    Science.gov (United States)

    Ferreira, Diogo V; Gentil, Paulo; Ferreira-Junior, João B; Soares, Saulo R S; Brown, Lee E; Bottaro, Martim

    2017-10-01

    To evaluate the time course of peak torque and total work recovery after a resistance training session involving the bench press exercise. Repeated measures with a within subject design. Twenty-six resistance-trained men (age: 23.7±3.7years; height: 176.0±5.7cm; mass: 79.65±7.61kg) performed one session involving eight sets of the bench press exercise performed to momentary muscle failure with 2-min rest between sets. Shoulder horizontal adductors peak torque (PT), total work (TW), delayed onset muscle soreness (DOMS) and subjective physical fitness were measured pre, immediately post, 24, 48, 72 and 96h following exercise. The exercise protocol resulted in significant pectoralis major DOMS that lasted for 72h. Immediately after exercise, the reduction in shoulder horizontal adductors TW (25%) was greater than PT (17%). TW, as a percentage of baseline values, was also less than PT at 24, 48 and 96h after exercise. Additionally, PT returned to baseline at 96h, while TW did not. Resistance trained men presented dissimilar PT and TW recovery following free weight bench press exercise. This indicates that recovery of maximal voluntary contraction does not reflect the capability to perform multiple contractions. Strength and conditioning professionals should be cautious when evaluating muscle recovery by peak torque, since it can lead to the repetition of a training session sooner than recommended. Copyright © 2017. Published by Elsevier Inc.

  16. Bacillus anthracis secretome time course under host-simulated conditions and identification of immunogenic proteins

    Directory of Open Access Journals (Sweden)

    Whittington Jessica

    2007-07-01

    Full Text Available Abstract Background The secretion time course of Bacillus anthracis strain RA3R (pXO1+/pXO2- during early, mid, and late log phase were investigated under conditions that simulate those encountered in the host. All of the identified proteins were analyzed by different software algorithms to characterize their predicted mode of secretion and cellular localization. In addition, immunogenic proteins were identified using sera from humans with cutaneous anthrax. Results A total of 275 extracellular proteins were identified by a combination of LC MS/MS and MALDI-TOF MS. All of the identified proteins were analyzed by SignalP, SecretomeP, PSORT, LipoP, TMHMM, and PROSITE to characterize their predicted mode of secretion, cellular localization, and protein domains. Fifty-three proteins were predicted by SignalP to harbor the cleavable N-terminal signal peptides and were therefore secreted via the classical Sec pathway. Twenty-three proteins were predicted by SecretomeP for secretion by the alternative Sec pathway characterized by the lack of typical export signal. In contrast to SignalP and SecretomeP predictions, PSORT predicted 171 extracellular proteins, 7 cell wall-associated proteins, and 6 cytoplasmic proteins. Moreover, 51 proteins were predicted by LipoP to contain putative Sec signal peptides (38 have SpI sites, lipoprotein signal peptides (13 have SpII sites, and N-terminal membrane helices (9 have transmembrane helices. The TMHMM algorithm predicted 25 membrane-associated proteins with one to ten transmembrane helices. Immunogenic proteins were also identified using sera from patients who have recovered from anthrax. The charge variants (83 and 63 kDa of protective antigen (PA were the most immunodominant secreted antigens, followed by charge variants of enolase and transketolase. Conclusion This is the first description of the time course of protein secretion for the pathogen Bacillus anthracis. Time course studies of protein secretion and

  17. Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

    Directory of Open Access Journals (Sweden)

    S.L. Amaral

    2008-05-01

    Full Text Available Exercise-induced vessel changes modulate arterial pressure (AP in male spontaneously hypertensive rats (SHR. Vascular endothelial growth factor (VEGF is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short- and long-term exercise training of female SHR and Wistar Kyoto (WKY rats, 8-9 weeks (200-250 g. Rats were allocated to daily training or remained sedentary for 3 days (N = 23 or 13 weeks (N = 23. After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis and non-locomotor skeletal muscles (temporalis were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28%, WKY = 64%, 3 days and (SHR = 141%, WKY = 122%, 13 weeks. SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg that were not altered by training. Three days of running increased VEGF expression (SHR = 28%, WKY = 36% simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19%, WKY = 15%. In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18%, WKY = 19%, without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time- and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

  18. PAVA: Physiological and Anatomical Visual Analytics for Mapping of Tissue-Specific Concentration and Time-Course Data

    Science.gov (United States)

    We describe the development and implementation of a Physiological and Anatomical Visual Analytics tool (PAVA), a web browser-based application, used to visualize experimental/simulated chemical time-course data (dosimetry), epidemiological data and Physiologically-Annotated Data ...

  19. CLINICAL-PHARMACOLOGY OF ROCURONIUM (ORG-9426) - STUDY OF THE TIME-COURSE OF ACTION, DOSE REQUIREMENT, REVERSIBILITY, AND PHARMACOKINETICS

    NARCIS (Netherlands)

    VANDENBROEK, L; WIERDA, JMKH; SMEULERS, NJ; VANSANTEN, GJ; LECLERCQ, MGL; HENNIS, PJ

    1994-01-01

    Study Objective: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol halothane, or isoflurane). Design: Prospective, randomized study. Setting: Operating

  20. Measurements of stimulated-Raman-scattering-induced tilt in spectral-amplitude-coding optical code-division multiple-access systems

    Science.gov (United States)

    Al-Qazwini, Zaineb A. T.; Abdullah, Mohamad K.; Mokhtar, Makhfudzah B.

    2009-01-01

    We measure the stimulated Raman scattering (SRS)-induced tilt in spectral-amplitude-coding optical code-division multiple-access (SAC-OCDMA) systems as a function of system main parameters (transmission distance, power per chip, and number of users) via computer simulations. The results show that SRS-induced tilt significantly increases as transmission distance, power per chip, or number of users grows.

  1. Optimization of multiple coils immersed in a conducting liquid for half-hemisphere or whole-brain deep transcranial magnetic stimulation: a simulation study.

    Science.gov (United States)

    Sousa, Sónia C P; Almeida, Jorge; Cavaleiro Miranda, Pedro; Salvador, Ricardo; Silvestre, João; Simões, Hugo; Crespo, Paulo

    2014-01-01

    Transcranial magnetic stimulation (TMS) was proposed in 1985. Nevertheless, its wider use in the treatment of several neurologic diseases has been hindered by its inability to stimulate deep-brain regions. This is mainly due to the physical limiting effect arising from the presence of surface discontinuities, particularly between the scalp and air. Here, we present the optimization of a system of large multiple coils for whole-brain and half-hemisphere deep TMS, termed orthogonal configuration. COMSOL(®)-based simulations show that the system is capable of reaching the very center of a spherical brain phantom with 58% induction relative to surface maximum. Such penetration capability surpasses to the best of our knowledge that of existing state of the art TMS systems. This induction capability strongly relies on the immersion of the stimulating coils and part of the head of the patient in a conducting liquid (e.g. simple saline solution). We show the impact of the presence of this surrounding conducting liquid by comparing the performance of our system with and without such liquid. In addition, we also compare the performance of the proposed coil with that of a circular coil, a figure-eight coil, and the H-coil. Finally, in addition to its whole-brain stimulation capability (e.g. potentially useful for prophylaxis of epileptic patients) the system is also able to stimulate mainly one brain hemisphere, which may be useful in stroke rehabilitation, among other applications.

  2. Time course of auditory streaming: Do CI users differ from normal-hearing listeners?

    Directory of Open Access Journals (Sweden)

    Martin eBöckmann-Barthel

    2014-07-01

    Full Text Available In a complex acoustical environment with multiple sound sources the auditory system uses streaming as a tool to organize the incoming sounds in one or more streams depending on the stimulus parameters. Streaming is commonly studied by alternating sequences of signals. These are often tones with different frequencies. The present study investigates stream segregation in cochlear implant (CI users, where hearing is restored by electrical stimulation of the auditory nerve. CI users listened to 30-s long sequences of alternating A and B harmonic complexes at four different fundamental frequency separations, ranging from 2 to 14 semitones. They had to indicate as promptly as possible after sequence onset, if they perceived one stream or two streams and, in addition, any changes of the percept throughout the rest of the sequence. The conventional view is that the initial percept is always that of a single stream which may after some time change to a percept of two streams. This general build-up hypothesis has recently been challenged on the basis of a new analysis of data of normal-hearing listeners which showed a build-up response only for an intermediate frequency separation. Using the same experimental paradigm and analysis, the present study found that the results of CI users agree with those of the normal-hearing listeners: (i the probability of the first decision to be a one-stream percept decreased and that of a two-stream percept increased as Δf increased, and (ii a build-up was only found for 6 semitones. Only the time elapsed before the listeners made their first decision of the percept was prolonged as compared to normal-hearing listeners. The similarity in the data of the CI user and the normal-hearing listeners indicates that the quality of stream formation is similar in these groups of listeners.

  3. Catecholaminergic activation in acute myocardial infarction: time course and relation to left ventricular performance

    DEFF Research Database (Denmark)

    Petersen, Claus Leth; Nielsen, Jens Rokkedal; Petersen, Bodil Laub

    2003-01-01

    AIM: The study was designed to assess (1) the time course of catecholaminergic activation in acute myocardial infarction (AMI) as estimated by adrenaline (ADR) and noradrenaline (NOR) concentrations, and (2) to relate activation of these hormones to predict the outcome of cardiac performance......-ventricular ejection fraction (LVEF). RESULTS: In the study group as a whole, the concentrations of ADR decreased from (mean +/- SEM) 0.80 +/- 0.12 nmol/l on admission to 0.33 +/- 0.03 nmol/l at discharge (p ... of both ADR and NOR on admission were correlated to LVEF at discharge (r = -0.56, p ADR and NOR after 1 year follow-up was 0...

  4. Time-course of attention for threatening pictures in high and low trait anxiety.

    Science.gov (United States)

    Koster, Ernst H W; Verschuere, Bruno; Crombez, Geert; Van Damme, Stefaan

    2005-08-01

    Cognitive studies about anxiety suggest that the interplay between automatic and strategic biases in attention to threat is related to the persistence of fear. In the present study, the time-course of attention to pictures with varying threat levels was investigated in high trait anxious (HTA, n=21) and low trait anxious (LTA, n=22) students. In a visual probe detection task, high and mild threat pictures were presented at three durations: 100, 500, and 1250 ms. Results indicated that all individuals attended to the high threat pictures for the 100 ms condition. Differential responding between HTA and LTA individuals was found for the 500 ms condition: only HTA individuals showed an attentional bias for mild threatening stimuli. For the 1250 ms condition, the HTA individuals attended away from high and mild threat pictures. The observed pattern of differential attention to threatening pictures may explain the persistence of fear in HTA individuals.

  5. Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers

    DEFF Research Database (Denmark)

    Hesse, Morten; Thylstrup, Birgitte

    2013-01-01

    Background Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacco...... the DSM-5 Withdrawal Symptom Check List with withdrawal symptoms from all classes of substances, with no indication that the described symptoms should be attributed to withdrawal. Self-reported time since last use of cannabis was used as a predictor of cannabis withdrawal severity. Results...... With the exception of loss of appetite, time since last use of cannabis was associated with all types of withdrawal symptoms listed in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other substances were related to time since last use of cannabis, including vivid, unpleasant dreams...

  6. Time course of radiometric detection of positive blood cultures in childhood

    International Nuclear Information System (INIS)

    Meadow, W.L.; Schwartz, I.K.

    1986-01-01

    We have determined the time course of radiometric detection of microbial growth in 2348 positive blood culture specimens obtained at Wyler Children's Hospital during a 5-year interval. Overall 72 and 88% of isolates were detected within 48 and 72 hours after sampling, respectively. For pathogenic organisms aerobic detection was generally more rapid and more inclusive than anaerobic detection. At 48 hours of incubation the detection of six potential pathogens (Salmonella sp., Haemophilus influenzae, Group D streptococci, Neisseria meningitidis, coagulase-negative staphylococci, Candida sp.) was significantly delayed compared with detection of other pathogenic organisms recovered from blood. At 72 hours of incubation the detection rates remained less than 95% for H. influenzae, Staphylococcus aureus, Klebsiella sp., coagulase-negative staphylococci, Group D streptococci and Candida sp. These data should assist clinical decisions regarding duration of antibiotic therapy for the presumptive diagnosis of bacteremia in children

  7. Time course of primary and secondary hyperalgesia after heat injury to the skin

    DEFF Research Database (Denmark)

    Møiniche, S; Dahl, J B; Kehlet, H

    1993-01-01

    the injury in any volunteer. These findings suggest post-injury development of secondary hyperalgesia to be a dynamic process, closely related in time to a peripheral nociceptive input, with reversal to normal when the peripheral lesion disappears. These observations may be relevant to the concept of "pre......We have examined the time course of, and relationship between, primary and secondary hyperalgesia after thermal injury to the skin in humans. Burn injuries (15 x 25 mm rectangular thermode, 49 degrees C, 5 min) were produced in eight healthy, unmedicated male volunteers, on the medial side...... of the right calf, on two occasions at least 8 days apart. Heat pain detection thresholds (HPDT), heat pain tolerance (HPT), mechanical pain detection threshold (MPDT) and the intensity of burn-injury induced erythema (skin erythema index, SEI) were assessed inside the burn injury. HPT was assessed only in one...

  8. Time course of radiometric detection of positive blood cultures in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Meadow, W.L.; Schwartz, I.K.

    1986-05-01

    We have determined the time course of radiometric detection of microbial growth in 2348 positive blood culture specimens obtained at Wyler Children's Hospital during a 5-year interval. Overall 72 and 88% of isolates were detected within 48 and 72 hours after sampling, respectively. For pathogenic organisms aerobic detection was generally more rapid and more inclusive than anaerobic detection. At 48 hours of incubation the detection of six potential pathogens (Salmonella sp., Haemophilus influenzae, Group D streptococci, Neisseria meningitidis, coagulase-negative staphylococci, Candida sp.) was significantly delayed compared with detection of other pathogenic organisms recovered from blood. At 72 hours of incubation the detection rates remained less than 95% for H. influenzae, Staphylococcus aureus, Klebsiella sp., coagulase-negative staphylococci, Group D streptococci and Candida sp. These data should assist clinical decisions regarding duration of antibiotic therapy for the presumptive diagnosis of bacteremia in children.

  9. Time-course mortality and radiosensitivity indices in Tribolium spp. developing from irradiated pupae

    International Nuclear Information System (INIS)

    Hasan, Md Mahbub

    1999-01-01

    Effects of gamma irradiation (1-5 Krad) on the time-course mortality and radiosensitivity indices in adults of Tribolium anaphe, T. brevicornis, T. castaneum, T. destructor, T. freemani developing from irradiated 1 day old and pre-emergence (4-5 day old) pupae were studied. Adult longevity was significantly (P<0.001) affected by irradiation and was linearly dose dependent. T. destructor was markedly more radioresistant than the other species at all dose levels and had a longer life expectancy. The mean survival times of adults developing from irradiated early and late pupae were shorter in females than in males for all the species. The radiosensitivity indices did not vary widely among the species and these values decreased as the dose increased in all the species which clearly indicate that the resistance of the species was dose-dependent. (author)

  10. Homophonic and semantic priming of Japanese Kanji words: a time course study.

    Science.gov (United States)

    Chen, Hsi-Chin; Yamauchi, Takashi; Tamaoka, Katsuo; Vaid, Jyotsna

    2007-02-01

    In an examination of the time course of activation of phonological and semantic information in processing kanji script, two lexical decision experiments were conducted with native readers of Japanese. Kanji targets were preceded at short (85-msec) and long (150-msec) intervals by homophonic, semantically related, or unrelated primes presented in kanji (Experiment 1) or by hiragana transcriptions of the kanji primes (Experiment 2). When primes were in kanji, semantic relatedness facilitated kanji target recognition at both intervals but homophonic relatedness did not. When primes were in hiragana, kanji target recognition was facilitated by homophonic relatedness at both intervals and by semantic relatedness only at the longer interval. The absence of homophonic priming of kanji targets by kanji primes challenges the universal phonology principle's claim that phonology is central to accessing meaning from print. The stimuli used in the present study may be downloaded from www.psychonomic.org/archive.

  11. Time course based artifact identification for independent components of resting state fMRI

    Directory of Open Access Journals (Sweden)

    Christian eRummel

    2013-05-01

    Full Text Available In functional magnetic resonance imaging (fMRI coherent oscillations of the blood oxygen level dependent (BOLD signal can be detected. These arise when brain regions respond to external stimuli or are activated by tasks. The same networks have been characterized during wakeful rest when functional connectivity of the human brain is organized in generic resting state networks (RSN. Alterations of RSN emerge as neurobiological markers of pathological conditions such as altered mental state. In single-subject fMRI data the coherent components can be identified by blind source separation of the pre-processed BOLD data using spatial independent component analysis (ICA and related approaches. The resulting maps may represent physiological RSNs or may be due to various artifacts. In this methodological study, we propose a conceptually simple and fully automatic time course based filtering procedure to detect obvious artifacts in the ICA output for resting state fMRI. The filter is trained on six and tested on 29 healthy subjects, yielding mean filter accuracy, sensitivity and specificity of 0.80, 0.82 and 0.75 in out-of-sample tests. To estimate the impact of clearly artifactual single-subject components on group resting state studies we analyze unfiltered and filtered output with a second level ICA procedure. Although the automated filter does not reach performance values of visual analysis by human raters, we propose that resting state compatible analysis of ICA time courses could be very useful to complement the existing map or task/event oriented artifact classification algorithms.

  12. Safety and Time Course of Drip-and-Ship in Treatment of Acute Ischemic Stroke.

    Science.gov (United States)

    Ishihara, Hideyuki; Oka, Fumiaki; Oku, Takayuki; Shinoyama, Mizuya; Suehiro, Eiichi; Sugimoto, Kazutaka; Suzuki, Michiyasu

    2017-11-01

    The drip-and-ship approach allows intravenous tissue plasminogen activator therapy and adjuvant endovascular treatment in acute ischemic stroke, even in rural areas. Here, we examined the safety and time course of the drip-and-ship approach. Fifty consecutive cases treated with the drip-and-ship approach (drip-and-ship group) in June 2009 to March 2016 were retrospectively examined. Changes in mean blood pressure, systemic complications, and neurological complications were compared according to method of transportation. Time courses were compared between drip-and-ship and direct admission groups during the same period. In the drip-and-ship group, 33 and 17 patients were transferred to hospital by ambulance and helicopter, respectively. One patient suffered hemorrhagic infarction during transportation by ambulance. Mean blood pressure change was lower in patients transferred by helicopter than ambulance (<5 mmHg versus 12.2 mmHg, respectively). The mean onset-to-door times in the drip-and-ship and direct admission groups were 71 and 64 minutes, respectively, and mean door-to-needle times were 70 and 47 minutes, respectively (P =.002). Although mean transportation time from the primary stroke hospital to our hospital was 32 minutes, the entry-to-exit time from the primary stroke hospital was 113 minutes. Thereafter, there was an average delay of 100 minutes until reperfusion compared with the direct admission group. Drip-and-ship was relatively safe in this small series. Transportation by helicopter was less stressful for acute ischemic stroke patients. It is important to reduce door-to-needle time and needle-to-departure time in the primary stroke hospital to minimize the time until treatment in cases of acute ischemic stroke. Copyright © 2017. Published by Elsevier Inc.

  13. Hearing Shapes: Event-related Potentials Reveal the Time Course of Auditory-Visual Sensory Substitution.

    Science.gov (United States)

    Graulty, Christian; Papaioannou, Orestis; Bauer, Phoebe; Pitts, Michael A; Canseco-Gonzalez, Enriqueta

    2018-04-01

    In auditory-visual sensory substitution, visual information (e.g., shape) can be extracted through strictly auditory input (e.g., soundscapes). Previous studies have shown that image-to-sound conversions that follow simple rules [such as the Meijer algorithm; Meijer, P. B. L. An experimental system for auditory image representation. Transactions on Biomedical Engineering, 39, 111-121, 1992] are highly intuitive and rapidly learned by both blind and sighted individuals. A number of recent fMRI studies have begun to explore the neuroplastic changes that result from sensory substitution training. However, the time course of cross-sensory information transfer in sensory substitution is largely unexplored and may offer insights into the underlying neural mechanisms. In this study, we recorded ERPs to soundscapes before and after sighted participants were trained with the Meijer algorithm. We compared these posttraining versus pretraining ERP differences with those of a control group who received the same set of 80 auditory/visual stimuli but with arbitrary pairings during training. Our behavioral results confirmed the rapid acquisition of cross-sensory mappings, and the group trained with the Meijer algorithm was able to generalize their learning to novel soundscapes at impressive levels of accuracy. The ERP results revealed an early cross-sensory learning effect (150-210 msec) that was significantly enhanced in the algorithm-trained group compared with the control group as well as a later difference (420-480 msec) that was unique to the algorithm-trained group. These ERP modulations are consistent with previous fMRI results and provide additional insight into the time course of cross-sensory information transfer in sensory substitution.

  14. A method to identify differential expression profiles of time-course gene data with Fourier transformation.

    Science.gov (United States)

    Kim, Jaehee; Ogden, Robert Todd; Kim, Haseong

    2013-10-18

    Time course gene expression experiments are an increasingly popular method for exploring biological processes. Temporal gene expression profiles provide an important characterization of gene function, as biological systems are both developmental and dynamic. With such data it is possible to study gene expression changes over time and thereby to detect differential genes. Much of the early work on analyzing time series expression data relied on methods developed originally for static data and thus there is a need for improved methodology. Since time series expression is a temporal process, its unique features such as autocorrelation between successive points should be incorporated into the analysis. This work aims to identify genes that show different gene expression profiles across time. We propose a statistical procedure to discover gene groups with similar profiles using a nonparametric representation that accounts for the autocorrelation in the data. In particular, we first represent each profile in terms of a Fourier basis, and then we screen out genes that are not differentially expressed based on the Fourier coefficients. Finally, we cluster the remaining gene profiles using a model-based approach in the Fourier domain. We evaluate the screening results in terms of sensitivity, specificity, FDR and FNR, compare with the Gaussian process regression screening in a simulation study and illustrate the results by application to yeast cell-cycle microarray expression data with alpha-factor synchronization.The key elements of the proposed methodology: (i) representation of gene profiles in the Fourier domain; (ii) automatic screening of genes based on the Fourier coefficients and taking into account autocorrelation in the data, while controlling the false discovery rate (FDR); (iii) model-based clustering of the remaining gene profiles. Using this method, we identified a set of cell-cycle-regulated time-course yeast genes. The proposed method is general and can be

  15. Time course for tail regression during metamorphosis of the ascidian Ciona intestinalis.

    Science.gov (United States)

    Matsunobu, Shohei; Sasakura, Yasunori

    2015-09-01

    In most ascidians, the tadpole-like swimming larvae dramatically change their body-plans during metamorphosis and develop into sessile adults. The mechanisms of ascidian metamorphosis have been researched and debated for many years. Until now information on the detailed time course of the initiation and completion of each metamorphic event has not been described. One dramatic and important event in ascidian metamorphosis is tail regression, in which ascidian larvae lose their tails to adjust themselves to sessile life. In the present study, we measured the time associated with tail regression in the ascidian Ciona intestinalis. Larvae are thought to acquire competency for each metamorphic event in certain developmental periods. We show that the timing with which the competence for tail regression is acquired is determined by the time since hatching, and this timing is not affected by the timing of post-hatching events such as adhesion. Because larvae need to adhere to substrates with their papillae to induce tail regression, we measured the duration for which larvae need to remain adhered in order to initiate tail regression and the time needed for the tail to regress. Larvae acquire the ability to adhere to substrates before they acquire tail regression competence. We found that when larvae adhered before they acquired tail regression competence, they were able to remember the experience of adhesion until they acquired the ability to undergo tail regression. The time course of the events associated with tail regression provides a valuable reference, upon which the cellular and molecular mechanisms of ascidian metamorphosis can be elucidated. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Time course of scopolamine effect on memory consolidation and forgetting in rats.

    Science.gov (United States)

    Popović, Miroljub; Giménez de Béjar, Verónica; Popović, Natalija; Caballero-Bleda, María

    2015-02-01

    The effect of scopolamine on the consolidation and forgetting of emotional memory has not been completely elucidated yet. The aim of the present study was to investigate the time course of scopolamine effect on consolidation and forgetting of passive avoidance response. In a first experiment of the present study, we tested the effect of scopolamine (1mg/kg, i.p., immediately after acquisition), on 24h and 48h retention performance of the step-through passive avoidance task, in adult male Wistar rats. On the 24h retested trial, the latency of the passive avoidance response was significantly lower, while on the 48h retested trial it was significantly higher in scopolamine than in the saline-treated group. In a second experiment, we assessed the 24h time course of scopolamine (1mg/kg) effect on memory consolidation in passive avoidance task. We found that scopolamine administration only within the first six and half hours after acquisition improved memory consolidation in 48h retention performance. Finally, a third experiment was performed on the saline- and scopolamine-treated rats (given immediately after acquisition) that on the 48h retention test did not step through into the dark compartment during the cut-off time. These animals were retested weekly for up to first three months, and after that, every three months until the end of experiment (i.e., 15 months after acquisition). The passive avoidance response in the saline treated group lasted up to 6 weeks after acquisition, while in the scopolamine treated group 50% of animals conserved the initial level of passive avoidance response until the experiment end point. In conclusion, the present data suggest that (1) improving or impairment effect of scopolamine given in post-training periods depends on delay of retention trial, (2) memory consolidation process could be modify by scopolamine within first six and half hours after training and (3) scopolamine could delay forgetting of emotional memory. Copyright

  17. A time course analysis of the extracellular proteome of Aspergillus nidulans growing on sorghum stover

    Directory of Open Access Journals (Sweden)

    Saykhedkar Sayali

    2012-07-01

    Full Text Available Abstract Background Fungi are important players in the turnover of plant biomass because they produce a broad range of degradative enzymes. Aspergillus nidulans, a well-studied saprophyte and close homologue to industrially important species such as A. niger and A. oryzae, was selected for this study. Results A. nidulans was grown on sorghum stover under solid-state culture conditions for 1, 2, 3, 5, 7 and 14 days. Based on analysis of chitin content, A. nidulans grew to be 4-5% of the total biomass in the culture after 2 days and then maintained a steady state of 4% of the total biomass for the next 12 days. A hyphal mat developed on the surface of the sorghum by day one and as seen by scanning electron microscopy the hyphae enmeshed the sorghum particles by day 5. After 14 days hyphae had penetrated the entire sorghum slurry. Analysis (1-D PAGE LC-MS/MS of the secretome of A. nidulans, and analysis of the breakdown products from the sorghum stover showed a wide range of enzymes secreted. A total of 294 extracellular proteins were identified with hemicellulases, cellulases, polygalacturonases, chitinases, esterases and lipases predominating the secretome. Time course analysis revealed a total of 196, 166, 172 and 182 proteins on day 1, 3, 7 and 14 respectively. The fungus used 20% of the xylan and cellulose by day 7 and 30% by day 14. Cellobiose dehydrogenase, feruloyl esterases, and CAZy family 61 endoglucanases, all of which are thought to reduce the recalcitrance of biomass to hydrolysis, were found in high abundance. Conclusions Our results show that A. nidulans secretes a wide array of enzymes to degrade the major polysaccharides and lipids (but probably not lignin by 1 day of growth on sorghum. The data suggests simultaneous breakdown of hemicellulose, cellulose and pectin. Despite secretion of most of the enzymes on day 1, changes in the relative abundances of enzymes over the time course indicates that the set of enzymes

  18. Time course of gene expression profiling in the liver of experimental mice infected with Echinococcus multilocularis.

    Directory of Open Access Journals (Sweden)

    Renyong Lin

    Full Text Available BACKGROUND: Alveolar echinococcosis (AE is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1-2, that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3, MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR signaling pathway emerged; at the late stage (month 6, most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA was increased in the liver of E. multilocularis infected mice from 2 months to 6 months. CONCLUSIONS: E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene

  19. Onset of surface stimulated emission at 260 nm from AlGaN multiple quantum wells

    KAUST Repository

    Li, Xiaohang; Xie, Hongen; Ponce, Fernando A.; Ryou, Jae-Hyun; Detchprohm, Theeradetch; Dupuis, Russell D.

    2015-01-01

    We demonstrated onset of deep-ultraviolet (DUV) surface stimulated emission (SE) from c-plane AlGaNmultiple-quantum well(MQW)heterostructuresgrown on a sapphire substrate by optical pumping at room temperature. The onset of SE became observable at a

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

    Directory of Open Access Journals (Sweden)

    Vadas Gintautas

    2011-10-01

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

  1. Do bodily expressions compete with facial expressions? Time course of integration of emotional signals from the face and the body.

    Science.gov (United States)

    Gu, Yuanyuan; Mai, Xiaoqin; Luo, Yue-jia

    2013-01-01

    The decoding of social signals from nonverbal cues plays a vital role in the social interactions of socially gregarious animals such as humans. Because nonverbal emotional signals from the face and body are normally seen together, it is important to investigate the mechanism underlying the integration of emotional signals from these two sources. We conducted a study in which the time course of the integration of facial and bodily expressions was examined via analysis of event-related potentials (ERPs) while the focus of attention was manipulated. Distinctive integrating features were found during multiple stages of processing. In the first stage, threatening information from the body was extracted automatically and rapidly, as evidenced by enhanced P1 amplitudes when the subjects viewed compound face-body images with fearful bodies compared with happy bodies. In the second stage, incongruency between emotional information from the face and the body was detected and captured by N2. Incongruent compound images elicited larger N2s than did congruent compound images. The focus of attention modulated the third stage of integration. When the subjects' attention was focused on the face, images with congruent emotional signals elicited larger P3s than did images with incongruent signals, suggesting more sustained attention and elaboration of congruent emotional information extracted from the face and body. On the other hand, when the subjects' attention was focused on the body, images with fearful bodies elicited larger P3s than did images with happy bodies, indicating more sustained attention and elaboration of threatening information from the body during evaluative processes.

  2. Working memory accuracy for multiple targets is driven by reward expectation and stimulus contrast with different time-courses

    NARCIS (Netherlands)

    Klink, P. Christiaan; Jeurissen, Danique; Theeuwes, Jan; Denys, Damiaan; Roelfsema, Pieter R.

    2017-01-01

    The richness of sensory input dictates that the brain must prioritize and select information for further processing and storage in working memory. Stimulus salience and reward expectations influence this prioritization but their relative contributions and underlying mechanisms are poorly understood.

  3. Attentional bias to briefly presented emotional distractors follows a slow time course in visual cortex.

    Science.gov (United States)

    Müller, Matthias M; Andersen, Søren K; Hindi Attar, Catherine

    2011-11-02

    A central controversy in the field of attention is how the brain deals with emotional distractors and to what extent they capture attentional processing resources reflexively due to their inherent significance for guidance of adaptive behavior and survival. Especially, the time course of competitive interactions in early visual areas and whether masking of briefly presented emotional stimuli can inhibit biasing of processing resources in these areas is currently unknown. We recorded frequency-tagged potentials evoked by a flickering target detection task in the foreground of briefly presented emotional or neutral pictures that were followed by a mask in human subjects. We observed greater competition for processing resources in early visual cortical areas with shortly presented emotional relative to neutral pictures ~275 ms after picture offset. This was paralleled by a reduction of target detection rates in trials with emotional pictures ~400 ms after picture offset. Our finding that briefly presented emotional distractors are able to bias attention well after their offset provides evidence for a rather slow feedback or reentrant neural competition mechanism for emotional distractors that continues after the offset of the emotional stimulus.

  4. The time course of implicit processing of erotic pictures: an event-related potential study.

    Science.gov (United States)

    Feng, Chunliang; Wang, Lili; Wang, Naiyi; Gu, Ruolei; Luo, Yue-Jia

    2012-12-13

    The current study investigated the time course of the implicit processing of erotic stimuli using event-related potentials (ERPs). ERPs elicited by erotic pictures were compared with those by three other types of pictures: non-erotic positive, negative, and neutral pictures. We observed that erotic pictures evoked enhanced neural responses compared with other pictures at both early (P2/N2) and late (P3/positive slow wave) temporal stages. These results suggested that erotic pictures selectively captured individuals' attention at early stages and evoked deeper processing at late stages. More importantly, the amplitudes of P2, N2, and P3 only discriminated between erotic and non-erotic (i.e., positive, neutral, and negative) pictures. That is, no difference was revealed among non-erotic pictures, although these pictures differed in both valence and arousal. Thus, our results suggest that the erotic picture processing is beyond the valence and arousal. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Fast logic?: Examining the time course assumption of dual process theory.

    Science.gov (United States)

    Bago, Bence; De Neys, Wim

    2017-01-01

    Influential dual process models of human thinking posit that reasoners typically produce a fast, intuitive heuristic (i.e., Type-1) response which might subsequently be overridden and corrected by slower, deliberative processing (i.e., Type-2). In this study we directly tested this time course assumption. We used a two response paradigm in which participants have to give an immediate answer and afterwards are allowed extra time before giving a final response. In four experiments we used a range of procedures (e.g., challenging response deadline, concurrent load) to knock out Type 2 processing and make sure that the initial response was intuitive in nature. Our key finding is that we frequently observe correct, logical responses as the first, immediate response. Response confidence and latency analyses indicate that these initial correct responses are given fast, with high confidence, and in the face of conflicting heuristic responses. Findings suggest that fast and automatic Type 1 processing also cues a correct logical response from the start. We sketch a revised dual process model in which the relative strength of different types of intuitions determines reasoning performance. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Time course and dimensions of postural control changes following neuromuscular training in youth field hockey athletes.

    Science.gov (United States)

    Zech, Astrid; Klahn, Philipp; Hoeft, Jon; zu Eulenburg, Christine; Steib, Simon

    2014-02-01

    Injury prevention effects of neuromuscular training have been partly attributed to postural control adaptations. Uncertainty exists regarding the magnitude of these adaptations and on how they can be adequately monitored. The objective was to determine the time course of neuromuscular training effects on functional, dynamic and static balance measures. Thirty youth (14.9 ± 3 years) field hockey athletes were randomised to an intervention or control group. The intervention included a 20-min neuromuscular warm-up program performed twice weekly for 10 weeks. Balance assessments were performed at baseline, week three, week six and post-intervention. They included the star excursion balance test (SEBT), balance error scoring system (BESS), jump-landing time to stabilization (TTS) and center of pressure (COP) sway velocity during single-leg standing. No baseline differences were found between groups in demographic data and balance measures. Adherence was at 86%. All balance measures except the medial-lateral TTS improved significantly over time (p controls (31.8 ± 22.1%). There were no significant group by time interactions in the SEBT, TTS and COP sway velocity. Neuromuscular training was effective in improving postural control in youth team athletes. However, this effect was not reflected in all balance measures suggesting that the neuromuscular training did not influence all dimensions of postural control. Further studies are needed to confirm the potential of specific warm-up programs to improve postural control.

  7. Time Course of Resolution of Hyperprolactinemia After Transsphenoidal Surgery Among Patients Presenting with Pituitary Stalk Compression.

    Science.gov (United States)

    Zaidi, Hasan A; Cote, David J; Castlen, Joseph P; Burke, William T; Liu, Yong-Hui; Smith, Timothy R; Laws, Edward R

    2017-01-01

    Primary lactotroph disinhibition, or stalk effect, occurs when mechanical compression of the pituitary stalk disrupts the tonic inhibition by dopamine released by the hypothalamus. The resolution of pituitary stalk effect-related hyperprolactinemia postoperatively has not been studied in a large cohort of patients. We performed a retrospective review to investigate the time course of recovery of lactotroph disinhibition after transsphenoidal surgery. Medical records were retrospectively reviewed for all patients undergoing transsphenoidal surgery with the senior author from April 2008 to November 2014. Of 556 pituitary adenomas, 289 (52.0%) were eliminated: 77 (13.9%) had an immunohistochemically confirmed prolactinoma, 119 (21.4%) patients had previous surgery, 93 (16.7%) had incomplete medical records, leaving 267 patients (48.0%) for final analysis. Of these patients, 72 (27.0%) had increased serum prolactin levels (≥23.3 ng/mL), suggestive of pituitary stalk effect (maximum prolactin level = 148.0 ng/mL). Patients with stalk effect were more likely than those with normal serum prolactin levels to present with menstrual dysfunction (29.7% vs. 19.4%; P Transsphenoidal surgery can provide durable normalization of serum prolactin levels and related symptoms caused by pituitary stalk compression-related lactotroph disinhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Time course of emotion-related responding during distraction and reappraisal.

    Science.gov (United States)

    Schönfelder, Sandra; Kanske, Philipp; Heissler, Janine; Wessa, Michèle

    2014-09-01

    Theoretical accounts of emotion regulation (ER) discriminate various cognitive strategies to voluntarily modify emotional states. Amongst these, attentional deployment (i.e. distraction) and cognitive change (i.e. reappraisal), have been shown to successfully down-regulate emotions. Neuroimaging studies found that both strategies differentially engage neural structures associated with selective attention, working memory and cognitive control. The aim of this study was to further delineate similarities and differences between the ER strategies reappraisal and distraction by investigating their temporal brain dynamics using event-related potentials (ERPs) and their patterns of facial expressive behavior. Twenty-one participants completed an ER experiment in which they had to either passively view positive, neutral and negative pictures, reinterpret them to down-regulate affective responses (reappraisal), or solve a concurrently presented mathematical equation (distraction). Results demonstrate the efficacy of both strategies in the subjective control of emotion, accompanied by reductions of facial expressive activity (Corrugator supercilii and Zygomaticus major). ERP results indicated that distraction, compared with reappraisal, yielded a stronger and earlier attenuation of the late positive potential (LPP) magnitude for negative pictures. For positive pictures, only distraction but not reappraisal had significant effect on LPP attenuation. The results support the process model of ER, separating subtypes of cognitive strategies based on their specific time course. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Time course and degree of hyperinflation with metronome-paced tachypnea in COPD patients.

    Science.gov (United States)

    Weigt, S Samuel; Abrazado, Marlon; Kleerup, Eric C; Tashkin, Donald P; Cooper, Christopher B

    2008-10-01

    In COPD patients, tachypnea should increase (dynamic) hyperinflation by shortening expiratory time. We developed a method to evaluate the time course and degree of dynamic hyperinflation during metronome-paced tachypnea. Fourteen patients with stable COPD (FEV(1) 43 +/- 13% predicted) were studied. Inspiratory capacity (IC) was measured breathing through a flow transducer. Subjects paced their respiratory rate (f(R)) at 20/min, 30/min and 40/min for 60-second periods in response to audible tones generated by a computer. IC measurements were obtained at baseline and after 30 and 60 seconds at each f(R). End-tidal carbon dioxide was monitored and f(R) was allowed to return to baseline between periods of tachypnea. Tachypnea produced reductions in IC of 200 +/- 240 ml, 380 +/- 330 ml and 540 +/- 300 ml after 30 seconds at 20/min, 30/min and 40/min, respectively. IC reduction at 60 seconds was similar to 30 seconds for each f(R). In patients with moderate-to-severe COPD, the dynamic hyperinflation induced by metronome-paced tachypnea was shown to occur rapidly and be complete by 30 seconds for a given f(R). Controlled increments in f(R) produced stepwise increases in dynamic hyperinflation. This standardized method could be a useful and easier method of assessing dynamic hyperinflation in COPD patients before and after therapeutic interventions.

  10. The time course of short-term hypertrophy in the absence of eccentric muscle damage.

    Science.gov (United States)

    Stock, Matt S; Mota, Jacob A; DeFranco, Ryan N; Grue, Katherine A; Jacobo, A Unique; Chung, Eunhee; Moon, Jordan R; DeFreitas, Jason M; Beck, Travis W

    2017-05-01

    It has been proposed that the increase in skeletal muscle mass observed during the initial weeks of initiating a resistance training program is concomitant with eccentric muscle damage and edema. We examined the time course of muscle hypertrophy during 4 weeks of concentric-only resistance training. Thirteen untrained men performed unilateral concentric-only dumbbell curls and shoulder presses twice per week for 4 weeks. Sets of 8-12 repetitions were performed to failure, and training loads were increased during each session. Subjects consumed 500 ml of whole milk during training. Assessments of soreness, lean mass, echo intensity, muscle thickness, relaxed and flexed arm circumference, and isokinetic strength were performed every 72 or 96 h. Soreness, echo intensity, relaxed circumference, and peak torque data did not significantly change. Significant increases in lean mass, muscle thickness, and flexed circumference were observed within seven training sessions. Lean mass was elevated at tests #7 (+109.3 g, p = .002) and #8 (+116.1 g, p = .035), with eight different subjects showing changes above the minimal difference of 139.1 g. Muscle thickness was elevated at tests #6 (+0.23 cm, p = .004), #7 (+0.31 cm, p hypertrophy may occur in the absence of eccentric muscle damage within seven training sessions.

  11. Time course of development of metastasis in irradiated Lewis lung carcinoma

    International Nuclear Information System (INIS)

    Ohizumi, Yukio; Maezawa, Hiroshi; Mori, Tomoyuki

    1988-01-01

    The influence of local irradiation on the development of metastases and primary tumor volume was studied in Lewis lung carcinoma growing intramuscularly in the hind leg of C57BL/6 mice. The time course of development of metastases was determined from the size of the lung colonies at autopsy by determining the growth rate of the colonies. Irradiation within five days after tumor cell injection inhibited the incidence of metastases in accordance with irradiation dose. For irradiation more than seven days after the injection, promotion of metastases was observed around the time of the experiment as a function of irradiation dose and tumor volume. After the irradiation phase, the development of metastases was inhibited in accordance with radiation dose. When delay in metastasis was defined as additional days needed to develop two or ten colonies compared with controls, the relationship between delay and dose was linear. At the regrowth phase of the primary tumor, the incidence of metastases from the irradiated tumor was reduced in comparison with that from unirradiated tumors of the same size. Inhibition of metastases was observed only at 5 Gy and showed slight dose-dependency. Mechanisms in the development of metastases as they related to these findings are also discussed. (autho)

  12. Flavour generation during commercial barley and malt roasting operations: a time course study.

    Science.gov (United States)

    Yahya, Hafiza; Linforth, Robert S T; Cook, David J

    2014-02-15

    The roasting of barley and malt products generates colour and flavour, controlled principally by the time course of product temperature and moisture content. Samples were taken throughout the industrial manufacture of three classes of roasted product (roasted barley, crystal malt and black malt) and analysed for moisture content, colour and flavour volatiles. Despite having distinct flavour characteristics, the three products contained many compounds in common. The product concentrations through manufacture of 15 flavour compounds are used to consider the mechanisms (Maillard reaction, caramelisation, pyrolysis) by which they were formed. The use of water sprays resulted in transient increases in formation of certain compounds (e.g., 2-cyclopentene-1,4-dione) and a decrease in others (e.g., pyrrole). The study highlights rapid changes in colour and particularly flavour which occur at the end of roasting and onwards to the cooling floor. This highlights the need for commercial maltsters to ensure consistency of procedures from batch to batch. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Audiovisual semantic interactions between linguistic and nonlinguistic stimuli: The time-courses and categorical specificity.

    Science.gov (United States)

    Chen, Yi-Chuan; Spence, Charles

    2018-04-30

    We examined the time-courses and categorical specificity of the crossmodal semantic congruency effects elicited by naturalistic sounds and spoken words on the processing of visual pictures (Experiment 1) and printed words (Experiment 2). Auditory cues were presented at 7 different stimulus onset asynchronies (SOAs) with respect to the visual targets, and participants made speeded categorization judgments (living vs. nonliving). Three common effects were observed across 2 experiments: Both naturalistic sounds and spoken words induced a slowly emerging congruency effect when leading by 250 ms or more in the congruent compared with the incongruent condition, and a rapidly emerging inhibitory effect when leading by 250 ms or less in the incongruent condition as opposed to the noise condition. Only spoken words that did not match the visual targets elicited an additional inhibitory effect when leading by 100 ms or when presented simultaneously. Compared with nonlinguistic stimuli, the crossmodal congruency effects associated with linguistic stimuli occurred over a wider range of SOAs and occurred at a more specific level of the category hierarchy (i.e., the basic level) than was required by the task. A comprehensive framework is proposed to provide a dynamic view regarding how meaning is extracted during the processing of visual or auditory linguistic and nonlinguistic stimuli, therefore contributing to our understanding of multisensory semantic processing in humans. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. The Onset and Time Course of Semantic Priming during Rapid Recognition of Visual Words

    Science.gov (United States)

    Hoedemaker, Renske S.; Gordon, Peter C.

    2016-01-01

    In two experiments, we assessed the effects of response latency and task-induced goals on the onset and time course of semantic priming during rapid processing of visual words as revealed by ocular response tasks. In Experiment 1 (Ocular Lexical Decision Task), participants performed a lexical decision task using eye-movement responses on a sequence of four words. In Experiment 2, the same words were encoded for an episodic recognition memory task that did not require a meta-linguistic judgment. For both tasks, survival analyses showed that the earliest-observable effect (Divergence Point or DP) of semantic priming on target-word reading times occurred at approximately 260 ms, and ex-Gaussian distribution fits revealed that the magnitude of the priming effect increased as a function of response time. Together, these distributional effects of semantic priming suggest that the influence of the prime increases when target processing is more effortful. This effect does not require that the task include a metalinguistic judgment; manipulation of the task goals across experiments affected the overall response speed but not the location of the DP or the overall distributional pattern of the priming effect. These results are more readily explained as the result of a retrospective rather than a prospective priming mechanism and are consistent with compound-cue models of semantic priming. PMID:28230394

  15. The time course of spoken word recognition in Mandarin Chinese: a unimodal ERP study.

    Science.gov (United States)

    Huang, Xianjun; Yang, Jin-Chen; Zhang, Qin; Guo, Chunyan

    2014-10-01

    In the present study, two experiments were carried out to investigate the time course of spoken word recognition in Mandarin Chinese using both event-related potentials (ERPs) and behavioral measures. To address the hypothesis that there is an early phonological processing stage independent of semantics during spoken word recognition, a unimodal word-matching paradigm was employed, in which both prime and target words were presented auditorily. Experiment 1 manipulated the phonological relations between disyllabic primes and targets, and found an enhanced P2 (200-270 ms post-target onset) as well as a smaller early N400 to word-initial phonological mismatches over fronto-central scalp sites. Experiment 2 manipulated both phonological and semantic relations between monosyllabic primes and targets, and replicated the phonological mismatch-associated P2, which was not modulated by semantic relations. Overall, these results suggest that P2 is a sensitive electrophysiological index of early phonological processing independent of semantics in Mandarin Chinese spoken word recognition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Must analysis of meaning follow analysis of form? A time course analysis.

    Science.gov (United States)

    Feldman, Laurie B; Milin, Petar; Cho, Kit W; Moscoso Del Prado Martín, Fermín; O'Connor, Patrick A

    2015-01-01

    Many models of word recognition assume that processing proceeds sequentially from analysis of form to analysis of meaning. In the context of morphological processing, this implies that morphemes are processed as units of form prior to any influence of their meanings. Some interpret the apparent absence of differences in recognition latencies to targets (SNEAK) in form and semantically similar (sneaky-SNEAK) and in form similar and semantically dissimilar (sneaker-SNEAK) prime contexts at a stimulus onset asynchrony (SOA) of 48 ms as consistent with this claim. To determine the time course over which degree of semantic similarity between morphologically structured primes and their targets influences recognition in the forward masked priming variant of the lexical decision paradigm, we compared facilitation for the same targets after semantically similar and dissimilar primes across a range of SOAs (34-100 ms). The effect of shared semantics on recognition latency increased linearly with SOA when long SOAs were intermixed (Experiments 1A and 1B) and latencies were significantly faster after semantically similar than dissimilar primes at homogeneous SOAs of 48 ms (Experiment 2) and 34 ms (Experiment 3). Results limit the scope of form-then-semantics models of recognition and demonstrate that semantics influences even the very early stages of recognition. Finally, once general performance across trials has been accounted for, we fail to provide evidence for individual differences in morphological processing that can be linked to measures of reading proficiency.

  17. Time course of the response of carbohydrate metabolism to unloading of the soleus

    Science.gov (United States)

    Henriksen, Erik J.; Tischler, Marc E.

    1988-01-01

    The time course of the response of carbohydrate metabolism to unloading was studied in the soleus muscle of rats subjected to tail-cast suspension. In the fresh soleus, 12 hours of unloading led to higher concentrations of glycogen and lower activity ratios of both glycogen synthase and glycogen phosphorylase. These changes were still evident on day three. Thereafter, the increased glycogen concentration apparently diminished the activity ratio of glycogen synthase, leading to a subsequent fall in the total glycogen content after day one. After 24 hours of unloading, when no significant atrophy was detectable, there was no differential response to insulin for in vitro glucose metabolism. On day three, the soleus atrophied significantly and displayed a greater sensitivity to insulin for most of these parameters compared to the weight-bearing control muscle. However, insulin sensitivity for glycogen synthesis was unchanged. These results showed that the increased sensitivity to insulin of the unloaded soleus is associated with the degree of muscle atrophy, likely due to an increased insulin binding capacity relative to muscle mass. This study also showed that insulin regulation of glucose uptake and of glycogen synthesis is affected differentially in the unloaded soleus muscle.

  18. The time course of morphological processing during spoken word recognition in Chinese.

    Science.gov (United States)

    Shen, Wei; Qu, Qingqing; Ni, Aiping; Zhou, Junyi; Li, Xingshan

    2017-12-01

    We investigated the time course of morphological processing during spoken word recognition using the printed-word paradigm. Chinese participants were asked to listen to a spoken disyllabic compound word while simultaneously viewing a printed-word display. Each visual display consisted of three printed words: a semantic associate of the first constituent of the compound word (morphemic competitor), a semantic associate of the whole compound word (whole-word competitor), and an unrelated word (distractor). Participants were directed to detect whether the spoken target word was on the visual display. Results indicated that both the morphemic and whole-word competitors attracted more fixations than the distractor. More importantly, the morphemic competitor began to diverge from the distractor immediately at the acoustic offset of the first constituent, which was earlier than the whole-word competitor. These results suggest that lexical access to the auditory word is incremental and morphological processing (i.e., semantic access to the first constituent) that occurs at an early processing stage before access to the representation of the whole word in Chinese.

  19. Must analysis of meaning follow analysis of form? A time course analysis

    Directory of Open Access Journals (Sweden)

    Laurie eFeldman

    2015-03-01

    Full Text Available Many models of word recognition assume that processing proceeds sequentially from analysis of form to analysis of meaning. In the context of morphological processing, this implies that morphemes are processed as units of form prior to any influence of their meanings. Some interpret the apparent absence of differences in recognition latencies to targets (SNEAK in form and semantically similar (sneaky-SNEAK and in form similar and semantically dissimilar (sneaker-SNEAK prime contexts at an SOA of 48 ms as consistent with this claim. To determine the time course over which degree of semantic similarity between morphologically structured primes and their targets influences recognition in the forward masked priming variant of the lexical decision paradigm, we compared facilitation for the same targets after semantically similar and dissimilar primes across a range of SOAs. The effect of shared semantics on recognition latency increased linearly with SOA when long SOAs were intermixed (Exp. 1 and latencies were significantly faster after semantically similar than dissimilar primes at homogeneous SOAs of 48 ms (Exp. 2 and 34 ms (Exp. 3. Results limit the scope of form-then-semantics models of recognition and demonstrate that semantics influences even the very early stages of recognition. Finally, once general behavior across trials has been accounted for, we fail to provide evidence for individual differences in morphological processing that can be linked to measures of reading proficiency.

  20. A time-course study of long term over-expression of ARR19 in mice

    Science.gov (United States)

    Qamar, Imteyaz; Ahmad, Mohammad Faiz; Narayanasamy, Arul

    2015-01-01

    A leucine-rich protein, ARR19 (androgen receptor corepressor-19 kDa), is highly expressed in male reproductive organs and moderately in others. Previously, we have reported that ARR19 is differentially expressed in adult Leydig cells during the testis development and inhibits steroidogenesis by reducing the expression of steroidogenic enzymes. Whereas in prostate, ARR19 represses the transcriptional activity of AR (androgen receptor), it is important for male sexual differentiation and maturation in prostate and epididymis, through the recruitment of HDAC4. In this study we show that long term adenovirus mediated overexpression of ARR19 in mice testis has the potential of inhibiting the differentiation of testicular and prostatic cells by reducing the size of testis and prostate but has no effect on the growth of seminal vesicles. Further, it reduces the level of progesterone and testosterone by reducing the steroidogenic enzymes such as 3HSD, P450c17 and StAR. This is the first study reporting a time-course analysis of the implications of long term overexpression of ARR19 in mice testis and its effect on other organs such as prostate and seminal vesicles. Taken together, these results suggest that ARR19 may play an important role in the differentiation of male reproductive organs such as testis and prostate. PMID:26260329

  1. Reduced glomerular angiotensin II receptor density in diabetes mellitus in the rat: time course and mechanism

    International Nuclear Information System (INIS)

    Wilkes, B.M.

    1987-01-01

    Glomerular angiotensin II receptors are reduced in number in early diabetes mellitus, which may contribute to hyperfiltration and glomerular injury. The time course and role of the renin-angiotensin-aldosterone system in the pathogenesis of the receptor abnormality were studied in male Sprague-Dawley rats made diabetic with streptozotocin (65 mg, iv). Glomerular angiotensin II receptors were measured by Scatchard analysis; insulin, renin activity, angiotensin II, and aldosterone were measured by RIA. Diabetes mellitus was documented at 24 h by a rise in plasma glucose (vehicle-injected control, 133 +/- 4; diabetic, 482 +/- 22 mg/dl and a fall in plasma insulin (control, 53.1 +/- 5.7; diabetic, 35.6 +/- 4.0 microIU/ml. At 24 h glomerular angiotensin II receptor density was decreased by 26.5% in diabetic rats (control, 75.5 +/- 9.6 X 10(6); diabetic, 55.5 +/- 8.3 X 10(6) receptors/glomerulus. Receptor occupancy could not explain the defect, because there was reduced binding in diabetic glomeruli after pretreatment with 3 M MgCl 2 , a maneuver that caused dissociation of previously bound hormone. There was a progressive return of the receptor density toward normal over the 60 days following induction of diabetes, with diabetic glomeruli measuring 22.7%, 14.8%, and 3.7% fewer receptors than age-matched controls at 11 days, 1 month, and 2 months, respectively

  2. The time-course analysis of gene expression during wound healing in mouse skin.

    Science.gov (United States)

    Kagawa, Shinichiro; Matsuo, Aya; Yagi, Yoichi; Ikematsu, Kazuya; Tsuda, Ryouichi; Nakasono, Ichiro

    2009-03-01

    RNA analysis has been applied to forensic work to determine wound age. We investigated mRNA expression using quantitative RT-PCR of ten genes, including c-fos, fosB, mitogen-activated protein kinase phosphatase-1 (MKP-1), CD14, chemokine (C-C motif) ligand 9 (CCL9), placenta growth factor (PlGF), mast cell protease-5 (MCP-5), growth arrest specific 5 (Gas5), beta-2 microglobulin (B2M) and major urinary protein-1 (MUP-1), in terms of repair response in adult mice. The expression level of c-fos, fosB and MKP-1 transcripts increased drastically, peaked within 1h, and that of the CD14 and CCL9 transcripts peaked from 12 to 24h. An increase in PlGF and MCP-5 mRNA appeared on about day 5. Gas5, B2M and MUP-1 transcripts showed no significant change. Each gene had differentially expressional patterns with time-course. Our result implied that the observation of the 7 genes in wounded skin could serve to aid in the accurate diagnosis of wound age.

  3. The time course of activation of object shape and shape+colour representations during memory retrieval.

    Directory of Open Access Journals (Sweden)

    Toby J Lloyd-Jones

    Full Text Available Little is known about the timing of activating memory for objects and their associated perceptual properties, such as colour, and yet this is important for theories of human cognition. We investigated the time course associated with early cognitive processes related to the activation of object shape and object shape+colour representations respectively, during memory retrieval as assessed by repetition priming in an event-related potential (ERP study. The main findings were as follows: (1 we identified a unique early modulation of mean ERP amplitude during the N1 that was associated with the activation of object shape independently of colour; (2 we also found a subsequent early P2 modulation of mean amplitude over the same electrode clusters associated with the activation of object shape+colour representations; (3 these findings were apparent across both familiar (i.e., correctly coloured - yellow banana and novel (i.e., incorrectly coloured - blue strawberry objects; and (4 neither of the modulations of mean ERP amplitude were evident during the P3. Together the findings delineate the timing of object shape and colour memory systems and support the notion that perceptual representations of object shape mediate the retrieval of temporary shape+colour representations for familiar and novel objects.

  4. The time course of activation of object shape and shape+colour representations during memory retrieval.

    Science.gov (United States)

    Lloyd-Jones, Toby J; Roberts, Mark V; Leek, E Charles; Fouquet, Nathalie C; Truchanowicz, Ewa G

    2012-01-01

    Little is known about the timing of activating memory for objects and their associated perceptual properties, such as colour, and yet this is important for theories of human cognition. We investigated the time course associated with early cognitive processes related to the activation of object shape and object shape+colour representations respectively, during memory retrieval as assessed by repetition priming in an event-related potential (ERP) study. The main findings were as follows: (1) we identified a unique early modulation of mean ERP amplitude during the N1 that was associated with the activation of object shape independently of colour; (2) we also found a subsequent early P2 modulation of mean amplitude over the same electrode clusters associated with the activation of object shape+colour representations; (3) these findings were apparent across both familiar (i.e., correctly coloured - yellow banana) and novel (i.e., incorrectly coloured - blue strawberry) objects; and (4) neither of the modulations of mean ERP amplitude were evident during the P3. Together the findings delineate the timing of object shape and colour memory systems and support the notion that perceptual representations of object shape mediate the retrieval of temporary shape+colour representations for familiar and novel objects.

  5. The Development of LinguaBytes: An Interactive Tangible Play and Learning System to Stimulate the Language Development of Toddlers with Multiple Disabilities

    Directory of Open Access Journals (Sweden)

    Bart Hengeveld

    2008-01-01

    Full Text Available Young children with multiple disabilities (e.g., both cognitive and motor disabilities are confronted with severe limitations in language development from birth and later on. Stimulating the adult-child communication can decrease these limitations. Within LinguaBytes, a three-year research program, we try to stimulate language development by developing an interactive and adaptive play and learning environment, incorporating tangible objects and multimedia content, based on interactive storytelling and anchored instruction. The development of a product for such a heterogeneous user group presents substantial challenges. We use a Research-through-Design method, that is, an iterative process of developing subsequent experiential prototypes and then testing them in real-life settings, for example, a center for rehabilitation medicine. This article gives an outline of the development of the LinguaBytes play and learning environment from the earliest studies up to the current prototype, CLICK-IT.

  6. Distribution and time course of corticosterone excretion in faeces and urine of female mice with varying systemic concentrations

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Hau, Jann; Jacobsen, Kirsten R

    2010-01-01

    distribution and time course of corticosterone excretion, after intravenous injection of varying corticosterone concentrations, was investigated in female mice. Female BALB/c mice excreted 60% of all corticosterone in the urine with an approximate delay of 5h from tail vein administration. The remaining 40......% were excreted in faeces, with an approximate delay of 9h from administration. The faecal/urinary excretion ratio, as well as time course of excretion, remained unaltered by administration of various doses of corticosterone covering the entire physiological range of serum corticosterone. Although...

  7. Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors.

    Science.gov (United States)

    Sneed, Penny K; Mendez, Joe; Vemer-van den Hoek, Johanna G M; Seymour, Zachary A; Ma, Lijun; Molinaro, Annette M; Fogh, Shannon E; Nakamura, Jean L; McDermott, Michael W

    2015-08-01

    The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases. All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at UCSF were considered. Cases with less than 3 months of follow-up imaging, a gap of more than 8 months in imaging during the 1st year, or inadequate imaging availability were excluded. Brain scans and pathology reports were reviewed to ensure consistent scoring of dates of ARE, treatment failure, or both; in case of uncertainty, the cause of lesion worsening was scored as indeterminate. Cumulative incidence of ARE and failure were estimated with the Kaplan-Meier method with censoring at last imaging. Univariate and multivariate Cox proportional hazards analyses were performed. Among 435 patients and 2200 brain metastases evaluable, the median patient survival time was 17.4 months and the median lesion imaging follow-up was 9.9 months. Calculated on the basis of 2200 evaluable lesions, the rates of treatment failure, ARE, concurrent failure and ARE, and lesion worsening with indeterminate cause were 9.2%, 5.4%, 1.4%, and 4.1%, respectively. Among 118 cases of ARE, approximately 60% were symptomatic and 85% occurred 3-18 months after SRS (median 7.2 months). For 99 ARE cases managed without surgery or bevacizumab, the probabilities of improvement observed on imaging were 40%, 57%, and 76% at 6, 12, and 18 months after onset of ARE. The most important risk factors for ARE included prior SRS to the same lesion (with 20% 1-year risk of symptomatic ARE vs 3%, 4%, and 8% for no prior treatment, prior whole brain radiotherapy [WBRT], or concurrent WBRT) and any of these volume parameters: target, prescription isodose, 12-Gy, or 10-Gy volume. Excluding lesions treated with repeat SRS, the 1-year probabilities of ARE were 2.1 cm, target volume > 1.2 cm(3), prescription isodose volume > 1.8 cm(3

  8. Time course in calpain activity and autolysis in slow and fast skeletal muscle during clenbuterol treatment.

    Science.gov (United States)

    Douillard, Aymeric; Galbes, Olivier; Rossano, Bernadette; Vernus, Barbara; Bonnieu, Anne; Candau, Robin; Py, Guillaume

    2011-02-01

    Calpains are Ca2+ cysteine proteases that have been proposed to be involved in the cytoskeletal remodeling and wasting of skeletal muscle. Cumulative evidence also suggests that β2-agonists can lead to skeletal muscle hypertrophy through a mechanism probably related to calcium-dependent proteolytic enzyme. The aim of our study was to monitor calpain activity as a function of clenbuterol treatment in both slow and fast phenotype rat muscles. For this purpose, for 21 days we followed the time course of the calpain activity and of the ubiquitous calpain 1 and 2 autolysis, as well as muscle remodeling in the extensor digitorum longus (EDL) and soleus muscles of male Wistar rats treated daily with clenbuterol (4 mg·kg-1). A slow to fast fiber shift was observed in both the EDL and soleus muscles after 9 days of treatment, while hypertrophy was observed only in EDL after 9 days of treatment. Soleus muscle but not EDL muscle underwent an early apoptonecrosis phase characterized by hematoxylin and eosin staining. Total calpain activity was increased in both the EDL and soleus muscles of rats treated with clenbuterol. Moreover, calpain 1 autolysis increased significantly after 14 days in the EDL, but not in the soleus. Calpain 2 autolysis increased significantly in both muscles 6 hours after the first clenbuterol injection, indicating that clenbuterol-induced calpain 2 autolysis occurred earlier than calpain 1 autolysis. Together, these data suggest a preferential involvement of calpain 2 autolysis compared with calpain 1 autolysis in the mechanisms underlying the clenbuterol-induced skeletal muscle remodeling.

  9. Inference of RNA polymerase II transcription dynamics from chromatin immunoprecipitation time course data.

    Directory of Open Access Journals (Sweden)

    Ciira wa Maina

    2014-05-01

    Full Text Available Gene transcription mediated by RNA polymerase II (pol-II is a key step in gene expression. The dynamics of pol-II moving along the transcribed region influence the rate and timing of gene expression. In this work, we present a probabilistic model of transcription dynamics which is fitted to pol-II occupancy time course data measured using ChIP-Seq. The model can be used to estimate transcription speed and to infer the temporal pol-II activity profile at the gene promoter. Model parameters are estimated using either maximum likelihood estimation or via Bayesian inference using Markov chain Monte Carlo sampling. The Bayesian approach provides confidence intervals for parameter estimates and allows the use of priors that capture domain knowledge, e.g. the expected range of transcription speeds, based on previous experiments. The model describes the movement of pol-II down the gene body and can be used to identify the time of induction for transcriptionally engaged genes. By clustering the inferred promoter activity time profiles, we are able to determine which genes respond quickly to stimuli and group genes that share activity profiles and may therefore be co-regulated. We apply our methodology to biological data obtained using ChIP-seq to measure pol-II occupancy genome-wide when MCF-7 human breast cancer cells are treated with estradiol (E2. The transcription speeds we obtain agree with those obtained previously for smaller numbers of genes with the advantage that our approach can be applied genome-wide. We validate the biological significance of the pol-II promoter activity clusters by investigating cluster-specific transcription factor binding patterns and determining canonical pathway enrichment. We find that rapidly induced genes are enriched for both estrogen receptor alpha (ERα and FOXA1 binding in their proximal promoter regions.

  10. Time course of the hemoglobin mass response to natural altitude training in elite endurance cyclists.

    Science.gov (United States)

    Garvican, L; Martin, D; Quod, M; Stephens, B; Sassi, A; Gore, C

    2012-02-01

    To determine the time course of hemoglobin mass (Hb(mass)) to natural altitude training, Hb(mass), erythropoietin [EPO], reticulocytes, ferritin and soluble transferrin receptor (sTfR) were measured in 13 elite cyclists during, and 10 days after, 3 weeks of sea level (n=5) or altitude (n=8, 2760 m) training. Mean Hb(mass), with a typical error of ∼2%, increased during the first 11 days at altitude (mean ± standard deviation 2.9 ± 2.0%) and was 3.5 ± 2.5% higher than baseline after 19 days. [EPO] increased 64.2 ± 18.8% after 2 nights at altitude but was not different from baseline after 12 nights. Hb(mass) and [EPO] did not increase in sea level. Reticulocytes (%) were slightly elevated in altitude at Days 5 and 12 (18.9 ± 17.7% and 20.4 ± 25.3%), sTfR was elevated at Day 12 (18.9 ± 15.0%), but both returned to baseline by Day 20. Hb(mass) and [EPO] decreased on descent to sea level while ferritin increased. The mean increase in Hb(mass) observed after 11 days (∼300 h) of altitude training was beyond the measurement error and consitent with the mean increase after 300 h of simulated live high:train low altitude. Our results suggest that in elite cyclists, Hb(mass) increases progressively with 3 weeks of natural altitude exposure, with greater increases expected as exposure persists. © 2010 John Wiley & Sons A/S.

  11. Time course effects of lithium administration on spatial memory acquisition and cholinergic marker expression in rats

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    M H Karimfar

    2009-08-01

    Full Text Available Background: The effects of chronic lithium exposure on spatial memory in rats remain controversial. In this study a time course of the effects of lithium, administered systemically, on spatial memory acquisition in Morris water maze was investigated. Material and Methods: Lithium (600 mg/L was administered to four groups of rats in their drinking water; the first group of animals received lithium for one week, the second group for two weeks, the third group for three weeks, and the fourth group for four weeks.  As controls, four groups of animals received only normal drinking water for the same period of time.  Toward the end of their lithium or water treatment, all animals were trained for four days; each day included one block and each block contained four trials.  Test trials were conducted 48 hrs after completion of the lithium treatment. Escape latency, traveled distance and swimming speed were evaluated during testing trials. Brain tissues from animals were processed according to the standard protocols for immunohistochemical analysis.  Results: Lithium treatment decreased escape latency and traveled distance, but not swimming speed, compared with controls, suggesting significant spatial memory acquisition enhancement by lithium. Quantitative analysis showed that lithium, particularly after four weeks of exposure, significantly increased the number and density of immunostained ChAT-containing (choline acetyltransferase neurons in the medial septal area in comparison with control groups.  There was also a significant correlation between the number of immunostained ChAT neurons and behavioral measures. Conclusion: These results suggest that chronic oral administration of lithium causes spatial memory acquisition improvement in rats and an increase in ChAT immunostaining levels in medial septal nuclei.

  12. Molecular time-course and the metabolic basis of entry into dauer in Caenorhabditis elegans.

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    Pan-Young Jeong

    Full Text Available When Caenorhabditis elegans senses dauer pheromone (daumone, signaling inadequate growth conditions, it enters the dauer state, which is capable of long-term survival. However, the molecular pathway of dauer entry in C. elegans has remained elusive. To systematically monitor changes in gene expression in dauer paths, we used a DNA microarray containing 22,625 gene probes corresponding to 22,150 unique genes from C. elegans. We employed two different paths: direct exposure to daumone (Path 1 and normal growth media plus liquid culture (Path 2. Our data reveal that entry into dauer is accomplished through the multi-step process, which appears to be compartmentalized in time and according to metabolic flux. That is, a time-course of dauer entry in Path 1 shows that dauer larvae formation begins at post-embryonic stage S4 (48 h and is complete at S6 (72 h. Our results also suggest the presence of a unique adaptive metabolic control mechanism that requires both stage-specific expression of specific genes and tight regulation of different modes of fuel metabolite utilization to sustain the energy balance in the context of prolonged survival under adverse growth conditions. It is apparent that worms entering dauer stage may rely heavily on carbohydrate-based energy reserves, whereas dauer larvae utilize fat or glyoxylate cycle-based energy sources. We created a comprehensive web-based dauer metabolic database for C. elegans (www.DauerDB.org that makes it possible to search any gene and compare its relative expression at a specific stage, or evaluate overall patterns of gene expression in both paths. This database can be accessed by the research community and could be widely applicable to other related nematodes as a molecular atlas.

  13. EEG can track the time course of successful reference resolution in small visual worlds

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    Christian eBrodbeck

    2015-11-01

    Full Text Available Previous research has shown that language comprehenders resolve reference quickly and incrementally, but not much is known about the neural processes and representations that are involved. Studies of visual short-term memory suggest that access to the representation of an item from a previously seen display is associated with a negative evoked potential at posterior electrodes contralateral to the spatial location of that item in the display. In this paper we demonstrate that resolving the reference of a noun phrase in a recently seen visual display is associated with an event-related potential that is analogous to this effect. Our design was adapted from the visual world paradigm: in each trial, participants saw a display containing 3 simple objects, followed by a question about the objects, such as Was the pink fish next to a boat?, presented word by word. Questions differed in whether the color adjective allowed the reader to identify the referent of the noun phrase or not (i.e., whether one or more objects of the named color were present. Consistent with our hypothesis, we observed that reference resolution by the adjective was associated with a negative evoked potential at posterior electrodes contralateral to spatial location of the referent, starting approximately 333 ms after the onset of the adjective. The fact that the laterality of the effect depended upon the location of the referent within the display suggests that reference resolution in visual domains involves, at some level, a modality-specific representation. In addition, the effect gives us an estimate of the time course of processing from perception of the written word to the point at which its meaning is brought into correspondence with the referential domain.

  14. Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice.

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    Song, Jeongah; Kim, Woojin; Kim, Yong-Bum; Kim, Bumseok; Lee, Kyuhong

    2018-04-15

    Pulmonary fibrosis is a chronic progressive disease with unknown etiology and has poor prognosis. Polyhexamethyleneguanidine phosphate (PHMG-P) causes acute interstitial pneumonia and pulmonary fibrosis in humans when it exposed to the lung. In a previous study, when rats were exposed to PHMG-P through inhalation for 3 weeks, lung inflammation and fibrosis was observed even after 3 weeks of recovery. In this study, we aimed to determine the time course of PHMG-P-induced lung inflammation and fibrosis. We compared pathological action of PHMG-P with that of bleomycin (BLM) and investigated the mechanism underlying PHMG-P-induced lung inflammation and fibrosis. PHMG-P (0.9 mg/kg) or BLM (1.5 mg/kg) was intratracheally administered to mice. At weeks 1, 2, 4 and 10 after instillation, the levels of inflammatory and fibrotic markers and the expression of inflammasome proteins were measured. The inflammatory and fibrotic responses were upregulated until 10 and 4 weeks in the PHMG-P and BLM groups, respectively. Immune cell infiltration and considerable collagen deposition in the peribronchiolar and interstitial areas of the lungs, fibroblast proliferation, and hyperplasia of type II epithelial cells were observed. NALP3 inflammasome activation was detected in the PHMG-P group until 4 weeks, which is suspected to be the main reason for the persistent inflammatory response and exacerbation of fibrotic changes. Most importantly, the pathological changes in the PHMG-P group were similar to those observed in humidifier disinfectant-associated patients. A single exposure of PHMG-P led to persistent pulmonary inflammation and fibrosis for at least 10 weeks. Copyright © 2018. Published by Elsevier Inc.

  15. Identifying significant temporal variation in time course microarray data without replicates

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    Porter Weston

    2009-03-01

    Full Text Available Abstract Background An important component of time course microarray studies is the identification of genes that demonstrate significant time-dependent variation in their expression levels. Until recently, available methods for performing such significance tests required replicates of individual time points. This paper describes a replicate-free method that was developed as part of a study of the estrous cycle in the rat mammary gland in which no replicate data was collected. Results A temporal test statistic is proposed that is based on the degree to which data are smoothed when fit by a spline function. An algorithm is presented that uses this test statistic together with a false discovery rate method to identify genes whose expression profiles exhibit significant temporal variation. The algorithm is tested on simulated data, and is compared with another recently published replicate-free method. The simulated data consists both of genes with known temporal dependencies, and genes from a null distribution. The proposed algorithm identifies a larger percentage of the time-dependent genes for a given false discovery rate. Use of the algorithm in a study of the estrous cycle in the rat mammary gland resulted in the identification of genes exhibiting distinct circadian variation. These results were confirmed in follow-up laboratory experiments. Conclusion The proposed algorithm provides a new approach for identifying expression profiles with significant temporal variation without relying on replicates. When compared with a recently published algorithm on simulated data, the proposed algorithm appears to identify a larger percentage of time-dependent genes for a given false discovery rate. The development of the algorithm was instrumental in revealing the presence of circadian variation in the virgin rat mammary gland during the estrous cycle.

  16. Study on the P-wave feature time course as early predictors of paroxysmal atrial fibrillation

    International Nuclear Information System (INIS)

    Martínez, Arturo; Alcaraz, Raúl; Rieta, José J

    2012-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, increasing the risk of stroke and all-cause mortality. Its mechanisms are poorly understood, thus leading to different theories and controversial interpretation of its behavior. In this respect, it is unknown why AF is self-terminating in certain individuals, which is called paroxysmal AF (PAF), and not in others. Within the context of biomedical signal analysis, predicting the onset of PAF with a reasonable advance has been a clinical challenge in recent years. By predicting arrhythmia onset, the loss of normal sinus rhythm could be addressed by means of preventive treatments, thus minimizing risks for the patients and improving their quality of life. Traditionally, the study of PAF onset has been undertaken through a variety of features characterizing P-wave spatial diversity from the standard 12-lead electrocardiogram (ECG) or from signal-averaged ECGs. However, the variability of features from the P-wave time course before PAF onset has not been exploited yet. This work introduces a new alternative to assess time diversity of the P-wave features from single-lead ECG recordings. Furthermore, the method is able to assess the risk of arrhythmia 1 h before its onset, which is a relevant advance in order to provide clinically useful PAF risk predictors. Results were in agreement with the electrophysiological changes taking place in the atria. Hence, P-wave features presented an increasing variability as PAF onset approximates, thus suggesting intermittently disturbed conduction in the atrial tissue. In addition, high PAF risk prediction accuracy, greater than 90%, has been reached in the two considered scenarios, i.e. discrimination between healthy individuals and PAF patients and between patients far from PAF and close to PAF onset. Nonetheless, more long-term studies have to be analyzed and validated in future works. (paper)

  17. Time course of pulmonary burden in mice exposed to residual oil fly ash

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    Giovanna Marcella Cavalcante Carvalho

    2014-09-01

    Full Text Available Residual oil fly ash (ROFA is a common pollutant in areas where oil is burned. This particulate matter with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25±5 g were randomly divided into 7 groups and intranasally instilled with either 10 µL of sterile saline solution (0.9% NaCl, CTRL or ROFA (0.2 µg in 10 L of saline solution. Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure, neutrophils (in blood and bronchoalveolar lavage fluid were determined at 6 h in CTRL and at 6, 24, 48, 72, 96 and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons, and organochlorines. Lung resistive pressure augmented early (6 h in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for four days and disappeared spontaneously.

  18. Time course of pulmonary burden in mice exposed to residual oil fly ash.

    Science.gov (United States)

    Carvalho, Giovanna Marcella Cavalcante; Nagato, Lilian Katiê da Silva; Fagundes, Sheila da Silva; Dos Santos, Flávia Brandão; Calheiros, Andrea Surrage; Malm, Olaf; Bozza, Patricia Torres; Saldiva, Paulo Hilário N; Faffe, Débora Souza; Rocco, Patricia Rieken Macedo; Zin, Walter Araujo

    2014-01-01

    Residual oil fly ash (ROFA) is a common pollutant in areas where oil is burned. This particulate matter (PM) with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25 ± 5 g) were randomly divided into 7 groups and intranasally instilled with either 10 μL of sterile saline solution (0.9% NaCl, CTRL) or ROFA (0.2 μg in 10 μL of saline solution). Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure), neutrophils (in blood and bronchoalveolar lavage fluid) were determined at 6 h in CTRL and at 6, 24, 48, 72, 96, and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons (PAHs), and organochlorines. Lung resistive pressure augmented early (6 h) in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for 4 days and disappeared spontaneously.

  19. Time Course of Heart Rate Variability Response to PM2.5 Exposure from Secondhand Smoke.

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    Jennifer L Garza

    Full Text Available Exposure to secondhand smoke (SHS has been associated with decreased heart rate variability (HRV. However, the time course of this association is unclear. Therefore, the objective of this study was to investigate the association between 15-240 minute SHS-related fine particulate matter (PM2.5 moving averages and indices of HRV.With a panel study design, we used personal monitors to continuously measure PM2.5 and HRV of 35 participants who were exposed to SHS for approximately 6 hours.We observed negative, significant associations between 5-minute HRV indices and 15 minute PM2.5 moving averages and 240 minute PM2.5 moving averages: there was a significant (p<0.01 7.5% decrease in the 5-minute square root of the mean squared differences of successive normal heart beats associated with (RMSSD, and a significant (p<0.01 14.7% decrease in the 5-minute high frequency (HF power associated with the 15 minute PM2.5 moving averages; there was also a significant (p<0.01 46.9% decrease in the 5-minute RMSSD, and a significant (p<0.01 77.7% decrease in the 5-minute high frequency (HF power associated with the 240 minute PM2.5 moving averages.Our findings that exposure to SHS related PM2.5 was associated with HRV support the hypothesis that SHS can affect the cardiovascular system. The negative associations reported between short and longer term PM2.5 and HRV indicate adverse effects of SHS on the cardiovascular system.

  20. Time-course of exercise and its association with 12-month bone changes

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    Vainionpää Aki

    2009-11-01

    Full Text Available Abstract Background Exercise has been shown to have positive effects on bone density and strength. However, knowledge of the time-course of exercise and bone changes is scarce due to lack of methods to quantify and qualify daily physical activity in long-term. The aim was to evaluate the association between exercise intensity at 3, 6 and 12 month intervals and 12-month changes in upper femur areal bone mineral density (aBMD and mid-femur geometry in healthy premenopausal women. Methods Physical activity was continuously assessed with a waist-worn accelerometer in 35 healthy women (35-40 years participating in progressive high-impact training. To describe exercise intensity, individual average daily numbers of impacts were calculated at five acceleration levels (range 0.3-9.2 g during time intervals of 0-3, 0-6, and 0-12 months. Proximal femur aBMD was measured with dual x-ray absorptiometry and mid-femur geometry was evaluated with quantitative computed tomography at the baseline and after 12 months. Physical activity data were correlated with yearly changes in bone density and geometry, and adjusted for confounding factors and impacts at later months of the trial using multivariate analysis. Results Femoral neck aBMD changes were significantly correlated with 6 and 12 months' impact activity at high intensity levels (> 3.9 g, r being up to 0.42. Trochanteric aBMD changes were associated even with first three months of exercise exceeding 1.1 g (r = 0.39-0.59, p r = 0.38-0.52, p Conclusion The number of high acceleration impacts during 6 months of training was positively associated with 12-month bone changes at the femoral neck, trochanter and mid-femur. These results can be utilized when designing feasible training programs to prevent bone loss in premenopausal women. Trial registration Clinical trials.gov NCT00697957

  1. Time-course comparison of xenobiotic activators of CAR and PPARα in mouse liver

    International Nuclear Information System (INIS)

    Ross, Pamela K.; Woods, Courtney G.; Bradford, Blair U.; Kosyk, Oksana; Gatti, Daniel M.; Cunningham, Michael L.; Rusyn, Ivan

    2009-01-01

    Constitutive androstane receptor (CAR) and peroxisome proliferator activated receptor (PPAR)α are transcription factors known to be primary mediators of liver effects, including carcinogenesis, by phenobarbital-like compounds and peroxisome proliferators, respectively, in rodents. Many similarities exist in the phenotypes elicited by these two classes of agents in rodent liver, and we hypothesized that the initial transcriptional responses to the xenobiotic activators of CAR and PPARα will exhibit distinct patterns, but at later time-points these biological pathways will converge. In order to capture the global transcriptional changes that result from activation of these nuclear receptors over a time-course in the mouse liver, microarray technology was used. First, differences in basal expression of liver genes between C57Bl/6J wild-type and Car-null mice were examined and 14 significantly differentially expressed genes were identified. Next, mice were treated with phenobarbital (100 mg/kg by gavage for 24 h, or 0.085% w/w diet for 7 or 28 days), and liver gene expression changes with regards to both time and treatment were identified. While several pathways related to cellular proliferation and metabolism were affected by phenobarbital in wild-type mice, no significant changes in gene expression were found over time in the Car-nulls. Next, we determined commonalities and differences in the temporal response to phenobarbital and WY-14,643, a prototypical activator of PPAR α. Gene expression signatures from livers of wild-type mice C57Bl6/J mice treated with PB or WY-14,643 were compared. Similar pathways were affected by both compounds; however, considerable time-related differences were present. This study establishes common gene expression fingerprints of exposure to activators of CAR and PPARα in rodent liver and demonstrates that despite similar phenotypic changes, molecular pathways differ between classes of chemical carcinogens

  2. ISPC effect is not observed when the word comes too late: A time course analysis

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    Nart Bedin Atalay

    2014-12-01

    Full Text Available The item-specific proportion congruency (ISPC effect is demonstrated by a smaller Stroop effect observed for mostly incongruent items compared to mostly congruent items. Currently, there is a continuing debate on whether conflict driven item-specific control processes or stimulus-response contingency learning account for the ISPC effect. In the present study, we conducted two experiments to investigate the time course of the ISPC effect with a stimulus onset asynchrony (SOA manipulation. Both negative and positive SOAs were used in order to manipulate the contingency learning between the word and the color dimensions. We also combined this SOA manipulation with a set size manipulation (Bugg & Hutchison, 2013 to moderate the contribution of contingency learning and item-specific processes to the observed ISPC effect. We expected that the change in the magnitude of the ISPC effect as a result of SOA would follow different patterns for the 2-item and 4-item set conditions. Results showed that the SOA manipulation influenced the ISPC effect. Specifically, when the word followed the color with a 200 ms delay, the observed ISPC effect was smaller, if at all present, than the ISPC effects in other negative and positive SOA conditions, regardless of set size. In conclusion, our results showed that the ISPC effect was not observed if the word arrived too late. We also conducted additional awareness and RT distribution analyses (delta plots to further investigate the ISPC effect. These analyses showed that a higher percentage of participants were aware of the ISPC manipulation in the 2-item set condition compared to the 4-item set condition. Delta plots revealed that the ISPC effect was smaller for fastest responses and increased as the responses got slower.

  3. Time course of ongoing activity during neuritis and following axonal transport disruption.

    Science.gov (United States)

    Satkeviciute, Ieva; Goodwin, George; Bove, Geoffrey M; Dilley, Andrew

    2018-05-01

    Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or noninflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Because it is proposed that AMS underlies mechanically induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.

  4. Time Course Changes in Selected Biochemical Stress Indices in Broilers Exposed to Short-term Noise

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    Iveta Bedáňová

    2010-01-01

    Full Text Available Time course changes in selected biochemical stress indices (corticosterone, triglycerides, glucose, cholesterol following short-term noise exposure at 100 dB for 28 min were studied in broilers aged 42 days. Corticosterone concentrations were found to increase during the first 10 min of noise exposure and to differ significantly from the control (background sound – 50 dB at Time 10 min and 14 min, then decreased continually and at 28 min returned to the initial prestress value. Triglyceride concentrations increased in broilers exposed to 100 dB noise during the first 12 min with a significant difference from the control at 12 min and 14 min. Glucose concentrations were higher due to 100 dB noise exposure for almost the entire period monitored, with significant differences between 100 dB and control broilers at 6 min and from 10 min to 14 min. Similarly as for the corticosterone concentration, a drop in triglycerides and glucose concentrations was seen approximately from Time 14 min and a return to the pre-stress value at 28 min. The cholesterol concentrations showed various temporal patterns with no significant difference between 100 dB and control broilers in this experiment. The pattern of response found in the study indicates that 100 dB noise represents a stress factor in broilers, however, there is the ability of broilers to adapt to an increased level of noise at this intensity after the first 14 min of exposure. The findings obtained in the study may contribute to expanding detailed knowledge of physiological stress responses to this specific noise stimulus in poultry, and could thereby be used to improve the welfare of broilers in intensive housing systems.

  5. Postoperative enhancement on breast MRI: Time course and pattern of changes.

    Science.gov (United States)

    Mahoney, Mary C; Sharda, Radhika G

    2018-04-23

    Expected postoperative enhancement on breast MRI can appear similar to enhancement seen in recurrent or residual malignancy. Our aim was to assess the time course and patterns of enhancement at the surgical site, thereby helping to distinguish between benign and malignant postoperative enhancement. In 200 MRI scans performed in 153 patients after breast conservation treatment, 43 after surgical excision of atypia, and 4 patients after benign excisional biopsy were categorized by postoperative time interval. We defined 4 patterns of morphologic enhancement on MRI: cavity wall/seroma (Pattern I); thin linear (Pattern II); mass (Pattern III); and fat necrosis (Pattern IV). Of 200 MRI scans, 66 (33%) demonstrated enhancement at the surgical site. Enhancement typically decreased through the postoperative follow-up period. Enhancement was observed in 41% (28/68) of cases beyond the 18-month interval but was uncommon after 5 years. Pattern III enhancement was the morphologic pattern seen most commonly with malignancy (5/19 cases, 26%). When associated with delayed washout kinetics, it was even more strongly predictive of malignancy (4/5 cases, 80%). In patients with a history of excisional biopsy and no prior radiation treatment, the percentage of MRI scans showing enhancement was significantly lower than (21% vs 49% with P-value .0027) in patients who had undergone radiation. Enhancement at the surgical site occurred in one-third of cases up to 5 years after surgery, particularly in patients who underwent both radiation and surgery. Mass enhancement, particularly in conjunction with delayed washout kinetics, is most predictive of malignancy and should prompt biopsy or re-excision. © 2018 Wiley Periodicals, Inc.

  6. Time course of dichoptic masking in normals and suppression in amblyopes.

    Science.gov (United States)

    Zhou, Jiawei; McNeal, Suzanne; Babu, Raiju J; Baker, Daniel H; Bobier, William R; Hess, Robert F

    2014-04-17

    To better understand the relationship between dichoptic masking in normal vision and suppression in amblyopia we address three questions: First, what is the time course of dichoptic masking in normals and amblyopes? Second, is interocular suppression low-pass or band-pass in its spatial dependence? And third, in the above two regards, is dichoptic masking in normals different from amblyopic suppression? We measured the dependence of dichoptic masking in normal controls and amblyopes on the temporal duration of presentation under three conditions; monocular (the nontested eye-i.e., dominant eye of normals or nonamblyopic eye of amblyopes, being patched), dichoptic-luminance (the nontested eye seeing a mean luminance-i.e., a DC component) and dichoptic-contrast (the nontested eye seeing high-contrast visual noise). The subject had to detect a letter in the other eye, the contrast of which was varied. We found that threshold elevation relative to the patched condition occurred in both normals and amblyopes when the nontested eye saw either 1/f or band-pass filtered noise, but not just mean luminance (i.e., there was no masking from the DC component that corresponds to a channel responsive to a spatial frequency of 0 cyc/deg); longer presentation of the target (corresponding to lower temporal frequencies) produced greater threshold elevation. Dichoptic masking exhibits similar properties in both subject groups, being low-pass temporally and band-pass spatially, so that masking was greatest at the longest presentation durations and was not greatly affected by mean luminance in the nontested eye. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  7. Tracking difference in gene expression in a time-course experiment using gene set enrichment analysis.

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    Pui Shan Wong

    Full Text Available Fistulifera sp. strain JPCC DA0580 is a newly sequenced pennate diatom that is capable of simultaneously growing and accumulating lipids. This is a unique trait, not found in other related microalgae so far. It is able to accumulate between 40 to 60% of its cell weight in lipids, making it a strong candidate for the production of biofuel. To investigate this characteristic, we used RNA-Seq data gathered at four different times while Fistulifera sp. strain JPCC DA0580 was grown in oil accumulating and non-oil accumulating conditions. We then adapted gene set enrichment analysis (GSEA to investigate the relationship between the difference in gene expression of 7,822 genes and metabolic functions in our data. We utilized information in the KEGG pathway database to create the gene sets and changed GSEA to use re-sampling so that data from the different time points could be included in the analysis. Our GSEA method identified photosynthesis, lipid synthesis and amino acid synthesis related pathways as processes that play a significant role in oil production and growth in Fistulifera sp. strain JPCC DA0580. In addition to GSEA, we visualized the results by creating a network of compounds and reactions, and plotted the expression data on top of the network. This made existing graph algorithms available to us which we then used to calculate a path that metabolizes glucose into triacylglycerol (TAG in the smallest number of steps. By visualizing the data this way, we observed a separate up-regulation of genes at different times instead of a concerted response. We also identified two metabolic paths that used less reactions than the one shown in KEGG and showed that the reactions were up-regulated during the experiment. The combination of analysis and visualization methods successfully analyzed time-course data, identified important metabolic pathways and provided new hypotheses for further research.

  8. The Time Course of the Probability of Transition Into and Out of REM Sleep

    Science.gov (United States)

    Bassi, Alejandro; Vivaldi, Ennio A.; Ocampo-Garcés, Adrián

    2009-01-01

    Study Objectives: A model of rapid eye movement (REM) sleep expression is proposed that assumes underlying regulatory mechanisms operating as inhomogenous Poisson processes, the overt results of which are the transitions into and out of REM sleep. Design: Based on spontaneously occurring REM sleep episodes (“Episode”) and intervals without REM sleep (“Interval”), 3 variables are defined and evaluated over discrete 15-second epochs using a nonlinear logistic regression method: “Propensity” is the instantaneous rate of into-REM transition occurrence throughout an Interval, “Volatility” is the instantaneous rate of out-of-REM transition occurrence throughout an Episode, and “Opportunity” is the probability of being in non-REM (NREM) sleep at a given time throughout an Interval, a requisite for transition. Setting: 12:12 light:dark cycle, isolated boxes. Participants: Sixteen male Sprague-Dawley rats Interventions: None. Spontaneous sleep cycles. Measurements and Results: The highest levels of volatility and propensity occur, respectively, at the very beginning of Episodes and Intervals. The new condition stabilizes rapidly, and variables reach nadirs at minute 1.25 and 2.50, respectively. Afterward, volatility increases markedly, reaching values close to the initial level. Propensity increases moderately, the increment being stronger through NREM sleep bouts occurring at the end of long Intervals. Short-term homeostasis is evidenced by longer REM sleep episodes lowering propensity in the following Interval. Conclusions: The stabilization after transitions into Episodes or Intervals and the destabilization after remaining for some time in either condition may be described as resulting from continuous processes building up during Episodes and Intervals. These processes underlie the overt occurrence of transitions. Citation: Bassi A; Vivaldi EA; Ocampo-Garcées A. The time course of the probability of transition into and out of REM sleep. SLEEP 2009

  9. Time course of NMR images and T1 values associated with hypertensive intracerebral hematoma

    International Nuclear Information System (INIS)

    Inao, Suguru; Furuse, Masahiro; Saso, Katsuyoshi; Yoshida, Kazuo; Motegi, Yoshimasa; Kaneoke, Yoshiki; Kamata, Noriko; Izawa, Akira

    1986-01-01

    The present study describes time courses in tissue T 1 values, as well as in NMR imagings, associated with hypertensive intracerebral hematoma (ICH). Non-operative 21 cases of ICH were examined by FONAR QED 80-α NMR system, which possessed dual modes of image display and focal T 1 measurement (static magnetic field : 433 gauss). As the first step of examination SSFP images are displayed and then, at the regions of interest, absolute values of T 1 are measured by field focusing technique. The extent of ICH was revealed as high density zone in NMR imaging, occasionally represented much wider extent of high density area than the finding on X-ray CT. Prolonged T 1 values were obtained from such high density zone. This widespread high density area was regarded to reflect the spread of perifocal brain edema. T 1 value of the hematoma itself was rather shortened in its initial phase within 2 weeks, thereafter followed by prolongation in the time lapse. This seemed to reflect the alterations in the properties of hematoma such as clot formation in earlier phase and resolution in later phase. On the contrary, T 1 in the brain tissue surrounded to hematoma was apparently prolonged in the early phase within 2 weeks, representing the maximal values of 312 msec arround 2 to 4 weeks after the onset, and then gradually normalized in the period over 1 month. This alteration in tissue T 1 likely represents the processes of edema formation and its regression in perifocal zone. T 1 values measured in perifocal region might be available for the evaluation of edema state in association with cerebrovascular accident. (author)

  10. Time course of protein synthesis-dependent phase of olfactory memory in the cricket Gryllus bimaculatus.

    Science.gov (United States)

    Matsumoto, Yukihisa; Noji, Sumihare; Mizunami, Makoto

    2003-04-01

    The cricket Gryllus bimaculatus forms a stable olfactory memory that lasts for practically a lifetime. As a first step to elucidate the cellular mechanisms of olfactory learning and memory retention in crickets, we studied the dependency of memory retention on the de novo brain protein synthesis by injecting the protein synthesis inhibitor cycloheximide (CHX) into the head capsule. Injection of CHX inhibited (3)H-leucine incorporation into brain proteins by > 90% for 3 hr. Crickets were trained to associate peppermint odor with water (reward) and vanilla odor with saline solution (non-reward) and were injected with CHX before or at different times after training. Their odor preferences were tested at 2 hr, 1 day and 4 days after training. Memory retention at 2 hr after training was unaffected by CHX injection. However, the level of retention at 1 day and 4 days after training was lowered when CHX was injected 1 hour before training or at 1 hr or 6 hr after training. To study the time course of the development of CHX-sensitive memory phase, crickets that had been injected with CHX at 1 hr after training were tested at different times from 2 to 12 hr after training. The level of retention was unaffected up to 4 hr after training but significantly lowered at 5 hr after training, and the CHX-sensitive memory phase developed gradually during the next several hours. CHX dissociates two phases of olfactory memory in crickets: earlier protein synthesis-independent phase ( 5 hr) protein synthesis-dependent phase.

  11. Time course of reversed cardiac remodeling after pulmonary endarterectomy in patients with chronic pulmonary thromboembolism

    Energy Technology Data Exchange (ETDEWEB)

    Iino, Misako; Dymarkowski, Steven; Chaothawee, Lertlak; Bogaert, Jan [UZ Leuven, Department of Radiology, Leuven (Belgium); Delcroix, Marion [UZ Leuven, Department of Pneumology, Leuven (Belgium)

    2008-04-15

    To evaluate the time course of reversed remodeling after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension(CTPEH), we studied 22 patients (age: 60 {+-} 13 years) with MRI immediately before, 1 month, 3 months, and 6 months after PEA. MRI included assessment of biventricular function, aortic and pulmonary artery(PA) flow, and right ventricular (RV) overload using the ratio of RV-to-biventricular diameter. Except in one patient, who died 2 months post-surgery, clinical improvement occurred early after PEA (NYHA class: 3.3 {+-} 0.6 to 1.5 {+-} 0.8, p < 0.0001) with a decrease of systolic pulmonary artery pressures (79 {+-} 14 to 44 {+-} 14 mmHg, p < 0.0001). At 1 month post PEA, RV end-diastolic volumes decreased (198 {+-} 72 to 137 {+-} 59 ml, p < 0.0001), and the RV ejection fraction (EF) improved (31 {+-} 9 to 47 {+-} 10%, p < 0.0001). No further significant improvement in pulmonary pressures or RV function occurred at 3 months or 6 months. Although no significant change was found in LV volumes or function, aortic flow increased early after surgery. PEA had only a beneficial effect on right PA flow. RV overload decreased early after PEA (ratio RV-to-biventricular diameter: before: 0.67 {+-} 0.04, after: 0.54 {+-} 0.06, p < 0.0001), showing a good correlation with the improvement in RVEF (r = 0.7, P < 0.0001). In conclusion, reversed cardiac remodeling occurs early after PEA, to slow down after 1 month. At 6 months, cardiac remodeling is incomplete as witnessed by low-normal RV function and residually elevated PA pressures. (orig.)

  12. Time course of ozone-induced changes in breathing pattern in healthy exercising humans.

    Science.gov (United States)

    Schelegle, Edward S; Walby, William F; Adams, William C

    2007-02-01

    We examined the time course of O3-induced changes in breathing pattern in 97 healthy human subjects (70 men and 27 women). One- to five-minute averages of breathing frequency (f(B)) and minute ventilation (Ve) were used to generate plots of cumulative breaths and cumulative exposure volume vs. time and cumulative exposure volume vs. cumulative breaths. Analysis revealed a three-phase response; delay, no response detected; onset, f(B) began to increase; response, f(B) stabilized. Regression analysis was used to identify four parameters: time to onset, number of breaths at onset, cumulative inhaled dose of ozone at onset of O3-induced tachypnea, and the percent change in f(B). The effect of altering O3 concentration, Ve, atropine treatment, and indomethacin treatment were examined. We found that the lower the O3 concentration, the greater the number of breaths at onset of tachypnea at a fixed ventilation, whereas number of breaths at onset of tachypnea remains unchanged when Ve is altered and O3 concentration is fixed. The cumulative inhaled dose of O3 at onset of tachypnea remained constant and showed no relationship with the magnitude of percent change in f(B). Atropine did not affect any of the derived parameters, whereas indomethacin did not affect time to onset, number of breaths at onset, or cumulative inhaled dose of O3 at onset of tachypnea but did attenuate percent change in f(B). The results are discussed in the context of dose response and intrinsic mechanisms of action.

  13. Selective SWS suppression does not affect the time course of core body temperature in men

    NARCIS (Netherlands)

    Beersma, Domien G.M.; Dijk, Derk-Jan

    1992-01-01

    In eight healthy middle-aged men, sleep and core body temperature were recorded under baseline conditions, during all-night SWS suppression by acoustic stimulation, and during undisturbed recovery sleep. SWS suppression resulted in a marked reduction of sleep stages 3 and 4 but did not affect the

  14. Changes in H-Reflex Recruitment After Trans-Spinal Direct Current Stimulation With Multiple Electrode Configurations

    Directory of Open Access Journals (Sweden)

    Alexander Kuck

    2018-03-01

    Full Text Available Trans-spinal direct current stimulation (tsDCS is an electro-modulatory tool with possible application in the rehabilitation of spinal cord injury. TsDCS generates a small electric field, aiming to induce lasting, functional neuromodulation in the targeted neuronal networks. Earlier studies have shown significant modulatory effects after application of lumbar tsDCS. However, for clinical application, a better understanding of application specific factors is required. Our goal was to investigate the effect of different electrode configurations using lumbar spinal tsDCS on spinal excitability. We applied tsDCS (2.5 mA, 15 min in 10 healthy subjects with three different electrode configurations: (1 Anode and cathode placed over vertebra T11, and the posterior left shoulder respectively (LSC-S (one polarity, and (2 Both electrodes placed in equal distance (ED (7 cm above and below vertebra T11, investigated for two polarities (ED-Anodal/Cathodal. The soleus H-Reflex is measured before, during and after tsDCS in either electrode configuration or a sham condition. To account for genetic predispositions in response to direct current stimulation, subject BDNF genotype was assessed. Stimulation in configuration ED-Cathodal induced an amplitude reduction of the H-reflex, 30 min after tsDCS with respect to baseline, whereas none of the other configurations led to significant post intervention effects. BDNF genotype did not correlate with post intervention effects. Furthermore, we failed to replicate effects shown by a previous study, which highlights the need for a better understanding of methodological and subject specific influences on tsDCS outcome. The H-reflex depression after tsDCS (Config. ED-Cathodal provides new insights and may foster our understanding of the working mechanism of tsDCS.

  15. Resveratrol stimulates c-Fos gene transcription via activation of ERK1/2 involving multiple genetic elements.

    Science.gov (United States)

    Thiel, Gerald; Rössler, Oliver G

    2018-06-05

    The polyphenol resveratrol is found in many plant and fruits and is a constituent of our diet. Resveratrol has been proposed to have chemopreventive and anti-inflammatory activities. On the cellular level, resveratrol activates stimulus-regulated transcription factors. To identify resveratrol-responsive elements within a natural gene promoter, the molecular pathway leading to c-Fos gene expression by resveratrol was dissected. The c-Fos gene encodes a basic region leucine zipper transcription factor and is a prototype of an immediate-early gene that is regulated by a wide range of signaling molecules. We analyzed chromatin-integrated c-Fos promoter-luciferase reporter genes where transcription factor binding sites were destroyed by point mutations or deletion mutagenesis. The results show that mutation of the binding sites for serum response factor (SRF), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) significantly reduced reporter gene transcription following stimulation of the cells with resveratrol. Inactivation of the binding sites for signal transducer and activator of transcription (STAT) or ternary complex factors did not influence resveratrol-regulated c-Fos promoter activity. Thus, the c-Fos promoter contains three resveratrol-responsive elements, the cAMP response element (CRE), and the binding sites for SRF and AP-1. Moreover, we show that the transcriptional activation potential of the c-Fos protein is increased in resveratrol-stimulated cells, indicating that the biological activity of c-Fos is elevated by resveratrol stimulation. Pharmacological and genetic experiments revealed that the protein kinase ERK1/2 is the signal transducer that connects resveratrol treatment with the c-Fos gene. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. The gene expression and immunohistochemical time-course of diphenylcyclopropenone induced contact allergy in healthy humans following repeated epicutaneous challenges

    DEFF Research Database (Denmark)

    Mose, K F; Burton, M; Thomassen, M

    2017-01-01

    challenges with DPCP to find the predominant gene expression pattern, ii) the time-course of cell infiltration following repeated DPCP challenges, and iii) the transcriptome of a repeated CA exposure model. We obtained punch biopsies from control and DPCP exposed skin from ten DPCP sensitized individuals...

  17. Eye-movement evidence of the time-course of attentional bias for threatening pictures in test-anxious students

    NARCIS (Netherlands)

    Dong, Y.; Beuckelaer, A. de; Yu, L.; Zhou, R

    2017-01-01

    Protocols for measuring attentional bias to threat in test-anxiety, a special form of trait-anxiety, are rarely found in the literature. In our eye-tracking study, we introduced a new protocol, and studied the time-course of attention to test-related pictures with varying threat levels in 22 high

  18. Effects of Phonological and Orthographic Shifts on Children's Processing of Written Morphology: A Time-Course Study

    Science.gov (United States)

    Quémart, Pauline; Casalis, Séverine

    2014-01-01

    We report two experiments that investigated whether phonological and/or orthographic shifts in a base word interfere with morphological processing by French 3rd, 4th, and 5th graders and adults (as a control group) along the time course of visual word recognition. In both experiments, prime-target pairs shared four possible relationships:…

  19. Young Chinese Children's Anger and Distress: Emotion Category and Intensity Identified by the Time Course of Behaviors

    Science.gov (United States)

    He, Jie; Qiu, Peihua; Park, Ka Young; Xu, Qinmei; Potegal, Michael

    2013-01-01

    A hierarchical cluster analysis of the time course of the videotaped reactions of 75 Chinese 2-4-year olds to mothers' toy-removal identified Distress, Low Anger, and High Anger behavior clusters. Anger often begins at low intensity; some children then escalate. The face-validity of Low and High Anger-cluster classifications was supported in that…

  20. Time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury : a prospective cohort study

    NARCIS (Netherlands)

    Mueller, Gabi; de Groot, Sonja; van der Woude, Lucas; Hopman, Maria T E

    OBJECTIVE: To investigate the time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury. DESIGN: Multi-centre, prospective cohort study. SUBJECTS: One hundred and nine subjects with recent, motor complete spinal cord injury. METHODS: Lung function and

  1. Time Course of the Rabbit's Conditioned Nictitating Membrane Movements during Acquisition, Extinction, and Reacquisition

    Science.gov (United States)

    Kehoe, E. James; Ludvig, Elliot A.; Sutton, Richard S.

    2014-01-01

    The present experiment tested whether or not the time course of a conditioned eyeblink response, particularly its duration, would expand and contract, as the magnitude of the conditioned response (CR) changed massively during acquisition, extinction, and reacquisition. The CR duration remained largely constant throughout the experiment, while CR…

  2. Changes in cerebral blood flow during olfactory stimulation in patients with multiple chemical sensitivity: a multi-channel near-infrared spectroscopic study.

    Directory of Open Access Journals (Sweden)

    Kenichi Azuma

    Full Text Available Multiple chemical sensitivity (MCS is characterized by somatic distress upon exposure to odors. Patients with MCS process odors differently from controls. This odor-processing may be associated with activation in the prefrontal area connecting to the anterior cingulate cortex, which has been suggested as an area of odorant-related activation in MCS patients. In this study, activation was defined as a significant increase in regional cerebral blood flow (rCBF because of odorant stimulation. Using the well-designed card-type olfactory test kit, changes in rCBF in the prefrontal cortex (PFC were investigated after olfactory stimulation with several different odorants. Near-infrared spectroscopic (NIRS imaging was performed in 12 MCS patients and 11 controls. The olfactory stimulation test was continuously repeated 10 times. The study also included subjective assessment of physical and psychological status and the perception of irritating and hedonic odors. Significant changes in rCBF were observed in the PFC of MCS patients on both the right and left sides, as distinct from the center of the PFC, compared with controls. MCS patients adequately distinguished the non-odorant in 10 odor repetitions during the early stage of the olfactory stimulation test, but not in the late stage. In comparison to controls, autonomic perception and negative affectivity were poorer in MCS patients. These results suggest that prefrontal information processing associated with odor-processing neuronal circuits and memory and cognition processes from past experience of chemical exposure play significant roles in the pathology of this disorder.

  3. Catch the wave! Time-window sequential analysis of alertness stimulation in individuals with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Munde, V. S.; Vlaskamp, C.; Maes, B.; Ruijssenaars, A. J. J. M.

    BackgroundWhile optimally activities are provided at those moments when the individual with profound intellectual and multiple disabilities (PIMD) is focused on the environment' or alert', detailed information about the impact that the design and timing of the activity has on alertness is lacking.

  4. iStimulation: Apple iPad Use with Children Who Are Visually Impaired, Including Those with Multiple Disabilities

    Science.gov (United States)

    Campaña, Laura V.; Ouimet, Donald A.

    2015-01-01

    Since its creation in the early 1980s, Light Box, a product developed by the American Printing House for the Blind (APH) that is designed for working on functional vision tasks with children who have visual impairments or multiple disabilities, has been an effective tool to help teach children with visual impairments to locate and track items…

  5. Menopause-related brain activation patterns during visual sexual arousal in menopausal women: An fMRI pilot study using time-course analysis.

    Science.gov (United States)

    Kim, Gwang-Won; Jeong, Gwang-Woo

    2017-02-20

    The aging process and menopausal transition are important factors in sexual dysfunction of menopausal women. No neuroimaging study has assessed the age- and menopause-related changes on brain activation areas associated with sexual arousal in menopausal women. The purpose of this study was to evaluate the time course of regional brain activity associated with sexual arousal evoked by visual stimulation in premenopausal and menopausal women, and further to assess the effect of menopause on the brain areas associated with sexual arousal in menopausal women using functional magnetic resonance imaging (fMRI). Thirty volunteers consisting of 15 premenopausal and 15 menopausal women underwent the fMRI. For the activation condition, volunteers viewed sexually arousing visual stimulation. The brain areas with significantly higher activation in premenopausal women compared with menopausal women included the thalamus, amygdala, and anterior cingulate cortex (ACC) using analysis of covariance adjusting for age (psexual arousal. These findings might help elucidate the neural mechanisms associated with sexual dysfunction in menopausal women. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans.

    Science.gov (United States)

    Jindahra, Panitha; Petrie, Aviva; Plant, Gordon T

    2012-02-01

    Following damage to the human post-geniculate visual pathway retrograde trans-synaptic degeneration of the optic nerve fibres occurs. It has been known for some time from investigations carried out in primates that a decline in the number of retinal ganglion cells follows occipital lobectomy. However, this is not detectable in all species studied and whether this occurs in humans was controversial until recent studies that have shown that following lesions of the occipital lobe, the retinal nerve fibre layer thickness measured by optical coherence tomography is reduced and corresponding shrinkage of the optic tract can be demonstrated by magnetic resonance imaging. The time course of the degeneration in humans is, however, unknown. In the present study, we have used optical coherence tomography to demonstrate for the first time progressive thinning of the retinal nerve fibre layer following occipital lobe/optic radiation damage due to stroke. First, in a group of 38 patients the measurement was taken on a single occasion at a known time interval since the stroke, ranging from 6 days to 67 years. Here, a negative straight line relationship (linear regression r = 0.54, P < 0.001) was found between nerve fibre layer thickness and elapsed time since injury in log years, giving a rate of decline of 9.08 µm per log year after adjusting for age. This indicates a decelerating rate of loss that differs from the rate of decline found with chronological age in this same group, which shows a steady rate of thinning by 0.4 µm per year (P = 0.006) after adjusting for duration of the disease. In a second study serial measurements were taken following the acute event in a group of seven patients with homonymous hemianopia; here a negative straight line relationship was found between time and nerve fibre layer thickness in micrometres over a period of data collection beginning at a mean of 36.9 days post-stroke (range 5-112) and ending at a mean of 426.6 days post

  7. Time course of recovery following resistance training leading or not to failure.

    Science.gov (United States)

    Morán-Navarro, Ricardo; Pérez, Carlos E; Mora-Rodríguez, Ricardo; de la Cruz-Sánchez, Ernesto; González-Badillo, Juan José; Sánchez-Medina, Luis; Pallarés, Jesús G

    2017-12-01

    To describe the acute and delayed time course of recovery following resistance training (RT) protocols differing in the number of repetitions (R) performed in each set (S) out of the maximum possible number (P). Ten resistance-trained men undertook three RT protocols [S × R(P)]: (1) 3 × 5(10), (2) 6 × 5(10), and (3) 3 × 10(10) in the bench press (BP) and full squat (SQ) exercises. Selected mechanical and biochemical variables were assessed at seven time points (from - 12 h to + 72 h post-exercise). Countermovement jump height (CMJ) and movement velocity against the load that elicited a 1 m s -1 mean propulsive velocity (V1) and 75% 1RM in the BP and SQ were used as mechanical indicators of neuromuscular performance. Training to muscle failure in each set [3 × 10(10)], even when compared to completing the same total exercise volume [6 × 5(10)], resulted in a significantly higher acute decline of CMJ and velocity against the V1 and 75% 1RM loads in both BP and SQ. In contrast, recovery from the 3 × 5(10) and 6 × 5(10) protocols was significantly faster between 24 and 48 h post-exercise compared to 3 × 10(10). Markers of acute (ammonia, growth hormone) and delayed (creatine kinase) fatigue showed a markedly different course of recovery between protocols, suggesting that training to failure slows down recovery up to 24-48 h post-exercise. RT leading to failure considerably increases the time needed for the recovery of neuromuscular function and metabolic and hormonal homeostasis. Avoiding failure would allow athletes to be in a better neuromuscular condition to undertake a new training session or competition in a shorter period of time.

  8. Comparative Proteomics of Rubber Latex Revealed Multiple Protein Species of REF/SRPP Family Respond Diversely to Ethylene Stimulation among Different Rubber Tree Clones

    Directory of Open Access Journals (Sweden)

    Zheng Tong

    2017-05-01

    Full Text Available Rubber elongation factor (REF and small rubber particle protein (SRPP are two key factors for natural rubber biosynthesis. To further understand the roles of these proteins in rubber formation, six different genes for latex abundant REF or SRPP proteins, including REF138,175,258 and SRPP117,204,243, were characterized from Hevea brasiliensis Reyan (RY 7-33-97. Sequence analysis showed that REFs have a variable and long N-terminal, whereas SRPPs have a variable and long C-terminal beyond the REF domain, and REF258 has a β subunit of ATPase in its N-terminal. Through two-dimensional electrophoresis (2-DE, each REF/SRPP protein was separated into multiple protein spots on 2-DE gels, indicating they have multiple protein species. The abundance of REF/SRPP proteins was compared between ethylene and control treatments or among rubber tree clones with different levels of latex productivity by analyzing 2-DE gels. The total abundance of each REF/SRPP protein decreased or changed a little upon ethylene stimulation, whereas the abundance of multiple protein species of the same REF/SRPP changed diversely. Among the three rubber tree clones, the abundance of the protein species also differed significantly. Especially, two protein species of REF175 or REF258 were ethylene-responsive only in the high latex productivity clone RY 8-79 instead of in RY 7-33-97 and PR 107. Some individual protein species were positively related to ethylene stimulation and latex productivity. These results suggested that the specific protein species could be more important than others for rubber production and post-translational modifications might play important roles in rubber biosynthesis.

  9. Platelet-derived growth factor (PDGF) stimulates glycogen synthase activity in 3T3 cells

    International Nuclear Information System (INIS)

    Chan, C.P.; Bowen-Pope, D.F.; Ross, R.; Krebs, E.G.

    1986-01-01

    Hormonal regulation of glycogen synthase, an enzyme that can be phosphorylated on multiple sites, is often associated with changes in its phosphorylation state. Enzyme activation is conventionally monitored by determining the synthase activity ratio [(activity in the absence of glucose 6-P)/(activity in the presence of glucose 6-P)]. Insulin causes an activation of glycogen synthase with a concomitant decrease in its phosphate content. In a previous report, the authors showed that epidermal growth factor (EGF) increases the glycogen synthase activity ratio in Swiss 3T3 cells. The time and dose-dependency of this response was similar to that of insulin. Their recent results indicate that PDGF also stimulates glycogen synthase activity. Enzyme activation was maximal after 30 min. of incubation with PDGF; the time course observed was very similar to that with insulin and EGF. At 1 ng/ml (0.03nM), PDGF caused a maximal stimulation of 4-fold in synthase activity ratio. Half-maximal stimulation was observed at 0.2 ng/ml (6 pM). The time course of changes in enzyme activity ratio closely followed that of 125 I-PDGF binding. The authors data suggest that PDGF, as well as EFG and insulin, may be important in regulating glycogen synthesis through phosphorylation/dephosphorylation mechanisms

  10. Stimulation of pancreatic beta-cell replication by incretins involves transcriptional induction of cyclin D1 via multiple signalling pathways

    DEFF Research Database (Denmark)

    Friedrichsen, Birgitte N; Neubauer, Nicole; Lee, Ying C

    2006-01-01

    pathways leading to mitosis by incretins and cytokines, respectively. The response to both GLP-1 and GIP was completely blocked by the protein kinase A (PKA) inhibitor, H89. In addition, the phosphoinositol 3-kinase (PI3K) inhibitor wortmannin and the mitogen-activated protein kinase kinase (MEK) inhibitor...... and we have previously demonstrated hGH-induced cyclin D2 expression in the insulinoma cell line, INS-1. GLP-1 time-dependently induced the cyclin D1 mRNA and protein levels in INS-1E, whereas the cyclin D2 levels were unaffected. However, minor effect of GLP-1 stimulation was observed on the cyclin D3 m......RNA levels. Transient transfection of a cyclin D1 promoter-luciferase reporter construct into islet monolayer cells or INS-1 cells revealed approximately a 2-3 fold increase of transcriptional activity in response to GLP-1 and GIP, and a 4-7 fold increase in response to forskolin. However, treatment...

  11. Multiple relaxation processes in high-energy ion irradiated kapton-H polyimide: Thermally stimulated depolarization current study

    International Nuclear Information System (INIS)

    Garg, Maneesha; Quamara, J.K.

    2006-01-01

    High-energy ion irradiation effects on the thermally stimulated depolarization current (Tdc) behaviour of kapton-H samples (12.5 μm) irradiated with 50 MeV Li ion (fluence 5 x 10 4 , 10 5 and 5 x 10 5 ions/cm 2 ) have been investigated. The TSDC spectra of the irradiated samples reveal that the β-peak (appearing around 80-110 deg. C) associated with dipolar relaxation has been significantly affected owing to the demerization of carbonyl groups due to irradiation. The TSDC spectra also reveal a new relaxation process (termed as γ-relaxation) around 30 deg. C, due to increased water absorptivity in irradiated samples. The peak around 200 deg. C (α-peak) associated with space charge relaxation process also shows a behavioural change with ion irradiation. The peak not only shifts towards the higher temperature with increasing fluence but also show an increase in its activation energy (0.33-0.99 eV) with increasing polarizing field. The creation of new deep energy trap centers due to the formation of conjugated bonds after irradiation is responsible for this modification. The Cole-Cole distribution curves show the formation of new sub-polar group with different characteristic relaxation time

  12. Onset of surface stimulated emission at 260 nm from AlGaN multiple quantum wells

    KAUST Repository

    Li, Xiaohang

    2015-12-14

    We demonstrated onset of deep-ultraviolet (DUV) surface stimulated emission (SE) from c-plane AlGaNmultiple-quantum well(MQW)heterostructuresgrown on a sapphire substrate by optical pumping at room temperature. The onset of SE became observable at a pumping power density of 630 kW/cm2. Spectral deconvolution revealed superposition of a linearly amplified spontaneous emission peak at λ ∼ 257.0 nm with a full width at half maximum (FWHM) of ∼12 nm and a superlinearly amplified SE peak at λ ∼ 260 nm with a narrow FWHM of less than 2 nm. In particular, the wavelength of ∼260 nm is the shortest wavelength of surface SE from III-nitride MQWheterostructures to date. Atomic force microscopy and scanning transmission electron microscopy measurements were employed to investigate the material and structural quality of the AlGaNheterostructures, showing smooth surface and sharp layer interfaces. This study offers promising results for AlGaNheterostructuresgrown on sapphire substrates for the development of DUV vertical cavity surface emitting lasers(VCSELs).

  13. Association of Odor Thresholds and Responses in Cerebral Blood Flow of the Prefrontal Area during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity.

    Directory of Open Access Journals (Sweden)

    Kenichi Azuma

    Full Text Available Multiple chemical sensitivity (MCS is a disorder characterized by nonspecific and recurrent symptoms from various organ systems associated with exposure to low levels of chemicals. Patients with MCS process odors differently than controls do. Previously, we suggested that this odor processing was associated with increased regional cerebral blood flow (rCBF in the prefrontal area during olfactory stimulation using near-infrared spectroscopic (NIRS imaging. The aim of this study was to investigate the association of odor thresholds and changes in rCBF during olfactory stimulation at odor threshold levels in patients with MCS. We investigated changes in the prefrontal area using NIRS imaging and a T&T olfactometer during olfactory stimulation with two different odorants (sweet and fecal at three concentrations (zero, odor recognition threshold, and normal perceived odor level in 10 patients with MCS and six controls. The T&T olfactometer threshold test and subjective assessment of irritating and hedonic odors were also performed. The results indicated that the scores for both unpleasant and pungent odors were significantly higher for those for sweet odors at the normal perceived level in patients with MCS than in controls. The brain responses at the recognition threshold (fecal odor and normal perceived levels (sweet and fecal odors were stronger in patients with MCS than in controls. However, significant differences in the odor detection and recognition thresholds and odor intensity score between the two groups were not observed. These brain responses may involve cognitive and memory processing systems during past exposure to chemicals. Further research regarding the cognitive features of sensory perception and memory due to past exposure to chemicals and their associations with MCS symptoms is needed.

  14. Response to gravity by Zea mays seedlings. I. Time course of the response

    Science.gov (United States)

    Bandurski, R. S.; Schulze, A.; Dayanandan, P.; Kaufman, P. B.

    1984-01-01

    Gravistimulation induces an asymmetric distribution of free indole-3-acetic acid (IAA) in the cortex-epidermis of the Zea mays L. cv 'Stowells Evergreen' mesocotyl within 15 minutes, the shortest time tested. IAA was measured by an isotope dilution method as the pentaflurobenzyl ester. The per cent IAA in the lower half of the mescotyl cortex was 56 to 57% at 15, 30, and 90 minutes after stimulus initiation. Curvature is detectable in the mescotyl within 3 minutes after beginning gravitropic stimulation. The rate of curvature of the mesocotyl increases during the first 60 minutes to maximum of about 30 degrees per hour. Thus, the growth asymmetry continues to increase for 45 minutes after hormone asymmetry is established. Free IAA occurs predominantly in the stele of the mesocotyl whereas esterified IAA is mainly in the mesocotyl cortex-epidermis. This compartmentation may permit determining in which tissue the hormone asymmetry arises. Current data suggest the asymmetry originated in the stele.

  15. The neural time course of art perception: an ERP study on the processing of style versus content in art.

    Science.gov (United States)

    Augustin, M Dorothee; Defranceschi, Birgit; Fuchs, Helene K; Carbon, Claus-Christian; Hutzler, Florian

    2011-06-01

    A central prerequisite to understand the phenomenon of art in psychological terms is to investigate the nature of the underlying perceptual and cognitive processes. Building on a study by Augustin, Leder, Hutzler, and Carbon (2008) the current ERP study examined the neural time course of two central aspects of representational art, one of which is closely related to object- and scene perception, the other of which is art-specific: content and style. We adapted a paradigm that has repeatedly been employed in psycholinguistics and that allows one to examine the neural time course of two processes in terms of when sufficient information is available to allow successful classification. Twenty-two participants viewed pictures that systematically varied in style and content and conducted a combined go/nogo dual choice task. The dependent variables of interest were the Lateralised Readiness Potential (LRP) and the N200 effect. Analyses of both measures support the notion that in the processing of art style follows content, with style-related information being available at around 224 ms or between 40 and 94 ms later than content-related information. The paradigm used here offers a promising approach to further explore the time course of art perception, thus helping to unravel the perceptual and cognitive processes that underlie the phenomenon of art and the fascination it exerts. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity.

    Science.gov (United States)

    Querec, Troy; Bennouna, Soumaya; Alkan, Sefik; Laouar, Yasmina; Gorden, Keith; Flavell, Richard; Akira, Shizuo; Ahmed, Rafi; Pulendran, Bali

    2006-02-20

    The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-alpha. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.

  17. A pilot investigation of the hypoalgesic effects of transcutaneous electrical nerve stimulation upon low back pain in people with multiple sclerosis.

    Science.gov (United States)

    Al-Smadi, J; Warke, K; Wilson, I; Cramp, A F L; Noble, G; Walsh, D M; Lowe-Strong, A S

    2003-11-01

    To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) upon low back pain (LBP) in people with multiple sclerosis (MS). A randomized double-blind placebo controlled clinical pilot study. Fifteen people with MS were recruited and randomly allocated to one of the following groups under double blind conditions (n = 5 per group): TENS 1 (4 Hz, 200 micros), TENS 2 (110 Hz, 200 micros), placebo TENS. Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up. The following outcome measures were taken at weeks 1, 6, and 10: visual analogue scale (VAS) (for current LBP, right leg pain, left leg pain); Leeds Multiple Sclerosis Quality of Life Questionnaire; Roland Morris Disability Questionnaire; Short Form-36 (SF-36) Version 1; and the McGill Pain Questionnaire (MPQ). VAS for current LBP, right and left leg pain were also taken before and after treatment, and once a week during the follow-up period. Analysis showed no statistically significant effects for any of the data. However, both active treatment groups showed a trend of improvement in the majority of the outcome measures. Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant. Further work in this area is warranted and should include a larger number of participants in the form of a randomized controlled clinical trial to determine the efficacy of this modality.

  18. BDNF-induced nitric oxide signals in cultured rat hippocampal neurons: time course, mechanism of generation, and effect on neurotrophin secretion.

    Science.gov (United States)

    Kolarow, Richard; Kuhlmann, Christoph R W; Munsch, Thomas; Zehendner, Christoph; Brigadski, Tanja; Luhmann, Heiko J; Lessmann, Volkmar

    2014-01-01

    BDNF and nitric oxide signaling both contribute to plasticity at glutamatergic synapses. However, the role of combined signaling of both pathways at the same synapse is largely unknown. Using NO imaging with diaminofluoresceine in cultured hippocampal neurons we analyzed the time course of neurotrophin-induced NO signals. Application of exogenous BDNF, NT-4, and NT-3 (but not NGF) induced NO signals in the soma and in proximal dendrites of hippocampal neurons that were sensitive to NO synthase activity, TrkB signaling, and intracellular calcium elevation. The effect of NO signaling on neurotrophin secretion was analyzed in BDNF-GFP, and NT-3-GFP transfected hippocampal neurons. Exogenous application of the NO donor sodium-nitroprusside markedly inhibited neurotrophin secretion. However, endogenously generated NO in response to depolarization and neurotrophin stimulation, both did not result in a negative feedback on neurotrophin secretion. These results suggest that a negative feedback of NO signaling on synaptic secretion of neurotrophins operates only at high intracellular levels of nitric oxide that are under physiological conditions not reached by depolarization or BDNF signaling.

  19. Time course for the modulation of hepatic cytochrome P450 after administration of ethylbenzene and its correlation with toluene metabolism.

    Science.gov (United States)

    Yuan, W; Sequeira, D J; Cawley, G F; Eyer, C S; Backes, W L

    1997-03-01

    The goal of the present study was to examine the time course for changes in P450 expression and hydrocarbon metabolism after acute treatment with the simple aromatic hydrocarbon ethylbenzene (EB) and to correlate these alterations with the changes observed in alkylbenzene metabolism. Male Holtzman rats were treated with a single intraperitoneal injection of EB, and the effects on specific P450-dependent activities, immunoreactive P450 isozyme levels, and RNA levels were measured at various times after injection. Toluene was used as the test alkylbenzene for examination of the EB-mediated changes on in vitro hydrocarbon metabolism. In untreated rats, toluene was metabolized almost entirely by aliphatic hydroxylation (to benzyl alcohol); however, in EB-treated rats, significant quantities of benzyl alcohol, o-cresol, and p-cresol were produced. Interestingly, 5-10 h after EB treatment, there was a 40% decrease in benzyl alcohol production. By 24 h, rates of benzyl alcohol formation returned to control levels, whereas there was a 7-fold increase in o-cresol and a greater that 50-fold increase in p-cresol production. The changes in the disposition of toluene were then correlated with changes in particular P450 isozymes. Several P450 isozymes were induced after EB administration. P450 2B1/2-dependent testosterone 16 beta-hydroxylation and P450 2B1/2-immunoreactive protein were elevated 30-fold after EB administration, reaching maxima by 24 h and remaining elevated 48 h after exposure. Changes in P450 2B1 and 2B2 RNA preceded those of the proteins. Similar results were observed with P450 1A1. P450 2E1 RNA levels were elevated after a single EB injection. However, the elevation in P450 2E1-dependent activities and immunoreactive protein levels preceded the changes in RNA, suggesting that multiple steps are affected by EB exposure. In contrast to the increases in some isozymes, P450 2C11 protein was rapidly suppressed (within the first 2-10 h) after hydrocarbon exposure

  20. Impact of Plasmapheresis on the Time Course of Changes in Cytokines After Operations on the Heart and Great Vessels

    Directory of Open Access Journals (Sweden)

    A. A. Yeremenko

    2005-01-01

    Full Text Available Objective. To assess the impact of plasmapheresis on the time course of changes in pro- and anti-inflammatory interleukins and the results of treatment in patients after complicated operations on the heart and great vessels.Material and methods. 44 patients were examined. In 33 patients, the intra- and postoperative period was complicated by a prolonged extracorporeal circulation (EC, massive blood loss, acute hemolysis, the development of disseminated intravascular coagulation. The above complications gave grounds to perform plasmapheresis (PA in different postoperative periods. The patients were equally divided into 4 groups (each containing 11 patients: 1 patients with multiple organ dysfunction (MOD, in whom PA was conducted within 2—6 hours after surgery; 2 those without MOD, in whom PA was also performed within 2—6 hours after surgery; 3 those with MOD in whom PA was made 16-20 hours after surgery; 4 a control group (receiving no PA, the early postoperative period was normal. Interleukins (IL 6, 8, and 10 and the oxygenation index (OI after surgery and in the first 24 postoperative hours, the duration of EC, the volume of blood loss, and a postoperative clinical period were studied.Results. The duration of EC was highest in Group 1 patients and 37 and 130% greater in Groups 2 and 3, respectively. The elevated levels of IL-6 were noted in all the patients. In the early post-PA periods, the content of IL-6 was decreased by 30% in Groups 1 and 2 patients. In Group 3, the level of IL-6 remained unchanged within the first 24 hours. The postoperative concentration of IL-8 was increased in all the patients. There were no changes in the content of IL-8 after surgery and within the first 12 hours. In Group 3 patients, the level of IL-8 within the first 24 hours was 5 times higher than that observed just after surgery. In patients with developed MOD, a correlation was found between IL-8 and OI postoperatively and within the first 24 hours after

  1. FlowMax: A Computational Tool for Maximum Likelihood Deconvolution of CFSE Time Courses.

    Directory of Open Access Journals (Sweden)

    Maxim Nikolaievich Shokhirev

    Full Text Available The immune response is a concerted dynamic multi-cellular process. Upon infection, the dynamics of lymphocyte populations are an aggregate of molecular processes that determine the activation, division, and longevity of individual cells. The timing of these single-cell processes is remarkably widely distributed with some cells undergoing their third division while others undergo their first. High cell-to-cell variability and technical noise pose challenges for interpreting popular dye-dilution experiments objectively. It remains an unresolved challenge to avoid under- or over-interpretation of such data when phenotyping gene-targeted mouse models or patient samples. Here we develop and characterize a computational methodology to parameterize a cell population model in the context of noisy dye-dilution data. To enable objective interpretation of model fits, our method estimates fit sensitivity and redundancy by stochastically sampling the solution landscape, calculating parameter sensitivities, and clustering to determine the maximum-likelihood solution ranges. Our methodology accounts for both technical and biological variability by using a cell fluorescence model as an adaptor during population model fitting, resulting in improved fit accuracy without the need for ad hoc objective functions. We have incorporated our methodology into an integrated phenotyping tool, FlowMax, and used it to analyze B cells from two NFκB knockout mice with distinct phenotypes; we not only confirm previously published findings at a fraction of the expended effort and cost, but reveal a novel phenotype of nfkb1/p105/50 in limiting the proliferative capacity of B cells following B-cell receptor stimulation. In addition to complementing experimental work, FlowMax is suitable for high throughput analysis of dye dilution studies within clinical and pharmacological screens with objective and quantitative conclusions.

  2. THE INFLUENCE OF HYPOTHERMIA (SURFACE COOLING) ON THE TIME-COURSE OF ACTION AND ON THE PHARMACOKINETICS OF ROCURONIUM IN HUMANS

    NARCIS (Netherlands)

    BEAUFORT, AM; WIERDA, JMKH; BELOPAVLOVIC, M; NEDERVEEN, PJ; KLEEF, UW; AGOSTON, S

    Hypothermia prolongs the time-course of action of non-depolarizing neuromuscular blocking agents. The mechanism, however, is unknown. We studied the influence of hypothermia (by surface cooling, nasopharyngeal temperature less than or equal to 31 degrees C) on the time-course of action and on the

  3. The time course of altered brain activity during 7-day simulated microgravity

    Directory of Open Access Journals (Sweden)

    Yang eLiao

    2015-05-01

    Full Text Available Microgravity causes multiple changes in physical and mental levels in humans, which can induce performance deficiency among astronauts. Studying the variations in brain activity that occur during microgravity would help astronauts to deal with these changes. In the current study, resting-state functional magnetic resonance imaging (rs-fMRI was used to observe the variations in brain activity during a 7-day head down tilt (HDT bed rest, which is a common and reliable model for simulated microgravity. The amplitudes of low frequency fluctuation (ALFF of twenty subjects were recorded pre-head down tilt (pre-HDT, during a bed rest period (HDT0, and then each day in the HDT period (HDT1–HDT7. One-way analysis of variance of the ALFF values over these 8 days was used to test the variation across time period (P<0.05, corrected. Compared to HDT0, subjects presented lower ALFF values in the posterior cingulate cortex and higher ALFF values in the anterior cingulate cortex during the HDT period, which may partially account for the lack of cognitive flexibility and alterations in autonomic nervous system seen among astronauts in microgravity. Additionally, the observed improvement in function in CPL during the HDT period may play a compensatory role to the functional decline in the paracentral lobule to sustain normal levels of fine motor control for astronauts in a microgravity environment. Above all, those floating brain activities during 7 days of simulated microgravity may indicate that the brain self-adapts to help astronauts adjust to the multiple negative stressors encountered in a microgravity environment.

  4. Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study.

    Science.gov (United States)

    Timmermann, Lars; Jain, Roshini; Chen, Lilly; Maarouf, Mohamed; Barbe, Michael T; Allert, Niels; Brücke, Thomas; Kaiser, Iris; Beirer, Sebastian; Sejio, Fernando; Suarez, Esther; Lozano, Beatriz; Haegelen, Claire; Vérin, Marc; Porta, Mauro; Servello, Domenico; Gill, Steven; Whone, Alan; Van Dyck, Nic; Alesch, Francois

    2015-07-01

    High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinson's disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinson's disease. We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinson's disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinson's disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure

  5. Time course of recovery of erectile function after radical retropubic prostatectomy: does anyone recover after 2 years?

    Science.gov (United States)

    Rabbani, Farhang; Schiff, Jeffrey; Piecuch, Michael; Yunis, Luis Herran; Eastham, James A; Scardino, Peter T; Mulhall, John P

    2010-12-01

    Given the paucity of literature on the time course of recovery of erectile function (EF) after radical prostatectomy (RP), many publications have led patients and clinicians to believe that erections are unlikely to recover beyond 2 years after RP. We sought to determine the time course of recovery of EF beyond 2 years after bilateral nerve sparing (BNS) RP and to determine factors predictive of continued improved recovery beyond 2 years. EF was assessed prospectively on a 5-point scale: (i) full erections; (ii) diminished erections routinely sufficient for intercourse; (iii) partial erections occasionally satisfactory for intercourse; (iv) partial erections unsatisfactory for intercourse; and (v) no erections. From 01/1999 to 01/2007, 136 preoperatively potent (levels 1-2) men who underwent BNS RP without prior treatment and who had not recovered consistently functional erections (levels 1-2) at 24 months had further follow-up regarding EF. Median follow-up after the 2-year visit was 36.0 months. Recovery of improved erections at a later date: recovery of EF level 1-2 in those with level 3 EF at 2 years and recovery of EF level 1-3 in those with level 4-5 EF at 2 years. The actuarial rates of further improved recovery of EF to level 1-2 in those with level 3 EF at 2 years and to level 1-3 in those with level 4-5 EF at 2 years were 8%, 20%, and 23% at 3, 4, and 5 years postoperatively, and 5%, 17%, and 21% at 3, 4, and 5 years postoperatively, respectively. Younger age was predictive of greater likelihood of recovery beyond 2 years. There is continued improvement in EF beyond 2 years after BNS RP. Discussion of this prolonged time course of recovery may allow patients to have a more realistic expectation. © 2010 International Society for Sexual Medicine.

  6. Riding the lexical speedway: a critical review on the time course of lexical selection in speech production.

    Science.gov (United States)

    Strijkers, Kristof; Costa, Albert

    2011-01-01

    Speech requires time. How much time often depends on the amount of labor the brain has to perform in order to retrieve the linguistic information related to the ideas we want to express. Although most psycholinguistic research in the field of language production has focused on the net result of time required to utter words in various experimental conditions, over the last years more and more researchers pursued the objective to flesh out the time course of particular stages implicated in language production. Here we critically review these studies, with particular interest for the time course of lexical selection. First, we evaluate the data underlying the estimates of an influential temporal meta-analysis on language production (Indefrey and Levelt, 2004). We conclude that those data alone are not sufficient to provide a reliable time frame of lexical selection. Next, we discuss recent neurophysiological evidence which we argue to offer more explicit insights into the time course of lexical selection. Based on this evidence we suggest that, despite the absence of a clear time frame of how long lexical selection takes, there is sufficient direct evidence to conclude that the brain initiates lexical access within 200 ms after stimulus presentation, hereby confirming Indefrey and Levelt's estimate. In a final section, we briefly review the proposed mechanisms which could lead to this rapid onset of lexical access, namely automatic spreading activation versus specific concept selection, and discuss novel data which support the notion of spreading activation, but indicate that the speed with which this principle takes effect is driven by a top-down signal in function of the intention to engage in a speech act.

  7. Riding the Lexical Speedway: A Critical Review on the Time Course of Lexical Selection in Speech Production

    Science.gov (United States)

    Strijkers, Kristof; Costa, Albert

    2011-01-01

    Speech requires time. How much time often depends on the amount of labor the brain has to perform in order to retrieve the linguistic information related to the ideas we want to express. Although most psycholinguistic research in the field of language production has focused on the net result of time required to utter words in various experimental conditions, over the last years more and more researchers pursued the objective to flesh out the time course of particular stages implicated in language production. Here we critically review these studies, with particular interest for the time course of lexical selection. First, we evaluate the data underlying the estimates of an influential temporal meta-analysis on language production (Indefrey and Levelt, 2004). We conclude that those data alone are not sufficient to provide a reliable time frame of lexical selection. Next, we discuss recent neurophysiological evidence which we argue to offer more explicit insights into the time course of lexical selection. Based on this evidence we suggest that, despite the absence of a clear time frame of how long lexical selection takes, there is sufficient direct evidence to conclude that the brain initiates lexical access within 200 ms after stimulus presentation, hereby confirming Indefrey and Levelt’s estimate. In a final section, we briefly review the proposed mechanisms which could lead to this rapid onset of lexical access, namely automatic spreading activation versus specific concept selection, and discuss novel data which support the notion of spreading activation, but indicate that the speed with which this principle takes effect is driven by a top-down signal in function of the intention to engage in a speech act. PMID:22144973

  8. Training haptic stiffness discrimination: time course of learning with or without visual information and knowledge of results.

    Science.gov (United States)

    Teodorescu, Kinneret; Bouchigny, Sylvain; Korman, Maria

    2013-08-01

    In this study, we explored the time course of haptic stiffness discrimination learning and how it was affected by two experimental factors, the addition of visual information and/or knowledge of results (KR) during training. Stiffness perception may integrate both haptic and visual modalities. However, in many tasks, the visual field is typically occluded, forcing stiffness perception to be dependent exclusively on haptic information. No studies to date addressed the time course of haptic stiffness perceptual learning. Using a virtual environment (VE) haptic interface and a two-alternative forced-choice discrimination task, the haptic stiffness discrimination ability of 48 participants was tested across 2 days. Each day included two haptic test blocks separated by a training block Additional visual information and/or KR were manipulated between participants during training blocks. Practice repetitions alone induced significant improvement in haptic stiffness discrimination. Between days, accuracy was slightly improved, but decision time performance was deteriorated. The addition of visual information and/or KR had only temporary effects on decision time, without affecting the time course of haptic discrimination learning. Learning in haptic stiffness discrimination appears to evolve through at least two distinctive phases: A single training session resulted in both immediate and latent learning. This learning was not affected by the training manipulations inspected. Training skills in VE in spaced sessions can be beneficial for tasks in which haptic perception is critical, such as surgery procedures, when the visual field is occluded. However, training protocols for such tasks should account for low impact of multisensory information and KR.

  9. Time course of the acute effects of core stabilisation exercise on seated postural control.

    Science.gov (United States)

    Lee, Jordan B; Brown, Stephen H M

    2017-09-20

    Core stabilisation exercises are often promoted for purposes ranging from general fitness to high-performance athletics, and the prevention and rehabilitation of back troubles. These exercises, when performed properly, may have the potential to enhance torso postural awareness and control, yet the potential for achieving immediate gains has not been completely studied. Fourteen healthy young participants performed a single bout of non-fatiguing core stabilisation exercise that consisted of repeated sets of 2 isometric exercises, the side bridge and the four-point contralateral arm-and-leg extension. Seated postural control, using an unstable balance platform on top of a force plate, was assessed before and after exercise, including multiple time points within a 20-minute follow-up period. Nine standard postural control variables were calculated at each time point, including sway displacement and velocity ranges, root mean squares and cumulative path length. Statistical analysis showed that none of the postural control variables were significantly different at any time point following completion of core stabilisation exercise. Thus, we conclude that a single bout of acute core stabilisation exercise is insufficient to immediately improve seated trunk postural control in young healthy individuals.

  10. Reconstructing the hidden states in time course data of stochastic models.

    Science.gov (United States)

    Zimmer, Christoph

    2015-11-01

    Parameter estimation is central for analyzing models in Systems Biology. The relevance of stochastic modeling in the field is increasing. Therefore, the need for tailored parameter estimation techniques is increasing as well. Challenges for parameter estimation are partial observability, measurement noise, and the computational complexity arising from the dimension of the parameter space. This article extends the multiple shooting for stochastic systems' method, developed for inference in intrinsic stochastic systems. The treatment of extrinsic noise and the estimation of the unobserved states is improved, by taking into account the correlation between unobserved and observed species. This article demonstrates the power of the method on different scenarios of a Lotka-Volterra model, including cases in which the prey population dies out or explodes, and a Calcium oscillation system. Besides showing how the new extension improves the accuracy of the parameter estimates, this article analyzes the accuracy of the state estimates. In contrast to previous approaches, the new approach is well able to estimate states and parameters for all the scenarios. As it does not need stochastic simulations, it is of the same order of speed as conventional least squares parameter estimation methods with respect to computational time. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Efficacy of transcutaneous electrical nerve stimulation (tens) for chronic low-back pain in a multiple sclerosis population: a randomized, placebo-controlled clinical trial.

    Science.gov (United States)

    Warke, Kim; Al-Smadi, Jamal; Baxter, David; Walsh, Deirdre M; Lowe-Strong, Andrea S

    2006-01-01

    This study was designed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation (TENS) on chronic low-back pain (LBP) in a multiple sclerosis (MS) population. Ninety participants with probable or definite MS (aged 21 to 78 y) presenting with chronic LBP were recruited and randomized into 3 groups (n=30 per group): (1) low-frequency TENS group (4 Hz, 200 micros); (2) high-frequency TENS group (110 Hz, 200 micros); and (3) placebo TENS. Participants self-applied TENS for 45 minutes, a minimum of twice daily, for 6 weeks. Outcome measures were recorded at weeks 1, 6, 10, and 32. Primary outcome measures included: Visual Analog Scale for average LBP and the McGill Pain Questionnaire. Secondary outcome measures included: Visual Analog Scale for worst and weekly LBP, back and leg spasm; Roland Morris Disability Questionnaire; Barthel Index; Rivermead Mobility Index; Multiple Sclerosis Quality of Life-54 Instrument, and a daily logbook. Data were analyzed blind using parametric and nonparametric tests, as appropriate. Results indicated a statistically significant interactive effect between groups for average LBP (P=0.008); 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied (P>0.05). However, clinically important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods. Although not statistically significant, the observed effects may have implications for the clinical prescription and the use of TENS within this population.

  12. The Efficacy of Functional Electrical Stimulation of the Abdominal Muscles in the Treatment of Chronic Constipation in Patients with Multiple Sclerosis: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Christine Singleton

    2016-01-01

    Full Text Available Chronic constipation in patients with multiple sclerosis (MS is common and the current methods of treatment are ineffective in some patients. Anecdotal observations suggest that functional electrical stimulation (FES of the abdominal muscles may be effective in the management of constipation in these patients. Patients and Methods. In this exploratory investigation we studied the effects of FES on the whole gut transit time (WGTT and the colonic transit time (CTT. In addition, we evaluated the treatment effect on the patients’ constipation-related quality of life and on the use of laxatives and the use of manual bowel evacuation. FES was given for 30 minutes twice a day for a period of six weeks. Four female patients were studied. Results. The WGTT and CTT and constipation-related quality of life improved in all patients. The patients’ use of laxatives was reduced. No adverse effects of FES treatment were reported. Conclusion. The findings of this pilot study suggest that FES applied to the abdominal muscles may be an effective treatment modality for severe chronic constipation in patients with MS.

  13. Motor and sensory responses after percutaneous tibial nerve stimulation in multiple sclerosis patients with lower urinary tract symptoms treated in daily practice.

    Science.gov (United States)

    Zecca, C; Digesu, G A; Robshaw, P; Puccini, F; Khullar, V; Tubaro, A; Gobbi, C

    2014-03-01

    Posterior tibial nerve stimulation (PTNS) is an effective treatment option for lower urinary tract symptoms (LUTS) in multiple sclerosis (MS) patients. Patients with MS and LUTS unresponsive to medical treatment received PTNS for 12 weeks after saline urodynamics to evaluate the prevalence of motor, sensory and combined responses during PTNS and to determine whether the type of response can predict treatment outcome. LUTS were also assessed using a 3-day bladder diary, patient perception of bladder condition (PPBC) questionnaire, patient perception of intensity of urgency scale (PPIUS), Kings Health QOL questionnaire (KHQ) and Overactive Bladder Questionnaire (OAB-q) before and after treatment. Patients were considered as "responders" if they reported an improvement >50% in their LUTS according to the PPBC. Sensory, motor and combined sensory/motor responses were compared between responders and non-responders. Eighty-three patients were included. 61% (51/83) of patients were responders. Sensory, motor and combined sensory/motor responses were found in 64% (53/83), 6% (5/83) and 30% (25/83) of patients respectively. A sensory response alone, or in combination with a motor response, was better associated with a successful outcome than the presence of a motor response alone (P = 0.001). A sensory response, either alone or in combination with a motor response, is more frequent and seems to be better associated with a successful outcome of PTNS than motor response alone. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

  14. Tobacco Control Measures to Reduce Socioeconomic Inequality in Smoking: The Necessity, Time-Course Perspective, and Future Implications.

    Science.gov (United States)

    Tabuchi, Takahiro; Iso, Hiroyasu; Brunner, Eric

    2018-04-05

    Previous systematic reviews of population-level tobacco control interventions and their effects on smoking inequality by socioeconomic factors concluded that tobacco taxation reduce smoking inequality by income (although this is not consistent for other socioeconomic factors, such as education). Inconsistent results have been reported for socioeconomic differences, especially for other tobacco control measures, such as smoke-free policies and anti-tobacco media campaigns. To understand smoking inequality itself and to develop strategies to reduce smoking inequality, knowledge of the underlying principles or mechanisms of the inequality over a long time-course may be important. For example, the inverse equity hypothesis recognizes that inequality may evolve in stages. New population-based interventions are initially primarily accessed by the affluent and well-educated, so there is an initial increase in socioeconomic inequality (early stage). These inequalities narrow when the deprived population can access the intervention after the affluent have gained maximum benefit (late stage). Following this hypothesis, all tobacco control measures may have the potential to reduce smoking inequality, if they continue for a long term, covering and reaching all socioeconomic subgroups. Re-evaluation of the impact of the interventions on smoking inequality using a long time-course perspective may lead to a favorable next step in equity effectiveness. Tackling socioeconomic inequality in smoking may be a key public health target for the reduction of inequality in health.

  15. Time course of affective bias in visual attention: convergent evidence from steady-state visual evoked potentials and behavioral data.

    Science.gov (United States)

    Hindi Attar, Catherine; Andersen, Søren K; Müller, Matthias M

    2010-12-01

    Selective attention to a primary task can be biased by the occurrence of emotional distractors that involuntary attract attention due to their intrinsic stimulus significance. What is largely unknown is the time course and magnitude of competitive interactions between a to-be-attended foreground task and emotional distractors. We used pleasant, unpleasant and neutral pictures from the International Affective Picture System (IAPS) that were either presented in intact or phase-scrambled form. Pictures were superimposed by a flickering display of moving random dots, which constituted the primary task and enabled us to record steady-state visual evoked potentials (SSVEPs) as a continuous measure of attentional resource allocation directed to the task. Subjects were required to attend to the dots and to detect short intervals of coherent motion while ignoring the background pictures. We found that pleasant and unpleasant relative to neutral pictures more strongly influenced task-related processing as reflected in a significant decrease in SSVEP amplitudes and target detection rates, both covering a time window of several hundred milliseconds. Strikingly, the effect of semantic relative to phase-scrambled pictures on task-related activity was much larger, emerged earlier and lasted longer in time compared to the specific effect of emotion. The observed differences in size and duration of time courses of semantic and emotional picture processing strengthen the assumption of separate functional mechanisms for both processes rather than a general boosting of neural activity in favor of emotional stimulus processing. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Spectral Analysis on Time-Course Expression Data: Detecting Periodic Genes Using a Real-Valued Iterative Adaptive Approach

    Directory of Open Access Journals (Sweden)

    Kwadwo S. Agyepong

    2013-01-01

    Full Text Available Time-course expression profiles and methods for spectrum analysis have been applied for detecting transcriptional periodicities, which are valuable patterns to unravel genes associated with cell cycle and circadian rhythm regulation. However, most of the proposed methods suffer from restrictions and large false positives to a certain extent. Additionally, in some experiments, arbitrarily irregular sampling times as well as the presence of high noise and small sample sizes make accurate detection a challenging task. A novel scheme for detecting periodicities in time-course expression data is proposed, in which a real-valued iterative adaptive approach (RIAA, originally proposed for signal processing, is applied for periodogram estimation. The inferred spectrum is then analyzed using Fisher’s hypothesis test. With a proper -value threshold, periodic genes can be detected. A periodic signal, two nonperiodic signals, and four sampling strategies were considered in the simulations, including both bursts and drops. In addition, two yeast real datasets were applied for validation. The simulations and real data analysis reveal that RIAA can perform competitively with the existing algorithms. The advantage of RIAA is manifested when the expression data are highly irregularly sampled, and when the number of cycles covered by the sampling time points is very reduced.

  17. Contextual Change After Fear Acquisition Affects Conditioned Responding and the Time Course of Extinction Learning-Implications for Renewal Research.

    Science.gov (United States)

    Sjouwerman, Rachel; Niehaus, Johanna; Lonsdorf, Tina B

    2015-01-01

    Context plays a central role in retrieving (fear) memories. Accordingly, context manipulations are inherent to most return of fear (ROF) paradigms (in particular renewal), involving contextual changes after fear extinction. Context changes are, however, also often embedded during earlier stages of ROF experiments such as context changes between fear acquisition and extinction (e.g., in ABC and ABA renewal). Previous studies using these paradigms have however focused exclusively on the context switch after extinction (i.e., renewal). Thus, the possibility of a general effect of context switch on conditioned responding that may not be conditional to preceding extinction learning remains unstudied. Hence, the current study investigated the impact of a context switch between fear acquisition and extinction on immediate conditioned responding and on the time-course of extinction learning by using a multimodal approach. A group that underwent contextual change after fear conditioning (AB; n = 36) was compared with a group without a contextual change from acquisition to extinction (AA; n = 149), while measuring physiological (skin conductance and fear potentiated startle) measures and subjective fear ratings. Contextual change between fear acquisition and extinction had a pronounced effect on both immediate conditioned responding and on the time course of extinction learning in skin conductance responses and subjective fear ratings. This may have important implications for the mechanisms underlying and the interpretation of the renewal effect (i.e., contextual switch after extinction). Consequently, future studies should incorporate designs and statistical tests that disentangle general effects of contextual change from genuine ROF effects.

  18. 10-Month-Old Infants Are Sensitive to the Time Course of Perceived Actions: Eye-Tracking and EEG Evidence

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    Cathleen Bache

    2017-07-01

    Full Text Available Research has shown that infants are able to track a moving target efficiently – even if it is transiently occluded from sight. This basic ability allows prediction of when and where events happen in everyday life. Yet, it is unclear whether, and how, infants internally represent the time course of ongoing movements to derive predictions. In this study, 10-month-old crawlers observed the video of a same-aged crawling baby that was transiently occluded and reappeared in either a temporally continuous or non-continuous manner (i.e., delayed by 500 ms vs. forwarded by 500 ms relative to the real-time movement. Eye movement and rhythmic neural brain activity (EEG were measured simultaneously. Eye movement analyses showed that infants were sensitive to slight temporal shifts in movement continuation after occlusion. Furthermore, brain activity associated with sensorimotor processing differed between observation of continuous and non-continuous movements. Early sensitivity to an action’s timing may hence be explained within the internal real-time simulation account of action observation. Overall, the results support the hypothesis that 10-month-old infants are well prepared for internal representation of the time course of observed movements that are within the infants’ current motor repertoire.

  19. Effects of Multi-Session Repetitive Transcranial Magnetic Stimulation on Motor Control and Spontaneous Brain Activity in Multiple System Atrophy: A Pilot Study

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    Zhu Liu

    2018-05-01

    Full Text Available Background: Impaired motor control is one of the most common symptoms of multiple system atrophy (MSA. It arises from dysfunction of the cerebellum and its connected neural networks, including the primary motor cortex (M1, and is associated with altered spontaneous (i.e., resting-state brain network activity. Non-invasive repetitive transcranial magnetic stimulation (rTMS selectively facilitates the excitability of supraspinal networks. Repeated rTMS sessions have been shown to induce long-term changes to both resting-state brain dynamics and behavior in several neurodegenerative diseases. Here, we hypothesized that a multi-session rTMS intervention would improve motor control in patients with MSA, and that such improvements would correlate with changes in resting-state brain activity.Methods: Nine participants with MSA received daily sessions of 5 Hz rTMS for 5 days. rTMS targeted both the cerebellum and the bilateral M1. Before and within 3 days after the intervention, motor control was assessed by the motor item of the Unified Multiple System Atrophy Rating Scale (UMSARS. Resting-state brain activity was recorded by blood-oxygen-level dependency (BOLD functional magnetic resonance imaging. The “complexity” of resting-state brain activity fluctuations was quantified within seven well-known functional cortical networks using multiscale entropy, a technique that estimates the degree of irregularity of the BOLD time-series across multiple scales of time.Results: The rTMS intervention was well-attended and was not associated with any adverse events. Average motor scores were lower (i.e., better performance following the rTMS intervention as compared to baseline (t8 = 2.3, p = 0.003. Seven of nine participants exhibited such pre-to-post intervention improvements. A trend toward an increase in resting-state complexity was observed within the motor network (t8 = 1.86, p = 0.07. Participants who exhibited greater increases in motor network resting

  20. THE TIME COURSE OF ABNORMALITIES IN THE BRAIN SUBCORTICAL VISUAL CENTRE FOLLOWING EARLY IMPAIRMENT OF BINOCULAR EXPERIENCE

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    S. V. Alekseenko

    2016-01-01

    Full Text Available Background: Amblyopia related to congenital strabismus belongs to neurological disorders since it is caused by structural and functional remodeling of the visual parts of the brain without any baseline retinal pathology. Although a large number of animal studies on experimentally induced strabismus, as well as clinical cases have been published, the mechanisms and time course of the processes within the brain structures are not fully understood. Aim: To study the time course of abnormalities in the dorsal lateral geniculate nucleus (LGNd in animals with surgically induced convergent strabismus. LGNd is the structure through which the information from the retina goes to the visual cortex separately for each eye. Materials and methods: 14 strabismic and 17 intact kittens of four age groups were studied. Histochemical method was used to identify cytochrome oxidase which is a  mitochondrial respiratory chain enzyme whose activity correlates with neuronal functional activity. Optical density in eye-specific layers  A  and A1 was measured on the images of stained LGNd sections, with calculation of the contrast difference between them. Results: In strabismic kittens, there were changes in activity of A and A1 layers in the projection of the central part of visual field in LGNd of both hemispheres. At early stages of their formation, a relative decrease in activity was found in both hemispheres in the LGNd layers innervated through non-crossed pathways from both retinae. Thereafter, the time course of abnormalities in LGNd of both hemispheres was different. In the hemisphere ipsilateral to the squinting eye, the difference in layer activity was highest at the age from 3 to 5 months. However, in the opposite hemisphere the same difference indicating a decreased activity in the layer of the squinting eye were observed only at the age of 5 months. Conclusion: The process of amblyopia development during congenital convergent strabismus is

  1. Time course of the involvement of the right anterior superior temporal gyrus and the right fronto-parietal operculum in emotional prosody perception.

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    Marjolijn Hoekert

    Full Text Available In verbal communication, not only the meaning of the words convey information, but also the tone of voice (prosody conveys crucial information about the emotional state and intentions of others. In various studies right frontal and right temporal regions have been found to play a role in emotional prosody perception. Here, we used triple-pulse repetitive transcranial magnetic stimulation (rTMS to shed light on the precise time course of involvement of the right anterior superior temporal gyrus and the right fronto-parietal operculum. We hypothesized that information would be processed in the right anterior superior temporal gyrus before being processed in the right fronto-parietal operculum. Right-handed healthy subjects performed an emotional prosody task. During listening to each sentence a triplet of TMS pulses was applied to one of the regions at one of six time points (400-1900 ms. Results showed a significant main effect of Time for right anterior superior temporal gyrus and right fronto-parietal operculum. The largest interference was observed half-way through the sentence. This effect was stronger for withdrawal emotions than for the approach emotion. A further experiment with the inclusion of an active control condition, TMS over the EEG site POz (midline parietal-occipital junction, revealed stronger effects at the fronto-parietal operculum and anterior superior temporal gyrus relative to the active control condition. No evidence was found for sequential processing of emotional prosodic information from right anterior superior temporal gyrus to the right fronto-parietal operculum, but the results revealed more parallel processing. Our results suggest that both right fronto-parietal operculum and right anterior superior temporal gyrus are critical for emotional prosody perception at a relatively late time period after sentence onset. This may reflect that emotional cues can still be ambiguous at the beginning of sentences, but become

  2. Time course of the involvement of the right anterior superior temporal gyrus and the right fronto-parietal operculum in emotional prosody perception.

    Science.gov (United States)

    Hoekert, Marjolijn; Bais, Leonie; Kahn, René S; Aleman, André

    2008-05-21

    In verbal communication, not only the meaning of the words convey information, but also the tone of voice (prosody) conveys crucial information about the emotional state and intentions of others. In various studies right frontal and right temporal regions have been found to play a role in emotional prosody perception. Here, we used triple-pulse repetitive transcranial magnetic stimulation (rTMS) to shed light on the precise time course of involvement of the right anterior superior temporal gyrus and the right fronto-parietal operculum. We hypothesized that information would be processed in the right anterior superior temporal gyrus before being processed in the right fronto-parietal operculum. Right-handed healthy subjects performed an emotional prosody task. During listening to each sentence a triplet of TMS pulses was applied to one of the regions at one of six time points (400-1900 ms). Results showed a significant main effect of Time for right anterior superior temporal gyrus and right fronto-parietal operculum. The largest interference was observed half-way through the sentence. This effect was stronger for withdrawal emotions than for the approach emotion. A further experiment with the inclusion of an active control condition, TMS over the EEG site POz (midline parietal-occipital junction), revealed stronger effects at the fronto-parietal operculum and anterior superior temporal gyrus relative to the active control condition. No evidence was found for sequential processing of emotional prosodic information from right anterior superior temporal gyrus to the right fronto-parietal operculum, but the results revealed more parallel processing. Our results suggest that both right fronto-parietal operculum and right anterior superior temporal gyrus are critical for emotional prosody perception at a relatively late time period after sentence onset. This may reflect that emotional cues can still be ambiguous at the beginning of sentences, but become more apparent half

  3. Characterization of the time course of changes of the evoked electrical activity in a model of a chemically-induced neuronal plasticity

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    Ruaro Maria

    2009-01-01

    Full Text Available Abstract Background Neuronal plasticity is initiated by transient elevations of neuronal networks activity leading to changes of synaptic properties and providing the basis for memory and learning 1. An increase of electrical activity can be caused by electrical stimulation 2 or by pharmacological manipulations: elevation of extracellular K+ 3, blockage of inhibitory pathways 4 or by an increase of second messengers intracellular concentrations 5. Neuronal plasticity is mediated by several biochemical pathways leading to the modulation of synaptic strength, density of ionic channels and morphological changes of neuronal arborisation 6. On a time scale of a few minutes, neuronal plasticity is mediated by local protein trafficking 7 while, in order to sustain modifications beyond 2–3 h, changes of gene expression are required 8. Findings In the present manuscript we analysed the time course of changes of the evoked electrical activity during neuronal plasticity and we correlated it with a transcriptional analysis of the underlying changes of gene expression. Our investigation shows that treatment for 30 min. with the GABAA receptor antagonist gabazine (GabT causes a potentiation of the evoked electrical activity occurring 2–4 hours after GabT and the concomitant up-regulation of 342 genes. Inhibition of the ERK1/2 pathway reduced but did not abolish the potentiation of the evoked response caused by GabT. In fact not all the genes analysed were blocked by ERK1/2 inhibitors. Conclusion These results are in agreement with the notion that neuronal plasticity is mediated by several distinct pathways working in unison.

  4. Relationship between fetal heart rate patterns and a time course for evaluation of fetal well-being: “the 30 minutes rule” for decision of mechanical delivery

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    Shintaro Makino

    2017-12-01

    Conclusions: We confirmed the time indices for predicting and preventing acidosis in fetuses showing decelerations. To prevent fetal acidosis, the decision related to proper timing for performing assisted delivery by considering the time course is important.

  5. Normal time course of auditory recognition in schizophrenia, despite impaired precision of the auditory sensory ("echoic") memory code.

    Science.gov (United States)

    March, L; Cienfuegos, A; Goldbloom, L; Ritter, W; Cowan, N; Javitt, D C

    1999-02-01

    Prior studies have demonstrated impaired precision of processing within the auditory sensory memory (ASM) system in schizophrenia. This study used auditory backward masking to evaluate the degree to which such deficits resulted from impaired overall precision versus premature decay of information within the short-term auditory store. ASM performance was evaluated in 14 schizophrenic participants and 16 controls. Schizophrenic participants were severely impaired in their ability to match tones following delay. However, when no-mask performance was equated across participants, schizophrenic participants were no more susceptible to the effects of backward maskers than were controls. Thus, despite impaired precision of ASM performance, schizophrenic participants showed no deficits in the time course over which short-term representations could be used within the ASM system.

  6. Time-course investigation of the gene expression profile during Fasciola hepatica infection: A microarray-based study

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    Jose Rojas-Caraballo

    2015-12-01

    Full Text Available Fasciolosis is listed as one of the most important neglected tropical diseases according with the World Health Organization and is also considered as a reemerging disease in the human beings. Despite there are several studies describing the immune response induced by Fasciola hepatica in the mammalian host, investigations aimed at identifying the expression profile of genes involved in inducing hepatic injury are currently scarce. Data presented here belong to a time-course investigation of the gene expression profile in the liver of BALB/c mice infected with F. hepatica metacercariae at 7 and 21 days after experimental infection. The data published here have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE69588, previously published by Rojas-Caraballo et al. (2015 in PLoS One [1].

  7. The Time Course of Knee Swelling Post Total Knee Arthroplasty and Its Associations with Quadriceps Strength and Gait Speed.

    Science.gov (United States)

    Pua, Yong-Hao

    2015-07-01

    This study examines the time course of knee swelling post total knee arthroplasty (TKA) and its associations with quadriceps strength and gait speed. Eighty-five patients with unilateral TKA participated. Preoperatively and on post-operative days (PODs) 1, 4, 14, and 90, knee swelling was measured using bioimpedance spectrometry. Preoperatively and on PODs 14 and 90, quadriceps strength was measured using isokinetic dynamometry while fast gait speed was measured using the timed 10-meter walk. On POD1, knee swelling increased ~35% from preoperative levels after which, knee swelling reduced but remained at ~11% above preoperative levels on POD90. In longitudinal, multivariable analyses, knee swelling was associated with quadriceps weakness (P<0.01) and slower gait speed (P=0.03). Interventions to reduce post-TKA knee swelling may be indicated to improve quadriceps strength and gait speed. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. The time course of repair of ultraviolet-induced DNA damage; implications for the structural organization of repair

    International Nuclear Information System (INIS)

    Collins, A.; Squires, S.

    1986-01-01

    Alternative molecular mechanisms can be envisaged for the cellular repair of UV-damaged DNA. In the 'random collision' model, DNA damage distributed throughout the genome is recognised and repaired by a process of random collision between DNA damage and repair enzymes. The other model assumes a 'processive' mechanism, whereby DNA is scanned for damage by a repair complex moving steadily along its length. Random collision should result in a declining rate of repair with time as the concentration of lesions in the DNA falls; but the processive model predicts a constant rate until scanning is complete. The authors have examined the time course of DNA repair in human fibroblasts given low doses of UV light. Using 3 distinct assays, the authors find no sign of a constant repair rate after 4 J/m 2 or less, even when the first few hours after irradiation are examined. Thus DNA repair is likely to depend on random collision. (Auth.)

  9. Comparative efficacy and acceptability of electroconvulsive therapy versus repetitive transcranial magnetic stimulation for major depression: A systematic review and multiple-treatments meta-analysis.

    Science.gov (United States)

    Chen, Jian-Jun; Zhao, Li-Bo; Liu, Yi-Yun; Fan, Song-Hua; Xie, Peng

    2017-03-01

    The effects of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS) on major depressive disorder (MDD) have not been adequately addressed by previous studies. Here, a multiple-treatments meta-analysis, which incorporates evidence from direct and indirect comparisons from a network of trials, was performed to assess the efficacy and acceptability of these four treatment modalities on MDD. The literature was searched for randomized controlled trials (RCTs) on ECT, bilateral rTMS, and unilateral rTMS for treating MDD up to May 2016. The main outcome measures were response and drop-out rates. Data were obtained from 25 studies consisting of 1288 individuals with MDD. ECT was non-significantly more efficacious than B-rTMS, R-rTMS, and L-rTMS. Left prefrontal rTMS was non -significantly less efficacious than all other treatment modalities. In terms of acceptability, R-rTMS was non-significantly better tolerated than ECT, B-rTMS, and L-rTMS. ECT was the most efficacious treatment with the cumulative probabilities of being the most efficacious treatment being: ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best-tolerated treatment with the cumulative probabilities of being the best-tolerated treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%). Coherence analysis detected no statistically significant incoherence in any comparisons of direct with indirect evidence for the response rate and drop-out rate. ECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Assessment of auditory threshold using Multiple Magnitude-Squared Coherence and amplitude modulated tones monaural stimulation around 40 Hz.

    Science.gov (United States)

    Silva, Glaucia de Morais; Antunes, Felipe; Henrique, Catherine Salvador; Felix, Leonardo Bonato

    2018-06-01

    The use of objective detection techniques applied to the auditory steady-state responses (ASSRs) for the assessment of auditory thresholds has been investigated over the years. The idea consists in setting up the audiometric profile without subjective inference from patients and evaluators. The challenge encountered is to reduce the detection time of auditory thresholds reaching high correlation coefficients between the objective and the conventional thresholds, as well as reducing difference between thresholds. This paper evaluated the use of the Multiple Magnitude-Squared Coherence (MMSC) in Auditory Steady-State Responses (ASSRs) evoked by amplitude modulated tones around 40 Hz, attaining objective audiograms, which were, later, compared to conventional audiograms. It was proposed an analysis of the electroencephalogram signals of ten subjects, monaurally stimulated, in the intensities 15, 20, 25, 30, 40 and 50 dB SPL, for carrier frequencies of 0.5, 1, 2 and 4 kHz. After the detection protocol parameters variation, two detectors were selected according to behavioral thresholds. The method of this study resulted in a Maximum detector with correlation coefficient r = 0.9262, mean difference between the objective and behavioral thresholds of 6.44 dB SPL, average detection time per ear of 49.96 min and per stimulus of 2.08 min. Meanwhile, the Fast detector presented coefficient r = 0.8401, mean difference of 6.81 dB SPL, average detection time of 28.20 min per ear and 1.18 per stimulus. The results of this study indicate that the MMSC use in the auditory responses detection might provide a reliable and efficient estimation of auditory thresholds. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Thalamic deep brain stimulation for the treatment of tremor due to multiple sclerosis: a prospective study of tremor and quality of life.

    Science.gov (United States)

    Berk, Caglar; Carr, Jason; Sinden, Marci; Martzke, Jeff; Honey, Christopher R

    2002-10-01

    In several studies a significant reduction in tremor after thalamic deep brain stimulation (DBS) has been reported among patients with multiple sclerosis (MS). It has not been determined if this results in an improved quality of life. In this study the authors prospectively evaluated the effects of thalamic DBS on tremor and quality of life. Videotapes of the patients' tremor were made preoperatively and 2 and 12 months postoperatively, and tremor was scored by a neurologist blinded to the treatment. Patients were tested pre- and postoperatively to measure any changes in their reported ability to perform selected activities of daily living and in their health-related quality of life. Patients were asked to complete a questionnaire about their satisfaction with the surgery. Postoperative changes were examined using paired t-tests. There were significant reductions in postural, action, and overall tremor at 2 and 12 months postoperatively. The patients' reported ability to feed themselves was significantly improved 2 months after surgery (p = 0.01). There were short-term trends toward improvement in reported dressing ability, personal hygiene, and writing. There were no significant changes in the SF-36 subscales or total score. In this cohort of patients with MS who suffered from tremor, thalamic DBS significantly improved their tremor and ability to feed themselves. Patient satisfaction with the procedure, however, was variable. Preoperative patient education about what functions might (and might not) be improved is crucial to avoid unrealistic expectations. Our results indicate that younger patients with MS tremor who had a shorter disease duration and no superimposed ataxia benefited most from this surgery.

  12. Prevotella intermedia stimulates tissue-type plasminogen activator and plasminogen activator inhibitor-2 expression via multiple signaling pathways in human periodontal ligament cells.

    Science.gov (United States)

    Guan, Su-Min; He, Jian-Jun; Zhang, Ming; Shu, Lei

    2011-06-01

    Prevotella intermedia is an important periodontal pathogen that induces various inflammatory and immune responses. In this study, we investigated the effects of P. intermedia on the plasminogen system in human periodontal ligament (hPDL) cells and explored the signaling pathways involved. Using semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-qPCR, we demonstrated that P. intermedia challenge increased tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-2 expression in a concentration- and time-dependent manner, but exerted no influence on urokinase-type plasminogen activator and PAI-1mRNA expression in hPDL cells. Prevotella intermedia stimulation also enhanced tPA protein secretion as confirmed by enzyme-linked immunosorbent assay. Western blot results revealed that P. intermedia treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38). ERK, JNK and protein kinase C inhibitors significantly attenuated the P. intermedia-induced tPA and PAI-2 expression. Furthermore, p38 and phosphatidylinositol 3-kinase inhibitors markedly decreased PAI-2 expression, whereas they showed no or little inhibition on tPA expression. In contrast, inhibition of protein kinase A greatly enhanced the upregulatory effect of P. intermedia on tPA and PAI-2 expression. Our results suggest that P. intermedia may contribute to periodontal tissue destruction by upregulating tPA and PAI-2 expression in hPDL cells via multiple signaling pathways. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  13. At-Home Transcranial Direct Current Stimulation (tDCS With Telehealth Support for Symptom Control in Chronically-Ill Patients With Multiple Symptoms

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    Alexa Riggs

    2018-05-01

    Full Text Available Transcranial direct current stimulation (tDCS delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications.Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support.Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific elements for enhanced safety and remote adherence monitoring was created. Lay language instructional materials were written and revised based on expert feedback. The materials were loaded onto a tablet allowing for secure video-conferencing. The telehealth tablet was paired with an at-home tDCS device that allowed for remote dose control via electronic codes dispensed to patients prior to each session. tDCS was delivered in two phases: once daily on 10 consecutive days, followed by an as needed regimen for 20 days. Initial feasibility of this tDCS-telehealth system was evaluated in four patients with advanced chronic illness and multiple symptoms. Change in symptom burden and patient satisfaction were assessed with the Condensed Memorial Symptom Assessment Scale (CMSAS and a tDCS user survey.Results: The telehealth-tDCS protocol includes one home visit and has seven patient-tailored elements and six elements enhancing safety monitoring. Replicable electrode placement at home without 10–20 EEG measurement is achieved via a headband that holds electrodes in a pre-determined position. There were no difficulties with patients’ training, protocol adherence, or tolerability. A total of 60 tDCS sessions were applied. No session required discontinuation, and

  14. At-Home Transcranial Direct Current Stimulation (tDCS) With Telehealth Support for Symptom Control in Chronically-Ill Patients With Multiple Symptoms.

    Science.gov (United States)

    Riggs, Alexa; Patel, Vaishali; Paneri, Bhaskar; Portenoy, Russell K; Bikson, Marom; Knotkova, Helena

    2018-01-01

    Transcranial direct current stimulation (tDCS) delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications. Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support. Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific elements for enhanced safety and remote adherence monitoring was created. Lay language instructional materials were written and revised based on expert feedback. The materials were loaded onto a tablet allowing for secure video-conferencing. The telehealth tablet was paired with an at-home tDCS device that allowed for remote dose control via electronic codes dispensed to patients prior to each session. tDCS was delivered in two phases: once daily on 10 consecutive days, followed by an as needed regimen for 20 days. Initial feasibility of this tDCS-telehealth system was evaluated in four patients with advanced chronic illness and multiple symptoms. Change in symptom burden and patient satisfaction were assessed with the Condensed Memorial Symptom Assessment Scale (CMSAS) and a tDCS user survey. Results: The telehealth-tDCS protocol includes one home visit and has seven patient-tailored elements and six elements enhancing safety monitoring. Replicable electrode placement at home without 10-20 EEG measurement is achieved via a headband that holds electrodes in a pre-determined position. There were no difficulties with patients' training, protocol adherence, or tolerability. A total of 60 tDCS sessions were applied. No session required discontinuation, and there were no adverse

  15. Interoceptive Processes in Anorexia Nervosa in the Time Course of Cognitive-Behavioral Therapy: A Pilot Study.

    Science.gov (United States)

    Fischer, Dana; Berberich, Götz; Zaudig, Michael; Krauseneck, Till; Weiss, Sarah; Pollatos, Olga

    2016-01-01

    Previous studies report reduced interoceptive abilities in anorexia nervosa (AN) using various methods. Recent research suggests that different levels of interoceptive processes aiming at different subdomains of interoceptive abilities must be further distinguished as these levels can be differentially affected. Two important levels refer to interoceptive accuracy (IA) derived from objective performance tasks such as the heartbeat detection task and interoceptive sensibility (IS) as assessed by self-report. There is a lack of studies investigating both IA and IS in AN and examining them in the time course of therapy. The aim of this pilot study was to evaluate the different interoceptive processes - especially IA and IS - in the time course of therapy. Fifteen patients with AN (restricting type) from the Psychosomatic Clinic in Windach were investigated three times (T1, T2, T3) during a standardized cognitive-behavioral therapy and compared with 15 matched healthy controls assessed at Ulm University in a comparable design. All participants performed the heartbeat detection task examining IA and completed standard psychological assessments including an assessment of IS. Patients with AN showed a significantly decreased weight, higher levels of depression, and both reduced IA and IS compared to healthy controls at T1. Following therapy, patients recovered in terms of weight and depression symptomatology. A descriptive trend for recovering from IA and IS was observed. Our findings suggest that interoceptive deficits are present in recovered patients. Therefore, further investigations are needed with more patients, differentiating between relapsed and recovered patients, and more specific training methods to improve interoceptive processes.

  16. Differences in time course activation of dorsolateral prefrontal cortex associated with low or high risk choicesin a gambling task

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    Stefano eBembich

    2014-06-01

    Full Text Available Prefrontal cortex plays an important role in decision making (DM, supporting choices in the ordinary uncertainty of everyday life. To assess DM in an unpredictable situation, a playing card task, such as the Iowa Gambling Task (IGT, has been proposed. This task is supposed to specifically test emotion-based learning, linked to the integrity of the ventromedial prefrontal cortex (VMPFC. However, the dorsolateral prefrontal cortex (DLPFC has demonstrated a role in IGT performance too. Our aim was to study, by multichannel near-infrared spectroscopy, the contribution of DLPFC to the IGT execution over time. We tested the hypothesis that low and high risk choices would differentially activate DLPFC, as IGT execution progressed. We enrolled 11 healthy adults. To identify DLPFC activation associated with IGT choices, we compared regional differences in oxy-haemoglobin variation, from baseline to the event. The time course of task execution was divided in four periods, each one consisting of 25 choices, and DLPFC activation was distinctly analyzed for low and high risk choices in each period. We found different time courses in DLPFC activation, associated with low or high risk choices. During the first period, a significant DLPFC activation emerged with low risk choices, whereas, during the second period, we found a cortical activation with high risk choices. Then, DLPFC activation decreased to non-significant levels during the third and fourth period. This study shows that DLPFC involvement in IGT execution is differentiated over time and according to choice risk level. DLPFC is activated only in the first half of the task, earlier by low risk and later by high risk choices. We speculate that DLPFC may sustain initial and more cognitive functions, such as attention shifting and response inhibition. The lack of DLPFC activation, as the task progresses, may be due to VMPFC activation, not detectable by fNIRS, which takes over the IGT execution in its

  17. Interoceptive processes in anorexia nervosa in the time course of cognitive-behavioral therapy: A pilot study

    Directory of Open Access Journals (Sweden)

    Dana Fischer

    2016-12-01

    Full Text Available Objective: Previous studies report reduced interoceptive abilities in anorexia nervosa (AN using various methods. Recent research suggests that different levels of interoceptive processes aiming at different subdomains of interoceptive abilities must be further distinguished as these levels can be differentially affected. Two important levels refer to interoceptive accuracy (IA derived from objective performance tasks such as the heartbeat detection task, and interoceptive sensibility (IS as assessed by self-report. There is a lack of studies investigating both IA and IS in AN, and examining them in the time course of therapy. Aim of the pilot study was to evaluate the different interoceptive processes – especially IA and IS – in the time course of therapy.Methods: Fifteen patients with AN (restricting type from the Psychosomatic Clinic in Windach were investigated three times (T1, T2, T3 during a standardized cognitive-behavioral therapy and compared to fifteen matched healthy controls assessed at Ulm University in a comparable design. All participants performed the heartbeat detection task examining IA and completed standard psychological assessments including an assessment of IS. Results: Patients with AN showed a significantly decreased weight, higher levels of depression and both reduced IA and IS compared to healthy controls at T1. Following therapy, patients recovered in terms of weight and depression symptomatology. A descriptive trend for recovering from IA and IS was observed. Discussion: Our findings suggest that interoceptive deficits are present in recovered patients. Therefore, further investigations are needed with more patients, differentiating between relapsed and recovered patients, and more specific training methods to improve interoceptive processes.

  18. Acute and Time-Course Effects of Traditional and Dynamic Warm-Up Routines in Young Elite Junior Tennis Players.

    Directory of Open Access Journals (Sweden)

    Francisco Ayala

    Full Text Available Despite the large number of studies that have examined the acute effects of different warm up modalities (WU on physical performance, none of them have documented the time course of potential performance recovery in tennis players. The aim of this study was twofold: (a to analyze and compare the acute effects of two different WU modalities (traditional WU [TWU] and dynamic WU [DWU] on physical performance (i.e., CMJ, sprint, serve speed and accuracy in elite junior players, as well as (b to monitor the time course of any WU-induced changes after 30 and 60 min of simulated match-play. Twelve junior elite players completed both WUs modalities (TWU and DWU in a counterbalanced order on separate days. In each experimental session, counter movement jump (CMJ, 20-m sprint, tennis serve speed and accuracy tests were performed before (immediately after TWU or DWU during (30 min and after 60 min of a simulated match play. Measures were compared via four factorial (WU intervention and time repeated measures ANOVAs. There were main effects of WU (TWU and DWU throughout the time for all the variables analysed. The results indicate that DWU routine led to significantly faster 20 m sprint times and higher CMJs as well as faster and more accurate tennis serves at both post warm-up and 30 min match-play testing moments in comparison with the scores reported by the TWU routine (p 75-99%. No significant intergroup differences were found at 60-min match-play testing moment in any variable (except for the 20 m sprint. Therefore, the findings of this study recommend for optimal performance in these elite tennis players, DWU routines should be performed prior to formal training and competition rather than TWU routines.

  19. Contextual change after fear acquisition affects conditioned responding and the time course of extinction learning – Implications for renewal research

    Directory of Open Access Journals (Sweden)

    Rachel eSjouwerman

    2015-12-01

    Full Text Available Context plays a central role in retrieving (fear memories. Accordingly, context manipulations are inherent to most return of fear (ROF paradigms (in particular renewal, involving contextual changes after fear extinction. Context changes are, however, also often embedded during earlier stages of ROF experiments such as context changes between fear acquisition and extinction (e.g. in ABC and ABA renewal. Previous studies using these paradigms have however focused exclusively on the context switch after extinction (i.e. renewal. Thus, the possibility of a general effect of a context switch on conditioned responding that may not be conditional to preceding extinction learning remains unstudied.Hence, the current study investigated the impact of a context switch between fear acquisition and extinction on immediate conditioned responding and on the time-course of extinction learning by using a multimodal approach. A group that underwent contextual change after fear conditioning (AB; n = 36 was compared with a group without a contextual change from acquisition to extinction (AA; n = 149, while measuring autonomic (skin conductance and fear potentiated startle measures and subjective fear ratings. Contextual change between fear acquisition and extinction had a pronounced effect on both immediate conditioned responding and on the time course of extinction learning in skin conductance responses and subjective fear ratings. This may have important implications for the mechanisms underlying and the interpretation of the renewal effect (i.e. contextual switch after extinction. Consequently, future studies should incorporate designs and statistical tests that disentangle general effects of contextual change from genuine ROF effects.

  20. Time course of late rectal- and urinary bladder side effects after MRI-guided adaptive brachytherapy for cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Georg, P.; Georg, D.; Poetter, R.; Doerr, W. [Medical University Vienna/ AKH Wien (Austria). Dept. of Radiooncology; Medical University Vienna (Austria). Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology; Medical University Vienna/ AKH Wien (Austria). Comprehensive Cancer Centre; Boni, A.; Ghabuous, A. [Medical University Vienna/ AKH Wien (Austria). Dept. of Radiooncology; Goldner, G.; Schmid, M.P. [Medical University Vienna/ AKH Wien (Austria). Dept. of Radiooncology; Medical University Vienna/ AKH Wien (Austria). Comprehensive Cancer Centre

    2013-07-15

    Background and purpose: To analyze the time course of late rectal- and urinary bladder complications after brachytherapy for cervical cancer and to compare the incidence- and prevalence rates thereof. Patients and methods: A total of 225 patients were treated with external-beam radiotherapy (EBRT) and magnetic resonance imaging (MRI)-guided brachytherapy with or without chemotherapy. Late side effects were assessed prospectively using the Late Effects in Normal Tissue - Subjective, Objective, Management and Analytic (LENT/SOMA) scale. The parameters analyzed were time to onset, duration, actuarial incidence- (occurrence of new side effects during a defined time period) and prevalence rates (side effects existing at a defined time point). Results: Median follow-up was 44 months. Side effects (grade 1-4) in rectum and bladder were present in 31 and 49 patients, 14 and 27 months (mean time to onset) after treatment, respectively. All rectal and 76 % of bladder side effects occurred within 3 years after radiotherapy. Mean duration of rectal events was 19 months; 81 % resolved within 3 years of their initial diagnosis. Mean duration of bladder side effects was 20 months; 61 % resolved within 3 years. The 3- and 5-year actuarial complication rates were 16 and 19 % in rectum and 18 and 28 % in bladder, respectively. The corresponding prevalence rates were 9 and 2 % (rectum) and 18 and 21 % (bladder), respectively. Conclusion: Late side effects after cervical cancer radiotherapy are partially reversible, but their time course is organ-dependent. The combined presentation of incidence- and prevalence rates provides the most comprehensive information. (orig.)

  1. Proteomic Investigation of the Time Course Responses of RAW 264.7 Macrophages to Infection with Salmonella enterica

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Liang; Chowdhury, Saiful M.; Smallwood, Heather S.; Yoon, Hyunjin; Mottaz-Brewer, Heather M.; Norbeck, Angela D.; McDermott, Jason E.; Clauss, Therese RW; Heffron, Fred; Smith, Richard D.; Adkins, Joshua N.

    2009-08-01

    Macrophages plan important roles in controlling Salmonella-mediated systemic infection. To investigate the responses of macrophages to Salmonella infection, we infected RAW 264.7 macrophages with Salmonella enterica serovar Typhimurium (STM) and then performed a comparative liquid chromatography-tandem mass spectrometry [LC-MS(/MS)]-based proteomics analysis of the infected macrophages. A total of 1006 macrophage and 115 STM proteins were indentified from this study. Most of STM proteins were found at late stage of the time course of infection, consistent with the fact that STM proliferates inside RAW 264.7 macrophages. Majority of the identified macrophage proteins were house keeping-related, including cytoplasmic superoxide dismutase 1 (SOD1), whose peptide abundances were relatively constant during the time course of infection. Compared to those in no infection control, the peptide abundances of 244 macrophage proteins (or 24% of total indentified macrophage proteins) changed considerably after STM infection. The functions of these STM infection-affected macrophage proteins were diverse and ranged from production of antibacterial nitric oxide (i.e., inducible nitric oxide synthase or iNOS) or production of prostaglandin H2 (i.e., prostaglandin-endoperoxide synthase 2, also know as cyclooxygenase-2 or COX-2) to regulation of intracellular traffic (e.g., sorting nexin or SNX 5, 6 and 9), demonstrating a global impact of STM infection on macrophage proteome. Western-blot analysis not only confirmed the LC-MS(/MS) results of SOD1, COX-2 and iNOS, but also revealed that the protein abundances of mitochondrial SOD2 increased after STM infection, indicating an infection-induced oxidative stress in mitochondria.

  2. Documenting the kinetic time course of lambda-cyhalothrin metabolites in orally exposed volunteers for the interpretation of biomonitoring data.

    Science.gov (United States)

    Khemiri, Rania; Côté, Jonathan; Fetoui, Hamadi; Bouchard, Michèle

    2017-07-05

    Lambda-cyhalothrin is a pyrethroid pesticide largely used in agriculture. Exposure assessment can be performed by measuring key urinary metabolites. For a proper use of biomonitoring data, it is however important to gain information on the toxicokinetics of these key biomarkers of exposure. A human volunteer study was performed to document the plasma and urinary time courses of major lambda-cyhalothrin metabolites. Seven volunteers ingested 0.025mgkg -1 body weight of lambda-cyhalothrin. Blood samples were withdrawn prior to dosing and at fixed time periods over the 72 h-period following ingestion and complete urine voids were collected pre-exposure and at pre-established intervals over 84h post-dosing. The cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) metabolites were quantified in these samples. Plasma concentrations of CFMP and 3-PBA increased rapidly after ingestion, with average peak values at 3.1 and 4.0h post-dosing, respectively; subsequent elimination phase showed a rapid decay with a mean half-life (t ½ ) of ≈5.3 and 6.4h for CFMP and 3-PBA, respectively. Urinary rate time courses displayed a profile similar to the plasma concentration-time curves with corresponding mean t ½ of ≈4.2 and 5.9h. In the 84-h period post-treatment, on average 21% of lambda-cyhalothrin dose were excreted in urine as CFMP as compared to 30% as 3-PBA. Overall, CFMP and 3-PBA metabolites were confirmed to be major metabolites of lambda-cyhalothrin and exhibited similar kinetics with short half-lives; they thus both appear as useful biomarkers of exposure to lambda-cyhalothrin in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Time course of late rectal- and urinary bladder side effects after MRI-guided adaptive brachytherapy for cervical cancer

    International Nuclear Information System (INIS)

    Georg, P.; Georg, D.; Poetter, R.; Doerr, W.; Medical University Vienna; Medical University Vienna/ AKH Wien; Boni, A.; Ghabuous, A.; Goldner, G.; Schmid, M.P.; Medical University Vienna/ AKH Wien

    2013-01-01

    Background and purpose: To analyze the time course of late rectal- and urinary bladder complications after brachytherapy for cervical cancer and to compare the incidence- and prevalence rates thereof. Patients and methods: A total of 225 patients were treated with external-beam radiotherapy (EBRT) and magnetic resonance imaging (MRI)-guided brachytherapy with or without chemotherapy. Late side effects were assessed prospectively using the Late Effects in Normal Tissue - Subjective, Objective, Management and Analytic (LENT/SOMA) scale. The parameters analyzed were time to onset, duration, actuarial incidence- (occurrence of new side effects during a defined time period) and prevalence rates (side effects existing at a defined time point). Results: Median follow-up was 44 months. Side effects (grade 1-4) in rectum and bladder were present in 31 and 49 patients, 14 and 27 months (mean time to onset) after treatment, respectively. All rectal and 76 % of bladder side effects occurred within 3 years after radiotherapy. Mean duration of rectal events was 19 months; 81 % resolved within 3 years of their initial diagnosis. Mean duration of bladder side effects was 20 months; 61 % resolved within 3 years. The 3- and 5-year actuarial complication rates were 16 and 19 % in rectum and 18 and 28 % in bladder, respectively. The corresponding prevalence rates were 9 and 2 % (rectum) and 18 and 21 % (bladder), respectively. Conclusion: Late side effects after cervical cancer radiotherapy are partially reversible, but their time course is organ-dependent. The combined presentation of incidence- and prevalence rates provides the most comprehensive information. (orig.)

  4. Kanpur epidemic: Time course

    Indian Academy of Sciences (India)

    The first peak was related to water contamination which began in December 1990. The second peak was related to failure of municipal authorities to chlorinate water during the 2nd week of February 1991. The epidemic came under control quickly after water contamination was controlled, providing confirmation for role of ...

  5. Performance Enhancement by Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Parisa Gazerani

    2017-09-01

    et al., 2017 has summarized that overall brain stimulation by some techniques including TMS and tDCS seem to speed up motor learning, and motor skills in sport activities. Considering that performance enhancement can be seen (Colzato et al., 2017, one would ask how and by which mechanism. Davis proposed that there would be two ways that brain stimulation could possibly improve sport performance (Davis, 2013. One way is to benefit from brain stimulation before performance to, for instance, reduce stress level or muscle tension or to enhance focus for a quicker action. The other way would be potential use during training for athletic performance that can eventually help athletes to learn motor skills better. Presented research results are mainly based on the experimental set up; therefore, it is important to identify whether physical and mental performance gains under experimental conditions would also be meaningful in a real world competition. To study actual gain by brain stimulation, future investigations must properly be designed, include placebo and control arms, remain blinded until after data analysis, and include objective assessments in addition to subjective outcomes. Time-course of beneficial effect in certain sport competition is not clear. It has been shown that repetitive applications of tDCS can increase the effects of stimulation (Nitsche and Paulus, 2011; but, it is not clear if this is the case for athletic performance. There is no evidence on side effects especially for long term use of these techniques. Overall, these techniques are considered non-invasive and safe (Rossi et al., 2009. Under medical application, it has been notified that some individuals are highly responders while others do not respond well. This might be the case for athletes. Additive or synergistic effects of these techniques together with other techniques or methods of performance enhancement have not yet been investigated either. Therefore, further studies are required to

  6. Treatment of Neuropathic Pain and Functional Limitations Associated With Multiple Sclerosis Using an MRI-Compatible Spinal Cord Stimulator: A Case Report With Two Year Follow-Up and Literature Review.

    Science.gov (United States)

    Provenzano, David A; Williams, Joseph R; Jarzabek, Gaye; DeRiggi, Leonard A; Scott, Thomas F

    2016-06-01

    To report a case with two years follow-up of neuropathic pain and functional limitations associated with multiple sclerosis (MS) effectively treated with an MRI conditional spinal cord stimulator (SCS) system that allowed for spinal imaging. To present a comprehensive literature review of spinal cord stimulator utilization in the treatment of multiple sclerosis. Case report and literature review. Treatment was a spinal cord stimulation implant after successful trial. Pain scores, medication utilization, and functional outcomes were reviewed. Pre- and post-SCS implant MRI spine images were obtained. At 24 months follow-up, the patient has had a 77% reduction in pain and a 99% reduction in opioid use. Furthermore, he had improvement in reported tactile sensation, spasticity levels, and ambulation. Post-SCS implant, MRI images at 18 months follow-up provided the ability to review the spinal cord with minimal artifact. No new MS documented plaques occurred during this time period. A literature review demonstrated 33 published reports including a total of 496 trialed and 744 implanted patients. Only 3 of the reports occurred after the year 2000. We report the successful treatment of MS-associated pain and functional limitations with an MRI conditional spinal cord stimulator system. The ability to obtain post-implant MRI imaging of not only the brain but also the spinal cord in MS patients allows for the continued need to document and follow disease progression, especially with the advancements in pharmacological therapy. © 2016 International Neuromodulation Society.

  7. The ATP hydrolysis and phosphate release steps control the time course of force development in rabbit skeletal muscle.

    Science.gov (United States)

    Sleep, John; Irving, Malcolm; Burton, Kevin

    2005-03-15

    The time course of isometric force development following photolytic release of ATP in the presence of Ca(2+) was characterized in single skinned fibres from rabbit psoas muscle. Pre-photolysis force was minimized using apyrase to remove contaminating ATP and ADP. After the initial force rise induced by ATP release, a rapid shortening ramp terminated by a step stretch to the original length was imposed, and the time course of the subsequent force redevelopment was again characterized. Force development after ATP release was accurately described by a lag phase followed by one or two exponential components. At 20 degrees C, the lag was 5.6 +/- 0.4 ms (s.e.m., n = 11), and the force rise was well fitted by a single exponential with rate constant 71 +/- 4 s(-1). Force redevelopment after shortening-restretch began from about half the plateau force level, and its single-exponential rate constant was 68 +/- 3 s(-1), very similar to that following ATP release. When fibres were activated by the addition of Ca(2+) in ATP-containing solution, force developed more slowly, and the rate constant for force redevelopment following shortening-restretch reached a maximum value of 38 +/- 4 s(-1) (n = 6) after about 6 s of activation. This lower value may be associated with progressive sarcomere disorder at elevated temperature. Force development following ATP release was much slower at 5 degrees C than at 20 degrees C. The rate constant of a single-exponential fit to the force rise was 4.3 +/- 0.4 s(-1) (n = 22), and this was again similar to that after shortening-restretch in the same activation at this temperature, 3.8 +/- 0.2 s(-1). We conclude that force development after ATP release and shortening-restretch are controlled by the same steps in the actin-myosin ATPase cycle. The present results and much previous work on mechanical-chemical coupling in muscle can be explained by a kinetic scheme in which force is generated by a rapid conformational change bracketed by two

  8. Time course of changes in sperm morphometry and semen variables during testosterone-induced suppression of human spermatogenesis.

    Science.gov (United States)

    Garrett, C; Liu, D Y; McLachlan, R I; Baker, H W G

    2005-11-01

    Quantification of changes in semen may give insight into the testosterone (T)-induced disruption of spermatogenesis in man. A model analogous to flushing of sperm from the genital tract after vasectomy was used to quantify the time course of semen changes in subjects participating in male contraceptive trials using 800 mg T-implant (n = 25) or 200 mg weekly intramuscular injection (IM-T; n = 33). A modified exponential decay model allowed for delayed onset and incomplete disruption to spermatogenesis. Semen variables measured weekly during a 91-day period after initial treatment were fitted to the model. Sperm concentration, total count, motility and morphometry exhibited similar average decay rates (5 day half-life). The mean delay to onset of decline in concentration was 15 (IM-T) and 18 (T-implant) days. The significantly longer (P sperm viability (43 and 55 days), and the change of morphometry to smaller more compact sperm heads are consistent with sperm being progressively cleared from the genital tract rather than continued shedding of immature or abnormal sperm by the seminiferous epithelium. A significant negative relationship was found between lag time and baseline sperm concentration, consistent with longer sperm-epididymal transit times associated with lower daily production rates.

  9. Time Course of Symptomatic Recovery After Endoscopic Transsphenoidal Surgery for Pituitary Adenoma Apoplexy in the Modern Era.

    Science.gov (United States)

    Zaidi, Hasan A; Cote, David J; Burke, William T; Castlen, Joseph P; Bi, Wenya Linda; Laws, Edward R; Dunn, Ian F

    2016-12-01

    Pituitary tumor apoplexy can result from either hemorrhagic or infarctive expansion of pituitary adenomas, and the related mass effect can result in compression of critical neurovascular structures. The time course of recovery of visual field deficits, headaches, ophthalmoparesis, and pituitary dysfunction after endoscopic transsphenoidal surgery has not been well established. Medical records were retrospectively reviewed for all patients who underwent endoscopic transsphenoidal surgery for pituitary tumor apoplexy from April 2008 to November 2014. Of 578 patients who underwent transsphenoidal surgery, pituitary tumor apoplexy was identified in 44 patients (7.6%). Two patients had prior surgery, leaving 42 patients for final analysis. These included infarction-related apoplexy in 7 (14.4%) patients, and hemorrhagic apoplexy in 35 (85.6%) patients. Hemorrhagic adenomas had a larger axial tumor diameter than patients with infarctive adenomas (4.4 ± 4.1 cm vs. 1.8 ± 0.8 cm; P surgery. Endoscopic transsphenoidal surgery can provide durable resolution of symptoms for patients presenting with pituitary tumor apoplexy. Recovery from headaches, visual, and pituitary dysfunction may be more rapid compared with ophthalmoparesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Health anxiety and attentional bias: the time course of vigilance and avoidance in light of pictorial illness information.

    Science.gov (United States)

    Jasper, Fabian; Witthöft, Michael

    2011-12-01

    Cognitive-behavioral models of health anxiety stress the importance of selective attention not only towards internal but also towards external health threat related stimuli. Yet, little is known about the time course of this attentional bias. The current study investigates threat related attentional bias in participants with varying degrees of health anxiety. Attentional bias was assessed using a visual dot-probe task with health-threat and neutral pictures at two exposure durations, 175ms and 500ms. A baseline condition was added to the dot-probe task to dissociate indices of vigilance towards threat and difficulties to disengage from threat. Substantial positive correlations of health anxiety, anxiety sensitivity, and absorption with difficulties to disengage from threat were detected at 500ms exposure time. At an early stage (i.e., at 175ms exposure time), we found significant positive correlations of health anxiety and absorption with orientation towards threat. Results suggest a vigilance avoidance pattern of selective attention associated with pictorial illness related stimuli in health anxiety. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Eye-movement evidence of the time-course of attentional bias for threatening pictures in test-anxious students.

    Science.gov (United States)

    Dong, Yunying; De Beuckelaer, Alain; Yu, Liang; Zhou, Renlai

    2017-06-01

    Protocols for measuring attentional bias to threat in test-anxiety, a special form of trait-anxiety, are rarely found in the literature. In our eye-tracking study, we introduced a new protocol, and studied the time-course of attention to test-related pictures with varying threat levels in 22 high test-anxious (HTA) and 22 low test-anxious (LTA) subjects. To determine whether attentional bias to test-related pictures is due to test-anxiety and not to state-anxiety, we also included a third group of 22 subjects with high state-anxiety but low test-anxiety (HSA). The subjects completed a free viewing task (FVT) in which high threat-neutral (HT-N) and low threat-neutral (LT-N) picture pairs were presented for 3 s. The results demonstrated that: (1) HTA subjects showed initial orienting to LT pictures, early attentional engagement with HT pictures later on and avoidance of HT pictures at the very end; (2) LTA subjects showed initial orienting to HT pictures and maintenance of attention on them later on; while (3) HSA subjects showed an initial orientation towards LT pictures and maintenance of attention on LT and HT pictures later on. These results suggest that, (high) test-anxiety is also prone to attentional bias towards test-related threat stimuli. Implications for future research are discussed.

  12. Chronic levothyroxine and acute T3 treatments enhance the amplitude and time course of uterine contractions in human.

    Science.gov (United States)

    Corriveau, Stéphanie; Pasquier, Jean-Charles; Blouin, Simon; Bellabarba, Diego; Rousseau, Éric

    2013-03-01

    This study compares the functional consequences of levothyroxine (T4) treatment during pregnancy as well as the acute affects of triiodothyronine (T3) on spontaneous uterine contractile activities observed in vitro. Uterine biopsies were obtained from consenting women undergoing elective caesarean at term (n = 28). Spontaneous contractile activities from T4-treated pregnant women (n = 8) were compared with control patients (n = 20) by isometric tension measurements. Effects of acute T3 and T4 on control tissues were also monitored. Area under the curve, amplitude, time to peak, duration, and frequency were quantified. In uterine strips from women treated for hypothyroidism, phasic uterine contractions of larger amplitude (+77%) were observed, with a prolonged duration at 90% relaxation (+138%) and reduced frequency (-55%) compared with values of the control group. The addition of exogenous T3 in vitro on control strips induced a significant increase in the duration of the contractions and a significant decrease in frequency (P women. Significant modifications of contractile properties were observed in strips from pregnant women treated with levothyroxine, consistent with those observed with the addition of exogenous T3. Clinical practices of modern obstetrics should take into account the effect of thyroid hormones on uterine contractions' time course to ensure a tighter followup at the end of pregnancy to achieve safer delivery.

  13. Time course of hydrogen peroxide-thioredoxin balance and its influence on the intracellular signalling in myocardial infarction.

    Science.gov (United States)

    Schenkel, Paulo Cavalheiro; Tavares, Angela Maria Vicente; Fernandes, Rafael Oliveira; Diniz, Gabriela Placoná; Ludke, Ana Raquel Lehenbauer; Ribeiro, Maria Flavia Marques; Araujo, Alex Sander da Rosa; Barreto-Chaves, Maria Luiza; Belló-Klein, Adriane

    2012-06-01

    We investigated the myocardial thioredoxin-1 and hydrogen peroxide concentrations and their association with some prosurvival and pro-apoptotic proteins, during the transition from myocardial infarction (MI) to heart failure in rats. Male Wistar rats were divided into the following six groups: three sham-operated groups and three MI groups, each at at 2, 7 and 28 days postsurgery. Cardiac function was analysed by echocardiography; the concentration of H(2)O(2) and the ratio of reduced to oxidized glutathione were measured spectrophotometrically, while the myocardial immunocontent of thioredoxin-1, angiotensin II, angiotensin II type 1 and type 2 receptors, p-JNK/JNK, p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK3β/GSK3β was evaluated by Western blot. Our results show that thioredoxin-1 appears to make an important contribution to the reduced H(2)O(2) concentration. It was associated with lower JNK expression in the early period post-MI (2 days). However, thioredoxin-1 decreased, while renin-angiotensin system markers and levels of H(2)O(2) increased, over 28 days post-MI, in parallel with some signalling proteins involved in maladaptative cardiac remodelling and ventricular dysfunction. These findings provide insight into the time course profile of endogenous antioxidant adaptation to ischaemic injury, which may be useful for the design of therapeutical strategies targeting oxidative stress post-MI.

  14. Time-course of attentional bias for positive social words in individuals with high and low social anxiety.

    Science.gov (United States)

    Yu, Hongyu; Li, Songwei; Qian, Mingyi; Yang, Peng; Wang, Xiaoling; Lin, Muyu; Yao, Nisha

    2014-07-01

    Although accumulating research demonstrates the association between attentional bias and social anxiety, the bias for positive stimuli has so far not been adequately studied. The aim is to investigate the time-course of attentional bias for positive social words in participants with high and low social anxiety. In a modified dot-probe task, word-pairs of neutral and positive social words were randomly presented for 100, 500, and 1250 milliseconds in a nonclinical sample of students to test their attentional bias. Non-significant interaction of Group × Exposure Duration was found. However, there was a significant main effect of group, with significantly different response latencies between the high social anxiety (HSA) and low social anxiety (LSA) groups in the 100 ms condition, without for 500 or 1250 ms. With respect to attentional bias, the LSA group showed enhanced preferential attention for positive social words to which the HSA group showed avoidance in the 100 ms condition. In the 500 ms condition, preferential attention to positive social words was at trend in the LSA group, relative to the HSA group. Neither group showed attentional bias in the 1250 ms condition. These findings extend recent research about the attention training program and add to the empirical literature suggesting that the initial avoidance of positive stimuli may contribute to maintaining social anxiety.

  15. I scan, therefore I decline: The time course of difficulty monitoring in humans (homo sapiens) and macaques (macaca mulatta).

    Science.gov (United States)

    Smith, J David; Boomer, Joseph; Church, Barbara A; Zakrzewski, Alexandria C; Beran, Michael J; Baum, Michael L

    2018-05-01

    The study of nonhumans' metacognitive judgments about trial difficulty has grown into an important comparative literature. However, the potential for associative-learning confounds in this area has left room for behaviorist interpretations that are strongly asserted and hotly debated. This article considers how researchers may be able to observe animals' strategic cognitive processes more clearly by creating temporally extended problems within which associative cues are not always immediately available. We asked humans and rhesus macaques to commit to completing spatially extended mazes or to decline completing them through a trial-decline response. The mazes could sometimes be completed successfully, but other times had a constriction that blocked completion. A deliberate, systematic scanning process could preevaluate a maze and determine the appropriate response. Latency analyses charted the time course of the evaluative process. Both humans and macaques appeared, from the pattern of their latencies, to scan the mazes through before committing to completing them. Thus monkeys, too, can base trial-decline responses on temporally extended evaluation processes, confirming that those responses have strategic cognitive-processing bases in addition to behavioral-reactive bases. The results also show the value of temporally and spatially extended problems to let researchers study the trajectory of animals' online cognitive processes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  16. The time course of episodic associative retrieval: electrophysiological correlates of cued recall of unimodal and crossmodal pair-associate learning.

    Science.gov (United States)

    Tibon, Roni; Levy, Daniel A

    2014-03-01

    Little is known about the time course of processes supporting episodic cued recall. To examine these processes, we recorded event-related scalp electrical potentials during episodic cued recall following pair-associate learning of unimodal object-picture pairs and crossmodal object-picture and sound pairs. Successful cued recall of unimodal associates was characterized by markedly early scalp potential differences over frontal areas, while cued recall of both unimodal and crossmodal associates were reflected by subsequent differences recorded over frontal and parietal areas. Notably, unimodal cued recall success divergences over frontal areas were apparent in a time window generally assumed to reflect the operation of familiarity but not recollection processes, raising the possibility that retrieval success effects in that temporal window may reflect additional mnemonic processes beyond familiarity. Furthermore, parietal scalp potential recall success differences, which did not distinguish between crossmodal and unimodal tasks, seemingly support attentional or buffer accounts of posterior parietal mnemonic function but appear to constrain signal accumulation, expectation, or representational accounts.

  17. Tracking the time course of word-frequency effects in auditory word recognition with event-related potentials.

    Science.gov (United States)

    Dufour, Sophie; Brunellière, Angèle; Frauenfelder, Ulrich H

    2013-04-01

    Although the word-frequency effect is one of the most established findings in spoken-word recognition, the precise processing locus of this effect is still a topic of debate. In this study, we used event-related potentials (ERPs) to track the time course of the word-frequency effect. In addition, the neighborhood density effect, which is known to reflect mechanisms involved in word identification, was also examined. The ERP data showed a clear frequency effect as early as 350 ms from word onset on the P350, followed by a later effect at word offset on the late N400. A neighborhood density effect was also found at an early stage of spoken-word processing on the PMN, and at word offset on the late N400. Overall, our ERP differences for word frequency suggest that frequency affects the core processes of word identification starting from the initial phase of lexical activation and including target word selection. They thus rule out any interpretation of the word frequency effect that is limited to a purely decisional locus after word identification has been completed. Copyright © 2012 Cognitive Science Society, Inc.

  18. Get rich quick: the signal to respond procedure reveals the time course of semantic richness effects during visual word recognition.

    Science.gov (United States)

    Hargreaves, Ian S; Pexman, Penny M

    2014-05-01

    According to several current frameworks, semantic processing involves an early influence of language-based information followed by later influences of object-based information (e.g., situated simulations; Santos, Chaigneau, Simmons, & Barsalou, 2011). In the present study we examined whether these predictions extend to the influence of semantic variables in visual word recognition. We investigated the time course of semantic richness effects in visual word recognition using a signal-to-respond (STR) paradigm fitted to a lexical decision (LDT) and a semantic categorization (SCT) task. We used linear mixed effects to examine the relative contributions of language-based (number of senses, ARC) and object-based (imageability, number of features, body-object interaction ratings) descriptions of semantic richness at four STR durations (75, 100, 200, and 400ms). Results showed an early influence of number of senses and ARC in the SCT. In both LDT and SCT, object-based effects were the last to influence participants' decision latencies. We interpret our results within a framework in which semantic processes are available to influence word recognition as a function of their availability over time, and of their relevance to task-specific demands. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Quantitation of intracellular metabolites of [35S]-6-mercaptopurine in L5178Y cells grown in time-course incubates.

    Science.gov (United States)

    Breter, H J; Zahn, R K

    1979-09-01

    6-Mercaptopurine (6MP) metabolism was quantitatively determined in L5178Y murine lymphoma. Cells grown in time-course incubates with [35S]-6MP were extracted with cold perchloric acid, and the buffered extracts were subjected to high-performance liquid cation-exchange chromatography prior to and after hydrolysis with alkaline phosphatase. Free sulfate, 6-thiouric acid, 6-thioxanthosine, 6-thioguanosine, 6-thioinosine, free 6MP, and 6-methylthioinosine were separated from each other; identified in the radiochromatograms by elution volume, UV spectroscopic data, and enzymatic peak-shifting analyses with purine nucleoside phosphorylase; and quantitatively determined by means of 35S radioactivity. Gross intracellular 35S concentrations remained constant at 5 x 10(-5) M after 1 hr of incubation. 6MP metabolism in L5178Y cells was distinguished into an early phase (to 1 hr of incubation) in which 6MP was predominantly catabolized to 6-thiouric acid and free sulfate, into an intermediate phase (to 8 hr) in which substantial amounts of free 6MP and of ribonucleotides of 6-thioxanthosine and 6-thioguanosine were present while the concentrations of nonnucleotide oxidation products sharply decreased, and into a late phase (to 24 hr) in which the ribonucleotides of 6MP, of 6-thioguanosine and, in particular, of 6-methylthioinosine were the most abundant metabolites.

  20. Time course of physiological and psychological responses in humans during a 20-day severe-cold-acclimation programme.

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    Marius Brazaitis

    Full Text Available The time course of physiological and psychological markers during cold acclimation (CA was explored. The experiment included 17 controlled (i.e., until the rectal temperature reached 35.5°C or 170 min had elapsed; for the CA-17 session, the subjects (n = 14 were immersed in water for the same amount of time as that used in the CA-1 session head-out water immersions at a temperature of 14°C over 20 days. The data obtained in this study suggest that the subjects exhibited a thermoregulatory shift from peripheral-to-central to solely central input thermoregulation, as well as from shivering to non-shivering thermogenesis throughout the CA. In the first six CA sessions, a hypothermic type of acclimation was found; further CA (CA-7 to CA-16 led to a transitional shift to a hypothermic-insulative type of acclimation. Interestingly, when the subjects were immersed in water for the same time as that used in the CA-1 session (CA-17, the CA led to a hypothermic type of acclimation. The presence of a metabolic type of thermogenesis was evident only under thermoneutral conditions. Cold-water immersion decreased the concentration of cold-stress markers, reduced the activity of the innate immune system, suppressed specific immunity to a lesser degree and yielded less discomfort and cold sensation. We found a negative correlation between body mass index and Δ metabolic heat production before and after CA.

  1. Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination.

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    Steven C Munger

    Full Text Available In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. To elucidate the first steps of sexual fate specification, we profiled the XX and XY gonad transcriptomes at fine granularity during this period and resolved cascades of gene activation and repression. C57BL/6J (B6 XY gonads showed a consistent ~5-hour delay in the activation of most male pathway genes and repression of female pathway genes relative to 129S1/SvImJ, which likely explains the sensitivity of the B6 strain to male-to-female sex reversal. Using this fine time course data, we predicted novel regulatory genes underlying expression QTLs (eQTLs mapped in a previous study. To test predictions, we developed an in vitro gonad primary cell assay and optimized a lentivirus-based shRNA delivery method to silence candidate genes and quantify effects on putative targets. We provide strong evidence that Lmo4 (Lim-domain only 4 is a novel regulator of sex determination upstream of SF1 (Nr5a1, Sox9, Fgf9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems.

  2. Time-course correlation of biofilm properties and electrochemical performance in single-chamber microbial fuel cells

    KAUST Repository

    Ren, Zhiyong; Ramasamy, Ramaraja P.; Cloud-Owen, Susan Red; Yan, Hengjing; Mench, Matthew M.; Regan, John M.

    2011-01-01

    The relationship between anode microbial characteristics and electrochemical parameters in microbial fuel cells (MFCs) was analyzed by time-course sampling of parallel single-bottle MFCs operated under identical conditions. While voltage stabilized within 4. days, anode biofilms continued growing during the six-week operation. Viable cell density increased asymptotically, but membrane-compromised cells accumulated steadily from only 9% of total cells on day 3 to 52% at 6. weeks. Electrochemical performance followed the viable cell trend, with a positive correlation for power density and an inverse correlation for anode charge transfer resistance. The biofilm architecture shifted from rod-shaped, dispersed cells to more filamentous structures, with the continuous detection of Geobacter sulfurreducens-like 16S rRNA fragments throughout operation and the emergence of a community member related to a known phenazine-producing Pseudomonas species. A drop in cathode open circuit potential between weeks two and three suggested that uncontrolled biofilm growth on the cathode deleteriously affects system performance. © 2010 Elsevier Ltd.

  3. Determination of the action modes of cellulases from hydrolytic profiles over a time course using fluorescence-assisted carbohydrate electrophoresis.

    Science.gov (United States)

    Zhang, Qing; Zhang, Xiaomei; Wang, Peipei; Li, Dandan; Chen, Guanjun; Gao, Peiji; Wang, Lushan

    2015-03-01

    Fluorescence-assisted carbohydrate electrophoresis (FACE) is a sensitive and simple method for the separation of oligosaccharides. It relies on labeling the reducing ends of oligosaccharides with a fluorophore, followed by PAGE. Concentration changes of oligosaccharides following hydrolysis of a carbohydrate polymer could be quantitatively measured continuously over time using the FACE method. Based on the quantitative analysis, we suggested that FACE was a relatively high-throughput, repeatable, and suitable method for the analysis of the action modes of cellulases. On account of the time courses of their hydrolytic profiles, the apparent processivity was used to show the different action modes of cellulases. Cellulases could be easily differentiated as exoglucanases, β-glucosidases, or endoglucanases. Moreover, endoglucanases from the same glycoside hydrolases family had a variety of apparent processivity, indicating the different modes of action. Endoglucanases with the same binding capacities and hydrolytic activities had similar oligosaccharide profiles, which aided in their classification. The hydrolytic profile of Trichoderma reesei Cel12A, an endoglucanases from T. reesei, contained glucose, cellobiose, and cellotriose, which revealed that it may have a new glucosidase activity, corresponding to that of EC 3.2.1.74. A hydrolysate study of a T. reesei Cel12A-N20A mutant demonstrated that the FACE method was sufficiently sensitive to detect the influence of a single-site mutation on enzymatic activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Time course of bone mineral density changes during 4-year rituximab therapy in postmenopausal women with rheumatoid arthritis

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    T. A. Raskina

    2015-01-01

    Full Text Available Objective: to estimate the time course of bone mineral density (BMD changes during 4-year rituximab (RTM therapy in postmenopausal women with rheumatoid arthritis (RA.Subjects and methods. Seventy-nine postmenopausal women with a valid diagnosis of RA were followed up. According to the basic therapy option, all the patients were allocated into two groups: 1 44 patients who received combination therapy with RTM and methotrexate (MT; 2 35 patients who had MT monotherapy. BMD was estimated by dual-energy X-ray absorptiometry using an Excell XR-46 stationary dualenergy X-ray bone densitometer (Norland, USA.Results. There was a statistically significant increase in femoral neck BMD and T score as compared to the baseline values in the RTM group after 3 years of follow-up. The MT monotherapy group showed no statistically significant densitometric changes in the femoral neck. The similar positive BMD changes were observed 4 years following RTM and MT therapy.Conclusion. Following 2 therapy cycles, femoral neck BMD parameters were noted to be stabilized in the patients with RA. After 3 therapy cycles, there was a positive densitometric change that remained by the fourth therapy cycle.

  5. The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control.

    Science.gov (United States)

    Silton, Rebecca Levin; Heller, Wendy; Towers, David N; Engels, Anna S; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

    2010-04-15

    A network of brain regions has been implicated in top-down attentional control, including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC). The present experiment evaluated predictions of the cascade-of-control model (Banich, 2009), which predicts that during attentionally-demanding tasks, LDLPFC imposes a top-down attentional set which precedes late-stage selection performed by dACC. Furthermore, the cascade-of-control model argues that dACC must increase its activity to compensate when top-down control by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense-array ERP data collected from the same 80 participants in separate sessions. fMRI results guided ERP source modeling to characterize the time course of activity in LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity distinguished congruent and incongruent conditions on the Stroop task. Furthermore, when LDLPFC activity was low, the level of dACC activity was related to performance outcome. These results demonstrate that dACC responds to attentional demand in a flexible manner that is dependent on the level of LDLPFC activity earlier in a trial. Overall, results were consistent with the temporal course of regional brain function proposed by the cascade-of-control model. Copyright 2009 Elsevier Inc. All rights reserved.

  6. Behavioral performance follows the time course of neural facilitation and suppression during cued shifts of feature-selective attention.

    Science.gov (United States)

    Andersen, S K; Müller, M M

    2010-08-03

    A central question in the field of attention is whether visual processing is a strictly limited resource, which must be allocated by selective attention. If this were the case, attentional enhancement of one stimulus should invariably lead to suppression of unattended distracter stimuli. Here we examine voluntary cued shifts of feature-selective attention to either one of two superimposed red or blue random dot kinematograms (RDKs) to test whether such a reciprocal relationship between enhancement of an attended and suppression of an unattended stimulus can be observed. The steady-state visual evoked potential (SSVEP), an oscillatory brain response elicited by the flickering RDKs, was measured in human EEG. Supporting limited resources, we observed both an enhancement of the attended and a suppression of the unattended RDK, but this observed reciprocity did not occur concurrently: enhancement of the attended RDK started at 220 ms after cue onset and preceded suppression of the unattended RDK by about 130 ms. Furthermore, we found that behavior was significantly correlated with the SSVEP time course of a measure of selectivity (attended minus unattended) but not with a measure of total activity (attended plus unattended). The significant deviations from a temporally synchronized reciprocity between enhancement and suppression suggest that the enhancement of the attended stimulus may cause the suppression of the unattended stimulus in the present experiment.

  7. Effects of aging, aphasia, and Parkinson’s disease on the time course of lemma selection during sentence production: evidence from eyetracking

    Directory of Open Access Journals (Sweden)

    Jiyeon Lee

    2015-05-01

    Full Text Available Sentence production involves intricate coordination of planning and speaking. In the word-by-word incremental model, speakers start their speech upon preparing a single lemma, taxing the pre-speech memory buffer minimally (deSmedt, 1990; Griffin, 2001; Kempen & Hoenkamp, 1987. Alternatively, speakers may prepare multiple words in advance, such as up to the verb (Ferreria, 2000; Lindsley, 1975 or the entire clause (Garret, 1982; Ford, 1982 to avoid producing disfluencies and momentary word retrieval difficulties during speech. Sentence production in young healthy speakers is largely incremental, with some strategic flexibility (Ferreira & Swets, 2000; Schriefers et al., 1998. However, how the time course of lexical selection during sentence production is affected in speakers with reduced cognitive-linguistic capacity remains unclear. The present study examined the effects of aging, aphasia, and Parkinson’s disease (PD on the time course of lemma selection during sentence production, using eyetracking. Data from a group of 16 young, 14 older, 12 PD, and 12 agrammatic aphasic speakers are reported. Young and aphasic speakers’ data are drawn from Lee, Yoshida, & Thompson (accepted to compare with PD and older speakers’ data. Participants described three object pictures (A, B, C using the sentence frame “the A and the B are above the C” (Griffin, 2001. Each picture’s codability (name agreement was manipulated to be high (clock or low (couch/sofa. Speakers experience increased lemma selection difficulty when naming low codable pictures, resulting in increased gaze durations. Participants’ gaze durations to each picture were measured and aligned with the speech onset of sentences to see ‘when’ each lemma was prepared. Results showed that aphasic and PD speakers produced significantly fewer target sentences than young and older speakers, with this difference pronounced only when sentences included low-codable pictures for the PD group

  8. Time course of cell death due to acoustic overstimulation in the mouse medial geniculate body and primary auditory cortex

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    Felix Frohlich

    2017-01-01

    Full Text Available It has previously been shown that acoustic overstimulation induces cell death and extensive cell loss in key structures of the central auditory pathway. A correlation between noise-induced apoptosis and cell loss was hypothesized for the cochlear nucleus and colliculus inferior. To determine the role of cell death in noise-induced cell loss in thalamic and cortical structures, the present mouse study (NMRI strain describes the time course following noise exposure of cell death mechanisms for the ventral medial geniculate body (vMGB, medial MGB (mMGB, and dorsal MGB (dMGB and the six histological layers of the primary auditory cortex (AI 1–6. Therefore, a terminal deoxynucleotidyl transferase dioxyuridine triphosphate nick-end labeling assay (TUNEL was performed in these structures 24 h, 7 days, and 14 days after noise exposure (3 h, 115 dB sound pressure level, 5–20 kHz, as well as in unexposed controls. In the dMGB, TUNEL was statistically significant elevated 24 h postexposure. AI-1 showed a decrease in TUNEL after 14 days. There was no statistically significant difference between groups for the other brain areas investigated. dMGB’s widespread connection within the central auditory pathway and its nontonotopical organization might explain its prominent increase in TUNEL compared to the other MGB subdivisions and the AI. It is assumed that the onset and peak of noise-induced cell death is delayed in higher areas of the central auditory pathway and takes place between 24 h and 7 days postexposure in thalamic and cortical structures.

  9. Time course of physiological, biochemical, and gene expression changes under short-term salt stress in Brassica juncea L.

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    Manish Pandey

    2017-06-01

    Full Text Available Salinity-imposed limitations on plant growth are manifested through osmotic and ionic imbalances. However, because salinity-induced responses vary considerably among crop plants, monitoring of such responses at an early stage has relevance. In this study, physiological (seed germination, seed vigor index, root length, shoot length, fresh weight, dry weight and biochemical attributes (osmoprotectants, K+/Na+ ratio were analyzed for a time-course assessment of salt responses in Indian mustard (Brassica juncea L. with an emphasis on early monitoring. The results showed strong correlations for total soluble sugars at germination phase (24 h, proline content in the seedling establishment phase (48 h and various physiological parameters including seed vigor index (R2 = 0.901, shoot length (R2 = 0.982, and fresh weight (R2 = 0.980 at 72 h (adaptation under stress. In addition, transcriptional changes were observed under NaCl treatment for key genes belonging to the family of selective ion transporters (NHX, HKT and abscisic acid synthesis (AAO-3. The status of mitochondrial respiration was also examined as a probe for salinity tolerance at an early stage. The results suggested that although all the analyzed parameters showed correlations (negative or positive with salt stress magnitude, their critical response times differed, with most of the studied biochemical, physiological, or molecular markers providing valuable information only after radicle emergence, whereas mitochondrial respiration via alternative oxidase was useful for the early detection of salt responses.

  10. Time course evaluation of N-nitrosodialkylamines-induced DNA alkylation and oxidation in liver of mosquito fish

    International Nuclear Information System (INIS)

    Chao, M.-R.; Chang, Y.-Z.; Wong, R.-H.; Hu, C.-W.

    2009-01-01

    Here we simultaneously measured N7-alkylguanines and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in liver of small fish, respectively, to assess the time course of the formation and removal of alkylation and oxidative damage to DNA caused by N-nitrosodialkylamines. Mosquito fish (Gambusia affinis) were killed at various times during (4 days) and post-exposure (16 days) to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) alone or their combination with concentrations of 10 and 50 mg/l. The modified guanine adducts were sensitively and selectively quantitated by isotope-dilution LC-MS/MS methods. During exposure, N7-methylguanine (N7-MeG) and N7-ethylguanine (N7-EtG) in liver DNA increased with the duration and dose of N-nitrosodialkylamine exposure, while 8-oxodG was dose-dependently induced within 1 day. It was found that NDMA formed substantially more N7-alkylated guanines and 8-oxodG than NDEA on the basis of adducts formed per micromolar concentration, suggesting that NDMA can be more easily bioactivated than NDEA to form reactive alkylating agents with the concomitant formation of oxygen radicals. After cessation of exposure, N7-alkylguanines remained elevated for 1 day and then gradually decreased over time but still higher than the background levels, even at day 16 (half-lives of 7-8 days). However, 8-oxodG was excised quickly from liver DNA and returned to the background level within 4 days post-exposure (half-lives less than 2 days). Taken together, this study firstly demonstrated that in addition to alkylation, N-nitrosodialkylamines can concurrently cause oxidative damage to DNA in vivo

  11. Time course evaluation of N-nitrosodialkylamines-induced DNA alkylation and oxidation in liver of mosquito fish

    Energy Technology Data Exchange (ETDEWEB)

    Chao, M -R [Department of Occupational Safety and Health, Chung Shan Medical University, Taichung 402, Taiwan (China); Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Y -Z [Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 402, Taiwan (China); Wong, R -H [Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan (China); Hu, C.-W. [Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan (China)], E-mail: windyhu@csmu.edu.tw

    2009-01-15

    Here we simultaneously measured N7-alkylguanines and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in liver of small fish, respectively, to assess the time course of the formation and removal of alkylation and oxidative damage to DNA caused by N-nitrosodialkylamines. Mosquito fish (Gambusia affinis) were killed at various times during (4 days) and post-exposure (16 days) to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) alone or their combination with concentrations of 10 and 50 mg/l. The modified guanine adducts were sensitively and selectively quantitated by isotope-dilution LC-MS/MS methods. During exposure, N7-methylguanine (N7-MeG) and N7-ethylguanine (N7-EtG) in liver DNA increased with the duration and dose of N-nitrosodialkylamine exposure, while 8-oxodG was dose-dependently induced within 1 day. It was found that NDMA formed substantially more N7-alkylated guanines and 8-oxodG than NDEA on the basis of adducts formed per micromolar concentration, suggesting that NDMA can be more easily bioactivated than NDEA to form reactive alkylating agents with the concomitant formation of oxygen radicals. After cessation of exposure, N7-alkylguanines remained elevated for 1 day and then gradually decreased over time but still higher than the background levels, even at day 16 (half-lives of 7-8 days). However, 8-oxodG was excised quickly from liver DNA and returned to the background level within 4 days post-exposure (half-lives less than 2 days). Taken together, this study firstly demonstrated that in addition to alkylation, N-nitrosodialkylamines can concurrently cause oxidative damage to DNA in vivo.

  12. The Effects of Money on Fake Rating Behavior in E-Commerce: Electrophysiological Time Course Evidence From Consumers

    Directory of Open Access Journals (Sweden)

    Cuicui Wang

    2018-03-01

    Full Text Available Online ratings impose significant effects on the behaviors of potential customers. Thus, online merchants try to adopt strategies that affect this rating behavior, and most of these strategies are connected to money, such as the strategies of returning cash coupons if a consumer gives a five-star rating (RI strategy, an acronym for “returning” and “if” or returning cash coupons directly with no additional requirements (RN strategy, an acronym for “returning” and “no”. The current study explored whether a certain strategy (RN or RI was more likely to give rise to false rating behaviors, as assessed by event-related potentials. A two-stimulus paradigm was used in this experiment. The first stimulus (S1 was the picture of a product with four Chinese characters that reflected the product quality (slightly defective vs. seriously defective vs. not defective, and the second stimulus (S2 displayed the coupon strategy (RN or RI. The participants were asked to decide whether or not to give a five-star rating. The behavioral results showed that the RI strategy led to a higher rate of five-star ratings than the RN strategy. For the electrophysiological time courses, the N1, N2, and LPP components were evaluated. The slightly defective products elicited a larger amplitude of the N1 component than the seriously defective and not-defective products, reflecting that perceptual difficulty was associated with the processing of the slightly defective products. The RI strategy evoked a less negative N2 and a more positive LPP than the RN strategy, indicating that the subjects perceived less conflict and experienced stronger incentives when processing the RI strategy. These findings will benefit future studies of fake online comments and provide evidence supporting the policy of forbidding the use of the RI strategy in e-commerce.

  13. Regular cannabis and alcohol use is associated with resting-state time course power spectra in incarcerated adolescents.

    Science.gov (United States)

    Thijssen, Sandra; Rashid, Barnaly; Gopal, Shruti; Nyalakanti, Prashanth; Calhoun, Vince D; Kiehl, Kent A

    2017-09-01

    Cannabis and alcohol are believed to have widespread effects on the brain. Although adolescents are at increased risk for substance use, the adolescent brain may also be particularly vulnerable to the effects of drug exposure due to its rapid maturation. Here, we examined the association between cannabis and alcohol use duration and resting-state functional connectivity in a large sample of male juvenile delinquents. The present sample was drawn from the Southwest Advanced Neuroimaging Cohort, Youth sample, and from a youth detention facility in Wisconsin. All participants were scanned at the maximum-security facilities using The Mind Research Network's 1.5T Avanto SQ Mobile MRI scanner. Information on cannabis and alcohol regular use duration was collected using self-report. Resting-state networks were computed using group independent component analysis in 201 participants. Associations with cannabis and alcohol use were assessed using Mancova analyses controlling for age, IQ, smoking and psychopathy scores in the complete case sample of 180 male juvenile delinquents. No associations between alcohol or cannabis use and network spatial maps were found. Longer cannabis use was associated with decreased low frequency power of the default mode network, the executive control networks (ECNs), and several sensory networks, and with decreased functional network connectivity. Duration of alcohol use was associated with decreased low frequency power of the right frontoparietal network, salience network, dorsal attention network, and several sensory networks. Our findings suggest that adolescent cannabis and alcohol use are associated with widespread differences in resting-state time course power spectra, which may persist even after abstinence. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Extracting Fluorescent Reporter Time Courses of Cell Lineages from High-Throughput Microscopy at Low Temporal Resolution

    Science.gov (United States)

    Downey, Mike J.; Jeziorska, Danuta M.; Ott, Sascha; Tamai, T. Katherine; Koentges, Georgy; Vance, Keith W.; Bretschneider, Till

    2011-01-01

    The extraction of fluorescence time course data is a major bottleneck in high-throughput live-cell microscopy. Here we present an extendible framework based on the open-source image analysis software ImageJ, which aims in particular at analyzing the expression of fluorescent reporters through cell divisions. The ability to track individual cell lineages is essential for the analysis of gene regulatory factors involved in the control of cell fate and identity decisions. In our approach, cell nuclei are identified using Hoechst, and a characteristic drop in Hoechst fluorescence helps to detect dividing cells. We first compare the efficiency and accuracy of different segmentation methods and then present a statistical scoring algorithm for cell tracking, which draws on the combination of various features, such as nuclear intensity, area or shape, and importantly, dynamic changes thereof. Principal component analysis is used to determine the most significant features, and a global parameter search is performed to determine the weighting of individual features. Our algorithm has been optimized to cope with large cell movements, and we were able to semi-automatically extract cell trajectories across three cell generations. Based on the MTrackJ plugin for ImageJ, we have developed tools to efficiently validate tracks and manually correct them by connecting broken trajectories and reassigning falsely connected cell positions. A gold standard consisting of two time-series with 15,000 validated positions will be released as a valuable resource for benchmarking. We demonstrate how our method can be applied to analyze fluorescence distributions generated from mouse stem cells transfected with reporter constructs containing transcriptional control elements of the Msx1 gene, a regulator of pluripotency, in mother and daughter cells. Furthermore, we show by tracking zebrafish PAC2 cells expressing FUCCI cell cycle markers, our framework can be easily adapted to different cell

  15. Extracting fluorescent reporter time courses of cell lineages from high-throughput microscopy at low temporal resolution.

    Directory of Open Access Journals (Sweden)

    Mike J Downey

    Full Text Available The extraction of fluorescence time course data is a major bottleneck in high-throughput live-cell microscopy. Here we present an extendible framework based on the open-source image analysis software ImageJ, which aims in particular at analyzing the expression of fluorescent reporters through cell divisions. The ability to track individual cell lineages is essential for the analysis of gene regulatory factors involved in the control of cell fate and identity decisions. In our approach, cell nuclei are identified using Hoechst, and a characteristic drop in Hoechst fluorescence helps to detect dividing cells. We first compare the efficiency and accuracy of different segmentation methods and then present a statistical scoring algorithm for cell tracking, which draws on the combination of various features, such as nuclear intensity, area or shape, and importantly, dynamic changes thereof. Principal component analysis is used to determine the most significant features, and a global parameter search is performed to determine the weighting of individual features. Our algorithm has been optimized to cope with large cell movements, and we were able to semi-automatically extract cell trajectories across three cell generations. Based on the MTrackJ plugin for ImageJ, we have developed tools to efficiently validate tracks and manually correct them by connecting broken trajectories and reassigning falsely connected cell positions. A gold standard consisting of two time-series with 15,000 validated positions will be released as a valuable resource for benchmarking. We demonstrate how our method can be applied to analyze fluorescence distributions generated from mouse stem cells transfected with reporter constructs containing transcriptional control elements of the Msx1 gene, a regulator of pluripotency, in mother and daughter cells. Furthermore, we show by tracking zebrafish PAC2 cells expressing FUCCI cell cycle markers, our framework can be easily adapted

  16. Cardiovascular alterations at different stages of hypertension development during ethanol consumption: Time-course of vascular and autonomic changes

    Energy Technology Data Exchange (ETDEWEB)

    Crestani, Carlos C. [Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, Univ. Estadual Paulista—UNESP (Brazil); Lopes da Silva, Andréia [Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Scopinho, América A. [Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Ruginsk, Silvia G.; Uchoa, Ernane T. [Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Correa, Fernando M.A. [Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Elias, Lucila L.K.; Antunes-Rodrigues, José [Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Resstel, Leonardo B.M., E-mail: leoresstel@yahoo.com.br [Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil)

    2014-10-15

    The aim of the present work was to establish a time-course correlation between vascular and autonomic changes that contribute to the development of hypertension during ethanol ingestion in rats. For this, male Wistar rats were subjected to the intake of increasing ethanol concentrations in their drinking water during four weeks. Ethanol effects were investigated at the end of each week. Mild hypertension was already observed at the first week of treatment, and a progressive blood pressure increase was observed along the evaluation period. Increased pressor response to phenylephrine was observed from first to fourth week. α{sub 1}-adrenoceptor protein in the mesenteric bed was enhanced at the first week, whereas β{sub 2}-adrenoceptor protein in the aorta was reduced after the second week. In the third week, ethanol intake facilitated the depressor response to sodium nitroprusside, whereas in the fourth week it reduced nitrate content in aorta and increased it plasma. The bradycardic component of the baroreflex was impaired, whereas baroreflex tachycardia was enhanced at the third and fourth weeks. AT{sub 1A} receptor and C-type natriuretic peptide (CNP) mRNAs in the nucleus tractus solitarius were increased at the fourth week. These findings suggest that increased vascular responsiveness to vasoconstrictor agents is possibly a link factor in the development and maintenance of the progressive hypertension induced by ethanol consumption. Additionally, baroreflex changes are possibly mediated by alterations in angiotensinergic mechanisms and CNP content within the brainstem, which contribute to maintaining the hypertensive state in later phases of ethanol ingestion. Facilitated vascular responsiveness to nitric oxide seems to counteract ethanol-induced hypertension. - Highlights: • Mild hypertension was observed during the entire period of ethanol ingestion. • Ethanol facilitated vascular reactivity to vasoactive agents. • Changes in baroreflex activity

  17. Time course and hemispheric lateralization effects of complex pitch processing: evoked magnetic fields in response to rippled noise stimuli.

    Science.gov (United States)

    Hertrich, Ingo; Mathiak, Klaus; Lutzenberger, Werner; Ackermann, Hermann

    2004-01-01

    To delineate the time course and processing stages of pitch encoding at the level of the supratemporal plane, the present study recorded evoked magnetic fields in response to rippled noise (RN) stimuli. RN largely masks simple tonotopic representations and addresses pitch processing within the temporal domain (periodicity encoding). Four dichotic stimulus types (111 or 133 Hz RN at one ear, white noise to the other one) were applied in randomized order during either visual distraction or selective auditory attention. Strictly periodic signals, noise-like events, and mixtures of both signals served as control conditions. (1) Attention-dependent ear x hemisphere interactions were observed within the time domain of the M50 field, indicating early streaming of auditory information. (2) M100 responses to strictly periodic stimuli were found lateralized to the right hemisphere. Furthermore, the higher-pitched stimuli yielded enhanced activation as compared to the lower-pitch signals (pitch scaling), conceivably reflecting sensory memory operations. (3) Besides right-hemisphere pitch scaling, the relatively late M100 component in association with the RN condition (latency = 136 ms) showed significantly stronger field strengths over the left hemisphere. Control experiments revealed this lateralization effect to be related to noise rather than pitch processing. Furthermore, subtle noise variations interacted with signal periodicity. Obviously, thus, complex task demands such as RN encoding give rise to functional segregation of auditory processing across the two hemispheres (left hemisphere: noise, right hemisphere: periodicity representation). The observed noise/periodicity interactions, furthermore, might reflect pitch-synchronous spectral evaluation at the level of the left supratemporal plane, triggered by right-hemisphere representation of signal periodicity. Copyright 2004 Elsevier Ltd.

  18. A spatio-temporal nonparametric Bayesian variable selection model of fMRI data for clustering correlated time courses.

    Science.gov (United States)

    Zhang, Linlin; Guindani, Michele; Versace, Francesco; Vannucci, Marina

    2014-07-15

    In this paper we present a novel wavelet-based Bayesian nonparametric regression model for the analysis of functional magnetic resonance imaging (fMRI) data. Our goal is to provide a joint analytical framework that allows to detect regions of the brain which exhibit neuronal activity in response to a stimulus and, simultaneously, infer the association, or clustering, of spatially remote voxels that exhibit fMRI time series with similar characteristics. We start by modeling the data with a hemodynamic response function (HRF) with a voxel-dependent shape parameter. We detect regions of the brain activated in response to a given stimulus by using mixture priors with a spike at zero on the coefficients of the regression model. We account for the complex spatial correlation structure of the brain by using a Markov random field (MRF) prior on the parameters guiding the selection of the activated voxels, therefore capturing correlation among nearby voxels. In order to infer association of the voxel time courses, we assume correlated errors, in particular long memory, and exploit the whitening properties of discrete wavelet transforms. Furthermore, we achieve clustering of the voxels by imposing a Dirichlet process (DP) prior on the parameters of the long memory process. For inference, we use Markov Chain Monte Carlo (MCMC) sampling techniques that combine Metropolis-Hastings schemes employed in Bayesian variable selection with sampling algorithms for nonparametric DP models. We explore the performance of the proposed model on simulated data, with both block- and event-related design, and on real fMRI data. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. The Effects of Money on Fake Rating Behavior in E-Commerce: Electrophysiological Time Course Evidence From Consumers.

    Science.gov (United States)

    Wang, Cuicui; Li, Yun; Luo, Xuan; Ma, Qingguo; Fu, Weizhong; Fu, Huijian

    2018-01-01

    Online ratings impose significant effects on the behaviors of potential customers. Thus, online merchants try to adopt strategies that affect this rating behavior, and most of these strategies are connected to money, such as the strategies of returning cash coupons if a consumer gives a five-star rating (RI strategy, an acronym for "returning" and "if") or returning cash coupons directly with no additional requirements (RN strategy, an acronym for "returning" and "no"). The current study explored whether a certain strategy (RN or RI) was more likely to give rise to false rating behaviors, as assessed by event-related potentials. A two-stimulus paradigm was used in this experiment. The first stimulus (S1) was the picture of a product with four Chinese characters that reflected the product quality (slightly defective vs. seriously defective vs. not defective), and the second stimulus (S2) displayed the coupon strategy (RN or RI). The participants were asked to decide whether or not to give a five-star rating. The behavioral results showed that the RI strategy led to a higher rate of five-star ratings than the RN strategy. For the electrophysiological time courses, the N1, N2, and LPP components were evaluated. The slightly defective products elicited a larger amplitude of the N1 component than the seriously defective and not-defective products, reflecting that perceptual difficulty was associated with the processing of the slightly defective products. The RI strategy evoked a less negative N2 and a more positive LPP than the RN strategy, indicating that the subjects perceived less conflict and experienced stronger incentives when processing the RI strategy. These findings will benefit future studies of fake online comments and provide evidence supporting the policy of forbidding the use of the RI strategy in e-commerce.

  20. Self-esteem modulates the time course of self-positivity bias in explicit self-evaluation.

    Science.gov (United States)

    Zhang, Hua; Guan, Lili; Qi, Mingming; Yang, Juan

    2013-01-01

    Researchers have suggested that certain individuals may show a self-positivity bias, rating themselves as possessing more positive personality traits than others. Previous evidence has shown that people evaluate self-related information in such a way as to maintain or enhance self-esteem. However, whether self-esteem would modulate the time course of self-positivity bias in explicit self-evaluation has never been explored. In the present study, 21 participants completed the Rosenberg self-esteem scale and then completed a task where they were instructed to indicate to what extent positive/negative traits described themselves. Behavioral data showed that participants endorsed positive traits as higher in self-relevance compared to the negative traits. Further, participants' self-esteem levels were positively correlated with their self-positivity bias. Electrophysiological data revealed smaller N1 amplitude and larger late positive component (LPC) amplitude to stimuli consistent with the self-positivity bias (positive-high self-relevant stimuli) when compared to stimuli that were inconsistent with the self-positivity bias (positive-low self-relevant stimuli). Moreover, only in individuals with low self-esteem, the latency of P2 was more pronounced in processing stimuli that were consistent with the self-positivity bias (negative-low self-relevant stimuli) than to stimuli that were inconsistent with the self-positivity bias (positive-low self-relevant stimuli). Overall, the present study provides additional support for the view that low self-esteem as a personality variable would affect the early attentional processing.

  1. The Effects of Money on Fake Rating Behavior in E-Commerce: Electrophysiological Time Course Evidence From Consumers

    Science.gov (United States)

    Wang, Cuicui; Li, Yun; Luo, Xuan; Ma, Qingguo; Fu, Weizhong; Fu, Huijian

    2018-01-01

    Online ratings impose significant effects on the behaviors of potential customers. Thus, online merchants try to adopt strategies that affect this rating behavior, and most of these strategies are connected to money, such as the strategies of returning cash coupons if a consumer gives a five-star rating (RI strategy, an acronym for “returning” and “if”) or returning cash coupons directly with no additional requirements (RN strategy, an acronym for “returning” and “no”). The current study explored whether a certain strategy (RN or RI) was more likely to give rise to false rating behaviors, as assessed by event-related potentials. A two-stimulus paradigm was used in this experiment. The first stimulus (S1) was the picture of a product with four Chinese characters that reflected the product quality (slightly defective vs. seriously defective vs. not defective), and the second stimulus (S2) displayed the coupon strategy (RN or RI). The participants were asked to decide whether or not to give a five-star rating. The behavioral results showed that the RI strategy led to a higher rate of five-star ratings than the RN strategy. For the electrophysiological time courses, the N1, N2, and LPP components were evaluated. The slightly defective products elicited a larger amplitude of the N1 component than the seriously defective and not-defective products, reflecting that perceptual difficulty was associated with the processing of the slightly defective products. The RI strategy evoked a less negative N2 and a more positive LPP than the RN strategy, indicating that the subjects perceived less conflict and experienced stronger incentives when processing the RI strategy. These findings will benefit future studies of fake online comments and provide evidence supporting the policy of forbidding the use of the RI strategy in e-commerce. PMID:29615851

  2. Chloride ions in the pore of glycine and GABA channels shape the time course and voltage dependence of agonist currents

    Science.gov (United States)

    Moroni, Mirko; Biro, Istvan; Giugliano, Michele; Vijayan, Ranjit; Biggin, Philip C.; Beato, Marco; Sivilotti, Lucia G.

    2011-01-01

    In the vertebrate CNS, fast synaptic inhibition is mediated by GABA and glycine receptors. We recently reported that the time course of these synaptic currents is slower when intracellular chloride is high. Here we extend these findings to measure the effects of both extracellular and intracellular chloride on the deactivation of glycine and GABA currents at both negative and positive holding potentials. Currents were elicited by fast agonist application to outside-out patches from HEK293 cells expressing rat glycine or GABA receptors. The slowing effect of high extracellular chloride on current decay was detectable only in low intracellular chloride (4 mM). Our main finding is that glycine and GABA receptors “sense” chloride concentrations because of interactions between the M2 pore-lining domain and the permeating ions. This hypothesis is supported by the observation that the sensitivity of channel gating to intracellular chloride is abolished if the channel is engineered to become cation-selective, or if positive charges in the external pore vestibule are eliminated by mutagenesis. The appropriate interaction between permeating ions and channel pore is also necessary to maintain the channel voltage sensitivity of gating, which prolongs current decay at depolarized potentials. Voltage-dependence is abolished by the same mutations that suppress the effect of intracellular chloride and also by replacing chloride with another permeant ion, thiocyanate. These observations suggest that permeant chloride affects gating by a foot-in-the-door effect, binding to a channel site with asymmetrical access from the intracellular and extracellular sides of the membrane. PMID:21976494

  3. Time-Course Analysis of Main Markers of Primary Infection in Cats with the Feline Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    B. Ribba

    2012-01-01

    Full Text Available Studies of the response of the immune system to feline immunodeficiency virus (FIV during primary infection have shown that a subpopulation of CD8+ T-cells with an activated phenotype and reduced expression of the CD8β chain (denoted CD8βlow T cells expands to reach up to 80% of the total CD8+ T cell count. The expansion of this subpopulation is considered to be a signature of FIV and an indicator of immune system alteration. We use a simple mathematical formalism to study the relationships over time between the dose of infection, the size of the CD8βlow population, and the circulating viral load in cats infected with FIV. Viremia profiles are described using a combination of two exponential laws, whereas the CD8βlow percentage (out of the total CD8+ population is represented by a Gompertz law including an expansion phase and a saturation phase. Model parameters are estimated with a population approach using data from 102 experimentally infected cats. We examine the dose of infection as a potential covariate of parameters. We find that the rates of increase of viral load and of CD8βlow percentage are both correlated with the dose of infection. Cats that develop strong acute viremia also show the largest degree of CD8βlow expansion. The two simple models are robust tools for analysing the time course of CD8βlow percentage and circulating viral load in FIV-infected cats and may be useful for generating new insights on the disease and on the design of therapeutic strategies, potentially applicable to HIV infection.

  4. Time course evaluation of N-nitrosodialkylamines-induced DNA alkylation and oxidation in liver of mosquito fish

    Energy Technology Data Exchange (ETDEWEB)

    Chao, M.-R. [Department of Occupational Safety and Health, Chung Shan Medical University, Taichung 402, Taiwan (China); Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Y.-Z. [Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 402, Taiwan (China); Wong, R.-H. [Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan (China); Hu, C.-W. [Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan (China)], E-mail: windyhu@csmu.edu.tw

    2009-01-15

    Here we simultaneously measured N7-alkylguanines and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in liver of small fish, respectively, to assess the time course of the formation and removal of alkylation and oxidative damage to DNA caused by N-nitrosodialkylamines. Mosquito fish (Gambusia affinis) were killed at various times during (4 days) and post-exposure (16 days) to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) alone or their combination with concentrations of 10 and 50 mg/l. The modified guanine adducts were sensitively and selectively quantitated by isotope-dilution LC-MS/MS methods. During exposure, N7-methylguanine (N7-MeG) and N7-ethylguanine (N7-EtG) in liver DNA increased with the duration and dose of N-nitrosodialkylamine exposure, while 8-oxodG was dose-dependently induced within 1 day. It was found that NDMA formed substantially more N7-alkylated guanines and 8-oxodG than NDEA on the basis of adducts formed per micromolar concentration, suggesting that NDMA can be more easily bioactivated than NDEA to form reactive alkylating agents with the concomitant formation of oxygen radicals. After cessation of exposure, N7-alkylguanines remained elevated for 1 day and then gradually decreased over time but still higher than the background levels, even at day 16 (half-lives of 7-8 days). However, 8-oxodG was excised quickly from liver DNA and returned to the background level within 4 days post-exposure (half-lives less than 2 days). Taken together, this study firstly demonstrated that in addition to alkylation, N-nitrosodialkylamines can concurrently cause oxidative damage to DNA in vivo.

  5. Time Course of Changes in Extravascular Lung Water Index, Intracranial and Cerebral Perfusion Pressures in Acute Cerebral Circulatory Disorders

    Directory of Open Access Journals (Sweden)

    Yu. A. Churlyaev

    2009-01-01

    Full Text Available Objective: to study the time course of changes in extravascular lung water index (ELWI and intracranial and cerebral perfusion pressures (ICP and CPP and to determine their possible relationships in acute cerebral circulatory disorders (ACCD. Subject and methods. ELWI, pulmonary vascular permeability index (PVPI, ICP, CPP, and central hemodynamics were studied by transpulmonary thermodilution and current X-ray studies were conducted in 18 patients on days 1, 3, 5, and 7 of ACCD. Results. Examinations revealed a supratentorial dislocation of the brain in 6 persons; its subtento-rial dislocation was found in 1 case; supra- and subtentorial dislocations were seen in 6. In patients, ELWI and PVPI increased from days 1 and 5, respectively. The high baseline ICP increased over time. CPP remained unchanged. Preserved left ventricular contractility, enhanced myocardial one, a significant direct correlation between ELWI and PVPI, as well as their increase confirmed that the noncardiogenic genesis was responsible for increased ELWI. A direct significant correlation was found between ICP and ELWI, ICP and PVPI. Against this background, acute respiratory distress syndrome developed in 14 patients with pneumonia evolving in its presence in 7 patients. Conclusion. In ACCD, ELWI increases in the first 24 hours of the acute period. One of its causes is, along with others, primary and/or secondary damage to the brainstem structures with elevated ICP and progressive brain dislocation. The determination of ICP, unlike CPP, is crucial in the diagnosis and treatment of primary/secondary brain injuries and in prognosis. Key words: acute cerebral circulatory disorder, extravascular lung fluid, pulmonary vascular permeability, intracranial pressure, cerebral perfusion pressure, acute respiratory distress syndrome.

  6. Time Course of Peri-Implant Bone Regeneration around Loaded and Unloaded Implants in a Rat Model

    Science.gov (United States)

    Jariwala, Shailly H.; Wee, Hwabok; Roush, Evan P.; Whitcomb, Tiffany L.; Murter, Christopher; Kozlansky, Gery; Lakhtakia, Akhlesh; Kunselman, Allen R.; Donahue, Henry J.; Armstrong, April D.; Lewis, Gregory S.

    2018-01-01

    The time-course of cancellous bone regeneration surrounding mechanically loaded implants affects implant fixation, and is relevant to determining optimal rehabilitation protocols following orthopaedic surgeries. We investigated the influence of controlled mechanical loading of titanium-coated polyether-ether ketone (PEEK) implants on osseointegration using time-lapsed, non-invasive, in vivo micro-computed tomography (micro-CT) scans. Implants were inserted into proximal tibial metaphyses of both limbs of eight female Sprague-Dawley rats. External cyclic loading (60 μm or 100 μm displacement, 1 Hz, 60 seconds) was applied every other day for 14 days to one implant in each rat, while implants in contralateral limbs served as the unloaded controls. Hind limbs were imaged with high-resolution micro-CT (12.5 μm voxel size) at 2, 5, 9, and 12 days post-surgery. Trabecular changes over time were detected by 3D image registration allowing for measurements of bone-formation rate (BFR) and bone-resorption rate (BRR). At day 9, mean %BV/TV for loaded and unloaded limbs were 35.5 ± 10.0 % and 37.2 ± 10.0 %, respectively, and demonstrated significant increases in bone volume compared to day 2. BRR increased significantly after day 9. No significant differences between bone volumes, BFR, and BRR were detected due to implant loading. Although not reaching significance (p = 0.16), an average 119 % increase in pull-out strength was measured in the loaded implants. PMID:27381807

  7. Time course of surface characteristics of alkali- and heat-treated titanium dental implants during vacuum storage.

    Science.gov (United States)

    Kamo, Michimasa; Kyomoto, Masayuki; Miyaji, Fumiaki

    2017-08-01

    Current efforts to shorten the healing times of life-long dental implants and prevent their fouling by organic impurities have focused on using surface-modification treatments and alternative packaging, respectively. In this study, we investigated the time course of the surface characteristics, including the wettability, a protein-adsorption and apatite-formation abilities, of alkali- and heat-treated (AH-treated) Ti samples during storage in vacuum over a period of 52 weeks. The AH treatment resulted in the formation of a nanometer-scale needle-like rougher surface of the Ti samples. Although the water contact angle of the AH-treated Ti sample increased slightly, it remained as low as approximately 10° even after storage in vacuum for 52 weeks. There was no significant difference in the protein-adsorption and apatite-formation abilities of the AH-treated Ti sample before and after storage. Further, the AH-treated Ti sample exhibited greater protein-adsorption and apatite-formation abilities compared with the untreated one; regardless of the samples stored in vacuum or not. Apatite formed only on the AH-treated Ti surface. Therefore, subjecting Ti dental implants to the AH treatment and storing them in vacuum should help prevent their surfaces from getting contaminated. Further, it is expected that AH-treated Ti dental implants controllably aged during a shelf storage will exhibit high stability and bone-bonding bioactivity. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1453-1460, 2017. © 2016 Wiley Periodicals, Inc.

  8. Comparison of trophic factors' expression between paralyzed and recovering muscles after facial nerve injury. A quantitative analysis in time course.

    Science.gov (United States)

    Grosheva, Maria; Nohroudi, Klaus; Schwarz, Alisa; Rink, Svenja; Bendella, Habib; Sarikcioglu, Levent; Klimaschewski, Lars; Gordon, Tessa; Angelov, Doychin N

    2016-05-01

    After peripheral nerve injury, recovery of motor performance negatively correlates with the poly-innervation of neuromuscular junctions (NMJ) due to excessive sprouting of the terminal Schwann cells. Denervated muscles produce short-range diffusible sprouting stimuli, of which some are neurotrophic factors. Based on recent data that vibrissal whisking is restored perfectly during facial nerve regeneration in blind rats from the Sprague Dawley (SD)/RCS strain, we compared the expression of brain derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF2), insulin growth factors 1 and 2 (IGF1, IGF2) and nerve growth factor (NGF) between SD/RCS and SD-rats with normal vision but poor recovery of whisking function after facial nerve injury. To establish which trophic factors might be responsible for proper NMJ-reinnervation, the transected facial nerve was surgically repaired (facial-facial anastomosis, FFA) for subsequent analysis of mRNA and proteins expressed in the levator labii superioris muscle. A complicated time course of expression included (1) a late rise in BDNF protein that followed earlier elevated gene expression, (2) an early increase in FGF2 and IGF2 protein after 2 days with sustained gene expression, (3) reduced IGF1 protein at 28 days coincident with decline of raised mRNA levels to baseline, and (4) reduced NGF protein between 2 and 14 days with maintained gene expression found in blind rats but not the rats with normal vision. These findings suggest that recovery of motor function after peripheral nerve injury is due, at least in part, to a complex regulation of lesion-associated neurotrophic factors and cytokines in denervated muscles. The increase of FGF-2 protein and concomittant decrease of NGF (with no significant changes in BDNF or IGF levels) during the first week following FFA in SD/RCS blind rats possibly prevents the distal branching of regenerating axons resulting in reduced poly-innervation of motor endplates. Copyright

  9. Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization.

    Science.gov (United States)

    Pogrmic-Majkic, Kristina; Samardzija, Dragana; Fa, Svetlana; Hrubik, Jelena; Glisic, Branka; Kaisarevic, Sonja; Andric, Nebojsa

    2014-11-01

    Premature luteinization is a possible cause of infertility in women. It is currently unknown whether environmental chemicals can induce changes associated with premature luteinization. Using rat granulosa cells (GC) in vitro, we demonstrated that exposure to atrazine (ATR), a widely used herbicide, causes GC phenotype that resembles that of human premature luteinization. At the end of the 48-h stimulation with FSH, ATR-exposed GC showed (1) higher levels of progesterone, (2) overexpression of luteal markers (Star and Cyp11a1), and (3) an increase in progesterone:estradiol ratio above 1. Mechanistic experiments were conducted to understand the signaling events engaged by ATR that lead to this phenotype. Western blot analysis revealed prolonged phosphorylation of protein kinase B (AKT) and cAMP response element-binding protein (CREB) in ATR- and FSH-exposed GC. An increased level of ERK1/2-dependent transcriptional factor CCATT/enhancer-binding protein beta (CEBPB) was observed after 4 h of ATR exposure. Inhibitors of PI3K (wortmannin) and MEK (U0126) prevented ATR-induced rise in progesterone level and expression of luteal markers in FSH-stimulated GC. Atrazine intensified AKT and CEBPB signaling and caused Star overexpression in forskolin-stimulated GC but not in epidermal growth factor (EGF)-stimulated GC. In the presence of rolipram, a specific inhibitor of phosphodiesterase 4 (PDE4), ATR was not able to further elevate AKT phosphorylation, CEBPB protein level, and Star mRNA in FSH-stimulated GC, suggesting that ATR inhibits PDE4. Overall, this study showed that ATR acts as a FSH sensitizer leading to enhanced cAMP, AKT, and CEBPB signaling and progesterone biosynthesis, which promotes premature luteinization phenotype in GC. © 2014 by the Society for the Study of Reproduction, Inc.

  10. The gene expression and immunohistochemical time-course of diphenylcyclopropenone-induced contact allergy in healthy humans following repeated epicutaneous challenges

    DEFF Research Database (Denmark)

    Mose, Kristian F; Burton, Mark; Thomassen, Mads

    2017-01-01

    DPCP challenges to find the predominant gene expression pattern, (ii) the time-course of cell infiltration following repeated DPCP challenges and (iii) the transcriptome of a repeated CA exposure model. We obtained punch biopsies from control and DPCP-exposed skin from ten DPCP sensitized individuals...

  11. Time Course of Visual Attention in Infant Categorization of Cats versus Dogs: Evidence for a Head Bias as Revealed through Eye Tracking

    Science.gov (United States)

    Quinn, Paul C.; Doran, Matthew M.; Reiss, Jason E.; Hoffman, James E.

    2009-01-01

    Previous looking time studies have shown that infants use the heads of cat and dog images to form category representations for these animal classes. The present research used an eye-tracking procedure to determine the time course of attention to the head and whether it reflects a preexisting bias or online learning. Six- to 7-month-olds were…

  12. Time course of action of sugammadex (Org 25969) on rocuronium-induced block in the Rhesus monkey, using a simple model of equilibration of complex formation.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Driessen, J.J.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Reversal of neuromuscular block can be accomplished by chemical encapsulation of rocuronium by sugammadex (Org 25969), a synthetic gamma-cyclodextrin derivative. The present study determined the time course of the reversal action of sugammadex on rocuronium-induced block in the

  13. Spasticity and contractures at the wrist after stroke: time course of development and their association with functional recovery of the upper limb

    NARCIS (Netherlands)

    Malhotra, S.; Malhotra, S.; Pandyan, A.D.; Rosewilliam, S.; Roffe, C.; Hermens, Hermanus J.

    Objective: To investigate the time course of development of spasticity and contractures at the wrist after stroke and to explore if these are associated with upper limb functional recovery. - Design: Longitudinal observational study using secondary data from the control group of a randomized

  14. Time course study of in situ expression of antigens following DNA-vaccination against VHS in rainbow trout (Oncorhynchus mykiss Walbaum) fry

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Lorenzen, Niels; Einer-Jensen, Katja

    2005-01-01

    The present study was performed as a time course study of fish vaccinated with 20 mu g plasmid DNA vaccine encoding either the VHSV G-protein or the VHSV N-protein. Samples of the injection site were collected sequentially over a 7-week period. The study revealed an intense positive staining by i...

  15. Dose-response and time-course of neurotoxicity and tissue concentrations of carbaryl in Brown Norway rats from preweaning to senescence.

    Science.gov (United States)

    Factors impacting sensitivity to chemicals across life stages include toxicokinetic and toxicodynamic changes. We systematically compared the dose-response (3, 7.5, 15,22.5 mg/kg) and time-course (3 or 15 mg/kg at 30, 60, 120, 240 min) of acute effects of carbaryl (oral gavage) i...

  16. Time course of ocular surface and lacrimal gland changes in a new scopolamine-induced dry eye model.

    Science.gov (United States)

    Viau, Sabrina; Maire, Marie-Annick; Pasquis, Bruno; Grégoire, Stéphane; Fourgeux, Cynthia; Acar, Niyazi; Bretillon, Lionel; Creuzot-Garcher, Catherine P; Joffre, Corinne

    2008-06-01

    The aim of this study was to set up an animal model of dry eye showing disturbance in several components of the lacrimal functional unit, and to describe the time course of the appearance of clinical signs and inflammatory markers. Dry eye was induced in 6-week-old female Lewis rats by a systemic and continuous delivery of scopolamine via osmotic pumps implanted subcutaneously. We first determined the appropriate dose of scopolamine (6, 12.5, or 25 mg/day) for 28 days. In a second set of experiments, we determined markers after 1, 2, 3, 7, 10, 17, or 28 days of a 12.5-mg/day dose. Clinical signs of corneal dryness were evaluated in vivo using fluorescein staining. MHC II expression and mucin Muc5AC production were detected on the conjunctival epithelium using immunostaining. The level of IL-1beta, IL-6, TNF-alpha, and IFN-gamma mRNA was evaluated by real-time polymerase chain reaction in conjunctiva and exorbital lacrimal gland (LG). Lipids were extracted from the exorbital LG for fatty acid analysis. Daily scopolamine doses of 12.5 mg and 25 mg applied for a 28-day period induced keratitis, a decrease in Muc5AC immunostaining density in the conjunctival epithelium, and modifications in the fatty acid composition of the exorbital LG. Animals treated with a 12.5-mg/day dose of scopolamine exhibited an increase in corneal fluorescein staining after 2, 10, and 28 days. All animals exhibited unilateral or bilateral keratitis after 17 days. In the conjunctival epithelium, a significant decrease in Muc5AC immunostaining density was observed at early and late time points, and MHC II expression tended to be increased after 1, 7, 10, and 28 days, without reaching statistical significance. The levels of TNF-alpha, IL-1beta and IL-6 mRNA were increased with scopolamine treatment in both conjunctiva and exorbital LG. Arachidonic acid and the Delta5 desaturase index were significantly increased in the exorbital LG of dry eye animals at each time point. This systemic and

  17. Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur

    International Nuclear Information System (INIS)

    Padilla, S.; Marshall, R.S.; Hunter, D.L.; Lowit, A.

    2007-01-01

    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n = 4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r 2 = 0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r 2 = 0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides

  18. Identification of human circadian genes based on time course gene expression profiles by using a deep learning method.

    Science.gov (United States)

    Cui, Peng; Zhong, Tingyan; Wang, Zhuo; Wang, Tao; Zhao, Hongyu; Liu, Chenglin; Lu, Hui

    2018-06-01

    Circadian genes express periodically in an approximate 24-h period and the identification and study of these genes can provide deep understanding of the circadian control which plays significant roles in human health. Although many circadian gene identification algorithms have been developed, large numbers of false positives and low coverage are still major problems in this field. In this study we constructed a novel computational framework for circadian gene identification using deep neural networks (DNN) - a deep learning algorithm which can represent the raw form of data patterns without imposing assumptions on the expression distribution. Firstly, we transformed time-course gene expression data into categorical-state data to denote the changing trend of gene expression. Two distinct expression patterns emerged after clustering of the state data for circadian genes from our manually created learning dataset. DNN was then applied to discriminate the aperiodic genes and the two subtypes of periodic genes. In order to assess the performance of DNN, four commonly used machine learning methods including k-nearest neighbors, logistic regression, naïve Bayes, and support vector machines were used for comparison. The results show that the DNN model achieves the best balanced precision and recall. Next, we conducted large scale circadian gene detection using the trained DNN model for the remaining transcription profiles. Comparing with JTK_CYCLE and a study performed by Möller-Levet et al. (doi: https://doi.org/10.1073/pnas.1217154110), we identified 1132 novel periodic genes. Through the functional analysis of these novel circadian genes, we found that the GTPase superfamily exhibits distinct circadian expression patterns and may provide a molecular switch of circadian control of the functioning of the immune system in human blood. Our study provides novel insights into both the circadian gene identification field and the study of complex circadian-driven biological

  19. Time-course of cadmium-induced acute hepatotoxicity in the rat liver: the role of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Tzirogiannis, Konstantinos N.; Panoutsopoulos, Georgios I.; Hereti, Rosa I.; Alexandropoulou, Katerina N.; Basayannis, Aristidis C.; Mykoniatis, Michael G. [Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias St., 115 27, Athens (Greece); Demonakou, Maria D. [Histopathology Laboratory, Sismanoglion G.D. Hospital, Sismanogliou 1, Marousi, Attiki 151 27 (Greece)

    2003-12-01

    Exposure to toxic metals and pollutants is a major environmental problem. Cadmium is a metal causing acute hepatic injury but the mechanism of this phenomenon is poorly understood. In the present study, we investigated the mechanism and time-course of cadmium-induced liver injury in rats, with emphasis being placed on apoptosis in parenchymal and nonparenchymal liver cells. Cadmium (3.5 mg/kg body weight) was injected intraperitoneally and the rats were killed 0, 9, 12, 16, 24, 48 and 60 h later. The extent of liver injury was evaluated for necrosis, apoptosis, peliosis, mitoses and inflammatory infiltration in hematoxylin-eosin-stained liver sections, and by assaying serum enzyme activities. The number of cells that died via apoptosis was quantified by TUNEL assay. The identification of nonparenchymal liver cells and activated Kupffer cells was performed histochemically. Liver regeneration was evaluated by assaying the activity of liver thymidine kinase and by the rate of {sup 3}H-thymidine incorporation into DNA. Both cadmium-induced necrotic cell death and parenchymal cell apoptosis showed a biphasic elevation at 12 and 48 h and peaked at 48 and 12 h, respectively. Nonparenchymal cell apoptosis peaked at 48 h. Peliosis hepatis, another characteristic form of liver injury, was first observed at 16 h and, at all time points, closely correlated with the apoptotic index of nonparenchymal liver cells, where the lesion was also maximial at 48 h. Kupffer cell activation and neutrophil infiltration were minimal for all time points examined. Based on thymidine kinase activity, liver regeneration was found to discern a classic biphasic peak pattern at 12 and 48 h. It was very interesting to observe that cadmium-induced liver injury did not involve inflammation at any time point. Apoptosis seems to be a major mechanism for the removal of damaged cells, and constitutes the major type of cell death in nonparenchymal liver cells. Apoptosis of nonparenchymal cells is the basis

  20. Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: a potential paradigm shift

    Directory of Open Access Journals (Sweden)

    Leif eHertz

    2015-02-01

    Full Text Available It is firmly believed that the mechanism of action of SSRIs in major depression is to inhibit the serotonin transporter, SERT, and increase extracellular concentration of serotonin. However, this undisputed observation does not prove that SERT inhibition is the mechanism, let alone the only mechanism, by which SSRI’s exert their therapeutic effects. It has recently been demonstrated that 5-HT2B receptor stimulation is needed for the antidepressant effect of fluoxetine in vivo. The ability of all 5 currently used SSRIs to stimulate the 5-HT2B receptor equipotentially incultured astrocyteshas been known for several years,and increasing evidence has shown the importance of astrocytes and astrocyte-neuronal interactions for neuroplasticity and complex brain activity. This paper reviews acute and chronic effects of 5-HT2B receptor stimulation in cultured astrocytes and in astrocytes freshly isolated from brains of mice treated with fluoxetine for 14 daystogether with effects ofanti-depressant therapy on turnover of glutamate and GABA and metabolism of glucose and glycogen. It is suggested that these events are causally related to the mechanism of action of SSRIs and of interest for development of newer antidepressant drugs.

  1. Multiple sources of 1,2-diacylglycerol in isolated rat pancreatic acini stimulated by cholecystokinin. Involvement of phosphatidylinositol bisphosphate and phosphatidylcholine hydrolysis

    International Nuclear Information System (INIS)

    Matozaki, T.; Williams, J.A.

    1989-01-01

    Changes in the cellular content of 1,2-diacylglycerol (DAG) in isolated rat pancreatic acini in response to agonist stimulation were studied using a sensitive mass assay. When acini were stimulated by 10 nM COOH-terminal cholecystokinin-octapeptide (CCK8), the increase in DAG was biphasic, consisting of an early peak at 5 s and a second, larger, gradual increase that was maximal by 15 min. The basal level of DAG in acini was 1.04 nmol/mg of protein, which was increased to 1.24 nmol/mg of protein at 5 s and 2.76 nmol/mg of protein at 30 min. In comparison, the increase in DAG stimulated by 30 pM CCK8, a submaximal concentration for amylase release, was monophasic, increasing without an early peak but sustained to 60 min. Other Ca2+-mobilizing secretagogues such as carbamylcholine and bombesin increased DAG in acini, whereas vasoactive intestinal peptide, which acts to increase cAMP, had no effect. Phorbol ester and Ca2+ ionophore also stimulated DAG production. Analysis of the mass level of inositol 1,4,5-trisphosphate (1,4,5-IP3) showed that the generation of 1,4,5-IP3 stimulated by 10 nM CCK8 peaked at 5 s, a finding consistent with the early peak of DAG. The basal level was 4.7 pmol/mg of protein, which was increased to 144.6 pmol/mg of protein at 5 s by 10 nM CCK8. The levels of 1,4,5-IP3 then returned toward basal in contrast to the gradual and sustained increase of DAG. The dose dependencies of 1,4,5-IP3 and DAG formation at 5 s with respect to CCK8 were almost identical. This suggests that phosphatidylinositol 4,5-bisphosphate hydrolysis is a major source of the early increase in DAG but not of the sustained increase in DAG. Therefore, a possible contribution of phosphatidylcholine hydrolysis to DAG formation was examined utilizing acini prelabeled with [3H]choline. CCK8 (1 nM) maximally increased [3H]choline metabolite release by 133% of control at 30 min

  2. A case study on identification of airborne organic compounds and time courses of their concentrations in the cabin of a new car for private use.

    Science.gov (United States)

    Yoshida, Toshiaki; Matsunaga, Ichiro

    2006-01-01

    The cabin of an automobile can be considered to be a part of the living environment because many people spend long periods of time during business, shopping, recreation or travel activities. However, little is known about the interior air contamination due to organic compounds diffusing from the interior materials used in the interior of automobiles. In the present study, the compounds in the interior air of a new car were identified, and the time courses of their concentrations were examined for over 3 years after the delivery (July, 1999). A total of 162 organic compounds, involving many aliphatic hydrocarbons and aromatic hydrocarbons, were identified. High concentrations of n-nonane (458 microg/m(3) on the day following delivery), n-decane (1301 microg/m(3)), n-undecane (1616 microg/m(3)), n-dodecane (716 microg/m(3)), n-tridecane (320 microg/m(3)), 1-hexadecene (768 microg/m(3)), ethylbenzene (361 microg/m(3)), xylene (4003 microg/m(3)) and 2,2'-azobis(isobutyronitrile) (429 microg/m(3)) were detected, and the sum of the concentrations determined for all compounds excluding formaldehyde (TVOC) was approximately 14 mg/m(3) on the day after the delivery. The concentrations of most compounds decreased with time, but increased with a rise of the interior temperature. The TVOC concentration in the next summer (July, 2000) was approximately one-tenth of the initial concentration. During the 3-year study period, the TVOC concentrations in summer exceeded the indoor guideline value (300 mug/m(3)) proposed by [Seifert B. Volatile organic compounds. In: Maroni M, Seifert B, Lindvall T, editors. Indoor air quality. A comprehensive reference book. Air quality monographs, vol. 3. Netherlands: Elsevier Science; 1995. p. 819-21]. The interior temperature and days lapsed after delivery were the main factors affecting the interior concentrations of most compounds according to multiple linear regression analysis. The results of this study offer useful fundamental data for

  3. A distributed current stimulator ASIC for high density neural stimulation.

    Science.gov (United States)

    Jeong Hoan Park; Chaebin Kim; Seung-Hee Ahn; Tae Mok Gwon; Joonsoo Jeong; Sang Beom Jun; Sung June Kim

    2016-08-01

    This paper presents a novel distributed neural stimulator scheme. Instead of a single stimulator ASIC in the package, multiple ASICs are embedded at each electrode site for stimulation with a high density electrode array. This distributed architecture enables the simplification of wiring between electrodes and stimulator ASIC that otherwise could become too complex as the number of electrode increases. The individual ASIC chip is designed to have a shared data bus that independently controls multiple stimulating channels. Therefore, the number of metal lines is determined by the distributed ASICs, not by the channel number. The function of current steering is also implemented within each ASIC in order to increase the effective number of channels via pseudo channel stimulation. Therefore, the chip area can be used more efficiently. The designed chip was fabricated with area of 0.3 mm2 using 0.18 μm BCDMOS process, and the bench-top test was also conducted to validate chip performance.

  4. The impact of farmers’ participation in field trials in creating awareness and stimulating compliance with the World Health Organization’s farm-based multiple-barrier approach

    DEFF Research Database (Denmark)

    Amponsah, Owusu; Vigre, Håkan; Schou, Torben Wilde

    2016-01-01

    -barrier approach field trials. The results of the study show that participation in the field trials has statistically significant effects on farmers’ awareness of the farm-based multiple-barrier approach. Compliance has, however, been undermined by the farmers’ perception that the cost of compliance is more......The results of a study aimed as assessing the extent to which urban vegetable farmers’ participation in field trials can impact on their awareness and engender compliance with the World Health Organization’s farm-based multiple-barrier approach are presented in this paper. Both qualitative...... and quantitative approaches have been used in this paper. One hundred vegetable farmers and four vegetable farmers’ associations in the Kumasi Metropolis in Ghana were covered. The individual farmers were grouped into two, namely: (1) participants and (2) non-participants of the farm-based multiple...

  5. A correction method for systematic error in (1)H-NMR time-course data validated through stochastic cell culture simulation.

    Science.gov (United States)

    Sokolenko, Stanislav; Aucoin, Marc G

    2015-09-04

    The growing ubiquity of metabolomic techniques has facilitated high frequency time-course data collection for an increasing number of applications. While the concentration trends of individual metabolites can be modeled with common curve fitting techniques, a more accurate representation of the data needs to consider effects that act on more than one metabolite in a given sample. To this end, we present a simple algorithm that uses nonparametric smoothing carried out on all observed metabolites at once to identify and correct systematic error from dilution effects. In addition, we develop a simulation of metabolite concentration time-course trends to supplement available data and explore algorithm performance. Although we focus on nuclear magnetic resonance (NMR) analysis in the context of cell culture, a number of possible extensions are discussed. Realistic metabolic data was successfully simulated using a 4-step process. Starting with a set of metabolite concentration time-courses from a metabolomic experiment, each time-course was classified as either increasing, decreasing, concave, or approximately constant. Trend shapes were simulated from generic functions corresponding to each classification. The resulting shapes were then scaled to simulated compound concentrations. Finally, the scaled trends were perturbed using a combination of random and systematic errors. To detect systematic errors, a nonparametric fit was applied to each trend and percent deviations calculated at every timepoint. Systematic errors could be identified at time-points where the median percent deviation exceeded a threshold value, determined by the choice of smoothing model and the number of observed trends. Regardless of model, increasing the number of observations over a time-course resulted in more accurate error estimates, although the improvement was not particularly large between 10 and 20 samples per trend. The presented algorithm was able to identify systematic errors as small

  6. Comparing the Efficacy of Excitatory Transcranial Stimulation Methods Measuring Motor Evoked Potentials

    Directory of Open Access Journals (Sweden)

    Vera Moliadze

    2014-01-01

    Full Text Available The common aim of transcranial stimulation methods is the induction or alterations of cortical excitability in a controlled way. Significant effects of each individual stimulation method have been published; however, conclusive direct comparisons of many of these methods are rare. The aim of the present study was to compare the efficacy of three widely applied stimulation methods inducing excitability enhancement in the motor cortex: 1 mA anodal transcranial direct current stimulation (atDCS, intermittent theta burst stimulation (iTBS, and 1 mA transcranial random noise stimulation (tRNS within one subject group. The effect of each stimulation condition was quantified by evaluating motor-evoked-potential amplitudes (MEPs in a fixed time sequence after stimulation. The analyses confirmed a significant enhancement of the M1 excitability caused by all three types of active stimulations compared to sham stimulation. There was no significant difference between the types of active stimulations, although the time course of the excitatory effects slightly differed. Among the stimulation methods, tRNS resulted in the strongest and atDCS significantly longest MEP increase compared to sham. Different time courses of the applied stimulation methods suggest different underlying mechanisms of action. Better understanding may be useful for better targeting of different transcranial stimulation techniques.

  7. Experimental hyperthyroidism in rats increases the expression of the ubiquitin ligases atrogin-1 and MuRF1 and stimulates multiple proteolytic pathways in skeletal muscle.

    Science.gov (United States)

    O'Neal, Patrick; Alamdari, Nima; Smith, Ira; Poylin, Vitaliy; Menconi, Michael; Hasselgren, Per-Olof

    2009-11-01

    Muscle wasting is commonly seen in patients with hyperthyroidism and is mainly caused by stimulated muscle proteolysis. Loss of muscle mass in several catabolic conditions is associated with increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF1 but it is not known if atrogin-1 and MuRF1 are upregulated in hyperthyroidism. In addition, it is not known if thyroid hormone increases the activity of proteolytic mechanisms other than the ubiquitin-proteasome pathway. We tested the hypotheses that experimental hyperthyroidism in rats, induced by daily intraperitoneal injections of 100 microg/100 g body weight of triiodothyronine (T3), upregulates the expression of atrogin-1 and MuRF1 in skeletal muscle and stimulates lysosomal, including cathepsin L, calpain-, and caspase-3-dependent protein breakdown in addition to proteasome-dependent protein breakdown. Treatment of rats with T3 for 3 days resulted in an approximately twofold increase in atrogin-1 and MuRF1 mRNA levels. The same treatment increased proteasome-, cathepsin L-, and calpain-dependent proteolytic rates by approximately 40% but did not influence caspase-3-dependent proteolysis. The expression of atrogin-1 and MuRF1 remained elevated during a more prolonged period (7 days) of T3 treatment. The results provide support for a role of the ubiquitin-proteasome pathway in muscle wasting during hyperthyroidism and suggest that other proteolytic pathways as well may be activated in the hyperthyroid state. (c) 2009 Wiley-Liss, Inc.

  8. BioCichlid: central dogma-based 3D visualization system of time-course microarray data on a hierarchical biological network.

    Science.gov (United States)

    Ishiwata, Ryosuke R; Morioka, Masaki S; Ogishima, Soichi; Tanaka, Hiroshi

    2009-02-15

    BioCichlid is a 3D visualization system of time-course microarray data on molecular networks, aiming at interpretation of gene expression data by transcriptional relationships based on the central dogma with physical and genetic interactions. BioCichlid visualizes both physical (protein) and genetic (regulatory) network layers, and provides animation of time-course gene expression data on the genetic network layer. Transcriptional regulations are represented to bridge the physical network (transcription factors) and genetic network (regulated genes) layers, thus integrating promoter analysis into the pathway mapping. BioCichlid enhances the interpretation of microarray data and allows for revealing the underlying mechanisms causing differential gene expressions. BioCichlid is freely available and can be accessed at http://newton.tmd.ac.jp/. Source codes for both biocichlid server and client are also available.

  9. The time-course relationship between endogenous spleen colony formation and marrow cellularity after midlethal irradiation of mice

    International Nuclear Information System (INIS)

    Koch, I.; Wiktor-Jedrzejczak, W.; Wojskowa Akademia Medyczna, Warsaw

    1981-01-01

    The kinetics of appearance and disappearance of endogenous spleen colonies following 4 and 6 Gy of X-irradiation was compared with the kinetics of changes of cellular contents of femur cavities. Additionally, the effect of postirradiation bleeding and this way of the subsequent increase in the level of endogenous erythropoietin was studied. It was found that the kinetics of endogenous haemopoietic recovery in the marrow follows the same characteristic biphasic pattern as in the spleen although it is slightly delayed in time. First wave of regeneration corresponded in time with the formation of transient endogenous spleen colonies 4-7 days postirradiation, and the 2nd wave corresponded in time witn the formation of classical haemopoietic stem-cell derived endogenous spleen colonies 9-12 days following irradiation. Postirradiation bleeding markedly stimulated particularly the first wave of regeneration both in the marrow and in the spleen. (orig.) [de

  10. A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles

    OpenAIRE

    Kitayama, Tomoya; Kinoshita, Ayako; Sugimoto, Masahiro; Nakayama, Yoichi; Tomita, Masaru

    2006-01-01

    Abstract Background In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law...

  11. Time Course of Detection of Human Male DNA from Stained Blood Sample on Various Surfaces by Loop Mediated Isothermal Amplification and Polymerase Chain Reaction

    OpenAIRE

    Panan Kanchanaphum

    2018-01-01

    This study explores determining the sex of humans from blood stains taken from different surfaces and compares the time course of detection with the conventional PCR, Conventional Loop Mediated Isothermal Amplification (LAMP), and LAMP-Lateral Flow Dipstick (LFD). For the DNA templates, 7 male and 7 female blood stained samples were extracted and added to LAMP and PCR reaction solution to amplify the SRY gene. The DNA samples were extracted from the following blood stained materials: cloth, w...

  12. [Pelvic floor muscles training, electrical stimulation, bladder training and lifestyle interventions to manage lower urinary tract dysfunction in multiple sclerosis: a systematic review].

    Science.gov (United States)

    Gaspard, L; Tombal, B; Castille, Y; Opsomer, R-J; Detrembleur, C

    2014-03-01

    To assess the effectiveness of conservative therapeutic approaches in a multiple sclerosis population. Review was performed in PubMed, PEDro, Scopus and Cochrane Library using combinations of the following keywords: multiple sclerosis; bladder dysfunction; overactive bladder; detrusor hyperreflexia; urge incontinence; urgency; stress incontinence; pelvic floor muscle; biofeedback; PTNS; tibial nerve; bladder training; physical therapy; physiotherapy; conservative treatment and behavioral therapy. Six randomized articles including 289 patients were selected. Four papers exhibited strong scores for the methodological quality assessment. The parameters always significantly improved concerned: number of incontinence episodes (decreased from 64% to 86% after treatment versus before treatment), quality of life (P≤0.001), severity of irritative symptoms (decreased by more than 50% after treatment versus before treatment), and nocturia (P=0.035 to Ptreatment of urinary disorders in multiple sclerosis populations with mild disability. However, the analyses are based on six studies within only four showed good methodological quality. No strong conclusions regarding treatment approaches can be drawn from this review. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Sensory adaptation to electrical stimulation of the somatosensory nerves.

    Science.gov (United States)

    Graczyk, Emily Lauren; Delhaye, Benoit; Schiefer, Matthew A; Bensmaia, Sliman J; Tyler, Dustin J

    2018-03-19

    Sensory systems adapt their sensitivity to ambient stimulation levels to improve their responsiveness to changes in stimulation. The sense of touch is also subject to adaptation, as evidenced by the desensitization produced by prolonged vibratory stimulation of the skin. Electrical stimulation of nerves elicits tactile sensations that can convey feedback for bionic limbs. In this study, we investigate whether artificial touch is also subject to adaptation, despite the fact that the peripheral mechanotransducers are bypassed. Approach: Using well-established psychophysical paradigms, we characterize the time course and magnitude of sensory adaptation caused by extended electrical stimulation of the residual somatosensory nerves in three human amputees implanted with cuff electrodes. Main results: We find that electrical stimulation of the nerve also induces perceptual adaptation that recovers after cessation of the stimulus. The time course and magnitude of electrically-induced adaptation are equivalent to their mechanically-induced counterparts. Significance: We conclude that, in natural touch, the process of mechanotransduction is not required for adaptation, and artificial touch naturally experiences adaptation-induced adjustments of the dynamic range of sensations. Further, as it does for native hands, adaptation confers to bionic hands enhanced sensitivity to changes in stimulation and thus a more natural sensory experience. . Creative Commons Attribution license.

  14. No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults.

    Science.gov (United States)

    Külzow, Nadine; Cavalcanti de Sousa, Angelica Vieira; Cesarz, Magda; Hanke, Julie-Marie; Günsberg, Alida; Harder, Solvejg; Koblitz, Swantje; Grittner, Ulrike; Flöel, Agnes

    2017-01-01

    Object-location memory (OLM) is known to decline with normal aging, a process accelerated in pathological conditions like mild cognitive impairment (MCI). In order to maintain cognitive health and to delay the transition from healthy to pathological conditions, novel strategies are being explored. Tentative evidence suggests that combining cognitive training and anodal transcranial direct current stimulation (atDCS), both reported to induce small and often inconsistent behavioral improvements, could generate larger or more consistent improvements or both, compared to each intervention alone. Here, we explored the combined efficacy of these techniques on OLM. In a subject-blind sham-controlled cross-over design 32 healthy older adults underwent a 3-day visuospatial training paired with either anodal (20 min) or sham (30 s) atDCS (1 mA, temporoparietal). Subjects were asked to learn the correct object-location pairings on a street map, shown over five learning blocks on each training day. Acquisition performance was assessed by accuracy on a given learning block in terms of percentage of correct responses. Training success (performance on last training day) and delayed memory after 1-month were analyzed by mixed model analysis and were controlled for gender, age, education, sequence of stimulation and baseline performance. Exploratory analysis of atDCS effects on within-session (online) and between-session (offline) memory performance were conducted. Moreover, transfer effects on similar trained (visuospatial) and less similar (visuo-constructive, verbal) untrained memory tasks were explored, both immediately after training, and on follow-up. We found that atDCS paired with OLM-training did not enhance success in training or performance in 1-month delayed memory or transfer tasks. In sum, this study did not support the notion that the combined atDCS-training approach improves immediate or delayed OLM in older adults. However, specifics of the experimental design, and

  15. No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults

    Directory of Open Access Journals (Sweden)

    Nadine Külzow

    2018-01-01

    Full Text Available Object-location memory (OLM is known to decline with normal aging, a process accelerated in pathological conditions like mild cognitive impairment (MCI. In order to maintain cognitive health and to delay the transition from healthy to pathological conditions, novel strategies are being explored. Tentative evidence suggests that combining cognitive training and anodal transcranial direct current stimulation (atDCS, both reported to induce small and often inconsistent behavioral improvements, could generate larger or more consistent improvements or both, compared to each intervention alone. Here, we explored the combined efficacy of these techniques on OLM. In a subject-blind sham-controlled cross-over design 32 healthy older adults underwent a 3-day visuospatial training paired with either anodal (20 min or sham (30 s atDCS (1 mA, temporoparietal. Subjects were asked to learn the correct object-location pairings on a street map, shown over five learning blocks on each training day. Acquisition performance was assessed by accuracy on a given learning block in terms of percentage of correct responses. Training success (performance on last training day and delayed memory after 1-month were analyzed by mixed model analysis and were controlled for gender, age, education, sequence of stimulation and baseline performance. Exploratory analysis of atDCS effects on within-session (online and between-session (offline memory performance were conducted. Moreover, transfer effects on similar trained (visuospatial and less similar (visuo-constructive, verbal untrained memory tasks were explored, both immediately after training, and on follow-up. We found that atDCS paired with OLM-training did not enhance success in training or performance in 1-month delayed memory or transfer tasks. In sum, this study did not support the notion that the combined atDCS-training approach improves immediate or delayed OLM in older adults. However, specifics of the experimental

  16. Sustained Reduction of Ventilator-Associated Pneumonia Rates Using Real-Time Course Correction With a Ventilator Bundle Compliance Dashboard.

    Science.gov (United States)

    Talbot, Thomas R; Carr, Devin; Parmley, C Lee; Martin, Barbara J; Gray, Barbara; Ambrose, Anna; Starmer, Jack

    2015-11-01

    The effectiveness of practice bundles on reducing ventilator-associated pneumonia (VAP) has been questioned. To implement a comprehensive program that included a real-time bundle compliance dashboard to improve compliance and reduce ventilator-associated complications. DESIGN Before-and-after quasi-experimental study with interrupted time-series analysis. SETTING Academic medical center. In 2007 a comprehensive institutional ventilator bundle program was developed. To assess bundle compliance and stimulate instant course correction of noncompliant parameters, a real-time computerized dashboard was developed. Program impact in 6 adult intensive care units (ICUs) was assessed. Bundle compliance was noted as an overall cumulative bundle adherence assessment, reflecting the percentage of time all elements were concurrently in compliance for all patients. The VAP rate in all ICUs combined decreased from 19.5 to 9.2 VAPs per 1,000 ventilator-days following program implementation (Pdashboard was associated with significant sustained decreases in VAP rates and an increase in bundle compliance among adult ICU patients.

  17. Clinical study on the time courses of serum myosin light chain I levels in patients with acute myocardial infarction

    International Nuclear Information System (INIS)

    Nakanishi, Masako; Saiki, Yasuhiko; Ui, Kazuyo

    1992-01-01

    Changes of serum myosin light chain I (Myosin LCI) concentrations and creatine kinase (CK) activities were serially measured in 23 patients with acute myocardial infarction. Intracoronary thrombolysis was performed in 14 patients (ICT group) while the remaining 9 patients were treated in the conventional manner (non ICT group). The relationships between the maximum levels of serum Myosin LCI or CK and a myocardial infarct size index or left ventricular function were evaluated in 18 patients. The myocardial infarct size index was determined by 201 Tl myocardial scintigrams performed in the chronic phase. Multiple peaks of Myosin LCI were observed in 64% (9/14) of the ICT group and the first peak in 6 of these patients appeared much earlier in the same time as CK peak than in the non-ICT group, while multiple peaks were seen only in one case in the non-ICT group. The infarct size index by 201 Tl myocardial SPECT correlated with maximum Myosin LCI levels (r=0.88, p<0.001, n=10) and CK activities (r=0.67, p<0.05, n=10). These results indicate that the measurement of serum Myosin LCI is very useful for estimating the extent of myocardial damage and suggest that myocardial degeneration occurs at a very early phase of myocardial infarction. (author)

  18. Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial.

    Science.gov (United States)

    Oliveria, Seth F; Rodriguez, Ramon L; Bowers, Dawn; Kantor, Daniel; Hilliard, Justin D; Monari, Erin H; Scott, Bonnie M; Okun, Michael S; Foote, Kelly D

    2017-09-01

    Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius-ventralis oralis posterior nucleus border [the VIM lead] and one targeting the ventralis oralis anterior-ventralis oralis posterior border [the VO lead]) for the treatment of multiple sclerosis tremor. We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA). We recruited adult patients with a clinical diagnosis of multiple sclerosis tremor refractory to previous medical therapy. Before surgery to implant both leads, we randomly assigned patients (1:1) to receive 3 months of optimised single-lead DBS-either VIM or VO. We did the randomisation with a computer-generated sequence, using three blocks of four patients, and independent members of the Center did the assignment. Patients and all clinicians other than the DBS programming nurse were masked to the choice of lead. Patients underwent surgery 1 month after their baseline visit for implantation of the dual lead DBS system. A pulse generator and two extension cables were implanted in a second surgery 3-4 weeks later. Patients then received an initial 3-month period of continuous stimulation of either the VIM or VO lead followed by blinded safety assessment of their tremor with the Tolosa-Fahn-Marin Tremor Rating Scale (TRS) during optimised VIM or VO lead stimulation at the end of the 3 months. After this visit, both leads were activated in all patients for an additional 3 months, and optimally programmed during serial visits as dictated by a prespecified programming algorithm. At the 6-month follow-up visit, TRS score was measured, and mood and psychological batteries were administered under four

  19. growth stimulant

    African Journals Online (AJOL)

    Effects of timing and duration of supplementation of LIVFIT VET ® (growth stimulant) as substitute for fish meal on the growth performance, haematology and clinical enzymes concentration of growing pigs.

  20. The dissimilar time course of temporary threshold shifts and reduction of inhibition in the inferior colliculus following intense sound exposure.

    Science.gov (United States)

    Heeringa, A N; van Dijk, P

    2014-06-01

    Excessive noise exposure is known to produce an auditory threshold shift, which can be permanent or transient in nature. Recent studies showed that noise-induced temporary threshold shifts are associated with loss of synaptic connections to the inner hair cells and with cochlear nerve degeneration, which is reflected in a decreased amplitude of wave I of the auditory brainstem response (ABR). This suggests that, despite normal auditory thresholds, central auditory processing may be abnormal. We recorded changes in central auditory processing following a sound-induced temporary threshold shift. Anesthetized guinea pigs were exposed for 1 h to a pure tone of 11 kHz (124 dB sound pressure level). Hearing thresholds, amplitudes of ABR waves I and IV, and spontaneous and tone-evoked firing rates in the inferior colliculus (IC) were assessed immediately, one week, two weeks, and four weeks post exposure. Hearing thresholds were elevated immediately following overexposure, but recovered within one week. The amplitude of the ABR wave I was decreased in all sound-exposed animals for all test periods. In contrast, the ABR wave IV amplitude was only decreased immediately after overexposure and recovered within a week. The proportion of IC units that show inhibitory responses to pure tones decreased substantially up to two weeks after overexposure, especially when stimulated with high frequencies. The proportion of excitatory responses to low frequencies was increased. Spontaneous activity was unaffected by the overexposure. Despite rapid normalization of auditory thresholds, our results suggest an increased central gain following sound exposure and an abnormal balance between excitatory and inhibitory responses in the midbrain up to two weeks after overexposure. These findings may be associated with hyperacusis after a sound-induced temporary threshold shift. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Low-threshold stimulated emission at 249 nm and 256 nm from AlGaN-based multiple-quantum-well lasers grown on sapphire substrates

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiao-Hang; Detchprohm, Theeradetch; Kao, Tsung-Ting; Satter, Md. Mahbub; Shen, Shyh-Chiang; Douglas Yoder, P.; Dupuis, Russell D., E-mail: dupuis@gatech.edu [Center for Compound Semiconductors and School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332-0250 (United States); Wang, Shuo; Wei, Yong O.; Xie, Hongen; Fischer, Alec M.; Ponce, Fernando A. [Department of Physics, Arizona State University, Tempe, Arizona 85287-1504 (United States); Wernicke, Tim; Reich, Christoph; Martens, Martin; Kneissl, Michael [Technical University of Berlin, Institute for Solid State Physics, Berlin D-10623 (Germany)

    2014-10-06

    Optically pumped deep-ultraviolet (DUV) lasing with low threshold was demonstrated from AlGaN-based multiple-quantum-well (MQW) heterostructures grown on sapphire substrates. The epitaxial layers were grown pseudomorphically by metalorganic chemical vapor deposition on (0001) sapphire substrates. Stimulated emission was observed at wavelengths of 256 nm and 249 nm with thresholds of 61 kW/cm{sup 2} and 95 kW/cm{sup 2} at room temperature, respectively. The thresholds are comparable to the reported state-of-the-art AlGaN-based MQW DUV lasers grown on bulk AlN substrates emitting at 266 nm. These low thresholds are attributed to the optimization of active region and waveguide layer as well as the use of high-quality AlN/sapphire templates. The stimulated emission above threshold was dominated by transverse-electric polarization. This work demonstrates the potential candidacy of sapphire substrates for DUV diode lasers.

  2. Low-threshold stimulated emission at 249 nm and 256 nm from AlGaN-based multiple-quantum-well lasers grown on sapphire substrates

    International Nuclear Information System (INIS)

    Li, Xiao-Hang; Detchprohm, Theeradetch; Kao, Tsung-Ting; Satter, Md. Mahbub; Shen, Shyh-Chiang; Douglas Yoder, P.; Dupuis, Russell D.; Wang, Shuo; Wei, Yong O.; Xie, Hongen; Fischer, Alec M.; Ponce, Fernando A.; Wernicke, Tim; Reich, Christoph; Martens, Martin; Kneissl, Michael

    2014-01-01

    Optically pumped deep-ultraviolet (DUV) lasing with low threshold was demonstrated from AlGaN-based multiple-quantum-well (MQW) heterostructures grown on sapphire substrates. The epitaxial layers were grown pseudomorphically by metalorganic chemical vapor deposition on (0001) sapphire substrates. Stimulated emission was observed at wavelengths of 256 nm and 249 nm with thresholds of 61 kW/cm 2 and 95 kW/cm 2 at room temperature, respectively. The thresholds are comparable to the reported state-of-the-art AlGaN-based MQW DUV lasers grown on bulk AlN substrates emitting at 266 nm. These low thresholds are attributed to the optimization of active region and waveguide layer as well as the use of high-quality AlN/sapphire templates. The stimulated emission above threshold was dominated by transverse-electric polarization. This work demonstrates the potential candidacy of sapphire substrates for DUV diode lasers.

  3. Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice.

    Science.gov (United States)

    Mouret, Stéphane; Wartelle, Julien; Batal, Mohamed; Emorine, Sandy; Bertoni, Marine; Poyot, Thomas; Cléry-Barraud, Cécile; Bakdouri, Nacera El; Peinnequin, André; Douki, Thierry; Boudry, Isabelle

    2015-01-05

    Sulfur mustard (SM) is a strong bifunctional alkylating agent that produces severe tissue injuries characterized by erythema, edema, subepidermal blisters and a delayed inflammatory response after cutaneous exposure. However, despite its long history, SM remains a threat because of the lack of effective medical countermeasures as the molecular mechanisms of these events remain unclear. This limited number of therapeutic options results in part of an absence of appropriate animal models. We propose here to use SKH-1 hairless mouse as the appropriate model for the design of therapeutic strategies against SM-induced skin toxicity. In the present study particular emphasis was placed on histopathological changes associated with inflammatory responses after topical exposure of dorsal skin to three different doses of SM (0.6, 6 and 60mg/kg) corresponding to a superficial, a second-degree and a third-degree burn. Firstly, clinical evaluation of SM-induced skin lesions using non invasive bioengineering methods showed that erythema and impairment of skin barrier increased in a dose-dependent manner. Histological evaluation of skin sections exposed to SM revealed that the time to onset and the severity of symptoms including disorganization of epidermal basal cells, number of pyknotic nuclei, activation of mast cells and neutrophils dermal invasion were dose-dependent. These histopathological changes were associated with a dose- and time-dependent increase in expression of specific mRNA for inflammatory mediators such as interleukins (IL1β and IL6), tumor necrosis factor (TNF)-α, cycloxygenase-2 (COX-2), macrophage inflammatory proteins (MIP-1α, MIP-2 and MIP-1αR) and keratinocyte chemoattractant (KC also called CXCL1) as well as adhesion molecules (L-selectin and vascular cell adhesion molecule (VCAM)) and growth factor (granulocyte colony-stimulating factor (Csf3)). A dose-dependent increase was also noted after SM exposure for mRNA of matrix metalloproteinases (MMP9

  4. Effect of time course application of nitrogen fertilizer on the N-fertilizer use efficiency, lint properties and seed cotton yield using 15N isotopic dilution technique

    International Nuclear Information System (INIS)

    Janat, M.; Khalifa, Kh

    2001-12-01

    Field experiment was carried out at Der El-Hajar research station during 1998 growing season to evaluate the effect of time course application of nitrogen fertilizer on N-recovery, seed cotton yield and lint properties using 15 N isotope dilution technique. Aleppo 40 variety was tested, irrigation scheduling was set up at 80% of field capacity. Phosphorus fertilizer was applied as TSP 46% before planting at a rate of 180 kg/ha. N fertilizer was applied as urea (46%) in four different applications follows: one application 180 kg N/ha before planting (T1), two split application 180 (90 + 90) kg N/ha (T2), three equally split applications 180 (60 + 60 + 60) kg N/ha (T3), and four equally split applications 180 (45 + 45 + 45 + 45) kg N/ha (T4). Labeled N-fertilizer (5.09 a.e%) was also applied as urea 46% to the subplots (1.0 m 2 each) of the corresponding treatments. All agricultural practices were carried out as the common practices locally employed. Soil samples were analyzed for CEC, ph, EC, OM, total N, available P, and CaCO 3 as outlined by our laboratory standard procedure. Plant samples were collected at physiological maturity and analyzed for 15 N enrichment to assess N recovery. Lint samples were analyzed for lint properties. the results showed no significant effect of the nitrogen fertilizer time course application on the tested parameters such as dry matter production, seed cotton yield, N uptake and lint properties. on the other hand the T2, T3 and T4 treatments where shown to have a positive significant response toward time course application relative to T1 treatment. (authors)

  5. Mas-allatotropin in the developing antennal lobe of the sphinx moth Manduca sexta: distribution, time course, developmental regulation, and colocalization with other neuropeptides.

    Science.gov (United States)

    Utz, Sandra; Huetteroth, Wolf; Vömel, Matthias; Schachtner, Joachim

    2008-01-01

    The paired antennal lobes (ALs) of the sphinx moth Manduca sexta serve as a well-established model for studying development of the primary integration centers for odor information in the brain. To further reveal the role of neuropeptides during AL development, we have analyzed cellular distribution, developmental time course, and regulation of the neuropeptide M. sexta allatotropin (Mas-AT). On the basis of morphology and appearance during AL formation, seven major types of Mas-AT-immunoreactive (ir) cells could be distinguished. Mas-AT-ir cells are identified as local, projection, and centrifugal neurons, which are either persisting larval or newly added adult-specific neurons. Complementary immunostaining with antisera against two other neuropeptide families (A-type allatostatins, RFamides) revealed colocalization within three of the Mas-AT-ir cell types. On the basis of this neurochemistry, the most prominent type of Mas-AT-ir neurons, the local AT neurons (LATn), could be divided in three subpopulations. The appearance of the Mas-AT-ir cell types occurring during metamorphosis parallels the rising titer of the developmental hormone 20-hydroxyecdysone (20E). Artificially shifting the 20E titer to an earlier developmental time point resulted in the precocious occurrence of Mas-AT immunostaining. This result supports the hypothesis that the pupal rise of 20E is causative for Mas-AT expression during AL development. Comparing localization and developmental time course of Mas-AT and other neuropeptides with the time course of AL formation suggests various functions for these neuropeptides during development, including an involvement in the formation of the olfactory glomeruli.

  6. Inferring Broad Regulatory Biology from Time Course Data: Have We Reached an Upper Bound under Constraints Typical of In Vivo Studies?

    Directory of Open Access Journals (Sweden)

    Saurabh Vashishtha

    Full Text Available There is a growing appreciation for the network biology that regulates the coordinated expression of molecular and cellular markers however questions persist regarding the identifiability of these networks. Here we explore some of the issues relevant to recovering directed regulatory networks from time course data collected under experimental constraints typical of in vivo studies. NetSim simulations of sparsely connected biological networks were used to evaluate two simple feature selection techniques used in the construction of linear Ordinary Differential Equation (ODE models, namely truncation of terms versus latent vector projection. Performance was compared with ODE-based Time Series Network Identification (TSNI integral, and the information-theoretic Time-Delay ARACNE (TD-ARACNE. Projection-based techniques and TSNI integral outperformed truncation-based selection and TD-ARACNE on aggregate networks with edge densities of 10-30%, i.e. transcription factor, protein-protein cliques and immune signaling networks. All were more robust to noise than truncation-based feature selection. Performance was comparable on the in silico 10-node DREAM 3 network, a 5-node Yeast synthetic network designed for In vivo Reverse-engineering and Modeling Assessment (IRMA and a 9-node human HeLa cell cycle network of similar size and edge density. Performance was more sensitive to the number of time courses than to sample frequency and extrapolated better to larger networks by grouping experiments. In all cases performance declined rapidly in larger networks with lower edge density. Limited recovery and high false positive rates obtained overall bring into question our ability to generate informative time course data rather than the design of any particular reverse engineering algorithm.

  7. Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions.

    Science.gov (United States)

    Wagatsuma, Nobuhiko; Sakai, Ko

    2016-01-01

    Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional

  8. Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions

    Science.gov (United States)

    Wagatsuma, Nobuhiko; Sakai, Ko

    2017-01-01

    Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional

  9. Network analysis reveals stage-specific changes in zebrafish embryo development using time course whole transcriptome profiling and prior biological knowledge.

    Science.gov (United States)

    Zhang, Yuji

    2015-01-01

    Molecular networks act as the backbone of molecular activities within cells, offering a unique opportunity to better understand the mechanism of diseases. While network data usually constitute only static network maps, integrating them with time course gene expression information can provide clues to the dynamic features of these networks and unravel the mechanistic driver genes characterizing cellular responses. Time course gene expression data allow us to broadly "watch" the dynamics of the system. However, one challenge in the analysis of such data is to establish and characterize the interplay among genes that are altered at different time points in the context of a biological process or functional category. Integrative analysis of these data sources will lead us a more complete understanding of how biological entities (e.g., genes and proteins) coordinately perform their biological functions in biological systems. In this paper, we introduced a novel network-based approach to extract functional knowledge from time-dependent biological processes at a system level using time course mRNA sequencing data in zebrafish embryo development. The proposed method was applied to investigate 1α, 25(OH)2D3-altered mechanisms in zebrafish embryo development. We applied the proposed method to a public zebrafish time course mRNA-Seq dataset, containing two different treatments along four time points. We constructed networks between gene ontology biological process categories, which were enriched in differential expressed genes between consecutive time points and different conditions. The temporal propagation of 1α, 25-Dihydroxyvitamin D3-altered transcriptional changes started from a few genes that were altered initially at earlier stage, to large groups of biological coherent genes at later stages. The most notable biological processes included neuronal and retinal development and generalized stress response. In addition, we also investigated the relationship among

  10. Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study

    DEFF Research Database (Denmark)

    Gideon, P; Henriksen, O; Sperling, B

    1992-01-01

    BACKGROUND AND PURPOSE: The early time course after acute stroke of cerebral N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline was studied in vivo by means of localized water-suppressed proton magnetic resonance spectroscopy. METHODS: Eight patients with acute stroke......, with the loss appearing to occur between 6 and 24 hours after the stroke incident. The reduction in N-acetylaspartate content was greater in the central part than in the peripheral part of the infarcted area. Creatine and phosphocreatine were also reduced in the infarcted area, whereas no significant change...

  11. A time course analysis of the electrophysiological properties of neurons differentiated from human induced pluripotent stem cells (iPSCs.

    Directory of Open Access Journals (Sweden)

    Deborah Prè

    Full Text Available Many protocols have been designed to differentiate human embryonic stem cells (ESCs and human induced pluripotent stem cells (iPSCs into neurons. Despite the relevance of electrophysiological properties for proper neuronal function, little is known about the evolution over time of important neuronal electrophysiological parameters in iPSC-derived neurons. Yet, understanding the development of basic electrophysiological characteristics of iPSC-derived neurons is critical for evaluating their usefulness in basic and translational research. Therefore, we analyzed the basic electrophysiological parameters of forebrain neurons differentiated from human iPSCs, from day 31 to day 55 after the initiation of neuronal differentiation. We assayed the developmental progression of various properties, including resting membrane potential, action potential, sodium and potassium channel currents, somatic calcium transients and synaptic activity. During the maturation of iPSC-derived neurons, the resting membrane potential became more negative, the expression of voltage-gated sodium channels increased, the membrane became capable of generating action potentials following adequate depolarization and, at day 48-55, 50% of the cells were capable of firing action potentials in response to a prolonged depolarizing current step, of which 30% produced multiple action potentials. The percentage of cells exhibiting miniature excitatory post-synaptic currents increased over time with a significant increase in their frequency and amplitude. These changes were associated with an increase of Ca2+ transient frequency. Co-culturing iPSC-derived neurons with mouse glial cells enhanced the development of electrophysiological parameters as compared to pure iPSC-derived neuronal cultures. This study demonstrates the importance of properly evaluating the electrophysiological status of the newly generated neurons when using stem cell technology, as electrophysiological properties of

  12. The relative importance of perceptual and memory sampling processes in determining the time course of absolute identification.

    Science.gov (United States)

    Guest, Duncan; Kent, Christopher; Adelman, James S

    2018-04-01

    In absolute identification, the extended generalized context model (EGCM; Kent & Lamberts, 2005, 2016) proposes that perceptual processing determines systematic response time (RT) variability; all other models of RT emphasize response selection processes. In the EGCM-RT the bow effect in RTs (longer responses for stimuli in the middle of the range) occurs because these middle stimuli are less isolated, and as perceptual information is accumulated, the evidence supporting a correct response grows more slowly than for stimuli at the ends of the range. More perceptual information is therefore accumulated in order to increase certainty in response for middle stimuli, lengthening RT. According to the model reducing perceptual sampling time should reduce the size of the bow effect in RT. We tested this hypothesis in 2 pitch identification experiments. Experiment 1 found no effect of stimulus duration on the size of the RT bow. Experiment 2 used multiple short stimulus durations as well as manipulating set size and stimulus spacing. Contrary to EGCM-RT predictions, the bow effect on RTs was large for even very short durations. A new version of the EGCM-RT could only capture this, alongside the effect of stimulus duration on accuracy, by including both a perceptual and a memory sampling process. A modified version of the selective attention, mapping, and ballistic accumulator model (Brown, Marley, Donkin, & Heathcote, 2008) could also capture the data, by assuming psychophysical noise diminishes with increased exposure duration. This modeling suggests systematic variability in RT in absolute identification is largely determined by memory sampling and response selection processes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  13. The Effects of Nicotine on the Stimulation of the Cholinergic System and Immune Responses Changes in Animal Models of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    M Shahmoradi

    2016-06-01

    Full Text Available Background & aim: Lately, it has been demonstrated that the signaling by the α7 nicotinic receptors produces the anti-inflammatory condition in both macrophages and T cells. Moreover, activation of macrophages and T cells play an important role in multiple sclerosis (MS.  In the present study, the therapeutic effect of nicotine on experimental autoimmune encephalomyelitis (EAE, an animal model of MS, and its effects on T-helper cells responses was evaluated. Methods: In the present experimental study, EAE was induced by homogenised guinea pig spinal cord and complete Freund’s adjuvant in wistar rats. Animals were allocated in two therapeutic groups (n=7 per group. Treatment with nicotine (2.5 mg/kg-daily was started in treatment group when the treatment group developed a disability score (at day 12. At the same time, the control group received only the solvent with the same program. Signs of disease were recorded daily until the day 36 when animals were sacrificed. The Splenocytes were checked for proliferation by MTT test and cytokine production by ELISA. The level of nitric oxide in serum was checked by griess test. The data was analyzed using the Student t test and Mann-Whitney U. Results: Nicotine administration in the treatment group significantly reduced the clinical symptoms after the onset of symptoms. Simultaneously with the decrease of the level of serum nitric oxide, nicotine significantly decreased the pro-inflammatory cytokine IL-17 and IFN-γ. The levels of anti-inflammatory IL-10 were not changed significantly. Lymphocyte proliferation was significantly decreased in treatment group compared to control group Conclusion: The results of this study indicated that nicotine had immune modulatory effects and could be used to control MS disease.

  14. A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles.

    Science.gov (United States)

    Kitayama, Tomoya; Kinoshita, Ayako; Sugimoto, Masahiro; Nakayama, Yoichi; Tomita, Masaru

    2006-07-17

    In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems. The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations. The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.

  15. Differentiation of hypertensive heart disease with hypertrophy and hepertrophic cardiomyopathy using consecutive time-course images of Gd-DTPA enhanced MRI

    International Nuclear Information System (INIS)

    Ochiai, Kouichi; Isibashi, Yutaka; Shimada, Toshio; Tsukihashi, Hironori; Sato, Hidetoshi; Kitamura, Jun; Morioka, Shigefumi; Kawamitsu, Hideaki; Sugimura, Kazuro

    1996-01-01

    We used consecutive time-course Gd-DTPA contrast magnetic resonance images to differentiate hypertrophic cardiomyopathy (HCM) from hypertensive heart disease with hypertrophy (HHD). Seventeen patients with HCM, 6 patients with HHD and 5 normal subjects (control) were studied. ECG-gated MRI with 1.5T system was performed before and after intravenous injection of Gd-DTPA (0.1mmol/Kg) using spin echo sequence. Gd-DTPA enhanced MRI was repeated every 10 to 55 minutes. We measured signal intensity (SI) of midleft ventricular myocardium and skeletal muscle, and then calculated the ratio between myocardial SI and skeletal muscle SI. Myocardium was enhanced by Gd-DTPA in all patients. However, there was difference in the decay of enhancement effect by Gd-DTPA between HCM and HHD. The decay in HCM was more slowly than in both HHD and control. There was no difference in the decay between HHD and control. The difference in the decay between HCM and HHD became significant 25 minutes after Gd-DTPA injection and lasted until 55 minutes. We conclude that the time-course of the decay of enhancement effect by Gd-DTPA is helpful to differentiate HCM from HHD and the difference of the decay might reflect structural changes of myocardium. (author)

  16. On the time course of lexical stress priming in speech production: Behavioral and ERPs evidence from a free-stress language.

    Science.gov (United States)

    Sulpizio, Simone; Vespignani, Francesco; Job, Remo

    2016-10-01

    The goal of the present research was to study the time course of lexical stress encoding in a free-stress language with unpredictable stress. To this aim we measured event-related brain potentials (ERPs) during lexical priming. Participants named pictures bearing either the dominant or non-dominant stress pattern, and preceded by either a congruent or an incongruent word prime (e.g., CInema-FRAgola'cinema-strawberry' vs. benZIna-FRAgola'petrol-strawberry'). Behavioral results show that participants were slower in naming targets that had the same stress pattern as the prime, and were also faster in producing words with the dominant stress pattern in the language. The electrophysiological results show that both the effects are compatible with the time course of phonological encoding in speech production. Surprisingly, a dominant stress effect occurred in the ERPs elicited by the primes, with a larger positivity for non-dominant stress words in a 150-250ms time-window. The pattern of results indicates that during speech production: a) the system is sensitive to the stress patterns distribution; b) the automatic pre-activation of a metrical frame may interfere with the phonological encoding of a to-be-uttered word. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Time course of oxidative stress, inflammation and muscle damage markers for five days after a soccer match: effects of sex and playing position.

    Science.gov (United States)

    Souglis, Athanasios; Bogdanis, Gregory C; Chryssanthopoulos, Costas; Apostolidis, Nikolaos; Geladas, Nikos D

    2018-01-03

    This study examined the influence of sex and playing position on the time-course of selected oxidative stress, inflammation and muscle damage markers following an official soccer match. Sixty professional soccer players (30 male and 30 female) were divided into three groups, according to their playing position: defenders, midfielders and attackers. Each group consisted of 10 male and 10 female players. Sixty healthy volunteers (30 males and 30 females) served as control. Blood samples were taken before and after the match and daily for five days after the match. Analysis of variance revealed different responses over time between sex and playing positions, as shown by the 3-way interaction, for creatine kinase (CK), protein carbonyls (PC), catalase, fibrinogen (FIB), uric acid (UA), lactate dehydrogenase (LDH), reduced glutathione, C-reactive protein and interleukin-6 (IL-6) (p position, for all oxidative, inflammatory and muscle damage indices (psexes, midfielders had higher peaks in all indices compared with defenders (p sex and playing position influence the time-course of selected oxidative stress, inflammation and muscle damage markers following an official soccer game. This information should be taken into account by practitioners for the design of training programs following match play.

  18. Accumulation of thorium and uranium by microbes. The effect of pH, concentration of metals, and time course on the accumulation of both elements using streptomyces levoris

    International Nuclear Information System (INIS)

    Tsuruta, Takehiko

    2006-01-01

    The accumulation of thorium and uranium by various microorganisms from a solution containing both metals at pH 3.5 was examined. Among the tested species, a high accumulation ability for thorium was exhibited by strains of gram-positive bacteria, such as Arthrobacter nicotianae, Bacillus megaterium, B. subtilis, Micrococcus luteus, Rhodococcus erythropolis, and Streptomyces levoris. Though uranium was accumulated in small amounts by most of microorganisms. A. nicotianae, S. flavoviridis, and S. levoris had relatively high uranium accumulation abilities. In these high performance thorium- and uranium-accumulating microorganisms, S. levoris, which accumulated the largest amount of uranium from the solution containing only uranium at pH 3.5, accumulated about 300 μmol thorium and 133 μmol uranium per gram dry weight of microbial cells from a solution containing both thorium and uranium at pH 3.5. The amount and time course of the thorium accumulation were almost unaffected by the co-existing uranium, while those of uranium were strongly affected by the co-existing thorium. The effects of pH, the thorium and uranium concentrations, and time course on both metal accumulations were also evaluated by numerical formulas. (author)

  19. A big data pipeline: Identifying dynamic gene regulatory networks from time-course Gene Expression Omnibus data with applications to influenza infection.

    Science.gov (United States)

    Carey, Michelle; Ramírez, Juan Camilo; Wu, Shuang; Wu, Hulin

    2018-07-01

    A biological host response to an external stimulus or intervention such as a disease or infection is a dynamic process, which is regulated by an intricate network of many genes and their products. Understanding the dynamics of this gene regulatory network allows us to infer the mechanisms involved in a host response to an external stimulus, and hence aids the discovery of biomarkers of phenotype and biological function. In this article, we propose a modeling/analysis pipeline for dynamic gene expression data, called Pipeline4DGEData, which consists of a series of statistical modeling techniques to construct dynamic gene regulatory networks from the large volumes of high-dimensional time-course gene expression data that are freely available in the Gene Expression Omnibus repository. This pipeline has a consistent and scalable structure that allows it to simultaneously analyze a large number of time-course gene expression data sets, and then integrate the results across different studies. We apply the proposed pipeline to influenza infection data from nine studies and demonstrate that interesting biological findings can be discovered with its implementation.

  20. A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles

    Directory of Open Access Journals (Sweden)

    Sugimoto Masahiro

    2006-07-01

    Full Text Available Abstract Background In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems. Results The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations. Conclusion The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.

  1. Time course of EEG slow-wave activity in pre-school children with sleep disordered breathing: a possible mechanism for daytime deficits?

    Science.gov (United States)

    Biggs, Sarah N; Walter, Lisa M; Nisbet, Lauren C; Jackman, Angela R; Anderson, Vicki; Nixon, Gillian M; Davey, Margot J; Trinder, John; Hoffmann, Robert; Armitage, Roseanne; Horne, Rosemary S C

    2012-09-01

    Daytime deficits in children with sleep disordered breathing (SDB) are theorized to result from hypoxic insult to the developing brain or fragmented sleep. Yet, these do not explain why deficits occur in primary snorers (PS). The time course of slow wave EEG activity (SWA), a proxy of homeostatic regulation and cortical maturation, may provide insight. Clinical and control subjects (N=175: mean age 4.3±0.9 y: 61% male) participated in overnight polysomnography (PSG). Standard sleep scoring and power spectral analyses were conducted on EEG (C4/A1; 0.5-sleep stages and respiratory parameters. Repeated-measures ANCOVA evaluated group differences in the time course of SWA. Four groups were classified: controls (OAHI ≤ 1 event/h; no clinical history); PS (OAHI ≤ 1 event/h; clinical history); mild OSA (OAHI=1-5 events/h); and moderate to severe OSA (MS OSA: OAHI>5 events/h). Group differences were found in the percentage of time spent in NREM Stages 1 and 4 (psleep pressure but impaired restorative sleep function in pre-school children with SDB, providing new insights into the possible mechanism for daytime deficits observed in all severities of SDB. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Tempts to determine radon entry rate and air exchange rate variable in time from the time course of indoor radon concentration

    International Nuclear Information System (INIS)

    Thomas, J.

    1996-01-01

    For the study and explanation of the diurnal variability of the indoor radon concentration a(t) [Bq/m 3 ], which is proportional to the ratio of the radon entry rate A [Bq/h] and the air exchange rate k [1/h], it would be of advantage to know separately the diurnal variability of both determining quantities A(t) and k(t). To measure directly and continuously the radon entry rate A(t) is possible only in special studies (mostly in experimental rooms) and also continuous measuring of the air exchange rate k(t) is possible also only in special studies for a short time. But continuously measuring radon meters are now common, do not trouble people in normal living regime during day and night. The goal of this endeavour would be the evaluation of the time courses of both determining quantities from the time courses of the indoor radon concentration directly without additional experimental work and so a better utilisation of such measurements. (author)

  3. Brain Stimulation Therapies

    Science.gov (United States)

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  4. The representation of time course events in visual arts and the development of the concept of time in children: a preliminary study.

    Science.gov (United States)

    Actis-Grosso, Rossana; Zavagno, Daniele

    2008-01-01

    By means of a careful search we found several representations of dynamic contents of events that show how the depiction of the passage of time in the visual arts has evolved gradually through a series of modifications and adaptations. The general hypothesis we started to investigate is that the evolution of the representation of the time course in visual arts is mirrored in the evolution of the concept of time in children, who, according to Piaget (1946), undergo three stages in their ability to conceptualize time. Crucial for our hypothesis is Stage II, in which children become progressively able to link the different phases of an event, but vacillate between what Piaget termed 'intuitive regulations', not being able to understand all the different aspects of a given situation. We found several pictorial representations - mainly dated back to the 14th to 15th century - that seem to fit within a Stage II of children's comprehension of time. According to our hypothesis, this type of pictorial representations should be immediately understood only by those children who are at Piaget's Stage II of time conceptualization. This implies that children at Stages I and III should not be able to understand the representation of time courses in the aforementioned paintings. An experiment was run to verify the agreement between children's collocation within Piaget's three stages - as indicated by an adaptation of Piaget's original experiment - and their understanding of pictorial representations that should be considered as Stage II type of representations of time courses. Despite the small sample of children examined so far, results seem to support our hypothesis. A follow-up (Experiment 2) on the same children was also run one year later in order to verify other possible explanations. Results from the two experiments suggest that the study of the visual arts can aid our understanding of the development of the concept of time, and it can also help to distinguish between the

  5. Time courses of improvement and symptom remission in children treated with atomoxetine for attention-deficit/hyperactivity disorder: analysis of Canadian open-label studies

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    Turgay Atilla

    2011-05-01

    Full Text Available Abstract Background The relatively short durations of the initial pivotal randomized placebo-controlled trials involving atomoxetine HCl for the treatment of attention-deficit/hyperactivity disorder (ADHD provided limited insight into the time courses of ADHD core symptom responses to this nonstimulant, selective norepinephrine reuptake inhibitor. The aim of this analysis was to evaluate time courses of treatment responses or remission, as assessed by attainment of prespecified scores on the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI and the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S scales, during up to 1 year of atomoxetine treatment in children with ADHD. Methods Using pooled data from three Canadian open-label studies involving 338 children ages 6-11 years with ADHD who were treated with atomoxetine for 3, 6 and 12 months, and survival analysis methods for interval-censored data, we estimated the time to: 1 improvement and robust improvement defined by ≥25% and ≥40% reductions from baseline ADHDRS-IV-PI total scores, respectively; and 2 remission using two definitions: a final score of ADHDRS-IV-PI ≤18 or a final score of CGI-ADHD-S ≤2. Results The median time to improvement was 3.7 weeks (~1 month, but remission of symptoms did not occur until a median of 14.3 weeks (~3.5 months using the most stringent CGI-ADHD-S threshold. Probabilities of robust improvement were 47% at or before 4 weeks of treatment; 76% at 12 weeks; 85% at 26 weeks; and 96% at 52 weeks. Probabilities of remission at these corresponding time points were 30%, 59%, 77%, and 85% (using the ADHDRS-IV scale and 8%, 47%, 67%, and 75% (using the CGI-ADHD-S scale. The change from atomoxetine treatment month 5 to month 12 of -1.01 (1.03 was not statistically significant (p = .33. Conclusions Reductions in core ADHD symptoms during atomoxetine treatment are gradual. Although approximately one-half of study

  6. Correlation-based iterative clustering methods for time course data: The identification of temporal gene response modules for influenza infection in humans

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    Michelle Carey

    2016-10-01

    Full Text Available Many pragmatic clustering methods have been developed to group data vectors or objects into clusters so that the objects in one cluster are very similar and objects in different clusters are distinct based on some similarity measure. The availability of time course data has motivated researchers to develop methods, such as mixture and mixed-effects modelling approaches, that incorporate the temporal information contained in the shape of the trajectory of the data. However, there is still a need for the development of time-course clustering methods that can adequately deal with inhomogeneous clusters (some clusters are quite large and others are quite small. Here we propose two such methods, hierarchical clustering (IHC and iterative pairwise-correlation clustering (IPC. We evaluate and compare the proposed methods to the Markov Cluster Algorithm (MCL and the generalised mixed-effects model (GMM using simulation studies and an application to a time course gene expression data set from a study containing human subjects who were challenged by a live influenza virus. We identify four types of temporal gene response modules to influenza infection in humans, i.e., single-gene modules (SGM, small-size modules (SSM, medium-size modules (MSM and large-size modules (LSM. The LSM contain genes that perform various fundamental biological functions that are consistent across subjects. The SSM and SGM contain genes that perform either different or similar biological functions that have complex temporal responses to the virus and are unique to each subject. We show that the temporal response of the genes in the LSM have either simple patterns with a single peak or trough a consequence of the transient stimuli sustained or state-transitioning patterns pertaining to developmental cues and that these modules can differentiate the severity of disease outcomes. Additionally, the size of gene response modules follows a power-law distribution with a consistent

  7. Increased mobilization and yield of stem cells using plerixafor in combination with granulocyte-colony stimulating factor for the treatment of non-Hodgkin’s lymphoma and multiple myeloma

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    Louis M Pelus

    2011-02-01

    Full Text Available Louis M Pelus1, Sherif S Farag21Department of Microbiology and Immunology, 2Division of Hematology and Oncology, Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IndianaAbstract: Multiple myeloma and non-Hodgkin’s lymphoma remain the most common indications for high-dose chemotherapy and autologous peripheral blood stem cell rescue. While a CD34+ cell dose of 1 × 106/kg is considered the minimum required for engraftment, higher CD34+ doses correlate with improved outcome. Numerous studies, however, support targeting a minimum CD34+ cell dose of 2.0 × 106/kg, and an “optimal” dose of 4 to 6 × 106/kg for a single transplant. Unfortunately, up to 40% of patients fail to mobilize an optimal CD34+ cell dose using myeloid growth factors alone. Plerixafor is a novel reversible inhibitor of CXCR4 that significantly increases the mobilization and collection of higher numbers of hematopoietic progenitor cells. Two randomized multi-center clinical trials in patients with non-Hodgkin’s lymphoma and multiple myeloma have demonstrated that the addition of plerixafor to granulocyte-colony stimulating factor increases the mobilization and yield of CD34+ cells in fewer apheresis days, which results in durable engraftment. This review summarizes the pharmacology and evidence for the clinical efficacy of plerixafor in mobilizing hematopoietic stem and progenitor cells, and discusses potential ways to utilize plerixafor in a cost-effective manner in patients with these diseases.Keywords: plerixafor, mobilization, stem cells, lymphoma, myeloma

  8. Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

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    Saba Pierluigi

    2005-05-01

    Full Text Available Abstract Background Previous studies by our group suggest that extracellular dopamine (DA and noradrenaline (NA may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC. This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC, occipital cortex (Occ, and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats. Results Twenty min electrical stimulation of the LC, with burst type pattern of pulses, increased NA and DA both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned to baseline within 20 min after the end of the stimulation period, while DA in the Occ reached a maximum increase during 20 min post-stimulation and remained higher than baseline values at 220 min post-stimulation. Local perfusion with tetrodotoxin (TTX, 10 μM markedly reduced baseline NA and DA in the mPFC and Occ and totally suppressed the effect of electrical stimulation in both areas. A sequence of five 20 min stimulations at 20 min intervals were delivered to the LC. Each stimulus increased NA to the same extent and duration as the first stimulus, whereas DA remained elevated at the time next stimulus was delivered, so that baseline DA progressively increased in the mPFC and Occ to reach about 130 and 200% the initial level, respectively. In the presence of the NA transport (NAT blocker desipramine (DMI, 100 μM, multiple LC stimulation still increased extracellular NA and DA levels. Electrical stimulation of the LC increased NA levels in the homolateral caudate nucleus, but failed to modify DA level. Conclusion The results confirm and extend that LC stimulation induces a concomitant

  9. Genomic analysis of microRNA time-course expression in liver of mice treated with genotoxic carcinogen N-ethyl-N-nitrosourea

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    Guo Lei

    2010-10-01

    Full Text Available Abstract Background Dysregulated expression of microRNAs (miRNAs has been previously observed in human cancer tissues and shown promise in defining tumor status. However, there is little information as to if or when expression changes of miRNAs occur in normal tissues after carcinogen exposure. Results To explore the possible time-course changes of miRNA expression induced by a carcinogen, we treated mice with one dose of 120 mg/kg N-ethyl-N-nitrosourea (ENU, a model genotoxic carcinogen, and vehicle control. The miRNA expression profiles were assessed in the mouse livers in a time-course design. miRNAs were isolated from the livers at days 1, 3, 7, 15, 30 and 120 after the treatment and their expression was determined using a miRNA PCR Array. Principal component analysis of the miRNA expression profiles showed that miRNA expression at post-treatment days (PTDs 7 and 15 were different from those at the other time points and the control. The number of differentially expressed miRNAs (DEMs changed over time (3, 5, 14, 32, 5 and 5 at PTDs 1, 3, 7, 15, 30 and 120, respectively. The magnitude of the expression change varied with time with the highest changes at PTDs 7 or 15 for most of the DEMs. In silico functional analysis of the DEMs at PTDs 7 and 15 indicated that the major functions of these ENU-induced DEMs were associated with DNA damage, DNA repair, apoptosis and other processes related to carcinogenesis. Conclusion Our results showed that many miRNAs changed their expression to respond the exposure of the genotoxic carcinogen ENU and the number and magnitude of the changes were highest at PTDs 7 to 15. Thus, one to two weeks after the exposure is the best time for miRNA expression sampling.

  10. Effects of load and maintenance duration on the time course of information encoding and retrieval in working memory: from perceptual analysis to post-categorization processes.

    Science.gov (United States)

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2014-01-01

    information encoding, maintenance, and retrieval; these are supported by brain activity in a network of frontal, parietal and temporal regions. Manipulation of WM load and duration of the maintenance period can modulate this activity. Although such modulations have been widely studied using the event-related potentials (ERP) technique, a precise description of the time course of brain activity during encoding and retrieval is still required. Here, we used this technique and principal component analysis to assess the time course of brain activity during encoding and retrieval in a delayed match to sample task. We also investigated the effects of memory load and duration of the maintenance period on ERP activity. Brain activity was similar during information encoding and retrieval and comprised six temporal factors, which closely matched the latency and scalp distribution of some ERP components: P1, N1, P2, N2, P300, and a slow wave. Changes in memory load modulated task performance and yielded variations in frontal lobe activation. Moreover, the P300 amplitude was smaller in the high than in the low load condition during encoding and retrieval. Conversely, the slow wave amplitude was higher in the high than in the low load condition during encoding, and the same was true for the N2 amplitude during retrieval. Thus, during encoding, memory load appears to modulate the processing resources for context updating and post-categorization processes, and during retrieval it modulates resources for stimulus classification and context updating. Besides, despite the lack of differences in task performance related to duration of the maintenance period, larger N2 amplitude and stronger activation of the left temporal lobe after long than after short maintenance periods were found during information retrieval. Thus, results regarding the duration of maintenance period were complex, and future work is required to test the time-based decay theory predictions.

  11. Time Course of Detection of Human Male DNA from Stained Blood Sample on Various Surfaces by Loop Mediated Isothermal Amplification and Polymerase Chain Reaction

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    Panan Kanchanaphum

    2018-01-01

    Full Text Available This study explores determining the sex of humans from blood stains taken from different surfaces and compares the time course of detection with the conventional PCR, Conventional Loop Mediated Isothermal Amplification (LAMP, and LAMP-Lateral Flow Dipstick (LFD. For the DNA templates, 7 male and 7 female blood stained samples were extracted and added to LAMP and PCR reaction solution to amplify the SRY gene. The DNA samples were extracted from the following blood stained materials: cloth, wood, clay, and tile. Then, the samples were stored at room temperature for 1, 7, 30, and 60 day(s. After the DNA amplification, the gel electrophoresis process was applied to detect LAMP product. The LFD was combined with the LAMP to detect LAMP product on the male cloth samples. For the male samples, the time course of detection on the first and seventh days indicated positive for both LAMP and PCR products on all the surfaces while no DNA amplification was found on any of the female samples. On day 30, positive LAMP product was still found on all the male samples. However, it had faded on the tiles. Moreover, all the male samples, which had tested positive for PCR product, were blurred and unclear. On day 60, LAMP product was still found on all the male samples. Conversely, the PCR method resulted in no bands showing for any of the male samples. However, the LAMP-LFD method detected product on all the male samples of cloth. The results show that the LAMP is an effective, practical, and reliable molecular-biological method. Moreover, the LFD can increase the efficiency and sensitivity of the LAMP, making it more suitable for field studies because gel electrophoresis apparatus is not required.

  12. Effects of load and maintenance duration on the time course of information encoding and retrieval in working memory: from perceptual analysis to post-categorization processes.

    Directory of Open Access Journals (Sweden)

    Diego ePinal

    2014-04-01

    Full Text Available Working memory (WM involves three cognitive events: information encoding, maintenance and retrieval; these are supported by brain activity in a network of frontal, parietal and temporal regions. Manipulation of WM load and duration of the maintenance period can modulate this activity. Although such modulations have been widely studied using the ERP technique, a precise description of the time course of brain activity during encoding and retrieval is still required. Here, we used this technique and principal component analysis to assess the time course of brain activity during encoding and retrieval in a delayed match to sample task. We also investigated the effects of memory load and duration of the maintenance period on ERP activity. Brain activity was similar during information encoding and retrieval and comprised six temporal factors, which closely matched the latency and scalp distribution of some ERP components: P1, N1, P2, N2, P300 and a slow wave. Changes in memory load modulated task performance and yielded variations in frontal lobe activation. Moreover, the P300 amplitude was smaller in the high than in the low load condition during encoding and retrieval. Conversely, the slow wave amplitude was higher in the high than in the low load condition during encoding, and the same was true for the N2 amplitude during retrieval. Thus, during encoding, memory load appears to modulate the processing resources for context updating and post-categorization processes, and during retrieval it modulates resources for stimulus classification and context updating. Besides, despite the lack of differences in task performance related to duration of the maintenance period, larger N2 amplitude and stronger activation of the left temporal lobe after long than after short maintenance periods were found during information retrieval. Thus, results regarding the duration of maintenance period were complex, and future work is required to test the time-based decay

  13. The Time-Course of Sentence Meaning Composition. N400 Effects of the Interaction between Context-Induced and Lexically Stored Affordances

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    Erica Cosentino

    2017-05-01

    Full Text Available Contemporary semantic theories can be classified along two dimensions: (i the way and time-course in which contextual factors influence sentence truth-conditions; and (ii whether and to what extent comprehension involves sensory, motor and emotional processes. In order to explore this theoretical space, our ERP study investigates the time-course of the interaction between the lexically specified telic component of a noun (the function of the object to which the noun refers to, e.g., a funnel is generally used to pour liquids into containers and an ad-hoc affordance contextually induced by the situation described in the discourse. We found that, if preceded by a neutral discourse context, a verb incongruent with the noun's telic component as in “She uses the funnel to hang her coat” elicited an enhanced N400 compared to a congruent verb as in “She uses the funnel to pour water into a container.” However, if the situation introduced in the preceding discourse induced a new function for the object as an ad-hoc affordance (e.g., the funnel is glued to the wall and the agent wants to hang the coat, we observed a crossing-over regarding the direction of the N400 effect: comparing the ad-hoc affordance-inducing context with the neutral context, the N400 for the incongruent verb was significantly reduced, whereas the N400 for the congruent verb was significantly enhanced. We explain these results as a consequence of the incorporation of the contextually triggered ad-hoc affordance into the meaning of the noun. Combining these results with an analysis of semantic similarity values between test sentences and contexts, we argue that one possibility is that the incorporation of an ad-hoc affordance may be explained on the basis of the mental simulation of concurrent motor information.

  14. Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation

    International Nuclear Information System (INIS)

    Siegel, Andrew M; Culver, Joseph P; Mandeville, Joseph B; Boas, David A

    2003-01-01

    The time courses of oxyhaemoglobin ([HbO 2 ]), deoxyhaemoglobin ([HbR]) and total haemoglobin ([HbT]) concentration changes following cortical activation in rats by electrical forepaw stimulation were measured using diffuse optical tomography (DOT) and compared to similar measurements performed previously with fMRI at 2.0 T and 4.7 T. We also explored the qualitative effects of varying stimulus parameters on the temporal evolution of the hemodynamic response. DOT images were reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16 detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO 2 ] time courses were compared to the fMRI BOLD time course during stimulation, and the DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time course. We believe that DOT and fMRI can provide similar temporal information for both blood volume and deoxyhaemoglobin changes, which helps to cross-validate these two techniques and to demonstrate that DOT can be useful as a complementary modality to fMRI for investigating the hemodynamic response to neuronal activity

  15. Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Siegel, Andrew M [Tufts University Bioengineering Center, Medford, MA 02155 (United States); Culver, Joseph P [Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129 (United States); Mandeville, Joseph B [Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129 (United States); Boas, David A [Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129 (United States)

    2003-05-21

    The time courses of oxyhaemoglobin ([HbO{sub 2}]), deoxyhaemoglobin ([HbR]) and total haemoglobin ([HbT]) concentration changes following cortical activation in rats by electrical forepaw stimulation were measured using diffuse optical tomography (DOT) and compared to similar measurements performed previously with fMRI at 2.0 T and 4.7 T. We also explored the qualitative effects of varying stimulus parameters on the temporal evolution of the hemodynamic response. DOT images were reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16 detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO{sub 2}] time courses were compared to the fMRI BOLD time course during stimulation, and the DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time course. We believe that DOT and fMRI can provide similar temporal information for both blood volume and deoxyhaemoglobin changes, which helps to cross-validate these two techniques and to demonstrate that DOT can be useful as a complementary modality to fMRI for investigating the hemodynamic response to neuronal activity.

  16. Deep Brain Stimulation Frequency—A Divining Rod for New and Novel Concepts of Nervous System Function and Therapy

    Directory of Open Access Journals (Sweden)

    Erwin B. Montgomery

    2016-08-01

    Full Text Available The efficacy of Deep Brain Stimulation (DBS for an expanding array of neurological and psychiatric disorders demonstrates directly that DBS affects the basic electroneurophysiological mechanisms of the brain. The increasing array of active electrode configurations, stimulation currents, pulse widths, frequencies, and pulse patterns provides valuable tools to probe electroneurophysiological mechanisms. The extension of basic electroneurophysiological and anatomical concepts using sophisticated computational modeling and simulation has provided relatively straightforward explanations of all the DBS parameters except frequency. This article summarizes current thought about frequency and relevant observations. Current methodological and conceptual errors are critically examined in the hope that future work will not replicate these errors. One possible alternative theory is presented to provide a contrast to many current theories. DBS, conceptually, is a noisy discrete oscillator interacting with the basal ganglia–thalamic–cortical system of multiple re-entrant, discrete oscillators. Implications for positive and negative resonance, stochastic resonance and coherence, noisy synchronization, and holographic memory (related to movement generation are presented. The time course of DBS neuronal responses demonstrates evolution of the DBS response consistent with the dynamics of re-entrant mechanisms. Finally, computational modeling demonstrates identical dynamics as seen by neuronal activities recorded from human and nonhuman primates, illustrating the differences of discrete from continuous harmonic oscillators and the power of conceptualizing the nervous system as composed on interacting discrete nonlinear oscillators.

  17. Growth hormone/IGF-1 axis longitudinal evaluation in clinically isolated syndrome patients on interferon β-1b therapy: stimulation tests and correlations with clinical and radiological conversion to multiple sclerosis.

    Science.gov (United States)

    Lanzillo, R; Di Somma, C; Quarantelli, M; Carotenuto, A; Pivonello, C; Moccia, M; Cianflone, A; Marsili, A; Puorro, G; Saccà, F; Russo, C V; De Luca Picione, C; Ausiello, F; Colao, A; Brescia Morra, V

    2017-02-01

    Growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis abnormalities in multiple sclerosis (MS) suggest their role in its pathogenesis. Interferon β (IFN-β) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome (CIS) patients and their correlation with conversion to MS in IFN treated patients. Clinical and demographic features of CIS patients were collected before the start of IFN-β-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years. Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency (GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age (P IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence. Growth hormone/IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression. © 2016 EAN.

  18. Time course of electrophysiologic effects induced by di-n-butyl-2,2-dichlorovinyl phosphate (DBCV) in the adult hen.

    Science.gov (United States)

    Robertson, D G; Mattson, A M; Bestervelt, L L; Richardson, R J; Anderson, R J

    1988-01-01

    Previous work in our laboratory indicated that di-n-butyl-2,2-dichlorovinyl phosphate (DBCV) produced electrophysiologic changes in hen peripheral nerve that coincided with the development of histopathologic changes and neurologic signs of peripheral neuropathy. The purpose of the present study was to follow the time course for the development of the electrophysiologic changes and to determine whether pretreatment with the phosphinate analog of DBCV (DBCV-P), a nonageable organophosphorus compound, prevented these effects. Although significant electrophysiologic deficits occurred in the tibial and sciatic nerve 24 h after DBCV treatment, the most marked changes coincided with the onset of clinical signs of organophosphorus-induced delayed neuropathy (14-21 d). The sciatic and tibial nerves were equally susceptible to DBCV in producing deficits characterized by changes in the relative refractory period and an increased strength-duration threshold. Pretreatment with DBCV-P prevented the clinical signs and also attenuated the electrophysiologic deficits induced by DBCV treatment. These data suggest that electrophysiologic deficits occur before clinical signs of organophosphorus-induced delayed neuropathy (OPIDN) and may be indicative of a link between neurotoxic esterase (NTE) inhibition and onset of overt clinical toxicity.

  19. Time course of the effects of lisdexamfetamine dimesylate in two phase 3, randomized, double-blind, placebo-controlled trials in adults with binge-eating disorder.

    Science.gov (United States)

    McElroy, Susan L; Hudson, James I; Gasior, Maria; Herman, Barry K; Radewonuk, Jana; Wilfley, Denise; Busner, Joan

    2017-08-01

    This study examined the time course of efficacy-related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol-defined moderate to severe binge-eating disorder (BED). In two 12-week, double-blind, placebo-controlled studies, adults meeting DSM-IV-TR BED criteria were randomized 1:1 to receive placebo or dose-optimized LDX (50 or 70 mg). Analyses across visits used mixed-effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE] scores, percentage body weight change) and chi-square tests (Clinical Global Impressions-Improvement [CGI-I; from the perspective of BED symptoms] scale dichotomized as improved or not improved). These analyses were not part of the prespecified testing strategy, so reported p values are nominal (unadjusted and descriptive only). Least squares mean treatment differences for change from baseline in both studies favored LDX over placebo (all nominal p values binge eating days/week, binge-eating episodes/week, and percentage weight change and at the first posttreatment assessment (Week 4) for Y-BOCS-BE total and domain scores. On the CGI-I, more participants on LDX than placebo were categorized as improved starting at Week 1 in both studies (both nominal p values Eating Disorders Published by Wiley Periodicals, Inc.

  20. The pattern and time course of somatosensory changes in the human UVB sunburn model reveal the presence of peripheral and central sensitization.

    Science.gov (United States)

    Gustorff, Burkhard; Sycha, Thomas; Lieba-Samal, Doris; Rolke, Roman; Treede, Rolf-Detlef; Magerl, Walter

    2013-04-01

    The ultraviolet B (UVB) sunburn model was characterized with a comprehensive battery of quantitative sensory testing (QST). Primary hyperalgesia in UVB-irradiated skin and secondary hyperalgesia in adjacent nonirradiated skin were studied in 22 healthy subjects 24h after irradiation with UVB at 3-fold minimal erythema dose of a skin area 5 cm in diameter at the thigh and compared to mirror-image contralateral control areas. The time course of hyperalgesia over 96 h was studied in a subgroup of 12 subjects. Within the sunburn area, cold hyperesthesia (P=.01), profound generalized hyperalgesia to heat (Psunburn was surrounded by large areas of pinprick hyperalgesia (mean±SEM, 218±32 cm(2)) and a small rim of dynamic mechanical allodynia but no other sensory changes. Although of smaller magnitude, secondary hyperalgesia and dynamic mechanical allodynia adjacent to the UVB-irradiated area were statistically highly significant. Primary and secondary hyperalgesia developed in parallel within hours, peaked after 24-32 h, and lasted for more than 96 h. These data reveal that the UVB sunburn model activates a broad spectrum of peripheral and central sensitization mechanisms and hence is a useful human surrogate model to be used as a screening tool for target engagement in phases 1 and 2a of drug development. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. An elevated neutrophil-lymphocyte ratio is associated with adverse outcomes following single time-point paracetamol (acetaminophen) overdose: a time-course analysis.

    Science.gov (United States)

    Craig, Darren G; Kitto, Laura; Zafar, Sara; Reid, Thomas W D J; Martin, Kirsty G; Davidson, Janice S; Hayes, Peter C; Simpson, Kenneth J

    2014-09-01

    The innate immune system is profoundly dysregulated in paracetamol (acetaminophen)-induced liver injury. The neutrophil-lymphocyte ratio (NLR) is a simple bedside index with prognostic value in a number of inflammatory conditions. To evaluate the prognostic accuracy of the NLR in patients with significant liver injury following single time-point and staggered paracetamol overdoses. Time-course analysis of 100 single time-point and 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Timed laboratory samples were correlated with time elapsed after overdose or admission, respectively, and the NLR was calculated. A total of 49/100 single time-point patients developed hepatic encephalopathy (HE). Median NLRs were higher at both 72 (P=0.0047) and 96 h after overdose (P=0.0041) in single time-point patients who died or were transplanted. Maximum NLR values by 96 h were associated with increasing HE grade (P=0.0005). An NLR of more than 16.7 during the first 96 h following overdose was independently associated with the development of HE [odds ratio 5.65 (95% confidence interval 1.67-19.13), P=0.005]. Maximum NLR values by 96 h were strongly associated with the requirement for intracranial pressure monitoring (Pparacetamol overdoses. Future studies should assess the value of incorporating the NLR into existing prognostic and triage indices of single time-point paracetamol overdose.

  2. Time course of syllabic and sub-syllabic processing in Mandarin word production: Evidence from the picture-word interference paradigm.

    Science.gov (United States)

    Wang, Jie; Wong, Andus Wing-Kuen; Chen, Hsuan-Chih

    2017-06-05

    The time course of phonological encoding in Mandarin monosyllabic word production was investigated by using the picture-word interference paradigm. Participants were asked to name pictures in Mandarin while visual distractor words were presented before, at, or after picture onset (i.e., stimulus-onset asynchrony/SOA = -100, 0, or +100 ms, respectively). Compared with the unrelated control, the distractors sharing atonal syllables with the picture names significantly facilitated the naming responses at -100- and 0-ms SOAs. In addition, the facilitation effect of sharing word-initial segments only appeared at 0-ms SOA, and null effects were found for sharing word-final segments. These results indicate that both syllables and subsyllabic units play important roles in Mandarin spoken word production and more critically that syllabic processing precedes subsyllabic processing. The current results lend strong support to the proximate units principle (O'Seaghdha, Chen, & Chen, 2010), which holds that the phonological structure of spoken word production is language-specific and that atonal syllables are the proximate phonological units in Mandarin Chinese. On the other hand, the significance of word-initial segments over word-final segments suggests that serial processing of segmental information seems to be universal across Germanic languages and Chinese, which remains to be verified in future studies.

  3. Attempt to determine radon entry rate and air exchange rate variable in time from the time course of indoor radon concentration

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, J [State Office for Nuclear Protection, Prague (Czech Republic)

    1996-12-31

    For radon diagnosis in houses the `ventilation experiment` was used as a standard method. After removal of indoor radon by draught the build-up of radon concentration a(t) [Bq/m{sup 3}] was measured continuously and from the time course the constant radon entry rate A [Bq/h] and the exchange rate k [h{sup -1}] was calculated by regression analysis using model relation a(t) A(1-e{sup -kt})/kV with V [m{sup 3}] for volume of the room. The conditions have to be stable for several hours so that the assumption of constant A and k was justified. During the day both quantities were independently (?) changing, therefore a method to determine variable entry rate A(t) and exchange rate k(t) is needed for a better understanding of the variability of the indoor radon concentration. Two approaches are given for the determination of variable in time radon entry rates and air exchange rates from continuously measured indoor radon concentration - numerical solution of the equivalent difference equations in deterministic or statistic form. The approaches are not always successful. Failures giving a right ration for the searched rates but not of the rates them self could not be explained.

  4. Time course of fibronectin in the peri-implant tissue and neointima formation after functional implantation of polyester-based vascular prostheses with different porosity in pigs

    Energy Technology Data Exchange (ETDEWEB)

    Patrzyk, Maciej; Hoene, Andreas [Department of Surgery, Ernst Moritz Arndt University Greifswald, Friedrich-Loeffler-Str. 23, D-17489 Greifswald (Germany); Jarchow, Raymond [Computation Centre, Ernst Moritz Arndt University Greifswald, Felix-Hausdorff-Str. 12, D-17489 Greifswald (Germany); Wilhelm, Lutz [Department of Surgery, Hospital Demmin, Loitzer Str. 1, D-17109 Demmin (Germany); Walschus, Uwe; Schlosser, Michael [Research Group of Predictive Diagnostics of the Department of Medical Biochemistry and Molecular Biology and Institute of Pathophysiology, Ernst Moritz Arndt University Greifswald, Greifswalder Str. 11c, D-17495 Karlsburg (Germany); Zippel, Roland, E-mail: schlosse@uni-greifswald.d [Department of Surgery, Elbland Hospital Center, Weinbergstr. 8, D-01589 Riesa (Germany)

    2010-10-01

    Intima hyperplasia, resulting from extracellular matrix (ECM) secretion, can lead to vascular prosthesis occlusion and is a major problem in vascular surgery. Fibronectin might contribute to ongoing ECM secretion. However, the exact role of fibronectin and its influence on neointima formation remains unclear. This study was aimed at investigating the time course of the fibronectin area fraction and neointima formation following the functional implantation of three different polyester vascular prostheses into pigs. The infrarenal aorta from 15 animals (n = 5/group) was replaced by prosthesis segments with low, medium and high primary porosity. After 7, 14, 21, 28 and 116 days, the prostheses were morphometrically examined. Overall, the fibronectin area fraction was inversely correlated with the neointima thickness, demonstrating high fibronectin levels in the early phase (days 7 and 14) and low levels in the later phase with almost complete neointima formation (days 21-116). Throughout the study, fibronectin levels were highest at the proximal anastomosis region. The low porosity prosthesis had the highest fibronectin area fraction and a delayed neointima formation in the middle phase (days 21 and 28) but the highest neointima lining on day 116. The results indicate a relationship between fibronectin and neointima formation with the prosthesis porosity, demonstrating the importance of the textile design for tissue reactions following implantation.

  5. Tracking the time course of multi-word noun phrase production with ERPs or on when (and why) cat is faster than the big cat.

    Science.gov (United States)

    Bürki, Audrey; Laganaro, Marina

    2014-01-01

    Words are rarely produced in isolation. Yet, our understanding of multi-word production, and especially its time course, is still rather poor. In this research, we use event-related potentials to examine the production of multi-word noun phrases in the context of overt picture naming. We track the processing costs associated with the production of these noun phrases as compared with the production of bare nouns, from picture onset to articulation. Behavioral results revealed longer naming latencies for French noun phrases with determiners and pre-nominal adjectives (D-A-N, the big cat) than for noun phrases with a determiner (D-N, the cat), or bare nouns (N, cat). The spatio-temporal analysis of the ERPs revealed differences in the duration of stable global electrophysiological patterns as a function of utterance format in two time windows, from ~190 to 300 ms after picture onset, and from ~530 ms after picture onset to 100 ms before articulation. These findings can be accommodated in the following model. During grammatical encoding (here from ~190 to 300 ms), the noun and adjective lemmas are accessed in parallel, followed by the selection of the gender-agreeing determiner. Phonological encoding (after ~530 ms) operates sequentially. As a consequence, the phonological encoding process is longer for longer utterances. In addition, when determiners are repeated across trials, their phonological encoding can be anticipated or primed, resulting in a shortened encoding process.

  6. Tracking the time course of multi-word noun phrase production with ERPs or on when (and why cat is faster than the big cat

    Directory of Open Access Journals (Sweden)

    Audrey eBürki

    2014-07-01

    Full Text Available Words are rarely produced in isolation. Yet, our understanding of multi-word production, and especially its time course, is still rather poor. In this research, we use event-related potentials to examine the production of multi-word noun phrases in the context of overt picture naming. We track the processing costs associated with the production of these noun phrases as compared with the production of bare nouns, from picture onset to articulation. Behavioral results revealed longer naming latencies for French noun phrases with determiners and pre-nominal adjectives (D-A-N, the big cat than for noun phrases with a determiner (D-N, the cat or bare nouns (N, cat. The spatio-temporal analysis of the ERPs revealed differences in the duration of stable global electrophysiological patterns as a function of utterance format in two time windows, from ~190 ms to 300 ms after picture onset, and from ~530 ms after picture onset to 100 ms before articulation. These findings can be accommodated in the following model. During grammatical encoding (here from ~190 ms to 300 ms, the noun and adjective lemmas are accessed in parallel, followed by the selection of the gender-agreeing determiner. Phonological encoding (after ~530 ms operates sequentially. As a consequence, the phonological encoding process is longer for longer utterances. In addition, when determiners are repeated across trials, their phonological encoding can be anticipated or primed, resulting in a shortened encoding process.

  7. Time course of gamma-band oscillation associated with face processing in the inferior occipital gyrus and fusiform gyrus: A combined fMRI and MEG study.

    Science.gov (United States)

    Uono, Shota; Sato, Wataru; Kochiyama, Takanori; Kubota, Yasutaka; Sawada, Reiko; Yoshimura, Sayaka; Toichi, Motomi

    2017-04-01

    Debate continues over whether the inferior occipital gyrus (IOG) or the fusiform gyrus (FG) represents the first stage of face processing and what role these brain regions play. We investigated this issue by combining functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in normal adults. Participants passively observed upright and inverted faces and houses. First, we identified the IOG and FG as face-specific regions using fMRI. We applied beamforming source reconstruction and time-frequency analysis to MEG source signals to reveal the time course of gamma-band activations in these regions. The results revealed that the right IOG showed higher gamma-band activation in response to upright faces than to upright houses at 100 ms from the stimulus onset. Subsequently, the right FG showed greater gamma-band response to upright faces versus upright houses at around 170 ms. The gamma-band activation in the right IOG and right FG was larger in response to inverted faces than to upright faces at the later time window. These results suggest that (1) the gamma-band activities occurs rapidly first in the IOG and next in the FG and (2) the gamma-band activity in the right IOG at later time stages is involved in configuration processing for faces. Hum Brain Mapp 38:2067-2079, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Time course of infarct healing and left ventricular remodelling in patients with reperfused ST segment elevation myocardial infarction using comprehensive magnetic resonance imaging

    International Nuclear Information System (INIS)

    Ganame, Javier; Messalli, Giancarlo; Dymarkowski, Steven; Abbasi, Kayvan; Bogaert, Jan; Masci, Pier Giorgio; Werf, Frans van de; Janssens, Stefan

    2011-01-01

    To describe the time course of myocardial infarct (MI) healing and left ventricular (LV) remodelling and to assess factors predicting LV remodelling using cardiac MRI. In 58 successfully reperfused MI patients, MRI was performed at baseline, 4 months (4M), and 1 year (1Y) post MI Infarct size decreased between baseline and 4M (p < 0.001), but not at 1Y; i.e. 18 ± 11%, 12 ± 8%, 11 ± 6% of LV mass respectively; this was associated with LV mass reduction. Infarct and adjacent wall thinning was found at 4M, whereas significant remote wall thinning was measured at 1Y. LV end-diastolic and end-systolic volumes significantly increased at 1Y, p < 0.05 at 1Y vs. baseline and vs. 4M; this was associated with increased LV sphericity index. No regional or global LV functional improvement was found at follow-up. Baseline infarct size was the strongest predictor of adverse LV remodelling. Infarct healing, with shrinkage of infarcted myocardium and wall thinning, occurs early post-MI as reflected by loss in LV mass and adjacent myocardial remodelling. Longer follow-up demonstrates ongoing remote myocardial and ventricular remodelling. Infarct size at baseline predicts long-term LV remodelling and represents an important parameter for tailoring future post-MI pharmacological therapies designed to prevent heart failure. (orig.)

  9. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study.

    Science.gov (United States)

    Li, Linxin; Geraghty, Olivia C; Mehta, Ziyah; Rothwell, Peter M

    2017-07-29

    Lifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70-90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages. We did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan-Meier risk estimates and relative risk reduction estimates from previous trials. 3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13 509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27-4·24; pbleeds (5·53, 2·65-11·54; pbleeds (≥75 years HR 4·13, 2·60-6·57; pbleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered

  10. Electrophysiological evidence of the time course of attentional bias in nonpatients reporting symptoms of depression with and without co-occurring anxiety

    Directory of Open Access Journals (Sweden)

    Sarah M. Sass

    2014-04-01

    Full Text Available Anxiety is characterized by attentional biases to threat, but findings are inconsistent for depression. To address this inconsistency, the present study systematically assessed the role of co-occurring anxiety in attentional bias in depression. In addition, the role of emotional valence, arousal, and gender was explored. Ninety-two nonpatients completed the Penn State Worry Questionnaire (PSWQ; Meyer et al., 1990; Molina & Borkovec, 1994 and portions of the Mood and Anxiety Symptom Questionnaire (MASQ; Watson, Clark, et al., 1995; Watson, Weber, et al., 1995. Individuals reporting high levels of depression and low levels of anxiety (depression only, high levels of depression and anxiety (combined, or low levels of both (control completed an emotion-word Stroop task during event-related brain potential (ERP recording. Pleasant and unpleasant words were matched on emotional arousal level. An attentional bias was not evident in the depression-only group. Women in the combined group had larger N200 amplitude for pleasant than unpleasant stimuli, and the combined group as a whole had larger right-lateralized P300 amplitude for pleasant than unpleasant stimuli, consistent with an early and later attentional bias that is specific to unpleasant valence in the combined group. Men in the control group had larger N200 amplitude for pleasant than unpleasant stimuli, consistent with an early attentional bias that is specific to pleasant valence. The present study indicates that the nature and time course of attention prompted by emotional valence and not arousal differentiates depression with and without anxiety, with some evidence of gender moderating early effects. Overall, results suggest that co-occurring anxiety is more important than previously acknowledged in demonstrating evidence of attentional biases in depression.

  11. Acute Postexercise Time Course Responses of Hypertrophic vs. Power-Endurance Squat Exercise Protocols on Maximal and Rapid Torque of the Knee Extensors.

    Science.gov (United States)

    Conchola, Eric C; Thiele, Ryan M; Palmer, Ty B; Smith, Doug B; Thompson, Brennan J

    2015-05-01

    The aim of this study was to examine the effects of a medium-intensity high-volume vs. explosive squat protocol on the postexercise time course responses of maximal and rapid strength of the knee extensors. Seventeen resistance-trained men (mean ± SD: age = 22.0 ± 2.6 years) performed maximal voluntary contractions (MVCs) of the knee extensors before and after performing a squat workout using either a low-intensity fast velocity (LIFV) (5 × 16 at 40% 1 repetition maximum) or a traditional high-intensity slow velocity (TISV) (5 × 8 at 80% 1RM) exercise protocol. For each MVC, peak torque (PT), peak rate of torque development (RTDpeak), absolute (RTDabs), and relative RTD (RTDnorm) at early (0-50 milliseconds) and late (100-200 milliseconds) phases of muscle contraction were examined at pre- (Pre) and post-exercise at 0, 7, 15, and 30 (Post0...30) minutes. There were no intensity × time interactions for any variables (p = 0.098-0.832). Peak torque was greater at Pre than Post0 and Post7 (p = 0.001-0.016) but was not greater than Post15 and Post30 (p = 0.010-0.189). RTDpeak and early absolute RTD (RTD50abs) were greater at Pre than all postexercise time phases (p = 0.001-0.050); however, later absolute RTD (RTD100-200abs) was only greater at Pre than Post0 and Post30 (p = 0.013-0.048). Early relative RTD (RTD50norm) was only higher at Pre compared with Post0 (p = 0.023), whereas no differences were observed for later relative RTD (RTD100-200norm) (p = 0.920-0.990). Low-intensity fast velocity and TISV squat protocols both yielded acute decreases in maximal and rapid strength capacities following free-weight squats, with rapid strength showing slower recovery characteristics than maximal strength.

  12. Time course of the effects of lisdexamfetamine dimesylate in two phase 3, randomized, double‐blind, placebo‐controlled trials in adults with binge‐eating disorder

    Science.gov (United States)

    Hudson, James I.; Gasior, Maria; Herman, Barry K.; Radewonuk, Jana; Wilfley, Denise; Busner, Joan

    2017-01-01

    Abstract Objective This study examined the time course of efficacy‐related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol‐defined moderate to severe binge‐eating disorder (BED). Methods In two 12‐week, double‐blind, placebo‐controlled studies, adults meeting DSM‐IV‐TR BED criteria were randomized 1:1 to receive placebo or dose‐optimized LDX (50 or 70 mg). Analyses across visits used mixed‐effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale‐Brown Obsessive Compulsive Scale modified for Binge Eating [Y‐BOCS‐BE] scores, percentage body weight change) and chi‐square tests (Clinical Global Impressions—Improvement [CGI‐I; from the perspective of BED symptoms] scale dichotomized as improved or not improved). These analyses were not part of the prespecified testing strategy, so reported p values are nominal (unadjusted and descriptive only). Results Least squares mean treatment differences for change from baseline in both studies favored LDX over placebo (all nominal p values binge eating days/week, binge‐eating episodes/week, and percentage weight change and at the first posttreatment assessment (Week 4) for Y‐BOCS‐BE total and domain scores. On the CGI‐I, more participants on LDX than placebo were categorized as improved starting at Week 1 in both studies (both nominal p values <  .001). Across these efficacy‐related endpoints, the superiority of LDX over placebo was maintained at each posttreatment assessment in both studies (all nominal p values <  .001). Discussion In adults with BED, LDX treatment appeared to be associated with improvement on efficacy measures as early as 1 week, which was maintained throughout the 12‐week studies. PMID:28481434

  13. SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, L; Esteve, F; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Isere (France); Tessier, A; Balosso, J [Centre Hospitalier Universitaire, La Tronche, Isere (France)

    2014-06-15

    Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0 and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.

  14. Prediction of the time course of callus stiffness as a function of mechanical parameters in experimental rat fracture healing studies--a numerical study.

    Directory of Open Access Journals (Sweden)

    Tim Wehner

    Full Text Available Numerous experimental fracture healing studies are performed on rats, in which different experimental, mechanical parameters are applied, thereby prohibiting direct comparison between each other. Numerical fracture healing simulation models are able to predict courses of fracture healing and offer support for pre-planning animal experiments and for post-hoc comparison between outcomes of different in vivo studies. The aims of this study are to adapt a pre-existing fracture healing simulation algorithm for sheep and humans to the rat, to corroborate it using the data of numerous different rat experiments, and to provide healing predictions for future rat experiments. First, material properties of different tissue types involved were adjusted by comparing experimentally measured callus stiffness to respective simulated values obtained in three finite element (FE models. This yielded values for Young's moduli of cortical bone, woven bone, cartilage, and connective tissue of 15,750 MPa, 1,000 MPa, 5 MPa, and 1 MPa, respectively. Next, thresholds in the underlying mechanoregulatory tissue differentiation rules were calibrated by modifying model parameters so that predicted fracture callus stiffness matched experimental data from a study that used rigid and flexible fixators. This resulted in strain thresholds at higher magnitudes than in models for sheep and humans. The resulting numerical model was then used to simulate numerous fracture healing scenarios from literature, showing a considerable mismatch in only 6 of 21 cases. Based on this corroborated model, a fit curve function was derived which predicts the increase of callus stiffness dependent on bodyweight, fixation stiffness, and fracture gap size. By mathematically predicting the time course of the healing process prior to the animal studies, the data presented in this work provides support for planning new fracture healing experiments in rats. Furthermore, it allows one to transfer and

  15. Time Course of Cerebrovascular Reactivity in Patients Treated for Unruptured Intracranial Aneurysms: A One-Year Transcranial Doppler and Acetazolamide Follow-Up Study

    Directory of Open Access Journals (Sweden)

    Marianne Lundervik Bøthun

    2018-01-01

    Full Text Available Background. Cerebrovascular reactivity (CVR is often impaired in the early phase after aneurysmal subarachnoid hemorrhage. There is, however, little knowledge about the time course of CVR in patients treated for unruptured intracranial aneurysms (UIA. Methods. CVR, assessed by transcranial Doppler and acetazolamide test, was examined within the first postoperative week after treatment for UIA and reexamined one year later. Results. Of 37 patients initially assessed, 34 were reexamined after one year. Bilaterally, baseline and acetazolamide-induced blood flow velocities were higher in the postoperative week compared with one year later (p<0.001. CVR on the ipsilateral side of treatment was lower in the initial examination compared with follow-up (58.9% versus 66.1%, p=0.04. There was no difference in CVR over time on the contralateral side (63.4% versus 65.0%, p=0.65. When mean values of right and left sides were considered there was no difference in CVR between exams. Larger aneurysm size was associated with increased change in CVR (p=0.04, and treatment with clipping was associated with 13.8%-point increased change in CVR compared with coiling (p=0.03. Conclusion. Patients with UIA may have a temporary reduction in CVR on the ipsilateral side after aneurysm treatment. The change in CVR appears more pronounced for larger-sized aneurysms and in patients treated with clipping. We recommend that ipsilateral and contralateral CVR should be assessed separately, as mean values can conceal side-differences.

  16. Alteration of hepatocellular antioxidant gene expression pattern and biomarkers of oxidative damage in diazinon-induced acute toxicity in Wistar rat: A time-course mechanistic study.

    Science.gov (United States)

    Hassani, Shokoufeh; Maqbool, Faheem; Salek-Maghsoudi, Armin; Rahmani, Soheila; Shadboorestan, Amir; Nili-Ahmadabadi, Amir; Amini, Mohsen; Norouzi, Parviz; Abdollahi, Mohammad

    2018-01-01

    In the present survey, the plasma level of diazinon after acute exposure was measured by HPLC method at a time-course manner. In addition, the impact of diazinon on the expression of the key genes responsible for hepatocellular antioxidative defense, including PON1, GPx and CAT were investigated. The increase in oxidative damages in treated rats was determined by measuring LPO, protein carbonyl content and total antioxidant power in plasma. After administration of 85 mg/kg diazinon in ten groups of male Wistar rats at different time points between 0-24 hours, the activity of AChE enzyme was inhibited to about 77.94 %. Significant increases in carbonyl groups and LPO after 0.75 and 1 hours were also observed while the plasma antioxidant power was significantly decreased. Despite the dramatic reduction of GP X and PON1 gene expression, CAT gene was significantly upregulated in mRNA level by 1.1 fold after 4 hours and 1.5-fold after 24 hours due to diazinon exposure, compared to control group. Furthermore, no significant changes in diazinon plasma levels were found after 4 hours in the treated rats. The limits of detection and quantification were 137.42 and 416.52 ng/mL, respectively. The average percentage recoveries from plasma were between 90.62 % and 95.72 %. In conclusion, acute exposure to diazinon increased oxidative stress markers in a time-dependent manner and the changes were consistent with effects on hepatic antioxidant gene expression pattern. The effect of diazinon even as a non-lethal dose was induced on the gene expression of antioxidant enzymes. The change in antioxidant defense system occurs prior to diazinon plasma peak time. These results provide biochemical and molecular evidence supporting potential acute toxicity of diazinon and is beneficial in the evaluation of acute toxicity of other organophosphorus pesticides as well.

  17. Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats

    Directory of Open Access Journals (Sweden)

    R.C.A. Maia

    2015-01-01

    Full Text Available Exercise training (Ex has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP, reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C hypertensive rats. Male Fischer rats (10 weeks old; 150–180 g underwent surgery (2K1C or SHAM and were subsequently divided into a sedentary (SED group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks. Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS in the left ventricle, and increased the catalase (CAT activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

  18. Theory of multichannel magnetic stimulation: toward functional neuromuscular rehabilitation.

    Science.gov (United States)

    Ruohonen, J; Ravazzani, P; Grandori, F; Ilmoniemi, R J

    1999-06-01

    Human excitable cells can be stimulated noninvasively with externally applied time-varying electromagnetic fields. The stimulation can be achieved either by directly driving current into the tissue (electrical stimulation) or by means of electro-magnetic induction (magnetic stimulation). While the electrical stimulation of the peripheral neuromuscular system has many beneficial applications, peripheral magnetic stimulation has so far only a few. This paper analyzes theoretically the use of multiple magnetic stimulation coils to better control the excitation and also to eventually mimic electrical stimulation. Multiple coils allow electronic spatial adjustment of the shape and location of the stimulus without moving the coils. The new properties may enable unforeseen uses for peripheral magnetic stimulation, e.g., in rehabilitation of patients with neuromuscular impairment.

  19. The use of genetically marked infection cohorts to study changes in establishment rates during the time course of a repeated Ascaridia galli infection in chickens

    DEFF Research Database (Denmark)

    Ferdushy, Tania; Luna Olivares, Luz Adilia; Nejsum, Peter

    2015-01-01

    This study investigated the changes in establishment rates during the time course of a 6week trickle infection of chickens with Ascaridia galli at two different dose levels, using a molecular marker. To differentiate early and late infection, two different egg cohorts (haplotype a and haplotype b...

  20. Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study.

    Science.gov (United States)

    Sriwijitkamol, Apiradee; Coletta, Dawn K; Wajcberg, Estela; Balbontin, Gabriela B; Reyna, Sara M; Barrientes, John; Eagan, Phyllis A; Jenkinson, Christopher P; Cersosimo, Eugenio; DeFronzo, Ralph A; Sakamoto, Kei; Musi, Nicolas

    2007-03-01

    Activation of AMP-activated protein kinase (AMPK) by exercise induces several cellular processes in muscle. Exercise activation of AMPK is unaffected in lean (BMI approximately 25 kg/m(2)) subjects with type 2 diabetes. However, most type 2 diabetic subjects are obese (BMI >30 kg/m(2)), and exercise stimulation of AMPK is blunted in obese rodents. We examined whether obese type 2 diabetic subjects have impaired exercise stimulation of AMPK, at different signaling levels, spanning from the upstream kinase, LKB1, to the putative AMPK targets, AS160 and peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, involved in glucose transport regulation and mitochondrial biogenesis, respectively. Twelve type 2 diabetic, eight obese, and eight lean subjects exercised on a cycle ergometer for 40 min. Muscle biopsies were done before, during, and after exercise. Subjects underwent this protocol on two occasions, at low (50% Vo(2max)) and moderate (70% Vo(2max)) intensities, with a 4-6 week interval. Exercise had no effect on LKB1 activity. Exercise had a time- and intensity-dependent effect to increase AMPK activity and AS160 phosphorylation. Obese and type 2 diabetic subjects had attenuated exercise-stimulated AMPK activity and AS160 phosphorylation. Type 2 diabetic subjects had reduced basal PGC-1 gene expression but normal exercise-induced increases in PGC-1 expression. Our findings suggest that obese type 2 diabetic subjects may need to exercise at higher intensity to stimulate the AMPK-AS160 axis to the same level as lean subjects.

  1. Time Course and Association of Functional and Biochemical Markers in Severe Semitendinosus Damage Following Intensive Eccentric Leg Curls: Differences between and within Subjects

    Directory of Open Access Journals (Sweden)

    Gerard Carmona

    2018-02-01

    Full Text Available Purpose: To investigate the extent and evolution of hamstring muscle damage caused by an intensive bout of eccentric leg curls (ELCs by (1 assessing the time course and association of different indirect markers of muscle damage such as changes in the force-generating capacity (FGC, functional magnetic resonance (fMRI, and serum muscle enzyme levels and (2 analyzing differences in the degree of hamstring muscle damage between and within subjects (limb-to-limb comparison.Methods: Thirteen male participants performed six sets of 10 repetitions of an ELC with each leg. Before and at regular intervals over 7 days after the exercise, FGC was measured with maximal isometric voluntary contraction (MVC. Serum enzyme levels, fMRI transverse relaxation time (T2 and perceived muscle soreness were also assessed and compared against the FGC.Results: Two groups of subjects were identified according to the extent of hamstring muscle damage based on decreased FGC and increased serum enzyme levels: high responders (n = 10, severe muscle damage and moderate responders (n = 3, moderate muscle damage. In the high responders, fMRI T2 analysis revealed that the semitendinosus (ST muscle suffered severe damage in the three regions measured (proximal, middle, and distal. The biceps femoris short head (BFsh muscle was also damaged and there were significant differences in the FGC within subjects in the high responders.Conclusion: FGC and serum enzyme levels measured in 10 of the subjects from the sample were consistent with severe muscle damage. However, the results showed a wide range of peak MVC reductions, reflecting different degrees of damage between subjects (high and moderate responders. fMRI analysis confirmed that the ST was the hamstring muscle most damaged by ELCs, with uniform T2 changes across all the measured sections of this muscle. During intensive ELCs, the ST muscle could suffer an anomalous recruitment pattern due to fatigue and damage, placing an

  2. Time course evaluation of myocardial perfusion after reperfusion therapy by 99mTc-tetrofosmin SPECT in patients with acute myocardial infarction.

    Science.gov (United States)

    Tanaka, R; Nakamura, T

    2001-09-01

    Myocardial perfusion imaging with 99mTc-labeled agents immediately after reperfusion therapy can underestimate myocardial salvage. It is also conceivable that delayed imaging is useful for assessing the risk area. However, to our knowledge, very few studies have sequentially evaluated these image changes. We conducted 99mTc-tetrofosmin (TF) and 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) SPECT before and after reperfusion to treat acute myocardial infarction and quantified changes in TF myocardial accumulation and reverse redistribution. Seventeen patients with a first myocardial infarction underwent successful reperfusion. We examined SPECT images obtained at the onset (preimage), those acquired 30 min (early image) and 6 h (delayed image) after TF injection, and images acquired 1, 4, 7, and 20 d after reperfusion (post-1-d, post-4-d, post-7-d, and post-20-d image, respectively). We also examined BMIPP SPECT images after 7 +/- 1.8 d (BMIPP image). Polar maps were divided into 48 segments to calculate percentage uptake, and time course changes in segment numbers below 60% were observed as abnormal area. Moreover, cardiac function was analyzed by gated TF SPECT on 1 and 20 d after reperfusion. In reference to the abnormal area on the early images, the post-1-d image was significantly improved compared with the preimage (P < 0.01) as was the post-7-d image compared with the post-1-d and post-4-d images (P < 0.05, respectively). However, post-20-d and post-7-d images did not significantly differ. Therefore, the improvement in myocardial accumulation reached a plateau 7 d after reperfusion. On the other hand, the abnormal area on the delayed images was significantly greater (P < 0.01) compared with that on the early images from 4 to 20 d after reperfusion, as the value was essentially constant. The correlations of the abnormal area between the preimage and the post-7-d delayed image, the preimage and the BMIPP image, and the post-7-d delayed image and the

  3. Time course and duration of changes in Kv7.2 and Kv11.1 mRNA expression in the hippocampus and piriform cortex following electroconvulsive stimulations

    DEFF Research Database (Denmark)

    Hjaeresen, Marie-Louise; Hageman, Ida; Wortwein, Gitta

    2012-01-01

    A minimum of six electroconvulsive therapy (ECT) treatments has to be delivered to achieve sustained improvement in major depression. However, the mechanisms of the therapeutic actions of ECT are still debated.......A minimum of six electroconvulsive therapy (ECT) treatments has to be delivered to achieve sustained improvement in major depression. However, the mechanisms of the therapeutic actions of ECT are still debated....

  4. Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation

    DEFF Research Database (Denmark)

    Rector, D M; Poe, G R; Kristensen, Morten Pilgaard

    1997-01-01

    , concurrently with larger population postsynaptic potentials. Optical signals occurred over a time course similar to that for electrical signals and increased with larger stimulation amplitude to a maximum, then decreased with further increases in stimulation current. Camera images revealed a topographic......We assessed relationships of evoked electrical and light scattering changes from cat dorsal hippocampus following Schaeffer collateral stimulation. Under anesthesia, eight stimulating electrodes were placed in the left hippocampal CA field and an optic probe, coupled to a photodiode or a charge....... Electrode recordings and photodiode output were simultaneously acquired at 2.4 kHz during single biphasic pulse stimuli 0.5 ms in duration with 0.1-Hz intervals. Camera images were digitized at 100 Hz. An average of 150 responses was calculated for each of six stimulating current levels. Stimuli elicited...

  5. Stimulation of DNA synthesis by 340nm/ 351nm UV laser irradiation

    International Nuclear Information System (INIS)

    Meldrum, R.A.; Wharton, C.W.

    1991-01-01

    During preliminary experiments designed to test the feasibility of using a 'caged' DNA break trapping agent, the authors observed a stimulation of incorporation of 3 H-thymidine into DNA when cells were irradiated with low doses (100-1000J/m 2 ) of 351nm UV laser irradiation. This wavelength is used to photolyse 'caged' dideoxynucleotides in our fast time course measurements of DNA repair in mammalian cells. The dose at which this stimulation was observed is well below that at which measurable damage is detected. (author)

  6. Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes

    International Nuclear Information System (INIS)

    Freemark, M.; D'Ercole, A.J.; Handwerger, S.

    1985-01-01

    The effects of somatomedin-C/insulin-like growth factor I (Sm-C) on glycogen metabolism in cultured hepatocytes from 20-day-old rat fetuses have been examined and compared with the effects of insulin. Sm-C (25-375 ng/ml; 3.25-50 nM) stimulated dose-dependent increases in [ 14 C]glucose incorporation into glycogen (14.4-72.9% and total cell glycogen content (10.6-34.3%. Maximal stimulation of glycogen synthesis by Sm-C occurred at 2-4 h of incubation. Insulin (10 nM to 10 microM) also stimulated [ 14 C]glucose incorporation but its potency was only 1/20th that of Sm-C. The time course of stimulation of glucose incorporation by insulin was identical to that of Sm-C, the dose-response curves of the two hormones were parallel, and the maximal effects of insulin were not enhanced by simultaneous exposure of cells to Sm-C. These findings suggest that Sm-C and insulin stimulate glycogenesis in fetal liver through similar or identical mechanisms. Since the potency of Sm-C was 20 times greater than that of insulin, the glycogenic action of insulin in fetal liver may be mediated through binding to a hepatic receptor which also binds Sm-C. In addition to having mitogenic effects on fetal tissues, Sm-C may have direct anabolic effects on fetal carbohydrate metabolism

  7. Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

    OpenAIRE

    Gunduz, Aysegul; Kumru, Hatice; Pascual-Leone, Alvaro

    2014-01-01

    Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhibits satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in improving ...

  8. Spinal cord stimulation

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007560.htm Spinal cord stimulation To use the sharing features on this page, please enable JavaScript. Spinal cord stimulation is a treatment for pain that uses ...

  9. Feldspar, Infrared Stimulated Luminescence

    DEFF Research Database (Denmark)

    Jain, Mayank

    2014-01-01

    This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars.......This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars....

  10. Growth hormone stimulation test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of ...

  11. A time course study of glucose levels and innate immune response in gilthead seabream (Sparus aurata L.) after exposure to clove oil-eugenol derived anaesthetic.

    Science.gov (United States)

    Bahi, A; Guardiola, F A; Esteban, M A

    2018-06-01

    Clove oil is used as an anaesthetic for many species of fish worldwide; however, relatively few studies have assessed its effects on the innate immune response on these species. The present work aimed to investigate the effects of clove oil-eugenol derived anaesthetic on some humoral and cellular immune response in gilthead seabream (Sparus aurata L.). To compare with an unexposed control group, fish were exposed to 55 ppm clove oil for 5 min, before being sampled at 1, 24 and 48 h post-exposure. Serum glucose level was also measured to obtain information on the fish physiological response after clove oil anaesthesia. One hour after exposure the haemolytic complement activity of fish was lower than in the unexposed group. By contrast, the leucocyte peroxidase activity in head-kidney was significantly stimulated 24 h after exposure to clove oil-eugenol. The rest of innate immune parameters evaluated and the glucose levels not were affected by clove oil exposure at any sampling point. Overall, the use of clove oil at 55 ppm as anaesthetic did not seem to alter the innate immune response and neither did it trigger a stress response. The use of clove oil-eugenol derived had become common practice in aquaculture, and its use with gilthead seabream can be considered safe as it does not cause immunodepression in anesthetized fish. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. TIME COURSE ALTERATIONS OF SATELLITE CELL EVENTS IN RESPONSE TO LIGHT MODERATE ENDURANCE TRAINING IN WHITE GASTROCNEMIUS MUSCLE OF THE RAT

    Directory of Open Access Journals (Sweden)

    Zong-Yan Cai

    2012-01-01

    Full Text Available This study investigated satellite cells and their related molecular events adapted to light moderate endurance training in the white gastrocnemius muscle of the rat. The white gastrocnemius muscle of male Sprague-Dawley rats that had been trained for 4 weeks and 8 weeks, with control rats being analysed alongside them, was selected for analysis (n=3 per group. The training protocol consisted of treadmill running at 20 m · min-1 for 30 min on a 0% grade, for 3 days · week-1. Immunohistochemical staining coupled with image analysis was used for quantification. To provide deeper insight into the cell layer, 40 sections per rat, corresponding to 120 values per group, were obtained as a mean value for statistical comparison. The results indicated that at week 4, training effects increased the vascular endothelial growth factor (VEGF content and c-met positive satellite cell numbers. At week 8, the training effect was attenuated for VEGF and c-met satellite cell numbers, but it increased in the muscle fibre area. Additionally, c-met positive satellite cell numbers correlated with VEGF content (r = 0.79, p<0.05. In conclusion, this study suggests that light moderate endurance training could stimulate satellite cell activation that might be related to VEGF signalling. Additionally, the satellite cells activated by moderate endurance training might contribute to slight growth in myocytes.

  13. Toward the restoration of hand use to a paralyzed monkey: brain-controlled functional electrical stimulation of forearm muscles.

    Directory of Open Access Journals (Sweden)

    Eric A Pohlmeyer

    2009-06-01

    Full Text Available Loss of hand use is considered by many spinal cord injury survivors to be the most devastating consequence of their injury. Functional electrical stimulation (FES of forearm and hand muscles has been used to provide basic, voluntary hand grasp to hundreds of human patients. Current approaches typically grade pre-programmed patterns of muscle activation using simple control signals, such as those derived from residual movement or muscle activity. However, the use of such fixed stimulation patterns limits hand function to the few tasks programmed into the controller. In contrast, we are developing a system that uses neural signals recorded from a multi-electrode array implanted in the motor cortex; this system has the potential to provide independent control of multiple muscles over a broad range of functional tasks. Two monkeys were able to use this cortically controlled FES system to control the contraction of four forearm muscles despite temporary limb paralysis. The amount of wrist force the monkeys were able to produce in a one-dimensional force tracking task was significantly increased. Furthermore, the monkeys were able to control the magnitude and time course of the force with sufficient accuracy to track visually displayed force targets at speeds reduced by only one-third to one-half of normal. Although these results were achieved by controlling only four muscles, there is no fundamental reason why the same methods could not be scaled up to control a larger number of muscles. We believe these results provide an important proof of concept that brain-controlled FES prostheses could ultimately be of great benefit to paralyzed patients with injuries in the mid-cervical spinal cord.

  14. Waddlia chondrophila infects and multiplies in ovine trophoblast cells stimulating an inflammatory immune response.

    Directory of Open Access Journals (Sweden)

    Nick Wheelhouse

    Full Text Available Waddlia chondrophila (W. chondrophila is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus. This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity.Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i. and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways.W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

  15. Waddlia chondrophila infects and multiplies in ovine trophoblast cells stimulating an inflammatory immune response.

    Science.gov (United States)

    Wheelhouse, Nick; Coyle, Christopher; Barlow, Peter G; Mitchell, Stephen; Greub, Gilbert; Baszler, Tim; Rae, Mick T; Longbottom, David

    2014-01-01

    Waddlia chondrophila (W. chondrophila) is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus). This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity. Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i.) and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways. W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

  16. SIMPATIQCO: a server-based software suite which facilitates monitoring the time course of LC-MS performance metrics on Orbitrap instruments.

    Science.gov (United States)

    Pichler, Peter; Mazanek, Michael; Dusberger, Frederico; Weilnböck, Lisa; Huber, Christian G; Stingl, Christoph; Luider, Theo M; Straube, Werner L; Köcher, Thomas; Mechtler, Karl

    2012-11-02

    While the performance of liquid chromatography (LC) and mass spectrometry (MS) instrumentation continues to increase, applications such as analyses of complete or near-complete proteomes and quantitative studies require constant and optimal system performance. For this reason, research laboratories and core facilities alike are recommended to implement quality control (QC) measures as part of their routine workflows. Many laboratories perform sporadic quality control checks. However, successive and systematic longitudinal monitoring of system performance would be facilitated by dedicated automatic or semiautomatic software solutions that aid an effortless analysis and display of QC metrics over time. We present the software package SIMPATIQCO (SIMPle AuTomatIc Quality COntrol) designed for evaluation of data from LTQ Orbitrap, Q-Exactive, LTQ FT, and LTQ instruments. A centralized SIMPATIQCO server can process QC data from multiple instruments. The software calculates QC metrics supervising every step of data acquisition from LC and electrospray to MS. For each QC metric the software learns the range indicating adequate system performance from the uploaded data using robust statistics. Results are stored in a database and can be displayed in a comfortable manner from any computer in the laboratory via a web browser. QC data can be monitored for individual LC runs as well as plotted over time. SIMPATIQCO thus assists the longitudinal monitoring of important QC metrics such as peptide elution times, peak widths, intensities, total ion current (TIC) as well as sensitivity, and overall LC-MS system performance; in this way the software also helps identify potential problems. The SIMPATIQCO software package is available free of charge.

  17. Time-course of occupational psychological and social factors as predictors of new-onset and persistent neck pain: a three-wave prospective study over 4 years.

    Science.gov (United States)

    Christensen, Jan Olav; Knardahl, Stein

    2014-07-01

    The current study estimated the impact of psychological and social work factors over time on neck pain. A sample of Norwegian employees (n=1250) was surveyed on 3 occasions spanning 4 years. Five exposures were studied: quantitative demands, decision control, social climate, empowering leadership, and role conflict. Group-based trajectory models suggested factors changed little over time-employees could be classified by mean levels of exposure into groups exhibiting stable "high", "middle", and "low" levels. The exception was decision control, for which a 4-level classification was derived: "high", "high-middle", "low-middle", and "low". Pain prevalence at the end of the study period was compared across groups. Risk and prognosis were also assessed separately by dividing the sample according to pain status at baseline. For all factors, distinct differences in risk were observed between exposure groups, controlled for pain at baseline, skill level, sex, and age. Statistically significant effects ranged from 0.38 (CI 0.20-0.73, Pempowering leadership to 2.61 (CI 1.09-6.21, P<0.05) for high role conflict. Pain persistence was predicted by high role conflict (OR 3.26, CI 1.30-8.18, P<0.05), high quantitative demands (odds ratio [OR] 3.66, CI 1.58-8.49, P<0.01), and high-middle decision control (OR 0.45, CI 0.21-0.99, P<0.05). Future studies should collect information at multiple time points to clarify the impact of prolonged and changing exposure on musculoskeletal pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  18. Optical stimulated luminescence (OSL) dating

    International Nuclear Information System (INIS)

    Banerjee, D.

    1999-01-01

    Since the pioneering work by Huntley et al. (1985), optical dating is being increasingly recognised as an important technique for establishing a time frame of deposition of sediments (Aitken, 1998). Optical dating differs from thermoluminescence (TL) dating in that visible/infrared light from lasers or LEDs (light-emitting-diodes) is used as a means of stimulation, in contrast to thermal stimulation. It has several advantages over TL dating: (i) the resetting of the OSL (optically stimulated luminescence) clock is more effective than that of TL clock; for sediments transported under water or in other situations where the sediment grains have undergone inhomogeneous bleaching, this property ensures that ages based on optical dating are generally more reliable than TL ages, (ii) the optical dating technique is non-destructive, and multiple readouts of the optical signal is possible; this feature has resulted in the development of single-aliquot and single-grain protocols (Murray and Wintle, 1999; Banerjee et al. 1999), (iii) the sample is not heated as in TL; thus, spurious luminescence is avoided and there is a significant reduction in blackbody radiation. Dating of materials which change phase on heating is also practical, and finally, (iv) thermal quenching of luminescence is negligible, allowing accurate estimation of kinetic parameters using standard techniques and providing access to deep OSL traps. This characteristic may be helpful in extending the limits of optical dating beyond the last 150 ka from a global point of view

  19. Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Andersen, Birgit; Westlund, Barbro; Krarup, Christian

    2003-01-01

    During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique....... This points to increased probability of repetitive spinal MN activation during fatigue even if some MNs in the pool failed to discharge. Silent period duration following cortical stimulation lengthened by an average of 55 ms after the contraction and recovered within a time course similar to that of the TST...

  20. Multiple Perspectives / Multiple Readings

    Directory of Open Access Journals (Sweden)

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  1. Minimal stimulation IVF vs conventional IVF: a randomized controlled trial

    NARCIS (Netherlands)

    Zhang, John J.; Merhi, Zaher; Yang, Mingxue; Bodri, Daniel; Chavez-Badiola, Alejandro; Repping, Sjoerd; van Wely, Madelon

    2016-01-01

    Minimal stimulation in vitro fertilization (mini-in vitro fertilization) is an alternative in vitro fertilization treatment protocol that may reduce ovarian hyperstimulation syndrome, multiple pregnancy rates, and cost while retaining high live birth rates. We performed a randomized noninferiority

  2. The ISMAAR proposal on terminology for ovarian stimulation for IVF

    NARCIS (Netherlands)

    Nargund, G.; Fauser, B. C. J. M.; Macklon, N. S.; Ombelet, W.; Nygren, K.; Frydman, R.

    IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific

  3. The ISMAAR proposal on terminology for ovarian stimulation for IVF

    NARCIS (Netherlands)

    Nargund, G.; Fauser, B. C. J. M.; Macklon, N. S.; Ombelet, W.; Nygren, K.; Frydman, R.

    2007-01-01

    IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific

  4. [Transcranial magnetic stimulation].

    Science.gov (United States)

    Tormos, J M; Catalá, M D; Pascual-Leone, A

    Transcranial magnetic stimulation (TMS) permits stimulation of the cerebral cortex in humans without requiring open access to the brain and is one of the newest tools available in neuroscience. There are two main types of application: single-pulse TMS and repetitive TMS. The magnetic stimulator is composed of a series of capacitors that store the voltage necessary to generate a stimulus of the sufficient intensity of generate an electric field in the stimulation coil. The safety of TMS is supported by the considerable experience derived from studies involving electrical stimulation of the cortex in animals and humans, and also specific studies on the safety of TMS in humans. In this article we review historical and technical aspects of TMS, describe its adverse effects and how to avoid them, summarize the applications of TMS in the investigation of different cerebral functions, and discuss the possibility of using TMS for the treatment of neuropsychiatric disorders.

  5. Music acupuncture stimulation method.

    Science.gov (United States)

    Brătilă, F; Moldovan, C

    2007-01-01

    Harmonic Medicine is the model using the theory that the body rhythms synchronize to an outer rhythm applied for therapeutic purpose, can restores the energy balance in acupuncture channels and organs and the condition of well-being. The purpose of this scientific work was to demonstrate the role played by harmonic sounds in the stimulation of the Lung (LU) Meridian (Shoutaiyin Feijing) and of the Kidney (KI) Meridian (Zushaoyin Shenjing). It was used an original method that included: measurement and electronic sound stimulation of the Meridian Entry Point, measurement of Meridian Exit Point, computer data processing, bio feed-back adjustment of the music stimulation parameters. After data processing, it was found that the sound stimulation of the Lung Meridian Frequency is optimal between 122 Hz and 128 Hz, with an average of 124 Hz (87% of the subjects) and for Kidney Meridian from 118 Hz to 121 Hz, with an average of 120 Hz (67% of the subjects). The acupuncture stimulation was more intense for female subjects (> 7%) than for the male ones. We preliminarily consider that an informational resonance phenomenon can be developed between the acupuncture music stimulation frequency and the cellular dipole frequency, being a really "resonant frequency signature" of an acupoint. The harmonic generation and the electronic excitation or low-excitation status of an acupuncture point may be considered as a resonance mechanism. By this kind of acupunctural stimulation, a symphony may act and play a healer role.

  6. Multiple scler