Short-Term Memory Trace in Rapidly Adapting Synapses of Inferior Temporal Cortex

PubMed Central

Sugase-Miyamoto, Yasuko; Liu, Zheng; Wiener, Matthew C.; Optican, Lance M.; Richmond, Barry J.

2008-01-01

Visual short-term memory tasks depend upon both the inferior temporal cortex (ITC) and the prefrontal cortex (PFC). Activity in some neurons persists after the first (sample) stimulus is shown. This delay-period activity has been proposed as an important mechanism for working memory. In ITC neurons, intervening (nonmatching) stimuli wipe out the delay-period activity; hence, the role of ITC in memory must depend upon a different mechanism. Here, we look for a possible mechanism by contrasting memory effects in two architectonically different parts of ITC: area TE and the perirhinal cortex. We found that a large proportion (80%) of stimulus-selective neurons in area TE of macaque ITCs exhibit a memory effect during the stimulus interval. During a sequential delayed matching-to-sample task (DMS), the noise in the neuronal response to the test image was correlated with the noise in the neuronal response to the sample image. Neurons in perirhinal cortex did not show this correlation. These results led us to hypothesize that area TE contributes to short-term memory by acting as a matched filter. When the sample image appears, each TE neuron captures a static copy of its inputs by rapidly adjusting its synaptic weights to match the strength of their individual inputs. Input signals from subsequent images are multiplied by those synaptic weights, thereby computing a measure of the correlation between the past and present inputs. The total activity in area TE is sufficient to quantify the similarity between the two images. This matched filter theory provides an explanation of what is remembered, where the trace is stored, and how comparison is done across time, all without requiring delay period activity. Simulations of a matched filter model match the experimental results, suggesting that area TE neurons store a synaptic memory trace during short-term visual memory. PMID:18464917

Contrasting phagosome pH regulation and maturation in human M1 and M2 macrophages

PubMed Central

Canton, Johnathan; Khezri, Rojyar; Glogauer, Michael; Grinstein, Sergio

2014-01-01

Macrophages respond to changes in environmental stimuli by assuming distinct functional phenotypes, a phenomenon referred to as macrophage polarization. We generated classically (M1) and alternatively (M2) polarized macrophages—two extremes of the polarization spectrum—to compare the properties of their phagosomes. Specifically, we analyzed the regulation of the luminal pH after particle engulfment. The phagosomes of M1 macrophages had a similar buffering power and proton (equivalent) leakage permeability but significantly reduced proton-pumping activity compared with M2 phagosomes. As a result, only the latter underwent a rapid and profound acidification. By contrast, M1 phagosomes displayed alkaline pH oscillations, which were caused by proton consumption upon dismutation of superoxide, followed by activation of a voltage- and Zn2+-sensitive permeation pathway, likely HV1 channels. The paucity of V-ATPases in M1 phagosomes was associated with, and likely caused by, delayed fusion with late endosomes and lysosomes. The delayed kinetics of maturation was, in turn, promoted by the failure of M1 phagosomes to acidify. Thus, in M1 cells, elimination of pathogens through deployment of the microbicidal NADPH oxidase is given priority at the expense of delayed acidification. By contrast, M2 phagosomes proceed to acidify immediately in order to clear apoptotic bodies rapidly and effectively. PMID:25165138

Utility of multi-channel surface electromyography in assessment of focal hand dystonia.

PubMed

Sivadasan, Ajith; Sanjay, M; Alexander, Mathew; Devasahayam, Suresh R; Srinivasa, Babu K

2013-09-01

Surface electromyography (SEMG) allows objective assessment and guides selection of appropriate treatment in focal hand dystonia (FHD). Sixteen-channel SEMG obtained during different phases of a writing task was used to study timing, activation patterns, and spread of muscle contractions in FHD compared with normal controls. Customized software was developed to acquire and analyze EMG signals. SEMG of FHD subjects (20) showed "early onset" during motor imagery, rapid proximal muscle recruitment, agonist-antagonist co-contraction involving proximal muscle groups, "delayed offset" after stopping writing, higher rectified mean amplitudes, and mirror activity in contralateral limb compared with controls (16). Muscle activation latencies were heterogenous in FHD. Anticipation, delayed relaxation, and mirror EMG activation were noted in FHD. A clear pattern of muscle activation cannot be ascertained. Multi-channel SEMG can aid in objective assessment of temporal-spatial distribution of activity and can refine targeted therapies like chemodenervation and biofeedback. Copyright © 2013 Wiley Periodicals, Inc.

Orientation-specific responses to sustained uniaxial stretching in focal adhesion growth and turnover

PubMed Central

Chen, Yun; Pasapera, Ana M.; Koretsky, Alan P.; Waterman, Clare M.

2013-01-01

Cells are mechanosensitive to extracellular matrix (ECM) deformation, which can be caused by muscle contraction or changes in hydrostatic pressure. Focal adhesions (FAs) mediate the linkage between the cell and the ECM and initiate mechanically stimulated signaling events. We developed a stretching apparatus in which cells grown on fibronectin-coated elastic substrates can be stretched and imaged live to study how FAs dynamically respond to ECM deformation. Human bone osteosarcoma epithelial cell line U2OS was transfected with GFP-paxillin as an FA marker and subjected to sustained uniaxial stretching. Two responses at different timescales were observed: rapid FA growth within seconds after stretching, and delayed FA disassembly and loss of cell polarity that occurred over tens of minutes. Rapid FA growth occurred in all cells; however, delayed responses to stretch occurred in an orientation-specific manner, specifically in cells with their long axes perpendicular to the stretching direction, but not in cells with their long axes parallel to stretch. Pharmacological treatments demonstrated that FA kinase (FAK) promotes but Src inhibits rapid FA growth, whereas FAK, Src, and calpain 2 all contribute to delayed FA disassembly and loss of polarity in cells perpendicular to stretching. Immunostaining for phospho-FAK after stretching revealed that FAK activation was maximal at 5 s after stretching, specifically in FAs oriented perpendicular to stretch. We hypothesize that orientation-specific activation of strain/stress-sensitive proteins in FAs upstream to FAK and Src promote orientation-specific responses in FA growth and disassembly that mediate polarity rearrangement in response to sustained stretch. PMID:23754369

Timing and teamwork--an observational pilot study of patients referred to a Rapid Response Team with the aim of identifying factors amenable to re-design of a Rapid Response System.

PubMed

Peebles, Emma; Subbe, Christian P; Hughes, Paul; Gemmell, Les

2012-06-01

Rapid Response Teams aim to accelerate recognition and treatment of acutely unwell patients. Delays in delivery might undermine efficiency of the intervention. Our understanding of the causes of these delays is, as yet, incomplete. To identify modifiable causes of delays in the treatment of critically ill patients outside intensive care with a focus on factors amenable to system design. Review of care records and direct observation with process mapping of care delivered to 17 acutely unwell patients attended by a Rapid Response Team in a District General Hospital in the United Kingdom. Delays were defined as processes with no added value for patient care. Essential diagnostic and therapeutic procedures accounted for only 31% of time of care processes. Causes for delays could be classified into themes as (1) delays in call-out of the Rapid Response Team, (2) problems with team cohesion including poor communication and team efficiency and (3) lack of resources including lack of first line antibiotics, essential equipment, experienced staff and critical care beds. We identified a number of potentially modifiable causes for delays in care of acutely ill patients. Improved process design could include automated call-outs, a dedicated kit for emergency treatment in relevant clinical areas, increased usage of standard operating procedures and staff training using crew resource management techniques. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of NaHCO3 treatments on the activity of cell wall-degrading enzymes produced by Penicillium digitatum during the pathogenesis process on grapefruit.

PubMed

Venditti, Tullio; D'hallewin, Guy; Ladu, Gianfranca; Petretto, Giacomo L; Pintore, Giorgio; Labavitch, John M

2018-03-25

The present study was performed to clarify the strategies of Penicillium digitatum during pathogenesis on citrus, assessing, on albedo plugs, the effects of treatment with NaHCO 3 , at two different pH (5 and 8.3), on cell wall-degrading enzymes activity, over a period of 72 h. The treatment with NaHCO 3 , under alkaline pH, delayed the polygalacturonase activity for 72 h, or 48 h in the case of the pectin lyase, if compared to the control or the same treatment at pH 5. On the contrary, the pectin methyl esterase activity rapidly increased after 24 h, in plugs dipped in the same solution. In this case, the activity remained higher than untreated or pH 5 treated plugs up to 72 h. The rapid increase in pectin methyl esterase activity, under alkaline conditions, is presumably the strategy of the pathogen to lower the pH, soon after the initiation of infection, in order to restore an optimal environment for the subsequent polygalacturonase and pectin lyase action. In fact at the same time, a low pH delayed the enzymatic activity of polygalacturonase and pectin lyase, the two enzymes that actually cleave the α-1,4-linkages between the galacturonic acid residues. This article is protected by copyright. All rights reserved.

Time delay between cardiac and brain activity during sleep transitions

NASA Astrophysics Data System (ADS)

Long, Xi; Arends, Johan B.; Aarts, Ronald M.; Haakma, Reinder; Fonseca, Pedro; Rolink, Jérôme

2015-04-01

Human sleep consists of wake, rapid-eye-movement (REM) sleep, and non-REM (NREM) sleep that includes light and deep sleep stages. This work investigated the time delay between changes of cardiac and brain activity for sleep transitions. Here, the brain activity was quantified by electroencephalographic (EEG) mean frequency and the cardiac parameters included heart rate, standard deviation of heartbeat intervals, and their low- and high-frequency spectral powers. Using a cross-correlation analysis, we found that the cardiac variations during wake-sleep and NREM sleep transitions preceded the EEG changes by 1-3 min but this was not the case for REM sleep transitions. These important findings can be further used to predict the onset and ending of some sleep stages in an early manner.

Rapid ambiguity resolution over medium-to-long baselines based on GPS/BDS multi-frequency observables

NASA Astrophysics Data System (ADS)

Gong, Xiaopeng; Lou, Yidong; Liu, Wanke; Zheng, Fu; Gu, Shengfeng; Wang, Hua

2017-02-01

Medium-long baseline RTK positioning generally needs a long initial time to find an accurate position due to non-negligible atmospheric delay residual. In order to shorten the initial or re-convergence time, a rapid phase ambiguity resolution method is employed based on GPS/BDS multi-frequency observables in this paper. This method is realized by two steps. First, double-differenced un-combined observables (i.e., L1/L2 and B1/B2/B3 observables) are used to obtain a float solution with atmospheric delay estimated as random walk parameter by using Kalman filter. This model enables an easy and consistent implementation for different systems and different frequency observables and can readily be extended to use more satellite navigation systems (e.g., Galileo, QZSS). Additional prior constraints for atmospheric information can be quickly added as well, because atmospheric delay is parameterized. Second, in order to fix ambiguity rapidly and reliably, ambiguities are divided into three types (extra-wide-lane (EWL), wide-lane (WL) and narrow-lane (NL)) according to their wavelengths and are to be fixed sequentially by using the LAMBDA method. Several baselines ranging from 61 km to 232 km collected by Trimble and Panda receivers are used to validate the method. The results illustrate that it only takes approximately 1, 2 and 6 epochs (30 s intervals) to fix EWL, WL and NL ambiguities, respectively. More epochs' observables are needed to fix WL and NL ambiguity around local time 14:00 than other time mainly due to more active ionosphere activity. As for the re-convergence time, the simulated results show that 90% of epochs can be fixed within 2 epochs by using prior atmospheric delay information obtained from previously 5 min. Finally, as for positioning accuracy, meter, decimeter and centimeter level positioning results are obtained according to different ambiguity resolution performances, i.e., EWL, WL and NL fixed solutions.

Reflexes in cat ankle muscles after landing from falls.

PubMed Central

Prochazka, A; Schofield, P; Westerman, R A; Ziccone, S P

1977-01-01

1. Electrical activity and length of ankle muscles were recorded by telemetry during free fall and landing in cats. 2. After foot contact, there was a delay in onset of stretch of ankle extensors of between 8 and 11 ms. High-speed cinematography showed the delay to be associated with rapid initial dorsiflexion of the toes. 3. Electromyograms (e.m.g.) from lateral gastrocnemius increased in amplitude prior to landing. An early depression of lateral gastrocnemius e.m.g. commenced at 8 ms after foot contact, and was followed by a large peak of activity commencing some 8 ms after the first increase in lateral gastrocnemius length. 4. Local anaesthesia of the plantar cushion did not alter this pattern of response. 5. The early inhibition of lateral gastrocnemius was attributed to the action on lateral gastrocnemius motoneurones of non-cutaneous afferents responding to the initial toe dorsiflexion. Additional autogenetic inhibition may also have contributed. 6. The subsequent peak of e.m.g. was at a latenty consistent with a rapid stretch reflex, and occurred soon enough for the resulting active tension to contribute significantly to the extensor force during body deceleration. PMID:592210

Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis.

PubMed

Saurin, Adrian T; van der Waal, Maike S; Medema, René H; Lens, Susanne M A; Kops, Geert J P L

2011-01-01

The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis.

Cognitive activities delay onset of memory decline in persons who develop dementia

PubMed Central

Hall, C B.; Lipton, R B.; Sliwinski, M; Katz, M J.; Derby, C A.; Verghese, J

2009-01-01

Background: Persons destined to develop dementia experience an accelerated rate of decline in cognitive ability, particularly in memory. Early life education and participation in cognitively stimulating leisure activities later in life are 2 factors thought to reflect cognitive reserve, which may delay the onset of the memory decline in the preclinical stages of dementia. Methods: We followed 488 initially cognitively intact community residing individuals with epidemiologic, clinical, and cognitive assessments every 12 to 18 months in the Bronx Aging Study. We assessed the influence of self-reported participation in cognitively stimulating leisure activities on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Results: Each additional self-reported day of cognitive activity at baseline delayed the onset of accelerated memory decline by 0.18 years. Higher baseline levels of cognitive activity were associated with more rapid memory decline after that onset. Inclusion of education did not significantly add to the fit of the model beyond the effect of cognitive activities. Conclusions: Our findings show that late life cognitive activities influence cognitive reserve independently of education. The effect of early life education on cognitive reserve may be mediated by cognitive activity later in life. Alternatively, early life education may be a determinant of cognitive reserve, and individuals with more education may choose to participate in cognitive activities without influencing reserve. Future studies should examine the efficacy of increasing participation in cognitive activities to prevent or delay dementia. GLOSSARY AD = Alzheimer disease; BL = baseline; CAS = Cognitive Activity Scale; CI = confidence interval; DSM = Diagnostic and Statistical Manual of Mental Disorders; dx = diagnosis; NIA = National Institute on Aging; SRT = Selective Reminding Test; WAIS VIQ = Wechsler Adult Intelligence Scale Verbal IQ. PMID:19652139

[Effect of Food Thickeners on the Disintegration, Dissolution, and Drug Activity of Rapid Oral-disintegrating Tablets].

PubMed

Tomita, Takashi; Kohda, Yukinao; Kudo, Kenzo

2018-01-01

　For patients with dysphagia in medical facilities and nursing homes, food thickeners are routinely used to aid the ingestion of medicines such as tablets. However, some types of thickeners affect the disintegration and dissolution of tablets, such as rapidly-disintegrating magnesium oxide tablets and donepezil hydrochloride orally disintegrating tablets. Additionally, delayed disintegration and dissolution of tablets affect a drug's efficacy. As an example, with Voglibose orally disintegrating tablets, marked differences are observed in changes in glucose levels during glucose tolerance testing. When using food thickeners to aid tablet ingestion, it is therefore necessary to select a product that has little effect on drug disintegration, dissolution, and activity.

Canine left ventricle electromechanical behavior under different pacing modes.

PubMed

Vo Thang, Thanh-Thuy; Thibault, Bernard; Finnerty, Vincent; Pelletier-Galarneau, Matthieu; Khairy, Paul; Grégoire, Jean; Harel, François

2012-10-01

Cardiac resynchronization therapy may improve survival and quality of life in patients suffering from heart failure with left ventricular (LV) contraction dyssynchrony. While several studies have investigated electrical or mechanical determinants of synchronous contraction, few have focused on activation contraction coupling at a macroscopic level. The objective of the study was to characterize LV electromechanical behavior and response to pacing in a heart failure model. We analyzed data from 3D electroanatomic non-contact mapping and blood pool SPECT for 12 dogs with right ventricular (RV) tachycardia pacing-induced dilated cardiomyopathy. Surfaces generated by the two modalities were registered. Electrical signals were analyzed, and endocardial wall displacement curves were portrayed. Rapid pacing decreased the mean LV ejection fraction (LVEF) to 20.9 % and prolonged the QRS duration to 79 ± 10 ms (normal range: 40-50 ms). QRS duration remained unchanged with biventricular pacing (88.5 ms), while single site pacing further prolonged the QRS duration (113.3 ms for RV pacing and 111.6 ms for LV pacing). No trend was observed in LV systolic function. Activation duration time was significantly increased with all pacing modes compared to baseline. Finally, electromechanical delay, as defined by the delay between electrical activation and mechanical response, was increased by single site pacing (172.9 ms for RV pacing and 174.6 ms for LV pacing) but not by biventricular pacing (162.4 ms). Combined temporal and spatial coregistration electroanatomic maps and baseline gated blood pool SPECT imaging allowed us to quantify activation duration time, electromechanical delay, and LVEF for different pacing modes. Even if pacing modes did not significantly modify LVEF or activation duration, they produced alterations in electromechanical delay, with biventricular pacing significantly decreasing the electromechanical delay as measured by surface tracings and endocardial non-contact mapping.

Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle

PubMed Central

Koh, S D; Ward, S M; Dick, G M; Epperson, A; Bonner, H P; Sanders, K M; Horowitz, B; Kenyon, J L

1999-01-01

We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm≈−60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1–10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, ⋧ 5 mM) caused continuous spiking.Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (τf = 96 ms, τs = 1.5 s at 0 mV). The half-activation voltage of the permeability was −27 mV, with significant activation at −50 mV.TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100–500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to −20 mV, potentials where TEA had no effect.Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvβ1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected.We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude. PMID:10050014

Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels revealed by low K+-induced hERG endocytic degradation.

PubMed

Guo, Jun; Wang, Tingzhong; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Fridman, Michael D; Fisher, John T; Zhang, Shetuan

2011-10-07

Cardiac repolarization is controlled by the rapidly (I(Kr)) and slowly (I(Ks)) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes I(Kr), whereas KCNQ1 and KCNE1 together encode I(Ks). Decreases in I(Kr) or I(Ks) cause long QT syndrome (LQTS), a cardiac disorder with a high risk of sudden death. A reduction in extracellular K(+) concentration ([K(+)](o)) induces LQTS and selectively causes endocytic degradation of mature hERG channels from the plasma membrane. In the present study, we investigated whether I(Ks) compensates for the reduced I(Kr) under low K(+) conditions. Our data show that when hERG and KCNQ1 were expressed separately in human embryonic kidney (HEK) cells, exposure to 0 mM K(+) for 6 h completely eliminated the mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1 were co-expressed, KCNQ1 significantly delayed 0 mM K(+)-induced hERG reduction. Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mM K(+) conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1-expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated with mature hERG channels that are localized in the plasma membrane. Biophysical and pharmacological analyses indicate that although hERG and KCNQ1 closely interact with each other, they form distinct hERG and KCNQ1 channels. These data extend our understanding of delayed rectifier potassium channel trafficking and regulation, as well as the pathology of LQTS.

Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

PubMed

Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

2017-04-01

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of simulations and experiments enabled novel insight into how the balance between cardiac K + currents influences ventricular arrhythmia susceptibility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Delayed childbearing: determining responsibilities for prime gamete quality.

PubMed

Campagne, Daniel M

2013-01-01

Delayed parenting affects fertility in women and in men, and cryopreservation of oocytes and sperm is becoming the latest trend as a solution for those who want or need to postpone procreation, in an attempt to avoid the damage medical conditions or time itself produces in gametes. Although "social freezing" is considered legitimate, its ethical and social aspects are in need of an overdue medical, public and legal debate. Assisted reproduction and cryopreservation, in combination with womb outsourcing, have opened the door to biological ectogenesis and the subsequent question of whether delayed childbearing means we should formally separate procreation from sexual activity. This article briefly summarizes what cryotechniques are capable of presently and in the near future, to separate fact from fiction. It names the implications for and discusses the practically virgin subject of the underlying responsibilities of delayed parenting techniques towards the child-to-be-not only the unborn but also the not-yet-conceived child. Considering the medical, economic, legal and social consequences of these rapidly growing developments in reproduction, several reasons point at the need to formally separate procreation from sexual activity, specifying responsibilities in the first while respecting personal choice in the second.

Delay Discounting in Lewis and Fischer 344 Rats: Steady-state and Rapid-determination Adjusting-amount Procedures

PubMed Central

Stein, Jeffrey S; Pinkston, Jonathan W; Brewer, Adam T; Francisco, Monica T; Madden, Gregory J

2012-01-01

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed. PMID:22693360

Delay discounting in Lewis and Fischer 344 rats: steady-state and rapid-determination adjusting-amount procedures.

PubMed

Stein, Jeffrey S; Pinkston, Jonathan W; Brewer, Adam T; Francisco, Monica T; Madden, Gregory J

2012-05-01

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed.

Drift in Neural Population Activity Causes Working Memory to Deteriorate Over Time.

PubMed

Schneegans, Sebastian; Bays, Paul M

2018-05-23

Short-term memories are thought to be maintained in the form of sustained spiking activity in neural populations. Decreases in recall precision observed with increasing number of memorized items can be accounted for by a limit on total spiking activity, resulting in fewer spikes contributing to the representation of each individual item. Longer retention intervals likewise reduce recall precision, but it is unknown what changes in population activity produce this effect. One possibility is that spiking activity becomes attenuated over time, such that the same mechanism accounts for both effects of set size and retention duration. Alternatively, reduced performance may be caused by drift in the encoded value over time, without a decrease in overall spiking activity. Human participants of either sex performed a variable-delay cued recall task with a saccadic response, providing a precise measure of recall latency. Based on a spike integration model of decision making, if the effects of set size and retention duration are both caused by decreased spiking activity, we would predict a fixed relationship between recall precision and response latency across conditions. In contrast, the drift hypothesis predicts no systematic changes in latency with increasing delays. Our results show both an increase in latency with set size, and a decrease in response precision with longer delays within each set size, but no systematic increase in latency for increasing delay durations. These results were quantitatively reproduced by a model based on a limited neural resource in which working memories drift rather than decay with time. SIGNIFICANCE STATEMENT Rapid deterioration over seconds is a defining feature of short-term memory, but what mechanism drives this degradation of internal representations? Here, we extend a successful population coding model of working memory by introducing possible mechanisms of delay effects. We show that a decay in neural signal over time predicts that the time required for memory retrieval will increase with delay, whereas a random drift in the stored value predicts no effect of delay on retrieval time. Testing these predictions in a multi-item memory task with an eye movement response, we identified drift as a key mechanism of memory decline. These results provide evidence for a dynamic spiking basis for working memory, in contrast to recent proposals of activity-silent storage. Copyright © 2018 Schneegans and Bays.

[Action of synthetic substance P (SP) on the respiration, general metabolism and systemic hemodynamics of the anesthetized dog].

PubMed

Pham-Huu-Chanh; Clavel, P; Sokan, I; Azum-Gélade, M C; Lehmann-Schad, W

1976-11-08

In the anaesthetized Dog, synthetic substance P in one dose (0.5 mug/kg i.v.) induced a quick hypotensive but short-lasting action and a respiratory analeptic activity which only appeared with some delay and lasted more than one hour. The possibility of a rapid metabolization of synthetic SP is discussed.

REM sleep and emotional face memory in typically-developing children and children with autism.

PubMed

Tessier, Sophie; Lambert, Andréane; Scherzer, Peter; Jemel, Boutheina; Godbout, Roger

2015-09-01

Relationship between REM sleep and memory was assessed in 13 neurotypical and 13 children with Autistic Spectrum Disorder (ASD). A neutral/positive/negative face recognition task was administered the evening before (learning and immediate recognition) and the morning after (delayed recognition) sleep. The number of rapid eye movements (REMs), beta and theta EEG activity over the visual areas were measured during REM sleep. Compared to neurotypical children, children with ASD showed more theta activity and longer reaction time (RT) for correct responses in delayed recognition of neutral faces. Both groups showed a positive correlation between sleep and performance but different patterns emerged: in neurotypical children, accuracy for recalling neutral faces and overall RT improvement overnight was correlated with EEG activity and REMs; in children with ASD, overnight RT improvement for positive and negative faces correlated with theta and beta activity, respectively. These results suggest that neurotypical and children with ASD use different sleep-related brain networks to process faces. Copyright © 2015 Elsevier B.V. All rights reserved.

Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation, and anaphase entry

PubMed Central

Fasulo, Barbara; Koyama, Carol; Yu, Kristina R.; Homola, Ellen M.; Hsieh, Tao S.; Campbell, Shelagh D.; Sullivan, William

2012-01-01

Defects in DNA replication and chromosome condensation are common phenotypes in cancer cells. A link between replication and condensation has been established, but little is known about the role of checkpoints in monitoring chromosome condensation. We investigate this function by live analysis, using the rapid division cycles in the early Drosophila embryo. We find that S-phase and topoisomerase inhibitors delay both the initiation and the rate of chromosome condensation. These cell cycle delays are mediated by the cell cycle kinases chk1 and wee1. Inhibitors that cause severe defects in chromosome condensation and congression on the metaphase plate result in delayed anaphase entry. These delays are mediated by wee1 and are not the result of spindle assembly checkpoint activation. In addition, we provide the first detailed live analysis of the direct effect of widely used anticancer agents (aclarubicin, ICRF-193, VM26, doxorubicin, camptothecin, aphidicolin, hydroxyurea, cisplatin, mechlorethamine and x-rays) on key nuclear and cytoplasmic cell cycle events. PMID:22262459

Delay in Apoptosome Formation Attenuates Apoptosis in Mouse Embryonic Stem Cell Differentiation

PubMed Central

Akbari-Birgani, Shiva; Hosseinkhani, Saman; Mollamohamadi, Sepideh; Baharvand, Hossein

2014-01-01

Differentiation is an inseparable process of development in multicellular organisms. Mouse embryonic stem cells (mESCs) represent a valuable research tool to conduct in vitro studies of cell differentiation. Apoptosis as a well known cell death mechanism shows some common features with cell differentiation, which has caused a number of ambiguities in the field. The research question here is how cells could differentiate these two processes from each other. We have investigated the role of the mitochondrial apoptotic pathway and cell energy level during differentiation of mESCs into the cardiomyocytes and their apoptosis. p53 expression, cytochrome c release, apoptosome formation, and caspase-3/7 activation are observed upon induction of both apoptosis and differentiation. However, remarkable differences are detected in time of cytochrome c appearance, apoptosome formation, and caspase activity upon induction of both processes. In apoptosis, apoptosome formation and caspase activity were observed rapidly following the cytochrome c release. Unlike apoptosis, the release of cytochrome c upon differentiation took more time, and the maximum caspase activity was also postponed for 24 h. This delay suggests that there is a regulatory mechanism during differentiation of mESCs into cardiomyocytes. The highest ATP content of cells was observed immediately after cytochrome c release 6 h after apoptosis induction and then decreased, but it was gradually increased up to 48 h after differentiation. These observations suggest that a delay in the release of cytochrome c or delay in ATP increase attenuate apoptosome formation, and caspase activation thereby discriminates apoptosis from differentiation in mESCs. PMID:24755221

Overexpression of Nitrate Reductase in Tobacco Delays Drought-Induced Decreases in Nitrate Reductase Activity and mRNA1

PubMed Central

Ferrario-Méry, Sylvie; Valadier, Marie-Hélène; Foyer, Christine H.

1998-01-01

Transformed (cauliflower mosaic virus 35S promoter [35S]) tobacco (Nicotiana plumbaginifolia L.) plants constitutively expressing nitrate reductase (NR) and untransformed controls were subjected to drought for 5 d. Drought-induced changes in biomass accumulation and photosynthesis were comparable in both lines of plants. After 4 d of water deprivation, a large increase in the ratio of shoot dry weight to fresh weight was observed, together with a decrease in the rate of photosynthetic CO2 assimilation. Foliar sucrose increased in both lines during water stress, but hexoses increased only in leaves from untransformed controls. Foliar NO3− decreased rapidly in both lines and was halved within 2 d of the onset of water deprivation. Total foliar amino acids decreased in leaves of both lines following water deprivation. After 4 d of water deprivation no NR activity could be detected in leaves of untransformed plants, whereas about 50% of the original activity remained in the leaves of the 35S-NR transformants. NR mRNA was much more stable than NR activity. NR mRNA abundance increased in the leaves of the 35S-NR plants and remained constant in controls for the first 3 d of drought. On the 4th d, however, NR mRNA suddenly decreased in both lines. Rehydration at d 3 caused rapid recovery (within 24 h) of 35S-NR transcripts, but no recovery was observed in the controls. The phosphorylation state of the protein was unchanged by long-term drought. There was a strong correlation between maximal extractable NR activity and ambient photosynthesis in both lines. We conclude that drought first causes increased NR protein turnover and then accelerates NR mRNA turnover. Constitutive NR expression temporarily delayed drought-induced losses in NR activity. 35S-NR expression may therefore allow more rapid recovery of N assimilation following short-term water deficit. PMID:9576799

Regulation of Cell Cycle and Stress Responses to Hydrostatic Pressure in Fission Yeast

PubMed Central

George, Vinoj T.; Brooks, Gavin

2007-01-01

We have investigated the cellular responses to hydrostatic pressure by using the fission yeast Schizosaccharomyces pombe as a model system. Exposure to sublethal levels of hydrostatic pressure resulted in G2 cell cycle delay. This delay resulted from Cdc2 tyrosine-15 (Y-15) phosphorylation, and it was abrogated by simultaneous disruption of the Cdc2 kinase regulators Cdc25 and Wee1. However, cell cycle delay was independent of the DNA damage, cytokinesis, and cell size checkpoints, suggesting a novel mechanism of Cdc2-Y15 phosphorylation in response to hydrostatic pressure. Spc1/Sty1 mitogen-activated protein (MAP) kinase, a conserved member of the eukaryotic stress-activated p38, mitogen-activated protein (MAP) kinase family, was rapidly activated after pressure stress, and it was required for cell cycle recovery under these conditions, in part through promoting polo kinase (Plo1) phosphorylation on serine 402. Moreover, the Spc1 MAP kinase pathway played a key role in maintaining cell viability under hydrostatic pressure stress through the bZip transcription factor, Atf1. Further analysis revealed that prestressing cells with heat increased barotolerance, suggesting adaptational cross-talk between these stress responses. These findings provide new insight into eukaryotic homeostasis after exposure to pressure stress. PMID:17699598

Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators, GABA, NPY and AgRP

PubMed Central

Krashes, Michael J.; Shah, Bhavik P.; Koda, Shuichi; Lowell, Bradford B.

2013-01-01

Summary Agouti-related peptide (AgRP) neurons of the hypothalamus release a fast transmitter (GABA) in addition to neuropeptides (NPY and AgRP). This raises questions as to their respective functions. Acute activation of AgRP neurons robustly promotes food intake, while central injections of AgRP, NPY or GABA agonist results in marked escalation of food consumption with temporal variance. Given the orexigenic capability of all three of these neuroactive substances in conjunction with their coexpression in AgRP neurons, we looked to unravel their relative temporal role in driving food intake. Following acute stimulation of AgRP neurons using DREADD technology, we found that either GABA or NPY is required for rapid stimulation of feeding, and the neuropeptide AgRP, through action on MC4 receptors, is sufficient to induce feeding over a delayed, yet prolonged period. These studies help to elucidate the neurochemical mechanisms of AgRP neurons in controlling temporally distinct phases of eating. PMID:24093681

Femtosecond pump-probe photoionization-photofragmentation spectroscopy: photoionization-induced twisting and coherent vibrational motion of azobenzene cation.

PubMed

Ho, Jr-Wei; Chen, Wei-Kan; Cheng, Po-Yuan

2009-10-07

We report studies of ultrafast dynamics of azobenzene cation using femtosecond photoionization-photofragmentation spectroscopy. In our experiments, a femtosecond pump pulse first produces an ensemble of azobenzene cations via photoionization of the neutrals. A delayed probe pulse then brings the evolving ionic system to excited states that ultimately undergo ion fragmentation. The dynamics is followed by monitoring either the parent-ion depletion or fragment-ion formation as a function of the pump-probe delay time. The observed transients for azobenzene cation are characterized by a constant ion depletion modulated by a rapidly damped oscillatory signal with a period of about 1 ps. Theoretical calculations suggest that the oscillation arises from a vibration motion along the twisting inversion coordinate involving displacements in CNNC and phenyl-ring torsions. The oscillation is damped rapidly with a time constant of about 1.2 ps, suggesting that energy dissipation from the active mode to bath modes takes place in this time scale.

Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier K+ current by different G-protein coupled receptors.

PubMed

Liu, Xueli; Wang, Yuhong; Zhang, Hua; Shen, Li; Xu, Yanfang

2017-12-01

Elevated angiotensin II (Ang II) and sympathetic activity contributes to a high risk of ventricular arrhythmias in heart disease. The rapidly activating delayed rectifier K + current (I Kr ) carried by the hERG channels plays a critical role in cardiac repolarization, and decreased I Kr is involved in increased cardiac arrhythmogenicity. Stimulation of α 1A -adrenoreceptors or angiotensin II AT 1 receptors is known to inhibit I Kr via PKC. Here, we have identified the PKC isoenzymes mediating the inhibition of I Kr by activation of these two different GPCRs. The whole-cell patch-clamp technique was used to record I Kr in guinea pig cardiomyocytes and HEK293 cells co-transfected with hERG and α 1A -adrenoreceptor or AT 1 receptor genes. A broad spectrum PKC inhibitor Gö6983 (not inhibiting PKCε), a selective cPKC inhibitor Gö6976 and a PKCα-specific inhibitor peptide, blocked the inhibition of I Kr by the α 1A -adrenoreceptor agonist A61603. However, these inhibitors did not affect the reduction of I Kr by activation of AT 1 receptors, whereas the PKCε-selective inhibitor peptide did block the effect. The effects of angiotensin II and the PKCε activator peptide were inhibited in mutant hERG channels in which 17 of the 18 PKC phosphorylation sites were deleted, whereas a deletion of the N-terminus of the hERG channels selectively prevented the inhibition elicited by A61603 and the cPKC activator peptide. Our results indicated that inhibition of I Kr by activation of α 1A -adrenoreceptors or AT 1 receptors were mediated by PKCα and PKCε isoforms respectively, through different molecular mechanisms. © 2017 The British Pharmacological Society.

Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine.

PubMed

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-06-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K(+) currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC(50) for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 microM at -40 mV, 28.3 microM at 0 mV and 22.9 microM at +40 mV), whereas the IC(50) for the clozapine-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 2.5 microM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36 degrees C, treatment with 1 and 5 microM clozapine blocked the rapidly activating delayed rectifier K(+) current (I(Kr)) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K(+) current (I(Ks)). Our findings collectively suggest that blockade of HERG currents and I(Kr), but not I(Ks), may contribute to the arrhythmogenic side effects of clozapine.

Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine

PubMed Central

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-01-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K+ currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC50 for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 μM at −40 mV, 28.3 μM at 0 mV and 22.9 μM at +40 mV), whereas the IC50 for the clozapine-induced blockade of HERG currents in HEK293 cells at 36°C was 2.5 μM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36°C, treatment with 1 and 5 μM clozapine blocked the rapidly activating delayed rectifier K+ current (IKr) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K+ current (IKs). Our findings collectively suggest that blockade of HERG currents and IKr, but not IKs, may contribute to the arrhythmogenic side effects of clozapine. PMID:16633353

Maximising platelet availability by delaying cold storage.

PubMed

Wood, B; Johnson, L; Hyland, R A; Marks, D C

2018-04-06

Cold-stored platelets may be an alternative to conventional room temperature (RT) storage. However, cold-stored platelets are cleared more rapidly from circulation, reducing their suitability for prophylactic transfusion. To minimise wastage, it may be beneficial to store platelets conventionally until near expiry (4 days) for prophylactic use, transferring them to refrigerated storage to facilitate an extended shelf life, reserving the platelets for the treatment of acute bleeding. Two ABO-matched buffy-coat-derived platelets (30% plasma/70% SSP+) were pooled and split to produce matched pairs (n = 8 pairs). One unit was stored at 2-6°C without agitation (day 1 postcollection; cold); the second unit was stored at 20-24°C with constant agitation until day 4 then stored at 2-6°C thereafter (delayed-cold). All units were tested for in vitro quality periodically over 21 days. During storage, cold and delayed-cold platelets maintained a similar platelet count. While pH and HSR were significantly higher in delayed-cold platelets, other metabolic markers, including lactate production and glucose consumption, did not differ significantly. Furthermore, surface expression of phosphatidylserine and CD62P, release of soluble CD62P and microparticles were not significantly different, suggesting similar activation profiles. Aggregation responses of delayed-cold platelets followed the same trend as cold platelets once transferred to cold storage, gradually declining over the storage period. The metabolic and activation profile of delayed-cold platelets was similar to cold-stored platelets. These data suggest that transferring platelets to refrigerated storage when near expiry may be a viable option for maximising platelet inventories. © 2018 International Society of Blood Transfusion.

Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.

PubMed

Oliver, Dominik; Lien, Cheng-Chang; Soom, Malle; Baukrowitz, Thomas; Jonas, Peter; Fakler, Bernd

2004-04-09

Voltage-gated potassium (Kv) channels control action potential repolarization, interspike membrane potential, and action potential frequency in excitable cells. It is thought that the combinatorial association between distinct alpha and beta subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating A-type channels. We show that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. The bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system.

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

PubMed

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

2015-05-01

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

Optimisation of GaN LEDs and the reduction of efficiency droop using active machine learning

DOE PAGES

Rouet-Leduc, Bertrand; Barros, Kipton Marcos; Lookman, Turab; ...

2016-04-26

A fundamental challenge in the design of LEDs is to maximise electro-luminescence efficiency at high current densities. We simulate GaN-based LED structures that delay the onset of efficiency droop by spreading carrier concentrations evenly across the active region. Statistical analysis and machine learning effectively guide the selection of the next LED structure to be examined based upon its expected efficiency as well as model uncertainty. This active learning strategy rapidly constructs a model that predicts Poisson-Schrödinger simulations of devices, and that simultaneously produces structures with higher simulated efficiencies.

Associative learning rapidly establishes neuronal representations of upcoming behavioral choices in crows

PubMed Central

Veit, Lena; Pidpruzhnykova, Galyna; Nieder, Andreas

2015-01-01

The ability to form associations between behaviorally relevant sensory stimuli is fundamental for goal-directed behaviors. We investigated neuronal activity in the telencephalic area nidopallium caudolaterale (NCL) while two crows (Corvus corone) performed a delayed association task. Whereas some paired associates were familiar to the crows, novel associations had to be learned and mapped to the same target stimuli within a single session. We found neurons that prospectively encoded the chosen test item during the delay for both familiar and newly learned associations. These neurons increased their selectivity during learning in parallel with the crows' increased behavioral performance. Thus, sustained activity in the NCL actively processes information for the upcoming behavioral choice. These data provide new insights into memory representations of behaviorally meaningful stimuli in birds, and how such representations are formed during learning. The findings suggest that the NCL plays a role in learning arbitrary associations, a cornerstone of corvids’ remarkable behavioral flexibility and adaptability. PMID:26598669

Resynchronization of circadian sleep-wake and temperature cycles in the squirrel monkey following phase shifts of the environmental light-dark cycle

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

Wexler, D.B.; Moore-ede, M.C.

1986-12-01

Circadian rhythms in physiological and behavioral functions gradually resynchronize after phase shifts in environmental time cues. In order to characterize the rate of circadian resynchronization in a diurnal primate model, the temperature, locomotor activity, and polygraphically determined sleep-wake states were monitored in squirrel monkeys before and after 8-h phase shifts of an environmental light-dark cycle of 12 h light and 12 h dark (LD 12:12). For the temperature rhythm, resynchronization took 4 d after phase delay shift and 5 d after phase advance shift; for the rest-activity cycle, resynchronization times were 3 d and 6 d, respectively. The activity acrophasemore » shifted more rapidly than the temperature acrophase early in the post-delay shift interval, but this internal desynchronization between rhythms disappeared during the course of resynchronization. Further study of the early resynchronization process requires emphasis on identifying evoked effects and measuring circadian pacemaker function. 13 references.« less

Resynchronization of circadian sleep-wake and temperature cycles in the squirrel monkey following phase shifts of the environmental light-dark cycle

NASA Technical Reports Server (NTRS)

Wexler, D. B.; Moore-Ede, M. C.

1986-01-01

Circadian rhythms in physiological and behavioral functions gradually resynchronize after phase shifts in environmental time cues. In order to characterize the rate of circadian resynchronization in a diurnal primate model, the temperature, locomotor activity, and polygraphically determined sleep-wake states were monitored in squirrel monkeys before and after 8-h phase shifts of an environmental light-dark cycle of 12 h light and 12 h dark (LD 12:12). For the temperature rhythm, resynchronization took 4 d after phase delay shift and 5 d after phase advance shift; for the rest-activity cycle, resynchronization times were 3 d and 6 d, respectively. The activity acrophase shifted more rapidly than the temperature acrophase early in the post-delay shift interval, but this internal desynchronization between rhythms disappeared during the course of resynchronization. Further study of the early resynchronization process requires emphasis on identifying evoked effects and measuring circadian pacemaker function.

E-VLBI-activities at the FS Wettzell

NASA Astrophysics Data System (ADS)

Kronschnabl, Gerhard; Dassing, Reiner

The FS-Wettzell carries out the daily-INTENSIVE observations which were required for the rapid determination of DUT1. The data volume is roughly 40 GB. So fare the data were shipped via currier services to the correlator which requires 2-3 days transportation time. The INTENSIVE time series is a real candidate for E-VLBI. It will reduce the delay due to data transport strongly. Considering the remote location of Wettzell - apart from the fast INTERNET links, considering the current high cost for a fast connection, in the next future the installation of a 34 Gbps-internet connection will be realistic. It will strongly support the data transmission on start the delay time to only a few hours. This report give an overview about the activities on the realisation of such a fast link. First attempts are reported made from the next nodal point at the University Regensburg, making use of a 155Mbps connection.

β1-adrenergic regulation of rapid component of delayed rectifier K+ currents in guinea-pig cardiac myocytes.

PubMed

Wang, Sen; Xu, Di; Wu, Ting-Ting; Guo, Yan; Chen, Yan-Hong; Zou, Jian-Gang

2014-05-01

Human ether-à-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current (IKr), which is crucial for repolarization of cardiac action potential. Patients with hERG‑associated long QT syndrome usually develop tachyarrhythmias during physical and/or emotional stress, both known to stimulate adrenergic receptors. The present study aimed to investigate a putative functional link between β1-adrenergic stimulation and IKr in guinea-pig left ventricular myocytes and to analyze how IKr is regulated following activation of the β1-adrenergic signaling pathway. The IKr current was measured using a whole-cell patch-clamp technique. A selective β1-adrenergic receptor agonist, xamoterol, at concentrations of 0.01-100 µM decreased IKr in a concentration-dependent manner. The 10 µM xamoterol-induced inhibition of IKr was attenuated by the protein kinase A (PKA) inhibitor KT5720, the protein kinase C (PKC) inhibitor chelerythrine, and the phospholipase (PLC) inhibitor U73122, indicating involvement of PKA, PKC and PLC in β1-adrenergic inhibition of IKr. The results of the present study indicate an association between IKr and the β1-adrenergic receptor in arrhythmogenesis, involving the activation of PKA, PKC and PLC.

High-speed optical coherence tomography using fiberoptic acousto-optic phase modulation

NASA Astrophysics Data System (ADS)

Xie, Tuqiang; Wang, Zhenguo; Pan, Yingtian

2003-12-01

We report a new rapid-scanning optical delay device suitable for high-speed optical coherence tomography (OCT) in which an acousto-optic modulator (AOM) is used to independently modulate the Doppler frequency shift of the reference light beam for optical heterodyne detection. Experimental results show that the fluctuation of the measured Doppler frequency shift is less than +/-0.2% over 95% duty cycle of OCT imaging, thus allowing for enhanced signal-to-noise ratio of optical heterodyne detection. The increased Doppler frequency shift by AOM also permits complete envelop demodulation without the compromise of reducing axial resolution; if used with a resonant rapid-scanning optical delay, it will permit high-performance real-time OCT imaging. Potentially, this new rapid-scanning optical delay device will improve the performance of high-speed Doppler OCT techniques.

Single-scan dual-tracer FLT+FDG PET tumor characterization.

PubMed

Kadrmas, Dan J; Rust, Thomas C; Hoffman, John M

2013-02-07

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both (18)F-fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems--both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10-60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), K(net), and K(1) as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k(2), k(3)) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging.

Single-scan dual-tracer FLT+FDG PET tumor characterization

NASA Astrophysics Data System (ADS)

Kadrmas, Dan J.; Rust, Thomas C.; Hoffman, John M.

2013-02-01

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems—both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10-60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), Knet, and K1 as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k2, k3) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging.

Single-scan dual-tracer FLT+FDG PET tumor characterization

PubMed Central

Kadrmas, Dan J; Rust, Thomas C; Hoffman, John M

2013-01-01

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems—both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10–60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), Knet, and K1 as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k2, k3) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging. PMID:23296314

A novel method for rapid and non-invasive detection of plants senescence using delayed fluorescence technique

NASA Astrophysics Data System (ADS)

Zhang, Lingrui; Xing, Da; Wang, Junsheng; Zeng, Lizhang; Li, Qiang

2007-05-01

Plants senescence is a phase of plants ontogeny marked by declining photosynthetic activity that is paralleled by a decline in chloroplast function. The photosystem II ( PSII ) in a plant is considered the primary site where light-induced delayed fluorescence (DF) is produced. With the leaves of Catharanthus roseus (Catharanthus roseus (L.) G.Don) as testing models, we have studied the effects of plants senescence induced by dark and/or exogenous hormones treatments on characteristics of DF by using a home-made portable DF detection system, which can enable various DF parameters, such as DF decay kinetic curve and DF intensity, to be rapidly produced for the plants in a short time. The results show that the changes in DF intensity of green plants can truly reflect the changes in photosynthetic capacity and chlorophyll content. Therefore, DF may be used an important means of evaluating in vivo plants senescence physiology. The changes in DF intensity may provide a new approach for the rapid and early detection of plants senescence caused by age or other senescence-related factors. DF technique could be potential useful for high throughput screening and less time-consuming and automated identifying the interesting mutants with genetic modifications that change plants senescence progress.

Natural history of Sanfilippo syndrome type A.

PubMed

Buhrman, Dakota; Thakkar, Kavita; Poe, Michele; Escolar, Maria L

2014-05-01

To describe the natural history of Sanfilippo syndrome type A. We performed a retrospective review of 46 children (21 boys, 25 girls) with Sanfilippo syndrome type A evaluated between January 2000 and April 2013. Assessments included neurodevelopmental evaluations, audiologic testing, and assessment of growth, adaptive behavior, cognitive behavior, motor function, and speech/language skills. Only the baseline evaluation was included for patients who received hematopoietic stem cell transplantation. Median age at diagnosis was 35 months, with a median delay between initial symptoms to diagnosis of 24 months. The most common initial symptoms were speech/language delay (48%), dysmorphology (22%), and hearing loss (20%). Early behavioral problems included perseverative chewing and difficulty with toilet training. All children developed sleep difficulties and behavioral changes (e.g., hyperactivity, aggression). More than 93% of the children experienced somatic symptoms such as hepatomegaly (67%), abnormal dentition (39%), enlarged tongue (37%), coarse facial features (76%), and protuberant abdomen (43%). Kaplan-Meier analysis showed a 60% probability of surviving past 17 years of age. Sanfilippo type A is characterized by severe hearing loss and speech delay, followed by a rapid decline in cognitive skills by 3 years of age. Significant somatic disease occurs in more than half of patients. Behavioral difficulties presented between 2 and 4 years of age during a rapid period of cognitive decline. Gross motor abilities are maintained during this period, which results in an active child with impaired cognition. Sleep difficulties are concurrent with the period of cognitive degeneration. There is currently an unacceptable delay in diagnosis, highlighting the need to increase awareness of this disease among clinicians.

Rapid Eradication of Listeria monocytogenes by Moxifloxacin in a Murine Model of Central Nervous System Listeriosis▿

PubMed Central

Grayo, Solène; Lott-Desroches, Marie-Catherine; Dussurget, Olivier; Respaud, Renaud; Fontanet, Arnaud; Join-Lambert, Olivier; Singlas, Eric; Le Monnier, Alban

2008-01-01

Listeriosis is a rare but life-threatening infection. A favorable outcome is greatly aided by early administration of antibiotics with rapid bactericidal activity against Listeria monocytogenes. Moxifloxacin, a new-generation fluoroquinolone with extended activity against gram-positive bacteria, has proved its effectiveness in vitro against intracellular reservoirs of bacteria. The efficacies of moxifloxacin and amoxicillin were compared in vivo by survival curve assays and by studying the kinetics of bacterial growth in blood and organs in a murine model of central nervous system (CNS) listeriosis. We combined pharmacokinetic and pharmacodynamic approaches to correlate the observed efficacy in vivo with plasma and tissue moxifloxacin concentrations. Death was significantly delayed for animals treated with a single dose of moxifloxacin compared to a single dose of amoxicillin. We observed rapid bacterial clearance from blood and organs of animals treated with moxifloxacin. The decrease in the bacterial counts in blood and brain correlated with plasma and cerebral concentrations of antibiotic. Moxifloxacin peaked in the brain at 1.92 ± 0.32 μg/g 1 hour after intraperitoneal injection. This suggests that moxifloxacin rapidly crosses the blood-brain barrier and diffuses into the cerebral parenchyma. Moreover, no resistant strains were selected during in vivo experiments. Our results indicate that moxifloxacin combines useful pharmacokinetic properties and rapid bactericidal activity and that it may be a valuable alternative for the treatment of CNS listeriosis. PMID:18573932

Mechanism of UES relaxation initiated by gastric air distension

PubMed Central

Medda, Bidyut K.; Shaker, Reza

2014-01-01

The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.05) affected by thoracotomy. Free air or bagged air (n = 6) activated TLESR, but only free air activated TUESR. Closure of the gastroesophageal junction blocked TUESR (9/9), but not TLESR (4/4), caused by air inflation of the stomach. Venting air from distal esophagus during air inflation of the stomach prevented TUESR (n = 12) but did not prevent air escape from the stomach to the esophagus (n = 4). Rapid injection of air on the esophageal mucosa always caused TUESR (9/9) but did not always (7/9) cause an increase in esophageal pressure. The time delay between the TUESR and the rapid air pulse was significantly more variable (P < 0.05) than the time delay between the rapid air pulse and the rise in esophageal pressure. We concluded that the TUESR caused by gastric air distension is dependent on air escape from the stomach, which stimulates receptors in the esophagus, but is not dependent on distension of the stomach or esophagus, or the TLESR. Therefore, the TUESR caused by gastric air distension is initiated by stimulation of receptors in the esophageal mucosa. PMID:24970778

Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABA, NPY, and AgRP.

PubMed

Krashes, Michael J; Shah, Bhavik P; Koda, Shuichi; Lowell, Bradford B

2013-10-01

Agouti-related peptide (AgRP) neurons of the hypothalamus release a fast transmitter (GABA) in addition to neuropeptides (neuropeptide Y [NPY] and Agouti-related peptide [AgRP]). This raises questions as to their respective functions. The acute activation of AgRP neurons robustly promotes food intake, while central injections of AgRP, NPY, or GABA agonist results in the marked escalation of food consumption with temporal variance. Given the orexigenic capability of all three of these neuroactive substances in conjunction with their coexpression in AgRP neurons, we looked to unravel their relative temporal role in driving food intake. After the acute stimulation of AgRP neurons with DREADD technology, we found that either GABA or NPY is required for the rapid stimulation of feeding, and the neuropeptide AgRP, through action on MC4 receptors, is sufficient to induce feeding over a delayed yet prolonged period. These studies help to elucidate the neurochemical mechanisms of AgRP neurons in controlling temporally distinct phases of eating. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantitative measurement of feline colonic transit

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

Krevsky, B.; Somers, M.B.; Maurer, A.H.

1988-10-01

Colonic transit scintigraphy, a method for quantitatively evaluating the movement of the fecal stream in vivo, was employed to evaluate colonic transit in the cat. Scintigraphy was performed in duplicate in five cats and repeated four times in one cat. After instillation of an 111In marker into the cecum through a surgically implanted silicone cecostomy tube, colonic movement of the instillate was quantitated for 24 h using gamma scintigraphy. Antegrade and retrograde motion of radionuclide was observed. The cecum and ascending colon emptied rapidly, with a half-emptying time of 1.68 +/- 0.56 h (mean +/- SE). After 24 h, 25.1more » +/- 5.2% of the activity remained in the transverse colon. The progression of the geometric center was initially rapid, followed later by a delayed phase. Geometric center reproducibility was found to be high when analyzed using simple linear regression (slope = 0.92; r = 0.73; P less than 0.01). Atropine (0.1 mg/kg im) was found to delay cecum and ascending colon emptying and delay progression of the geometric center. These results demonstrate both 1) the ability of colonic transit scintigraphy to detect changes in transit induced by pharmacological manipulation and 2) the fact that muscarinic blockade inhibits antegrade transit of the fecal stream. We conclude that feline colonic transit may be studied in a quantitative and reproducible manner with colonic transit scintigraphy.« less

"ATP1A3" Mutations in Infants: A New Rapid-Onset Dystonia-Parkinsonism Phenotype Characterized by Motor Delay and Ataxia

ERIC Educational Resources Information Center

Brashear, Allison; Mink, Jonathan W.; Hill, Deborah F.; Boggs, Niki; McCall, W. Vaughn; Stacy, Mark A.; Snively, Beverly; Light, Laney S.; Sweadner, Kathleen J.; Ozelius, Laurie J.; Morrison, Leslie

2012-01-01

We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the "ATP1A3" gene. In adults, mutations in "ATP1A3" cause rapid-onset dystonia-Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and…

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

PubMed

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

2015-12-01

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

Inhibitory Effect of Vascular Endothelial Growth Factor on the Slowly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes.

PubMed

Lin, Zhenhao; Xing, Wenlu; Gao, Chuanyu; Wang, Xianpei; Qi, Datun; Dai, Guoyou; Zhao, Wen; Yan, Ganxin

2018-01-26

Vascular endothelial growth factor (VEGF) exerts a number of beneficial effects on ischemic myocardium via its angiogenic properties. However, little is known about whether VEGF has a direct effect on the electrical properties of cardiomyocytes. In the present study, we investigated the effects of different concentrations of VEGF on delayed rectifier potassium currents (I K ) in guinea pig ventricular myocytes and their effects on action potential (AP) parameters. I K and AP were recorded by the whole-cell patch clamp method in ventricular myocytes. Cells were superfused with control solution or solution containing VEGF at different concentrations for 10 minutes before recording. Some ventricular myocytes were pretreated with a phosphatidylinositol 3-kinase inhibitor for 1 hour before the addition of VEGF. We found that VEGF inhibited the slowly activating delayed rectifier potassium current (I K s ) in a concentration-dependent manner (18.13±1.04 versus 12.73±0.34, n=5, P =0.001; 12.73±0.34 versus 9.05±1.20, n=5, P =0.036) and prolonged AP duration (894.5±36.92 versus 746.3±33.71, n=5, P =0.021). Wortmannin, a phosphatidylinositol 3-kinase inhibitor, eliminated these VEGF-induced effects. VEGF had no significant effect on the rapidly activating delayed rectifier potassium current (I K r ), resting membrane potential, AP amplitude, or maximal velocity of depolarization. VEGF inhibited I K s in a concentration-dependent manner through a phosphatidylinositol 3-kinase-mediated signaling pathway, leading to AP prolongation. The results indicate a promising therapeutic potential of VEGF in prevention of ventricular tachyarrhythmias under conditions of high sympathetic activity and ischemia. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Mismatch repair proteins recruited to ultraviolet light-damaged sites lead to degradation of licensing factor Cdt1 in the G1 phase.

PubMed

Tanaka, Miyuki; Takahara, Michiyo; Nukina, Kohei; Hayashi, Akiyo; Sakai, Wataru; Sugasawa, Kaoru; Shiomi, Yasushi; Nishitani, Hideo

2017-04-03

Cdt1 is rapidly degraded by CRL4 Cdt2 E3 ubiquitin ligase after UV (UV) irradiation. Previous reports revealed that the nucleotide excision repair (NER) pathway is responsible for the rapid Cdt1-proteolysis. Here, we show that mismatch repair (MMR) proteins are also involved in the degradation of Cdt1 after UV irradiation in the G1 phase. First, compared with the rapid (within ∼15 min) degradation of Cdt1 in normal fibroblasts, Cdt1 remained stable for ∼30 min in NER-deficient XP-A cells, but was degraded within ∼60 min. The delayed degradation was also dependent on PCNA and CRL4 Cdt2 . The MMR proteins Msh2 and Msh6 were recruited to the UV-damaged sites of XP-A cells in the G1 phase. Depletion of these factors with small interfering RNAs prevented Cdt1 degradation in XP-A cells. Similar to the findings in XP-A cells, depletion of XPA delayed Cdt1 degradation in normal fibroblasts and U2OS cells, and co-depletion of Msh6 further prevented Cdt1 degradation. Furthermore, depletion of Msh6 alone delayed Cdt1 degradation in both cell types. When Cdt1 degradation was attenuated by high Cdt1 expression, repair synthesis at the damaged sites was inhibited. Our findings demonstrate that UV irradiation induces multiple repair pathways that activate CRL4 Cdt2 to degrade its target proteins in the G1 phase of the cell cycle, leading to efficient repair of DNA damage.

Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.

PubMed

Wang, Huan; Wang, Hong-Fei; Wang, Chen; Chen, Yu-Fang; Ma, Rong; Xiang, Ji-Zhou; Du, Xin-Ling; Tang, Qiang

2016-10-15

In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 μΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300μM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30μM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30μM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K(+) current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor of Ikur (which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell. Copyright © 2016 Elsevier B.V. All rights reserved.

How long can fisheries management delay action in response to ecosystem and climate change?

PubMed

Brown, Christopher J; Fulton, Elizabeth A; Possingham, Hugh P; Richardson, Anthony J

2012-01-01

Sustainable management of fisheries is often compromised by management delaying implementation of regulations that reduce harvest, in order to maintain higher catches in the short-term. Decreases or increases in fish population growth rate driven by environmental change, including ecosystem and climate change, affect the harvest that can be taken sustainably. If not acted on rapidly, environmental change could result in unsustainable fishing or missed opportunity for higher catches. Using simulation models of harvested fish populations influenced by environmental change, we explore how long fisheries managers can afford to wait before changing harvest regulations in response to changes in population growth. If environmental change causes population declines, delays greater than five years increase the probability of population collapse. Species with fast and highly variable population growth rates are more susceptible to collapse under delays and should be a priority for revised management where delays occur. Generally, the long-term cost of delay, in terms of lost fishing opportunity, exceeds the short-term benefits of overfishing. Lowering harvest limits and monitoring for environmental change can alleviate the impact of delays; however, these measures may be more costly than reducing delays. We recommend that management systems that allow rapid responses to population growth changes be enacted for fisheries management to adapt to ecosystem and climate change.

Task-specificity of bilateral anticipatory activation of the deep abdominal muscles in healthy and chronic low back pain populations.

PubMed

Massé-Alarie, Hugo; Beaulieu, Louis-David; Preuss, Richard; Schneider, Cyril

2015-02-01

Cross-sectional study of lumbopelvic muscle activation during rapid limb movements in chronic low back pain (CLBP) patients and healthy controls. Controversy exists over whether bilateral anticipatory activation of the deep abdominal muscles represents a normal motor control strategy prior to all rapid limb movements, or if this is simply a task-specific strategy appropriate for only certain movement conditions. To assess the onset timing of the transversus abdominis/internal oblique muscles (TrA/IO) during two rapid limb movement tasks with different postural demands - bilateral shoulder flexion in standing, unilateral hip extension in prone lying - as well as differences between CLBP and controls. Twelve CLBP and 13 controls performed the two tasks in response to an auditory cue. Surface EMG was acquired bilaterally from five muscles, including TrA/IO. In both groups, 50% of bilateral shoulder flexion trials showed bilateral anticipatory TrA/IO activation. This was rare, however, in unilateral hip extension for which only the TrA/IO contralateral to the moving leg showed anticipatory activation. The only significant difference in lumbo-pelvic muscle onset timing between CLBP and controls was a delay in semitendinosus activation during bilateral shoulder flexion in standing. Our data suggest that bilateral anticipatory TrA/IO activation is a task-specific motor control strategy, appropriate for only certain rapid limb movement conditions. Furthermore, the presence of altered semitendinosus onset timing in the CLBP group during bilateral shoulder flexion may be reflective of other possible lumbo-pelvic motor control alterations among this population. Copyright © 2014 Elsevier B.V. All rights reserved.

Construction procedures using self hardening fly ash

NASA Astrophysics Data System (ADS)

Thornton, S. I.; Parker, D. G.

1980-07-01

Fly ash produced in Arkansas from burning Wyoming low sulfur coal is self-hardening and can be effective as a soil stabilizing agent for clays and sands. The strength of soil-self hardening fly ash develops rapidly when compacted immediately after mixing. Seven day unconfined compressive strengths up to 1800 psi were obtained from 20% fly ash and 80% sand mixtures. A time delay between mixing the fly ash with the soil and compaction of the mixture reduced the strength. With two hours delay, over a third of the strength was lost and with four hours delay, the loss was over half. Gypsum and some commercial concrete retarders were effective in reducing the detrimental effect of delayed compaction. Adequate mixing of the soil and fly ash and rapid compaction of the mixtures were found to be important parameters in field construction of stabilized bases.

Better concrete mixes for rapid repair in Wisconsin.

DOT National Transportation Integrated Search

2017-04-01

With the increasing demands on the highway system and increasing costs of user delay, the use and development of rapid-repairtechniques are expected to grow rapidly. High early strength (HES) portland cement concrete can help reduce the duration oftr...

Effects of different concentrations of metal ions on degradation of adenosine triphosphate in common carp (Cyprinus carpio) fillets stored at 4°C: An in vivo study.

PubMed

Li, Dapeng; Qin, Na; Zhang, Longteng; Lv, Jian; Li, Qingzheng; Luo, Yongkang

2016-11-15

The impact of different concentrations of Na(+), K(+), Ca(2+), Mg(2+), Fe(2+), and Zn(2+) on the degradation of adenosine triphosphate (ATP) and the influence of these ions on the activity of adenosine monophosphate deaminase (AMP-deaminase) and acid phosphatase (ACP) in common carp fillets (in vivo) during 4°C storage was examined. The content of ATP, inosine monophosphate (IMP), and hypoxanthine (Hx), and the activity of AMP-deaminase and ACP were determined. Results indicated that the effects of different concentrations of six kinds of metal ions on AMP-deaminase and ACP were not the same. Na(+), K(+), Fe(2+), and Zn(2+) enhanced AMP-deaminase activity, which led to the rapid degradation of ATP and to the generation of a large quantity of IMP within a short time. Ca(2+) and Mg(2+) delayed the change in AMP-deaminase and ACP activity in carp and caused a further delay in the degradation of ATP. Fe(2+) and Zn(2+) inhibited ACP activity, which reduced the decomposition of IMP and the formation of Hx. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanisms mediating Nitroglycerin-induced Delayed Onset Hyperalgesia in the Rat

PubMed Central

Ferrari, Luiz F.; Levine, Jon D.; Green, Paul G.

2016-01-01

Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN’s very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ~30 min in male and ~45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggest potential novel risk factors and targets for the treatment of migraine. PMID:26779834

Are superhydrophobic surfaces best for icephobicity?

PubMed

Jung, Stefan; Dorrestijn, Marko; Raps, Dominik; Das, Arindam; Megaridis, Constantine M; Poulikakos, Dimos

2011-03-15

Ice formation can have catastrophic consequences for human activity on the ground and in the air. Here we investigate water freezing delays on untreated and coated surfaces ranging from hydrophilic to superhydrophobic and use these delays to evaluate icephobicity. Supercooled water microdroplets are inkjet-deposited and coalesce until spontaneous freezing of the accumulated mass occurs. Surfaces with nanometer-scale roughness and higher wettability display unexpectedly long freezing delays, at least 1 order of magnitude longer than typical superhydrophobic surfaces with larger hierarchical roughness and low wettability. Directly related to the main focus on heterogeneous nucleation and freezing delay of supercooled water droplets, the observed ensuing crystallization process consisted of two distinct phases: one very rapid recalescent partial solidification phase and a subsequent slower phase. Observations of the droplet collision process employed for the continuous liquid mass accumulation up to the point of ice formation reveal a previously unseen atmospheric-pressure, subfreezing-temperature regime for liquid-on-liquid bounce. On the basis of the entropy reduction of water near a solid surface, we formulate a modification to the classical heterogeneous nucleation theory, which predicts the observed freezing delay trends. Our results bring to question recent emphasis on super water-repellent surface formulations for ice formation retardation and suggest that anti-icing design must optimize the competing influences of both wettability and roughness.

Effects of nisin on growth of bacteria attached to meat.

PubMed Central

Chung, K T; Dickson, J S; Crouse, J D

1989-01-01

Nisin had an inhibitory effect on gram-positive bacteria (Listeria monocytogenes, Staphylococcus aureus, and Streptococcus lactis) but did not have an inhibitory effect on gram-negative bacteria (Serratia marcescens, Salmonella typhimurium, and Pseudomonas aeruginosa) attached to meat. Nisin delayed bacterial growth on meats which were artificially inoculated with L. monocytogenes or Staphylococcus aureus for at least 1 day at room temperature. If the incubation temperature was 5 degrees C, growth of L. monocytogenes was delayed for more than 2 weeks, and growth of Staphylococcus aureus did not occur. We also found that the extractable activity of nisin decreased rapidly when the meats were incubated at ambient temperatures and that this decrease was inversely related to the observed inhibitory effect. These findings disclosed that nisin delays the growth of some gram-positive bacteria attached to meat. However, nisin alone may not be sufficient to prevent meat spoilage because of the presence of gram-negative and other nisin-resistant gram-positive bacteria. PMID:2764559

Experimental verification of arm-locking for LISA using electronic phase delay [rapid communication

NASA Astrophysics Data System (ADS)

Thorpe, J. I.; Mueller, G.

2005-07-01

We present results of an electronic model of arm-locking, a proposed technique for reducing the laser phase noise in the laser interferometer space antenna (LISA). The model is based on a delay of 500 ms, achieved using the electronic phase delay (EPD) method. The observed behavior is consistent with predictions.

Computational Analysis of AMPK-Mediated Neuroprotection Suggests Acute Excitotoxic Bioenergetics and Glucose Dynamics Are Regulated by a Minimal Set of Critical Reactions.

PubMed

Connolly, Niamh M C; D'Orsi, Beatrice; Monsefi, Naser; Huber, Heinrich J; Prehn, Jochen H M

2016-01-01

Loss of ionic homeostasis during excitotoxic stress depletes ATP levels and activates the AMP-activated protein kinase (AMPK), re-establishing energy production by increased expression of glucose transporters on the plasma membrane. Here, we develop a computational model to test whether this AMPK-mediated glucose import can rapidly restore ATP levels following a transient excitotoxic insult. We demonstrate that a highly compact model, comprising a minimal set of critical reactions, can closely resemble the rapid dynamics and cell-to-cell heterogeneity of ATP levels and AMPK activity, as confirmed by single-cell fluorescence microscopy in rat primary cerebellar neurons exposed to glutamate excitotoxicity. The model further correctly predicted an excitotoxicity-induced elevation of intracellular glucose, and well resembled the delayed recovery and cell-to-cell heterogeneity of experimentally measured glucose dynamics. The model also predicted necrotic bioenergetic collapse and altered calcium dynamics following more severe excitotoxic insults. In conclusion, our data suggest that a minimal set of critical reactions may determine the acute bioenergetic response to transient excitotoxicity and that an AMPK-mediated increase in intracellular glucose may be sufficient to rapidly recover ATP levels following an excitotoxic insult.

Computational Analysis of AMPK-Mediated Neuroprotection Suggests Acute Excitotoxic Bioenergetics and Glucose Dynamics Are Regulated by a Minimal Set of Critical Reactions

PubMed Central

Connolly, Niamh M. C.; D’Orsi, Beatrice; Monsefi, Naser; Huber, Heinrich J.; Prehn, Jochen H. M.

2016-01-01

Loss of ionic homeostasis during excitotoxic stress depletes ATP levels and activates the AMP-activated protein kinase (AMPK), re-establishing energy production by increased expression of glucose transporters on the plasma membrane. Here, we develop a computational model to test whether this AMPK-mediated glucose import can rapidly restore ATP levels following a transient excitotoxic insult. We demonstrate that a highly compact model, comprising a minimal set of critical reactions, can closely resemble the rapid dynamics and cell-to-cell heterogeneity of ATP levels and AMPK activity, as confirmed by single-cell fluorescence microscopy in rat primary cerebellar neurons exposed to glutamate excitotoxicity. The model further correctly predicted an excitotoxicity-induced elevation of intracellular glucose, and well resembled the delayed recovery and cell-to-cell heterogeneity of experimentally measured glucose dynamics. The model also predicted necrotic bioenergetic collapse and altered calcium dynamics following more severe excitotoxic insults. In conclusion, our data suggest that a minimal set of critical reactions may determine the acute bioenergetic response to transient excitotoxicity and that an AMPK-mediated increase in intracellular glucose may be sufficient to rapidly recover ATP levels following an excitotoxic insult. PMID:26840769

Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

PubMed

Waldinger, M D; Hengeveld, M W; Zwinderman, A H; Olivier, B

1998-08-01

Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p < 0.001, p < 0.001, p = 0.017, respectively) from placebo but the fluvoxamine group did not (p = 0.38). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, followed by fluoxetine and sertraline. There was no clinically relevant delay in ejaculation with fluvoxamine. In men with lifelong rapid ejaculation, paroxetine delayed ejaculation most strongly, whereas fluvoxamine delayed ejaculation the least. The second double-blind, placebo-controlled study was carried out in men with lifelong rapid ejaculation (IELT < or = 1 minute) and in men with lifelong less-rapid ejaculation (IELT > 1 minute) to investigate whether data about SSRI-induced delayed ejaculation in men with rapid ejaculation may be extrapolated to men with less-rapid ejaculation. After measurement of IELT at home (using a stopwatch) during a 1-month baseline assessment, 32 men with an IELT of 1 minute or less (group 1) or more than 1 minute (group 2) were randomly assigned to receive paroxetine 20 mg/day or placebo for 6 weeks in a double-blind manner. Patients continued to measure their IELTs at home during the 6 weeks of the study. At baseline, 24 patients consistently had IELTs of one minute or less (group 1), and eight patients had IELTs of more than 1 minute (group 2). The geometric mean IELT was 14 seconds in group 1 and 83 seconds in group 2. Twelve patients in group 1 and five in group 2 were randomized to the paroxetine 20 mg/day. The percentage increase in the geometric mean IELT compared with baseline in patients treated with paroxetine was 420% (95% confidence interval [CI], 216-758%) in group 1 and 480% (95% CI, 177-1,118%) in group 2 (p = 0.81). After 6 weeks of treatment with paroxetine, the geometric mean IELT was 92 seconds in group 1 and 602 seconds in group 2 (p < 0.001). Therefore, the paroxetine-induced percentage increase in IELT seems to be independent of the baseline IELT. This suggests that ejaculation-delaying side effects of some SSRIs investigated in men with lifelong rapid ejaculation may be generalized to men with less-rapid ejaculation.

Kinetics of activation of a Ca2+-dependent K+ current induced by flash photolysis of caged carbachol in isolated guinea-pig outer hair cells.

PubMed

Chan, E; Evans, M G

1998-09-18

It has been shown that the application of acetylcholine activates a Ca2+-dependent K+ current in outer hair cells, and the resulting hyperpolarization is thought to be an important part of the inhibition mediated by cholinergic efferent nerve fibres to the cochlea. In order to study the kinetics of the current, flash photolysis has been used to apply a cholinergic agonist, carbachol, rapidly to isolated outer hair cells. A delay in the onset of the outward potassium current following photorelease of carbachol was consistently observed, and the activation phase of the response could be described by a sigmoidal-like function with a mean delay of 59 ms and time constant of 71 ms. The sum of these values lies within the time scale reported for the onset of the inhibition following electrical stimulation of the efferent nerves. Although a distinct current attributable to an acetylcholine receptor was not visible in these experiments, indirect evidence for a carbachol-induced influx of Ca2+ was obtained.

Dynamics of in vivo ASC speck formation

PubMed Central

2017-01-01

Activated danger or pathogen sensors trigger assembly of the inflammasome adaptor ASC into specks, large signaling platforms considered hallmarks of inflammasome activation. Because a lack of in vivo tools has prevented the study of endogenous ASC dynamics, we generated a live ASC reporter through CRISPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong ASC expression in the skin and other epithelia that act as barriers to insult. A toxic stimulus triggered speck formation and rapid pyroptosis in keratinocytes in vivo. Macrophages engulfed and digested that speck-containing, pyroptotic debris. A three-dimensional, ultrastructural reconstruction, based on correlative light and electron microscopy of the in vivo assembled specks revealed a compact network of highly intercrossed filaments, whereas pyrin domain (PYD) or caspase activation and recruitment domain alone formed filamentous aggregates. The effector caspase is recruited through PYD, whose overexpression induced pyroptosis but only after substantial delay. Therefore, formation of a single, compact speck and rapid cell-death induction in vivo requires a full-length ASC. PMID:28701426

Sotos Syndrome. Clinical Exchange.

ERIC Educational Resources Information Center

Shuey, Elaine M.; Jamison, Kristen

1996-01-01

Sotos syndrome is characterized by high birth length, rapid bone growth, distinctive facial features, and possible verbal and motor delays. It is more common in males than females. Developmental deficits, specific learning problems, and speech/language delays may also occur. (DB)

Quantitative analysis of the Ca2+ -dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes.

PubMed

Bartos, Daniel C; Morotti, Stefano; Ginsburg, Kenneth S; Grandi, Eleonora; Bers, Donald M

2017-04-01

[Ca 2+ ] i enhanced rabbit ventricular slowly activating delayed rectifier K + current (I Ks ) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol. Rabbit ventricular rapidly activating delayed rectifier K + current (I Kr ) amplitude and voltage dependence were unaffected by high [Ca 2+ ] i . When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca 2+ transient or when [Ca 2+ ] i was buffered to 500 nm. The slowly activating delayed rectifier K + current (I Ks ) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca 2+ ([Ca 2+ ] i ) and β-adrenergic receptor (β-AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca 2+ ] i dependence of I Ks in steady-state conditions and with dynamically changing membrane potential and [Ca 2+ ] i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole-cell patch clamp. With intracellular pipette solutions that controlled free [Ca 2+ ] i , we found that raising [Ca 2+ ] i from 100 to 600 nm produced similar increases in I Ks as did β-AR activation, and the effects appeared additive. Both β-AR activation and high [Ca 2+ ] i increased maximally activated tail I Ks , negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well-established mathematical model of the rabbit myocyte. In both AP-clamp experiments and simulations, I Ks recorded during a normal physiological Ca 2+ transient was similar to I Ks measured with [Ca 2+ ] i clamped at 500-600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca 2+ ] i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca 2+ ] i , in the submembrane or junctional cleft space, is not required to maximize [Ca 2+ ] i -dependent I Ks activation during normal Ca 2+ transients. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Quantitative analysis of the Ca2+‐dependent regulation of delayed rectifier K+ current I Ks in rabbit ventricular myocytes

PubMed Central

Bartos, Daniel C.; Morotti, Stefano; Ginsburg, Kenneth S.; Grandi, Eleonora

2017-01-01

Key points [Ca2+]i enhanced rabbit ventricular slowly activating delayed rectifier K+ current (I Ks) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol.Rabbit ventricular rapidly activating delayed rectifier K+ current (I Kr) amplitude and voltage dependence were unaffected by high [Ca2+]i.When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca2+ transient or when [Ca2+]i was buffered to 500 nm. Abstract The slowly activating delayed rectifier K+ current (I Ks) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca2+ ([Ca2+]i) and β‐adrenergic receptor (β‐AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca2+]i dependence of I Ks in steady‐state conditions and with dynamically changing membrane potential and [Ca2+]i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole‐cell patch clamp. With intracellular pipette solutions that controlled free [Ca2+]i, we found that raising [Ca2+]i from 100 to 600 nm produced similar increases in I Ks as did β‐AR activation, and the effects appeared additive. Both β‐AR activation and high [Ca2+]i increased maximally activated tail I Ks, negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well‐established mathematical model of the rabbit myocyte. In both AP‐clamp experiments and simulations, I Ks recorded during a normal physiological Ca2+ transient was similar to I Ks measured with [Ca2+]i clamped at 500–600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca2+]i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca2+]i, in the submembrane or junctional cleft space, is not required to maximize [Ca2+]i‐dependent I Ks activation during normal Ca2+ transients. PMID:28008618

Delayed unlatching mechanism

DOEpatents

Bzorgi, Fariborz M.

2015-05-19

In various embodiments an apparatus is presented for securing a structure such as a door, window, hatch, or gate that moves between an open and a closed position relative to a fixed structure to provide or deny access to a compartment, a room, an outdoor area, or a facility. Various embodiments provide a delay in opening the closure of sufficient duration to frustrate a rapid activation that might be desired by a person who is attempting to pass through the closure for some illicit purpose. Typically, hydraulics are used to activate the apparatus and no electrical energy or electronic signals are employed. In one embodiment, a plurality of actuations of a hand lever operates a hydraulic pump that moves a locking bolt from a first position in which a locking bolt is engaged with a recess in the fixed structure (preventing opening of a gate) to a second position in which the locking bolt is disengaged from the recess to permit opening of the gate.

Mechanism of UES relaxation initiated by gastric air distension.

PubMed

Lang, Ivan M; Medda, Bidyut K; Shaker, Reza

2014-08-15

The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.05) affected by thoracotomy. Free air or bagged air (n = 6) activated TLESR, but only free air activated TUESR. Closure of the gastroesophageal junction blocked TUESR (9/9), but not TLESR (4/4), caused by air inflation of the stomach. Venting air from distal esophagus during air inflation of the stomach prevented TUESR (n = 12) but did not prevent air escape from the stomach to the esophagus (n = 4). Rapid injection of air on the esophageal mucosa always caused TUESR (9/9) but did not always (7/9) cause an increase in esophageal pressure. The time delay between the TUESR and the rapid air pulse was significantly more variable (P < 0.05) than the time delay between the rapid air pulse and the rise in esophageal pressure. We concluded that the TUESR caused by gastric air distension is dependent on air escape from the stomach, which stimulates receptors in the esophagus, but is not dependent on distension of the stomach or esophagus, or the TLESR. Therefore, the TUESR caused by gastric air distension is initiated by stimulation of receptors in the esophageal mucosa. Copyright © 2014 the American Physiological Society.

A telephone hotline for transient ischaemic attack and stroke: prospective audit of a model to improve rapid access to specialist stroke care.

PubMed

Kerr, Enda; Arulraj, Nolan; Scott, Maggie; McDowall, Mike; van Dijke, Margrethe; Keir, Sarah; Sandercock, Peter; Dennis, Martin

2010-07-02

Patients with transient ischaemic attack or stroke benefit from early diagnosis, specialist assessment, and treatment with thrombolysis, and from stroke unit care and secondary prevention. The challenge with such patients is to minimise delays and ensure that treatment is appropriate, and to provide this care with the available resources. An ongoing prospective audit of a transient ischaemic attack and stroke clinic (1 January 2005 to 30 September 2009), as part of the Scottish Stroke Care Audit, and a three month targeted audit of immediate telephone access to a specialist stroke consultant (1 February 2009 to 30 April 2009). Stroke and transient ischaemic attack services in Lothian, a region of Scotland with a population of 810,000. Delays to assessment at a rapid access transient ischaemic attack and stroke clinic; delays to appropriate treatment. In February 2007 we introduced a 24 hours a day, seven days a week hotline to a consultant, who provided immediate advice on diagnosis, investigation, and emergency treatment for patients with transient ischaemic attack or stroke, and suggested the most appropriate care pathway, which might include an early appointment in a transient ischaemic attack and stroke clinic. The introduction of the hotline was associated with an immediate and sustained reduction in delays to assessment (from 13 to three days) and treatment. The proportion of participants taking statins at the time of visiting the clinic increased from 40% before the introduction of the hotline to 60% after the hotline was in place. Also, the hotline contributed to a reduction in the delay from last event to carotid surgery, from 58 days to 21.5 days. A total of 376 calls were received during the three month audit. Of the 273 (88%) referrers who responded to our questionnaire, 257 (94%) were very satisfied with the advice given over the hotline. Although associated with some disruption to the activities of the consultants, a 24 hours a day, seven days a week telephone hotline to a consultant is a feasible and effective means of reducing delays to specialist assessment and treatment of patients with transient ischaemic attack or stroke.

Familial diagnostic experiences in paediatric oncology.

PubMed

Evans, N T; Wakefield, C E; McLoone, J K; Cohn, R J

2015-01-06

Diagnostic delays may not have significant prognostic implications in paediatric oncology, but psychological impacts remain understudied. Interviews exploring diagnostic experiences were conducted with childhood cancer survivors (n=19), parents (n=78) and siblings (n=15). Median diagnostic time was 3 weeks. Participants described a mixture of rapid diagnoses (28.9%), plus delayed appraisal intervals (that is, parent- or patient-associated diagnostic delays; 40.0%) and diagnostic intervals (that is, healthcare-associated delays; 46.7%). Families experiencing delays described guilt and anger and deleterious impacts on the family-clinician relationship. Some believed delays impacted on treatment and prognosis. The effect of the diagnostic experience can be considerable.

Delay of flower senescence by bacterial endophytes expressing 1-aminocyclopropane-1-carboxylate deaminase.

PubMed

Ali, S; Charles, T C; Glick, B R

2012-11-01

The ability of 1-aminocyclopropane-1-carboxylate (ACC) deaminase-containing plant growth-promoting bacterial (PGPB) endophytes Pseudomonas fluorescens YsS6 and Pseudomonas migulae 8R6, their ACC deaminase minus mutants and the rhizospheric plant growth-promoting bacterium Pseudomonas putida UW4 to delay the senescence of mini carnation cut flowers was assessed. Fresh cut flowers were incubated with either a bacterial cell suspension, the ethylene precursor ACC, the ethylene inhibitor l-α-(aminoethoxyvinyl)-glycine or 0·85% NaCl at room temperature for 11 days. Levels of flower senescence were recorded every other day. To verify the presence of endophytes inside the plant tissues, scanning electron microscopy was performed. Among all treatments, flowers treated with wild-type ACC deaminase-containing endophytic strains exhibited the most significant delay in flower senescence, while flowers treated with the ACC deaminase minus mutants senesced at a rate similar to the control. Flowers treated with Ps. putida UW4 senesced more rapidly than untreated control flowers. The only difference between wild-type and mutant bacterial endophytes was ACC deaminase activity so that it may be concluded that this enzyme is directly responsible for the significant delay in flower senescence. Despite containing ACC deaminase activity, Ps. putida UW4 is not taken up by the cut flowers and therefore has no effect on prolonging their shelf life. The world-wide cut flower industry currently uses expensive and potentially environmentally dangerous chemical inhibitors of ethylene to prolong the shelf life of cut flowers. The use of PGPB endophytes with ACC deaminase activity has the potential to replace the chemicals that are currently used by the cut flower industry. © 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat.

PubMed

Ferrari, L F; Levine, J D; Green, P G

2016-03-11

Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN's very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ∼ 30 min in male and ∼ 45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed-onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggests potential novel risk factors and targets for the treatment of migraine. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

PPARα autocrine regulation of Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: NO and cGMP accumulation.

PubMed

Tanaka, Saori; Sugiyama, Nanae; Takahashi, Yuko; Mantoku, Daiki; Sawabe, Yukinori; Kuwabara, Hiroko; Nakano, Takashi; Shimamoto, Chikao; Matsumura, Hitoshi; Marunaka, Yoshinori; Nakahari, Takashi

2014-12-15

In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca(2+)-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N(5)-[imino(propylamino)methyl]-L-ornithine hydrochloride (N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca(2+)-regulated exocytosis in antral mucous cells. Copyright © 2014 the American Physiological Society.

Combustion chemistry of ethanol: Ignition and speciation studies in a rapid compression facility [On the combustion chemistry of ethanol: Ignition and speciation studies in a rapid compression facility

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

Barraza-Botet, Cesar L.; Wagnon, Scott W.; Wooldridge, Margaret S.

Here, ethanol remains the most important alternative fuel for the transportation sector. This work presents new experimental data on ethanol ignition, including stable species measurements, obtained with the University of Michigan rapid compression facility. Ignition delay times were determined from pressure histories of ignition experiments with stoichiometric ethanol–air mixtures at pressures of ~3–10 atm. Temperatures (880–1150 K) were controlled by varying buffer gas composition (Ar, N 2, CO 2). High-speed imaging was used to record chemiluminescence during the experiments, which showed homogeneous ignition events. The results for ignition delay time agreed well with trends on the basis of previous experimentalmore » measurements. Speciation experiments were performed using fast gas sampling and gas chromatography to identify and quantify ethanol and 11 stable intermediate species formed during the ignition delay period. Simulations were carried out using a chemical kinetic mechanism available in the literature, and the agreement with the experimental results for ignition delay time and the intermediate species measured was excellent for the majority of the conditions studied. From the simulation results, ethanol + HO 2 was identified as an important reaction at the experimental conditions for both the ignition delay time and intermediate species measurements. Further studies to improve the accuracy of the rate coefficient for ethanol + HO 2 would improve the predictive understanding of intermediate and low-temperature ethanol combustion.« less

Combustion chemistry of ethanol: Ignition and speciation studies in a rapid compression facility [On the combustion chemistry of ethanol: Ignition and speciation studies in a rapid compression facility

DOE PAGES

Barraza-Botet, Cesar L.; Wagnon, Scott W.; Wooldridge, Margaret S.

2016-08-31

Here, ethanol remains the most important alternative fuel for the transportation sector. This work presents new experimental data on ethanol ignition, including stable species measurements, obtained with the University of Michigan rapid compression facility. Ignition delay times were determined from pressure histories of ignition experiments with stoichiometric ethanol–air mixtures at pressures of ~3–10 atm. Temperatures (880–1150 K) were controlled by varying buffer gas composition (Ar, N 2, CO 2). High-speed imaging was used to record chemiluminescence during the experiments, which showed homogeneous ignition events. The results for ignition delay time agreed well with trends on the basis of previous experimentalmore » measurements. Speciation experiments were performed using fast gas sampling and gas chromatography to identify and quantify ethanol and 11 stable intermediate species formed during the ignition delay period. Simulations were carried out using a chemical kinetic mechanism available in the literature, and the agreement with the experimental results for ignition delay time and the intermediate species measured was excellent for the majority of the conditions studied. From the simulation results, ethanol + HO 2 was identified as an important reaction at the experimental conditions for both the ignition delay time and intermediate species measurements. Further studies to improve the accuracy of the rate coefficient for ethanol + HO 2 would improve the predictive understanding of intermediate and low-temperature ethanol combustion.« less

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

PubMed

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

2010-04-01

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

Research and Development of Hazardous/Toxic Waste Analytical Screening Procedures. Available Field Methods for Rapid Screening of Hazardous Waste Materials at Waste Sites (Class A Poisons).

DTIC Science & Technology

1982-01-01

bromide is listed as a positive interference. Nitric oxide and nitrogen dioxide can be detected by using the Draeger nitrous fumes detector tube. A... fumes exhibit a delay from the time of exposure to the onset of symptoms. This time delay would not be conducive for a rapid field screening test. It...Dangerous when strongly heated, emits highly toxic fumes . THRESHOLD LIMIT VALUE: No information available PHYSIOLOGICAL EFFECTS: A. Intensely irritating to

Use of rapid needs assessment as a tool to identify vaccination delays in Guatemala and Peru.

PubMed

D'Ardenne, Katie K; Darrow, Juliana; Furniss, Anna; Chavez, Catia; Hernandez, Herminio; Berman, Stephen; Asturias, Edwin J

2016-03-29

To explore the use of rapid needs assessment (RNA) surveys to determine the prevalence and factors contributing to delays in vaccination of children in two low middle-income countries (LMIC). Data from two RNA surveys performed as part of program improvement evaluations in Guatemala and Peru were used for this analysis. The primary endpoint was the timeliness of immunization with delay defined as administration of vaccines beyond 28 days from recommended age for DTwP-HepB-Hib (Penta) and measles-mumps-rubella (MMR) vaccines, as well as past age-restrictions for rotavirus vaccine. Independent risk factors analyzed included child's gender, birth year, number of children in household, maternal age, maternal education, and food insecurity. Vaccine information was available from 811 children from 838 households surveyed. High rate of immunization delays was observed, with 75.6% of children in Guatemala and 57.8% of children in Peru being delayed for the third dose of Penta primary series. Factors associated with delayed vaccination in Guatemala included advanced maternal age and increased number of children in household. In Peru, significant associations were birth year before 2009, lower maternal education level, and increased number of children in household. RNA is a fast and effective method to identify timely vaccine coverage and derive a hypothesis of factors possibly associated with vaccination delay. Copyright © 2016 Elsevier Ltd. All rights reserved.

The mRNA cap-binding protein Cbc1 is required for high and timely expression of genes by promoting the accumulation of gene-specific activators at promoters.

PubMed

Li, Tianlu; De Clercq, Nikki; Medina, Daniel A; Garre, Elena; Sunnerhagen, Per; Pérez-Ortín, José E; Alepuz, Paula

2016-02-01

The highly conserved Saccharomyces cerevisiae cap-binding protein Cbc1/Sto1 binds mRNA co-transcriptionally and acts as a key coordinator of mRNA fate. Recently, Cbc1 has also been implicated in transcription elongation and pre-initiation complex (PIC) formation. Previously, we described Cbc1 to be required for cell growth under osmotic stress and to mediate osmostress-induced translation reprogramming. Here, we observe delayed global transcription kinetics in cbc1Δ during osmotic stress that correlates with delayed recruitment of TBP and RNA polymerase II to osmo-induced promoters. Interestingly, we detect an interaction between Cbc1 and the MAPK Hog1, which controls most gene expression changes during osmostress, and observe that deletion of CBC1 delays the accumulation of the activator complex Hot1-Hog1 at osmostress promoters. Additionally, CBC1 deletion specifically reduces transcription rates of highly transcribed genes under non-stress conditions, such as ribosomal protein (RP) genes, while having low impact on transcription of weakly expressed genes. For RP genes, we show that recruitment of the specific activator Rap1, and subsequently TBP, to promoters is Cbc1-dependent. Altogether, our results indicate that binding of Cbc1 to the capped mRNAs is necessary for the accumulation of specific activators as well as PIC components at the promoters of genes whose expression requires high and rapid transcription. Copyright © 2016 Elsevier B.V. All rights reserved.

FRET analysis demonstrates a rapid activating of caspase-3 during PDT-induced apoptosis

NASA Astrophysics Data System (ADS)

Wu, Yunxia; Chen, Qun

2006-09-01

Apoptosis is a very important cellular event that plays a key role in pathogeny and therapy of many diseases. In this study, a recombinant caspase-3 substrate was used as a fluorescence resonance energy transfer (FRET) probe to detect the activation of caspase-3, and to monitor apoptosis in human lung adenocarcinoma (ASTC-a- 1) cells. With laser scanning confocal microscopy, we found that Photofrin were localized primarily in mitochondria, the primary targets of Photofrin-PDT. By analyzing the dynamic changes of FRET fluorescence, the results indicate that the onset and completion of caspase-3 activation induced by PDT is more rapidly than that by tumor necrosis factor-α (TNF-α). The activation of caspase-3 by PDT started 20 minutes after treatment and completed in about 15 minutes. In comparison, the onset of caspase-3 activation by TNF-a was delayed by 3 hours and the completion of caspase-3 activation required a significantly longer time (approximately 90 minutes). These results indicated that the initiation and process of caspase-3 activation are different corresponding to different treatment methods. Our data suggest that caspase-3 activation mediated by the cell surface death receptors is slower than that of the mitochondrial pathway and the mitochondria is an efficient target to induce apoptosis.

Relativistic effects in photoionization: Wigner time delay for the noble gases and IIB atoms

NASA Astrophysics Data System (ADS)

Banerjee, Sourav; Deshmukh, Pranawa; Dolmatov, Valeriy; Kheifets, Anatoli; Manson, Steven

2017-04-01

Time delay in atomic photoionization has been observed in several experiments, and various theoretical and experimental approaches are developing rapidly to obtain a better understanding of this phenomena. Theoretical methods that account for many body correlations include the relativistic random phase approximation (RRPA) and its non-relativistic analogue, RPAE. Calculations using RRPA are performed and the impact of relativistic interactions on Wigner time delay are explored via comparison of this result with RPAE results. In addition, results on Wigner time delay for Zn Cd and Hg are presented.

Pathogenetic mechanisms of amyloid A amyloidosis

PubMed Central

Simons, J. Paul; Al-Shawi, Raya; Ellmerich, Stephan; Speck, Ivana; Aslam, Samrina; Hutchinson, Winston L.; Mangione, Palma P.; Disterer, Petra; Gilbertson, Janet A.; Hunt, Toby; Millar, David J.; Minogue, Shane; Bodin, Karl; Pepys, Mark B.; Hawkins, Philip N.

2013-01-01

Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflammation before presenting, most commonly with renal involvement. Using dose-dependent, doxycycline-inducible transgenic expression of SAA in mice, we show that AA amyloid deposition can occur independently of inflammation and that the time before amyloid deposition is determined by the circulating SAA concentration. High level SAA expression induced amyloidosis in all mice after a short, slightly variable delay. SAA was rapidly incorporated into amyloid, acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest SAA overexpression occasionally produced amyloidosis after long delays and primed most mice for explosive amyloidosis when SAA production subsequently increased. Endogenous priming and bulk amyloid deposition are thus separable events, each sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with restoration of normal SAA production after doxycycline withdrawal. Reinduction of SAA overproduction revealed that, following amyloid regression, all mice were primed, especially for rapid glomerular amyloid deposition leading to renal failure, closely resembling the rapid onset of renal failure in clinical AA amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis rarely involves the heart, but amyloidotic SAA transgenic mice consistently had minor cardiac amyloid deposits, enabling us to extend to the heart the demonstrable efficacy of our unique antibody therapy for elimination of visceral amyloid. PMID:23959890

Mobile Health Applications to Promote Active and Healthy Ageing

PubMed Central

Helbostad, Jorunn L.; Vereijken, Beatrix; Becker, Clemens; Todd, Chris; Taraldsen, Kristin; Pijnappels, Mirjam; Aminian, Kamiar; Mellone, Sabato

2017-01-01

The European population is ageing, and there is a need for health solutions that keep older adults independent longer. With increasing access to mobile technology, such as smartphones and smartwatches, the development and use of mobile health applications is rapidly growing. To meet the societal challenge of changing demography, mobile health solutions are warranted that support older adults to stay healthy and active and that can prevent or delay functional decline. This paper reviews the literature on mobile technology, in particular wearable technology, such as smartphones, smartwatches, and wristbands, presenting new ideas on how this technology can be used to encourage an active lifestyle, and discusses the way forward in order further to advance development and practice in the field of mobile technology for active, healthy ageing. PMID:28335475

Mobile Health Applications to Promote Active and Healthy Ageing.

PubMed

Helbostad, Jorunn L; Vereijken, Beatrix; Becker, Clemens; Todd, Chris; Taraldsen, Kristin; Pijnappels, Mirjam; Aminian, Kamiar; Mellone, Sabato

2017-03-18

The European population is ageing, and there is a need for health solutions that keep older adults independent longer. With increasing access to mobile technology, such as smartphones and smartwatches, the development and use of mobile health applications is rapidly growing. To meet the societal challenge of changing demography, mobile health solutions are warranted that support older adults to stay healthy and active and that can prevent or delay functional decline. This paper reviews the literature on mobile technology, in particular wearable technology, such as smartphones, smartwatches, and wristbands, presenting new ideas on how this technology can be used to encourage an active lifestyle, and discusses the way forward in order further to advance development and practice in the field of mobile technology for active, healthy ageing.

β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs.

PubMed

Zhao, Yuhui; Huang, Haixia; Du, Yunhui; Li, Xiao; Lv, Tingting; Zhang, Suli; Wei, Hua; Shang, Jianyu; Liu, Ping; Liu, Huirong

2015-01-01

β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

Effects of a Word-Learning Training on Children With Cochlear Implants

PubMed Central

Lund, Emily

2014-01-01

Preschool children with hearing loss who use cochlear implants demonstrate vocabulary delays when compared to their peers without hearing loss. These delays may be a result of deficient word-learning abilities; children with cochlear implants perform more poorly on rapid word-learning tasks than children with normal hearing. This study explored the malleability of rapid word learning of preschoolers with cochlear implants by evaluating the effects of a word-learning training on rapid word learning. A single-subject, multiple probe design across participants measured the impact of the training on children’s rapid word-learning performance. Participants included 5 preschool children with cochlear implants who had an expressive lexicon of less than 150 words. An investigator guided children to identify, repeat, and learn about unknown sets of words in 2-weekly sessions across 10 weeks. The probe measure, a rapid word-learning task with a different set of words than those taught during training, was collected in the baseline, training, and maintenance conditions. All participants improved their receptive rapid word-learning performance in the training condition. The functional relation indicates that the receptive rapid word-learning performance of children with cochlear implants is malleable. PMID:23981321

The Economic Benefits of Space Tourism

NASA Astrophysics Data System (ADS)

Collins, P.

The recent growth of activities towards developing passenger space travel services is very promising; however there is a widespread but mistaken idea that space tourism will remain a small-scale activity of the very wealthy. The truth is that, having been delayed for over three decades by government space agencies' failure to develop more than a small fraction of the commercial potential of space, the start of space travel services is long overdue, and so they are capable of growing rapidly into a major new industry. That is, the technical and business know-how exists to enable space tourism to grow to a turnover of 100 billion Euros/year within a few decades if it receives public support of even 10% of space agencies budgets. This development would sharply reduce the cost of accessing the resources of space, which could prevent the spread of the “resource wars” which have begun so ominously. No activity therefore offers greater economic benefits than the rapid development of low-cost space tourism services. A range of government policies should be revised to reflect this.

The actions of mdivi-1, an inhibitor of mitochondrial fission, on rapidly activating delayed-rectifier K⁺ current and membrane potential in HL-1 murine atrial cardiomyocytes.

PubMed

So, Edmund Cheung; Hsing, Chung-Hsi; Liang, Chia-Hua; Wu, Sheng-Nan

2012-05-15

Mdivi-1 is an inhibitor of dynamin related protein 1- (drp1)-mediated mitochondrial fission. However, the mechanisms through which this compound interacts directly with ion currents in heart cells remain unknown. In this study, its effects on ion currents and membrane potential in murine HL-1 cardiomyocytes were investigated. In whole-cell recordings, the addition of mdivi-1 decreased the amplitude of tail current (I(tail)) for the rapidly activating delayed-rectifier K⁺ current (I(Kr)) in a concentration-dependent manner with an IC₅₀ value at 11.6 μM, a value that resembles the inhibition requirement for mitochondrial division. It shifted the activation curve of I(tail) to depolarized voltages with no change in the gating charge. However, mdivi-1 did not alter the rate of recovery from current inactivation. In cell-attached configuration, mdivi-1 inside the pipette suppressed the activity of acetylcholine-activated K⁺ channels without modifying the single-channel conductance. Mdivi-1 (30 μM) slightly depressed the peak amplitude of Na⁺ current with no change in the overall current-voltage relationship. Under current-clamp recordings, addition of mdivi-1 resulted in prolongation for the duration of action potentials (APs) and to increase the firing of spontaneous APs in HL-1 cells. Similarly, in pituitary GH₃ cells, mdivi-1 was effective in directly suppressing the amplitude of ether-à-go-go-related gene-mediated K⁺ current. Therefore, the lengthening of AP duration and increased firing of APs caused by mdivi-1 can be primarily explained by its inhibition of these K⁺ channels enriched in heart cells. The observed effects of mdivi-1 on ion currents were direct and not associated with its inhibition of mitochondrial division. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of peak-free electromechanical piezo-impedance and electromagnetic contact sensing using metamaterial surface plasmons for load monitoring

NASA Astrophysics Data System (ADS)

Gopal Madhav Annamdas, Venu; Kiong Soh, Chee

2017-01-01

Continuous structural health monitoring (SHM) and delayed SHM techniques can be contact/ contactless, surface bonded/embedded, wired/wireless and active/passive actuator-sensor systems which transfer the recorded condition of the structure to the base station almost instantaneously or with time delay respectively. The time between fatal crack initiation and its propagation leading to the collapse of key infrastructures such as aerospace, nuclear facilities, oil and gas is mostly short. Timely discovery of structural problem depends heavily on the scanning period in well-established techniques like piezoelectric (PZT) based electromechanical impedance (EMI) technique. This often takes much scanning time due to the acquisition of resonant structural peaks at all frequencies in the considered bandwidth; thus poses a challenge for its implementation in practice. On the other hand, recently developed strain sensors based on metamaterials and their breeds such as nested split-ring resonators, localized surface plasmons (LSP), etc, employ measurement of reflected or transmitted signal, with super-fast scanning in the order of at most 1/100th of the time taken by the EMI technique. This paper articulates faster measurements by reducing unnecessary resonant structural peaks and focusing on rapid monitoring using PZT and metamaterial plasmons. Our research adopted wired PZT and wireless LSP communications with impedance analyser and vector network analyser respectively. We present integrated and complementary nature of these techniques, which can be processed rapidly for key infrastructures with great effectiveness. This integration can result in both continuous and delayed SHM techniques based on time or frequency or both domains.

Diagnostic delay of pulmonary tuberculosis in patients with acute respiratory distress syndrome associated with aspiration pneumonia: Two case reports and a mini-review from Japan

PubMed Central

Nakao, Makoto; Sone, Kazuki; Kagawa, Yusuke; Kurokawa, Ryota; Sato, Hidefumi; Kunieda, Takefumi; Muramatsu, Hideki

2016-01-01

Diagnosing active tuberculosis in elderly patients presents problems due to nonspecific symptoms and complications such as aspiration pneumonia. The current study presents two cases of pulmonary tuberculosis with bilateral pulmonary infiltrates associated with aspiration pneumonia. The two elderly patients developed acute respiratory distress syndrome as a result of aspiration pneumonia. The diagnoses of pulmonary tuberculosis were delayed in both cases, as the patients were diagnosed with active tuberculosis following discharge from hospital. The sputum test for acid-fast bacillus at the time of administration was smear-negative/culture-positive in these patients. They were treated with isoniazid, rifampicin and ethambutol, and nosocomial transmission of tuberculosis from these patients was not reported. The number of elderly patients with aspiration pneumonia is predicted to increase rapidly, and aspiration pneumonia combined with pulmonary tuberculosis is a major medical and healthcare concern in Japan. The present study concludes that physicians should always consider the complication of pulmonary tuberculosis when treating pneumonia patients, in particular in treating elderly patients with pulmonary infiltrates. PMID:27446284

Rapid naming, reading and comprehension in students with learning difficulties.

PubMed

Silva, Cláudia da; Cunha, Vera Lúcia Orlandi; Pinheiro, Fábio Henrique; Capellini, Simone Aparecida

2012-01-01

To compare and correlate the performance of students with learning difficulties in rapid naming, reading and comprehension. Participants were 32 students from 4th grade of elementary school of both genders, with ages between 11 years and 4 months and 12 years and 7 months. The first and second oral reading of a text selected based on the indication of 4th grade teachers were conducted, as well as the first and second reading comprehension task composed by four questions presented right after the reading, to which students should answered orally, and the rapid naming task from the Test of Cognitive-Linguistic Performance, individual version. Differences were found between the first and the second comprehension scores, and between rapid naming, first and second reading. There was a strong correlation between comprehension and reading, suggesting that the performance in the first reading significantly influenced the performance in the second reading, which also occurred for comprehension. The delay in the activities of naming, reading and comprehension in the first evaluation provoked failures in the phoneme-grapheme conversion that may be enough to cause learning difficulties in reading.

Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state.

PubMed

Wheeler, Robert A; Aragona, Brandon J; Fuhrmann, Katherine A; Jones, Joshua L; Day, Jeremy J; Cacciapaglia, Fabio; Wightman, R Mark; Carelli, Regina M

2011-06-01

Prominent neurobiological theories of addiction posit a central role for aberrant mesolimbic dopamine release but disagree as to whether repeated drug experience blunts or enhances this system. Although drug withdrawal diminishes dopamine release, drug sensitization augments mesolimbic function, and both processes have been linked to drug seeking. One possibility is that the dopamine system can rapidly switch from dampened to enhanced release depending on the specific drug-predictive environment. To test this, we examined dopamine release when cues signaled delayed cocaine delivery versus imminent cocaine self-administration. Fast-scan cyclic voltammetry was used to examine real-time dopamine release while simultaneously monitoring behavioral indexes of aversion as rats experienced a sweet taste cue that predicted delayed cocaine availability and during self-administration. Furthermore, the impact of cues signaling delayed drug availability on intracranial self-stimulation, a broad measure of reward function, was assessed. We observed decreased mesolimbic dopamine concentrations, decreased reward sensitivity, and negative affect in response to the cocaine-predictive taste cue that signaled delayed cocaine availability. Importantly, dopamine concentration rapidly switched to elevated levels to cues signaling imminent cocaine delivery in the subsequent self-administration session. These findings show rapid, bivalent contextual control over brain reward processing, affect, and motivated behavior and have implications for mechanisms mediating substance abuse. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication

PubMed Central

Chenoweth, Paul; Okayasu, Hiro; Donnelly, Christl A.; Aylward, R. Bruce; Grassly, Nicholas C.

2016-01-01

As the global eradication of poliomyelitis approaches the final stages, prompt detection of new outbreaks is critical to enable a fast and effective outbreak response. Surveillance relies on reporting of acute flaccid paralysis (AFP) cases and laboratory confirmation through isolation of poliovirus from stool. However, delayed sample collection and testing can delay outbreak detection. We investigated whether weekly testing for clusters of AFP by location and time, using the Kulldorff scan statistic, could provide an early warning for outbreaks in 20 countries. A mixed-effects regression model was used to predict background rates of nonpolio AFP at the district level. In Tajikistan and Congo, testing for AFP clusters would have resulted in an outbreak warning 39 and 11 days, respectively, before official confirmation of large outbreaks. This method has relatively high specificity and could be integrated into the current polio information system to support rapid outbreak response activities. PMID:26890053

Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication.

PubMed

Blake, Isobel M; Chenoweth, Paul; Okayasu, Hiro; Donnelly, Christl A; Aylward, R Bruce; Grassly, Nicholas C

2016-03-01

As the global eradication of poliomyelitis approaches the final stages, prompt detection of new outbreaks is critical to enable a fast and effective outbreak response. Surveillance relies on reporting of acute flaccid paralysis (AFP) cases and laboratory confirmation through isolation of poliovirus from stool. However, delayed sample collection and testing can delay outbreak detection. We investigated whether weekly testing for clusters of AFP by location and time, using the Kulldorff scan statistic, could provide an early warning for outbreaks in 20 countries. A mixed-effects regression model was used to predict background rates of nonpolio AFP at the district level. In Tajikistan and Congo, testing for AFP clusters would have resulted in an outbreak warning 39 and 11 days, respectively, before official confirmation of large outbreaks. This method has relatively high specificity and could be integrated into the current polio information system to support rapid outbreak response activities.

A Census of Broad-line Active Galactic Nuclei in Nearby Galaxies: Coeval Star Formation and Rapid Black Hole Growth

NASA Astrophysics Data System (ADS)

Trump, Jonathan R.; Hsu, Alexander D.; Fang, Jerome J.; Faber, S. M.; Koo, David C.; Kocevski, Dale D.

2013-02-01

We present the first quantified, statistical map of broad-line active galactic nucleus (AGN) frequency with host galaxy color and stellar mass in nearby (0.01 < z < 0.11) galaxies. Aperture photometry and z-band concentration measurements from the Sloan Digital Sky Survey are used to disentangle AGN and galaxy emission, resulting in estimates of uncontaminated galaxy rest-frame color, luminosity, and stellar mass. Broad-line AGNs are distributed throughout the blue cloud and green valley at a given stellar mass, and are much rarer in quiescent (red sequence) galaxies. This is in contrast to the published host galaxy properties of weaker narrow-line AGNs, indicating that broad-line AGNs occur during a different phase in galaxy evolution. More luminous broad-line AGNs have bluer host galaxies, even at fixed mass, suggesting that the same processes that fuel nuclear activity also efficiently form stars. The data favor processes that simultaneously fuel both star formation activity and rapid supermassive black hole accretion. If AGNs cause feedback on their host galaxies in the nearby universe, the evidence of galaxy-wide quenching must be delayed until after the broad-line AGN phase.

The Influence of Conduit Processes During Basaltic Plinian Eruptions.

NASA Astrophysics Data System (ADS)

Houghton, B. F.; Sable, J. E.; Wilson, C. J.; Coltelli, M.; Del Carlo, P.

2001-12-01

Basaltic volcanism is most typically thought to produce effusion of lava, with the most explosive manifestations ranging from mild Strombolian activity to more energetic fire fountain eruptions. However, some basaltic eruptions are now recognized as extremely violent, i.e. generating widespread phreatomagmatic, subplinian and Plinian fall deposits. These eruptions are particularly dangerous because the ascent rate of basaltic magma prior to eruption can be very rapid (giving warning times as little as a few hours) and because their precursors may be ignored or misunderstood. The main question addressed in this talk is: what conditions in the conduit cause basaltic magma to adopt an eruption style more typical of chemically evolved, highly viscous magmas? Possible mechanisms (acting singly, or in concert) are: (1) interaction between magma and water, (ii) very rapid ascent producing a delayed onset of degassing then exceptionally rapid "runaway" vesiculation at shallow levels in the conduit, (iii) microlite crystallization and degassing of the magma during ascent leading to increased viscosity. We focus here on two examples of basaltic Plinian volcanism: the 1886 eruption of Tarawera, New Zealand, which is the youngest known basaltic Plinian eruption and the only one for which there are detailed written eyewitness accounts, and the well documented 122 BC eruption of Mount Etna, Italy. Field and laboratory evidence suggests that the Plinian phase of the 1886 eruption was a consequence of two processes. Firstly rheologic changes during magma ascent accompanied early (pre-fragmentation) interaction between the basaltic melt and water-bearing rhyolitic units forming the conduit walls and, secondly, late-stage magma:water interaction. In contrast, during the 122 BC eruption tectonic processes, such as slope failure or permanent displacement of a mobile flank of the volcano, appear to have triggered exceptionally rapid ascent, delayed onset of degassing and exceptionally rapid vesiculation at shallow levels in the conduit.

Time-resolved coherent Raman spectroscopy by high-speed pump-probe delay scanning.

PubMed

Domingue, S R; Winters, D G; Bartels, R A

2014-07-15

Using a spinning window pump-probe delay scanner, we demonstrate a means of acquiring time-resolved vibrational spectra at rates up to 700 Hz. The time-dependent phase shift accumulated by the probe pulse in the presence of a coherently vibrating sample gives rise to a Raman-induced frequency shifting readily detectable in a balanced detector. This rapid delay scanning system represents a 23-fold increase in averaging speed and is >10× faster than state-of-the-art voice coil delay lines. These advancements make pump-probe spectroscopy a more practical means of imaging complex media.

"Fragment errors" in deep dysgraphia: further support for a lexical hypothesis.

PubMed

Bormann, Tobias; Wallesch, Claus-W; Blanken, Gerhard

2008-07-01

In addition to various lexical errors, the writing of patients with deep dysgraphia may include a large number of segmental spelling errors, which increase towards the end of the word. Frequently, these errors involve deletion of two or more letters resulting in so-called "fragment errors". Different positions have been brought forward regarding their origin, including rapid decay of activation in the graphemic buffer and an impairment of more central (i.e., lexical or semantic) processing. We present data from a patient (M.D.) with deep dysgraphia who showed an increase of segmental spelling errors towards the end of the word. Several tasks were carried out to explore M.D.'s underlying functional impairment. Errors affected word-final positions in tasks like backward spelling and fragment completion. In a delayed copying task, length of the delay had no influence. In addition, when asked to recall three serially presented letters, a task which had not been carried out before, M.D. exhibited a preference for the first and the third letter and poor performance for the second letter. M.D.'s performance on these tasks contradicts the rapid decay account and instead supports a lexical-semantic account of segmental errors in deep dysgraphia. In addition, the results fit well with an implemented computational model of deep dysgraphia and segmental spelling errors.

Shield ulcers and plaques of the cornea in vernal keratoconjunctivitis.

PubMed

Cameron, J A

1995-06-01

Shield-shaped corneal ulcers and plaques are serious sight-threatening corneal manifestations of vernal keratoconjunctivitis. There are few reports describing the management of these patients and their outcomes. The clinical presentation, treatment, and outcome of 66 shield ulcers and/or plaques in 55 eyes of 41 patients with vernal keratoconjunctivitis were studied in this retrospective study of patients treated at King Khaled Eye Specialist Hospital during an 11-year period. Patients with shield ulcers where the base of the ulcer was transparent usually had rapid re-epithelialization and an excellent visual outcome with medical treatment alone. Patients with shield ulcers and visible plaque formation had delayed re-epithelialization when receiving only medical treatment. Complications of delayed re-epithelialization consisted of bacterial keratitis in five eyes, amblyopia in one eye, and strabismus in one patient. Patients with shield ulcers and/or plaques that do not re-epithelialize once active vernal keratoconjunctivitis has been controlled should have surgical intervention. In this series, a simple scraping of the base and margins of the ulcer with removal of the inflammatory material (i.e., the plaque) resulted in rapid re-epithelialization in 20 of 23 ulcers and plaques. An algorithm for treating shield ulcers and/or plaques is presented based on the experience at this institution.

Temporal discounting and heart rate reactivity to stress.

PubMed

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

2011-07-01

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

Intended actions and unexpected outcomes: automatic and controlled processing in a rapid motor task

PubMed Central

Cheyne, Douglas O.; Ferrari, Paul; Cheyne, James A.

2012-01-01

Human action involves a combination of controlled and automatic behavior. These processes may interact in tasks requiring rapid response selection or inhibition, where temporal constraints preclude timely intervention by conscious, controlled processes over automatized prepotent responses. Such contexts tend to produce frequent errors, but also rapidly executed correct responses, both of which may sometimes be perceived as surprising, unintended, or “automatic”. In order to identify neural processes underlying these two aspects of cognitive control, we measured neuromagnetic brain activity in 12 right-handed subjects during manual responses to rapidly presented digits, with an infrequent target digit that required switching response hand (bimanual task) or response finger (unimanual task). Automaticity of responding was evidenced by response speeding (shorter response times) prior to both failed and fast correct switches. Consistent with this automaticity interpretation of fast correct switches, we observed bilateral motor preparation, as indexed by suppression of beta band (15–30 Hz) oscillations in motor cortex, prior to processing of the switch cue in the bimanual task. In contrast, right frontal theta activity (4–8 Hz) accompanying correct switch responses began after cue onset, suggesting that it reflected controlled inhibition of the default response. Further, this activity was reduced on fast correct switch trials suggesting a more automatic mode of inhibitory control. We also observed post-movement (event-related negativity) ERN-like responses and theta band increases in medial and anterior frontal regions that were significantly larger on error trials, and may reflect a combination of error and delayed inhibitory signals. We conclude that both automatic and controlled processes are engaged in parallel during rapid motor tasks, and that the relative strength and timing of these processes may underlie both optimal task performance and subjective experiences of automaticity or control. PMID:22912612

Brief Report: Impact of Early Antiretroviral Therapy on the Performance of HIV Rapid Tests and HIV Incidence Assays.

PubMed

Fogel, Jessica M; Piwowar-Manning, Estelle; Debevec, Barbara; Walsky, Tamara; Schlusser, Katherine; Laeyendecker, Oliver; Wilson, Ethan A; McCauley, Marybeth; Gamble, Theresa; Tegha, Gerald; Soko, Dean; Kumwenda, Johnstone; Hosseinipour, Mina C; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2017-08-01

Antiretroviral therapy (ART) can downregulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays. Samples were obtained from 207 participants in the HPTN 052 trial, who were stably suppressed on ART for ≥4 years [Malawi sites; pre-ART CD4 cell count 350-550 cells/mm (early ART arm, N = 180) or <250 cells/mm or an AIDS-defining illness (delayed ART arm, N = 27)]. Samples were tested with 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false-negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result). Ten (4.8%) samples had a nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher fourth-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection. False-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.

Rapid, generalized adaptation to asynchronous audiovisual speech

PubMed Central

Van der Burg, Erik; Goodbourn, Patrick T.

2015-01-01

The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. PMID:25716790

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

PubMed Central

Romiti, M. L.; Colognesi, C.; Cancrini, C.; Mas, A.; Berrino, M.; Salvatori, F.; Orlandi, P.; Jansson, M.; Palomba, E.; Plebani, A.; Bertran, J. M.; Hernandez, M.; de Martino, M.; Amoroso, A.; Tovo, P. A.; Rossi, P.; Espanol, T.; Scarlatti, G.

2000-01-01

BACKGROUND: A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. MATERIALS AND METHODS: To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. RESULTS: No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). CONCLUSIONS: Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment. PMID:10803406

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

PubMed

Romiti, M L; Colognesi, C; Cancrini, C; Mas, A; Berrino, M; Salvatori, F; Orlandi, P; Jansson, M; Palomba, E; Plebani, A; Bertran, J M; Hernandez, M; de Martino, M; Amoroso, A; Tovo, P A; Rossi, P; Espanol, T; Scarlatti, G

2000-01-01

A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis

PubMed Central

Hasler, W. L.; May, K. P.; Wilson, L. A.; Van Natta, M.; Parkman, H. P.; Pasricha, P. J.; Koch, K. L.; Abell, T. L.; McCallum, R. W.; Nguyen, L. A.; Snape, W. J.; Sarosiek, I.; Clarke, J. O.; Farrugia, G.; Calles-Escandon, J.; Grover, M.; Tonascia, J.; Lee, L. A.; Miriel, L.; Hamilton, F. A.

2018-01-01

Background Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. Methods A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. Key Results Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). Conclusions & Inferences Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities. PMID:28872760

The interaction evolution model of mass incidents with delay in a social network

NASA Astrophysics Data System (ADS)

Huo, Liang'an; Ma, Chenyang

2017-10-01

Recent years have witnessed rapid development of information technology. Today, modern media is widely used for the purpose of spreading information rapidly and widely. In particular, through micro-blog promotions, individuals tend to express their viewpoints and spread information on the internet, which could easily lead to public opinions. Moreover, government authorities also disseminate official information to guide public opinion and eliminate any incorrect conjecture. In this paper, a dynamical model with two delays is investigated to exhibit the interaction evolution between the public and official opinion fields in network mass incidents. Based on the theory of differential equations, the interaction mechanism between two public opinion fields in a micro-blog environment is analyzed. Two delays are proposed in the model to depict the response delays of public and official opinion fields. Some stable conditions are obtained, which shows that Hopf bifurcation can occur as delays cross critical values. Further, some numerical simulations are carried out to verify theoretical results. Our model indicates that there exists a golden time for government intervention, which should be emphasized given the impact of modern media and inaccurate rumors. If the government releases official information during the golden time, mass incidents on the internet can be controlled effectively.

Arousal mechanisms related to posture and locomotion: 1. Descending modulation.

PubMed

Garcia-Rill, Edgar; Homma, Yutaka; Skinner, Robert D

2004-01-01

Much of the controversy surrounding the induction of locomotion following stimulation of mesopontine sites, including the pedunculopontine nucleus (PPN), appears based on procedural differences, including stimulus onset, delay preceding stepping, and frequency of stimuli. The results reviewed in this chapter address these issues and provide novel information suggesting that descending projections from the PPN may exert a frequency-dependent effect. Stimulation at approximately 60 Hz (which induces prolonged tonic firing) may exercise a "push" towards locomotion (activation of pontine interneurons) as well as a "pull" away from decreased muscle tone (inhibiting giant pontine reticulospinal cells). Higher frequencies of stimulation (> 100 Hz, which induces phasic burst-like activity) may "push" towards decreases in muscle tone, including the atonia of rapid eye movement sleep (activating giant pontine reticulospinal cells).

The acoustic sensor for rapid analysis of bacterial cells in the conductive suspensions.

PubMed

Borodina, I A; Zaitsev, B D; Guliy, O; Teplykh, A A; Shikhabudinov, A M

2017-11-01

The possibility of using the acoustic sensor on the basis of a two-channel delay line for rapid analysis of bacterial cells in the conductive suspensions was investigated. The dependencies of change in phase and insertion loss of output signal of the sensor on conductivity of buffer solution with various concentrations of cells due to a specific interaction "bacterial cells - mini-antibodies" for electrically open and electrically shorted channels of delay line were measured. It has been found that these changes have the most values for the electrically open channel. It has been also shown that the sensor rapidly responds to the specific interaction and the time stabilization of the phase and insertion loss of output signal is less than 10min. Copyright © 2017 Elsevier B.V. All rights reserved.

Early and late components of EEG delay activity correlate differently with scene working memory performance

PubMed Central

Ng, Kenneth; Reichert, Chelsea P.

2017-01-01

Sustained and elevated activity during the working memory delay period has long been considered the primary neural correlate for maintaining information over short time intervals. This idea has recently been reinterpreted in light of findings generated from multiple neural recording modalities and levels of analysis. To further investigate the sustained or transient nature of activity, the temporal-spectral evolution (TSE) of delay period activity was examined in humans with high density EEG during performance of a Sternberg working memory paradigm with a relatively long six second delay and with novel scenes as stimuli. Multiple analyses were conducted using different trial window durations and different baseline periods for TSE computation. Sensor level analyses revealed transient rather than sustained activity during delay periods. Specifically, the consistent finding among the analyses was that high amplitude activity encompassing the theta range was found early in the first three seconds of the delay period. These increases in activity early in the delay period correlated positively with subsequent ability to distinguish new from old probe scenes. Source level signal estimation implicated a right parietal region of transient early delay activity that correlated positively with working memory ability. This pattern of results adds to recent evidence that transient rather than sustained delay period activity supports visual working memory performance. The findings are discussed in relation to synchronous and desynchronous intra- and inter-regional neural transmission, and choosing an optimal baseline for expressing temporal-spectral delay activity change. PMID:29016657

Embedding High-Fidelity Simulation Into a Foundations of Nursing Course.

PubMed

Talbot, Megan Sary

2015-01-01

Delay in recognizing the need for and initiating lifesaving measures is unacceptable in health care. It is never too early to teach novice nursing students to recognize and respond to early warning signs of patient deterioration. The rapid response system was developed to expedite recognition of and response to changes in a patient's condition. Use of high-fidelity simulation by beginning nursing students to practice recognizing and responding to patient deterioration is vital to both the welfare of patients and the edification of students. Recognizing and responding quickly to patients' early warning signs of deterioration can determine a patient's outcome. This article discusses the importance of instructing beginning nursing students in identifying and reacting appropriately to early signs of patient deterioration and in following the chain of command to activate the rapid response team.

Phrenic Arterial Injury Presenting as Delayed Hemothorax Complicating Simple Rib Fracture.

PubMed

Ahn, Hong Joon; Lee, Jun Wan; Kim, Kun Dong; You, In Sool

2016-04-01

Delayed hemothorax after blunt torso injury is rare, but might be associated with significant morbidity and mortality. We present a case of delayed hemothorax bleeding from phrenic artery injury in a 24-year-old woman. The patient suffered from multiple rib fractures on the right side, a right hemopneumothorax, thoracic vertebral injury and a pelvic bone fracture after a fall from a fourth floor window. Delayed hemothorax associated with phrenic artery bleeding, caused by a stab injury from a fractured rib segment, was treated successfully by a minimally invasive thoracoscopic surgery. Here, we have shown that fracture of a lower rib or ribs might be accompanied by delayed massive hemothorax that can be rapidly identified and promptly managed by thoracoscopic means.

Phrenic Arterial Injury Presenting as Delayed Hemothorax Complicating Simple Rib Fracture

PubMed Central

2016-01-01

Delayed hemothorax after blunt torso injury is rare, but might be associated with significant morbidity and mortality. We present a case of delayed hemothorax bleeding from phrenic artery injury in a 24-year-old woman. The patient suffered from multiple rib fractures on the right side, a right hemopneumothorax, thoracic vertebral injury and a pelvic bone fracture after a fall from a fourth floor window. Delayed hemothorax associated with phrenic artery bleeding, caused by a stab injury from a fractured rib segment, was treated successfully by a minimally invasive thoracoscopic surgery. Here, we have shown that fracture of a lower rib or ribs might be accompanied by delayed massive hemothorax that can be rapidly identified and promptly managed by thoracoscopic means. PMID:27051252

Sensing and imaging of oxygen with parts per billion limits of detection and based on the quenching of the delayed fluorescence of (13)C70 fullerene in polymer hosts.

PubMed

Kochmann, Sven; Baleizão, Carlos; Berberan-Santos, Mário N; Wolfbeis, Otto S

2013-02-05

We report on a new method for sensing trace oxygen in the gas phase. It is based on the extreme efficiency of the quenching of the thermally activated delayed fluorescence of isotopically enriched carbon-13 fullerene C(70) ((13)C(70)). This fullerene was dissolved in polymer matrixes of varying oxygen permeability, viz., polystyrene (PS), ethyl cellulose (EC) and an organically modified silica gel ("ormosil"; OS). The sensor films (5-10 μm thick), on photoexcitation at 470 nm, display a strong delayed photoluminescence with peaks between 670 and 700 nm. Its quenching by molecular oxygen was studied at 25 and 60 °C and at concentrations from zero up to 150 ppmv of oxygen in nitrogen. The rapid lifetime determination (RLD) method was applied to determine oxygen-dependent lifetimes and for fluorescence lifetime imaging of oxygen. The lower limits of detection (at 1% quenching) vary with the polymer used (EC ∼250 ppbv, OS ∼320 ppbv, PS ∼530 ppbv at 25 °C) and with temperature. The oxygen sensors reported here are the most sensitive ones described so far.

Effect of hypo- and hyperthyroidism on hexokinase in the developing cerebellum of the rat.

PubMed

Gutekunst, D I; Wilson, J E

1981-05-01

Total hexokinase levels (units/g tissue) have been measured during postnatal development of the cerebellum in control, hypothyroid, and hyperthyroid rats. In addition. distribution of hexokinase in the developing cerebellum has been observed with an immunofluorescence method. Hypothyroidism delays the normally observed postnatal increase in total hexokinase activity, whereas hyperthyroidism accelerates the increase. In normal animals, hexokinase levels in maturing Purkinje cells pass through a transient increase, with maximal levels at approximately 8 days postnatally followed by rapid decline to relatively low levels by 12 days; hypothyroidism delays this transient increase and subsequent decline, but hyperthyroidism does not appear to affect markedly the timing of this phenomenon. Cerebellar glomeruli are relatively enriched in hexokinase content, as judged by their intense fluorescence. Hypothyroidism delays the development of intensely stained glomeruli. Hyperthyroidism did not appear to cause precocious increase in numbers of glomeruli but may have increased the rate at which the hexokinase was assimilated by newly formed glomeruli. The effects of hypo- and hyperthyroidism on total cerebellar hexokinase levels are interpreted in terms of the effect of thyroid hormone on the biochemical maturation of synaptic structures rich in hexokinase.

Aging affects neural precision of speech encoding

PubMed Central

Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

2012-01-01

Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the auditory system’s temporal precision. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (ages 18 to 30) and older adult humans (60 to 67). Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Taken together, our results support the theory that older adults have a loss of temporal precision in subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception. PMID:23055485

Regulation of expression of the ligand for CD40 on T helper lymphocytes.

PubMed

Castle, B E; Kishimoto, K; Stearns, C; Brown, M L; Kehry, M R

1993-08-15

Activated Th cells deliver contact-dependent signals to resting B lymphocytes that initiate and drive B cell proliferation. Recently, a ligand for the B lymphocyte membrane protein, CD40, has been identified that delivers contact-dependent Th cell signals to B cells. A dimeric soluble form of CD40 was produced and used to further characterize the regulation of expression of the CD40 ligand. Expression of the CD40 ligand was rapidly induced after Th lymphocyte activation, and its stability depended upon whether Th cells were activated with soluble or plastic-bound stimuli. Th cells activated with soluble stimuli rapidly turned over cell-surface CD40 ligand whereas Th cells activated with plastic-bound stimuli exhibited more stable CD40 ligand expression for up to 48 h. Removal of activated Th cells from the plastic-bound stimulus resulted in a rapid turnover of CD40 ligand, suggesting that continuous stimulation could maintain CD40 ligand expression. Ligation by soluble CD40 could also stabilize expression of CD40 ligand on the Th cell surface. Both CD40 ligand and IL-2 were transiently synthesized from 1 to 12 h after Th cell activation and had similar kinetics of synthesis. In Con A-activated Th cells newly synthesized CD40 ligand exhibited an initial high turnover (1.5 h t1/2) and after 5 h of Th cell activation became more stable (10-h t1/2). In Th cells activated with plastic-bound anti-CD3, CD40 ligand exhibited a similar biphasic turnover except that the rapid turnover phase began significantly later. This delay could allow more time for newly synthesized CD40 ligand to assemble or associate with other molecules and thus become stabilized on the cell surface. Newly synthesized CD40 ligand in Con A-activated Th cells appeared to not be efficient in delivering Th cell-dependent contact signals to resting B cells, implying the need for assembly or accessory proteins. Regulation of CD40 ligand expression was consistent with all the characteristics of Th cell-delivered contact signals to B cells and may contribute to the high degree of specificity in B cell responses.

Costs Climb on Materials for Schools: Construction Projects Delayed, Scrapped

ERIC Educational Resources Information Center

Sack, Joetta L.

2004-01-01

The rapidly rising cost of steel and other construction materials is forcing some districts that are building new schools to scramble for more money, delay work, or redesign projects. Nationwide, contractors and architects are finding it harder to give accurate estimates on projects, and some have even had to renegotiate contracts with districts.…

Kinetics of micronucleus induction and cytotoxicity caused by distinct antineoplastics and alkylating agents in vivo.

PubMed

Morales-Ramírez, Pedro; Vallarino-Kelly, Teresita; Cruz-Vallejo, Virginia

2014-01-30

This mini-review aims to compare the differences in the kinetics of the induction of micronucleated polychromatic erythrocytes (MN-PCE) and cytotoxicity by distinct antineoplastic and genotoxic agents in murine peripheral blood in vivo and to correlate these kinetics with the underlying processes. Comparisons were carried out using our previously obtained data with nominal doses causing similar levels of cytotoxicity, as measured in terms reduction of PCE. The aneuploidogens caused the most rapid induction of MN-PCEs and had the highest rates of cytotoxicity and genotoxicity. The promutagens cyclophosphamide and dimethylnitrosamine showed the most delayed responses and had the lowest genotoxic and cytotoxic efficiencies. DNA crosslinking agents had a similar delay of 4-5 h, greater than those of aneuploidogens, but differed in their cytotoxic and genotoxic efficiencies. Methylnitrosourea and 5-aza-cytidine caused greater delays than crosslinking agents. These delays can be due to the methylnitrosourea-mediated induction of formation of mono alkyl adducts which are interpreted as mismatches during DNA duplication, whereas 5-aza-cytidine requires incorporation into the DNA to induce breakage. This review allows us to conclude that the requirement for metabolic activation and the mechanisms of DNA breakage and of micronucleus induction are the main factors that affect the time of maximal MN-PCE induction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

State and Federal project development procedures for bus rapid transit : managing differences and reducing implementation delays

DOT National Transportation Integrated Search

2011-08-01

This report documents an investigation into the transportation project development process in the : context of the implementation of bus rapid transit systems on the State Highway System as well as such : systems being part of the Federal New Starts ...

Current management of penetrating torso trauma: nontherapeutic is not good enough anymore.

PubMed

Ball, Chad G

2014-04-01

A highly organized approach to the evaluation and treatment of penetrating torso injuries based on regional anatomy provides rapid diagnostic and therapeutic consistency. It also minimizes delays in diagnosis, missed injuries and nontherapeutic laparotomies. This review discusses an optimal sequence of structured rapid assessments that allow the clinician to rapidly proceed to gold standard therapies with a minimal risk of associated morbidity.

Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

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

Kioka, Noriyuki, E-mail: nkioka@kais.kyoto-u.ac.jp; Ito, Takuya; Yamashita, Hiroshi

2010-06-10

In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin-containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantiallymore » suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo.« less

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

PubMed Central

Wu, Delin; Jiang, Linqing; Wu, Hongjin; Wang, Shengqi; Zheng, Sidao; Yang, Jiyuan; Liu, Yuna; Ren, Jianxun; Chen, Xianbing

2013-01-01

Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited I K (I Kr, I Ks) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K+ channel. PMID:24069049

Mnemonic neuronal activity in somatosensory cortex.

PubMed Central

Zhou, Y D; Fuster, J M

1996-01-01

Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory. PMID:8927629

Feasibility of Rapid Multitracer PET Tumor Imaging

NASA Astrophysics Data System (ADS)

Kadrmas, D. J.; Rust, T. C.

2005-10-01

Positron emission tomography (PET) can characterize different aspects of tumor physiology using various tracers. PET scans are usually performed using only one tracer since there is no explicit signal for distinguishing multiple tracers. We tested the feasibility of rapidly imaging multiple PET tracers using dynamic imaging techniques, where the signals from each tracer are separated based upon differences in tracer half-life, kinetics, and distribution. Time-activity curve populations for FDG, acetate, ATSM, and PTSM were simulated using appropriate compartment models, and noisy dual-tracer curves were computed by shifting and adding the single-tracer curves. Single-tracer components were then estimated from dual-tracer data using two methods: principal component analysis (PCA)-based fits of single-tracer components to multitracer data, and parallel multitracer compartment models estimating single-tracer rate parameters from multitracer time-activity curves. The PCA analysis found that there is information content present for separating multitracer data, and that tracer separability depends upon tracer kinetics, injection order and timing. Multitracer compartment modeling recovered rate parameters for individual tracers with good accuracy but somewhat higher statistical uncertainty than single-tracer results when the injection delay was >10 min. These approaches to processing rapid multitracer PET data may potentially provide a new tool for characterizing multiple aspects of tumor physiology in vivo.

Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

DOE PAGES

Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; ...

2014-11-02

Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delaymore » China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.« less

Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

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

Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth

Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delaymore » China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.« less

Activation of coherent lattice phonon following ultrafast molecular spin-state photo-switching: A molecule-to-lattice energy transfer

PubMed Central

Marino, A.; Cammarata, M.; Matar, S. F.; Létard, J.-F.; Chastanet, G.; Chollet, M.; Glownia, J. M.; Lemke, H. T.; Collet, E.

2015-01-01

We combine ultrafast optical spectroscopy with femtosecond X-ray absorption to study the photo-switching dynamics of the [Fe(PM-AzA)2(NCS)2] spin-crossover molecular solid. The light-induced excited spin-state trapping process switches the molecules from low spin to high spin (HS) states on the sub-picosecond timescale. The change of the electronic state (<50 fs) induces a structural reorganization of the molecule within 160 fs. This transformation is accompanied by coherent molecular vibrations in the HS potential and especially a rapidly damped Fe-ligand breathing mode. The time-resolved studies evidence a delayed activation of coherent optical phonons of the lattice surrounding the photoexcited molecules. PMID:26798836

Rapid Radiochemical Methods for Asphalt Paving Material ...

EPA Pesticide Factsheets

Technical Brief Validated rapid radiochemical methods for alpha and beta emitters in solid matrices that are commonly encountered in urban environments were previously unavailable for public use by responding laboratories. A lack of tested rapid methods would delay the quick determination of contamination levels and the assessment of acceptable site-specific exposure levels. Of special concern are matrices with rough and porous surfaces, which allow the movement of radioactive material deep into the building material making it difficult to detect. This research focuses on methods that address preparation, radiochemical separation, and analysis of asphalt paving materials and asphalt roofing shingles. These matrices, common to outdoor environments, challenge the capability and capacity of very experienced radiochemistry laboratories. Generally, routine sample preparation and dissolution techniques produce liquid samples (representative of the original sample material) that can be processed using available radiochemical methods. The asphalt materials are especially difficult because they do not readily lend themselves to these routine sample preparation and dissolution techniques. The HSRP and ORIA coordinate radiological reference laboratory priorities and activities in conjunction with HSRP’s Partner Process. As part of the collaboration, the HSRP worked with ORIA to publish rapid radioanalytical methods for selected radionuclides in building material matrice

Dual enhancement of electroluminescence efficiency and operational stability by rapid upconversion of triplet excitons in OLEDs

PubMed Central

Furukawa, Taro; Nakanotani, Hajime; Inoue, Munetomo; Adachi, Chihaya

2015-01-01

Recently, triplet harvesting via a thermally activated delayed fluorescence (TADF) process has been established as a realistic route for obtaining ultimate internal electroluminescence (EL) quantum efficiency in organic light-emitting diodes (OLEDs). However, the possibility that the rather long transient lifetime of the triplet excited states would reduce operational stability due to an increased chance for unwarranted chemical reactions has been a concern. Herein, we demonstrate dual enhancement of EL efficiency and operational stability in OLEDs by employing a TADF molecule as an assistant dopant and a fluorescent molecule as an end emitter. The proper combination of assistant dopant and emitter molecules realized a “one-way” rapid Förster energy transfer of singlet excitons from TADF molecules to fluorescent emitters, reducing the number of cycles of intersystem crossing (ISC) and reverse ISC in the TADF molecules and resulting in a significant enhancement of operational stability compared to OLEDs with a TADF molecule as the end emitter. In addition, we found that the presence of this rapid energy transfer significantly suppresses singlet-triplet annihilation. Using this finely-tuned rapid triplet-exciton upconversion scheme, OLED performance and lifetime was greatly improved. PMID:25673259

Current management of penetrating torso trauma: nontherapeutic is not good enough anymore

PubMed Central

Ball, Chad G.

2014-01-01

A highly organized approach to the evaluation and treatment of penetrating torso injuries based on regional anatomy provides rapid diagnostic and therapeutic consistency. It also minimizes delays in diagnosis, missed injuries and nontherapeutic laparotomies. This review discusses an optimal sequence of structured rapid assessments that allow the clinician to rapidly proceed to gold standard therapies with a minimal risk of associated morbidity. PMID:24666458

Rapid Acquisition of Preference in Concurrent Chains: Effects of "d"-Amphetamine on Sensitivity to Reinforcement Delay

ERIC Educational Resources Information Center

Ta, Wei-Min; Pitts, Raymond C.; Hughes, Christine E.; McLean, Anthony P.; Grace, Randolph C.

2008-01-01

The purpose of this study was to examine effects of "d"-amphetamine on choice controlled by reinforcement delay. Eight pigeons responded under a concurrent-chains procedure in which one terminal-link schedule was always fixed- interval 8 s, and the other terminal-link schedule changed from session to session between fixed-interval 4 s and…

Delay Assessment Framework for Automated Question-Answering System: An Approach for eLearning Paradigm

ERIC Educational Resources Information Center

Iqbal, Muhammad Munwar; Saleem, Yasir

2017-01-01

Adoption of Electronic Learning (eLearning) for the dissemination of higher education is rapidly increasing day by day. A large number of universities offering hundreds of course and a large number of the students are taking advantage from this type of learning paradigm. The purpose of this study is to investigate the delay factor in answering the…

Temporal Lobe Epilepsy and the Selective Reminding Test: The Conventional 30-Minute Delay Suffices

ERIC Educational Resources Information Center

Bell, Brian D.; Fine, Jason; Dow, Christian; Seidenberg, Michael; Hermann, Bruce P.

2005-01-01

Conventional memory assessment may fail to identify memory dysfunction characterized by intact recall for a relatively brief period but rapid forgetting thereafter. This study assessed learning and retention after 30-min and 24-hr delays on auditory and visual selective reminding tests (SRTs) in right (n=20) and left (n=22) temporal lobe epilepsy…

Rapid, generalized adaptation to asynchronous audiovisual speech.

PubMed

Van der Burg, Erik; Goodbourn, Patrick T

2015-04-07

The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Scaling of Optogenetically Evoked Signaling in a Higher-Order Corticocortical Pathway in the Anesthetized Mouse.

PubMed

Li, Xiaojian; Yamawaki, Naoki; Barrett, John M; Körding, Konrad P; Shepherd, Gordon M G

2018-01-01

Quantitative analysis of corticocortical signaling is needed to understand and model information processing in cerebral networks. However, higher-order pathways, hodologically remote from sensory input, are not amenable to spatiotemporally precise activation by sensory stimuli. Here, we combined parametric channelrhodopsin-2 (ChR2) photostimulation with multi-unit electrophysiology to study corticocortical driving in a parietofrontal pathway from retrosplenial cortex (RSC) to posterior secondary motor cortex (M2) in mice in vivo . Ketamine anesthesia was used both to eliminate complex activity associated with the awake state and to enable stable recordings of responses over a wide range of stimulus parameters. Photostimulation of ChR2-expressing neurons in RSC, the upstream area, produced local activity that decayed quickly. This activity in turn drove downstream activity in M2 that arrived rapidly (5-10 ms latencies), and scaled in amplitude across a wide range of stimulus parameters as an approximately constant fraction (~0.1) of the upstream activity. A model-based analysis could explain the corticocortically driven activity with exponentially decaying kernels (~20 ms time constant) and small delay. Reverse (antidromic) driving was similarly robust. The results show that corticocortical signaling in this pathway drives downstream activity rapidly and scalably, in a mostly linear manner. These properties, identified in anesthetized mice and represented in a simple model, suggest a robust basis for supporting complex non-linear dynamic activity in corticocortical circuits in the awake state.

On fundamental quality of fission chain reaction to oppose rapid runaways of nuclear reactors

NASA Astrophysics Data System (ADS)

Kulikov, G. G.; Shmelev, A. N.; Apse, V. A.; Kulikov, E. G.

2017-01-01

It has been shown that the in-hour equation characterizes the barriers and resistibility of fission chain reaction (FCR) against rapid runaways in nuclear reactors. Traditionally, nuclear reactors are characterized by the presence of barriers based on delayed and prompt neutrons. A new barrier based on the reflector neutrons that can occur when the fast reactor core is surrounded by a weakly absorbing neutron reflector with heavy atomic weight was proposed. It has been shown that the safety of this fast reactor is substantially improved, and considerable elongation of prompt neutron lifetime "devalues" the role of delayed neutron fraction as the maximum permissible reactivity for the reactor safety.

Heroin delay discounting: Modulation by pharmacological state, drug-use impulsivity, and intelligence.

PubMed

Stoltman, Jonathan J K; Woodcock, Eric A; Lister, Jamey J; Lundahl, Leslie H; Greenwald, Mark K

2015-12-01

Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Anger in brain and body: the neural and physiological perturbation of decision-making by emotion

PubMed Central

Zorab, Emma; Navaratnam, Nakulan; Engels, Miriam; Mallorquí-Bagué, Núria; Minati, Ludovico; Dowell, Nicholas G.; Brosschot, Jos F.; Thayer, Julian F.; Critchley, Hugo D.

2016-01-01

Emotion and cognition are dynamically coupled to bodily arousal: the induction of anger, even unconsciously, can reprioritise neural and physiological resources toward action states that bias cognitive processes. Here we examine behavioural, neural and bodily effects of covert anger processing and its influence on cognition, indexed by lexical decision-making. While recording beat-to-beat blood pressure, the words ANGER or RELAX were presented subliminally just prior to rapid word/non-word reaction-time judgements of letter-strings. Subliminal ANGER primes delayed the time taken to reach rapid lexical decisions, relative to RELAX primes. However, individuals with high trait anger were speeded up by subliminal anger primes. ANGER primes increased systolic blood pressure and the magnitude of this increase predicted reaction time prolongation. Within the brain, ANGER trials evoked an enhancement of activity within dorsal pons and an attenuation of activity within visual occipitotemporal and attentional parietal cortices. Activity within periaqueductal grey matter, occipital and parietal regions increased linearly with evoked blood pressure changes, indicating neural substrates through which covert anger impairs semantic decisions, putatively through its expression as visceral arousal. The behavioural and physiological impact of anger states compromises the efficiency of cognitive processing through action-ready changes in autonomic response that skew regional neural activity. PMID:26253525

Transitions between Multiband Oscillatory Patterns Characterize Memory-Guided Perceptual Decisions in Prefrontal Circuits.

PubMed

Wimmer, Klaus; Ramon, Marc; Pasternak, Tatiana; Compte, Albert

2016-01-13

Neuronal activity in the lateral prefrontal cortex (LPFC) reflects the structure and cognitive demands of memory-guided sensory discrimination tasks. However, we still do not know how neuronal activity articulates in network states involved in perceiving, remembering, and comparing sensory information during such tasks. Oscillations in local field potentials (LFPs) provide fingerprints of such network dynamics. Here, we examined LFPs recorded from LPFC of macaques while they compared the directions or the speeds of two moving random-dot patterns, S1 and S2, separated by a delay. LFP activity in the theta, beta, and gamma bands tracked consecutive components of the task. In response to motion stimuli, LFP theta and gamma power increased, and beta power decreased, but showed only weak motion selectivity. In the delay, LFP beta power modulation anticipated the onset of S2 and encoded the task-relevant S1 feature, suggesting network dynamics associated with memory maintenance. After S2 onset the difference between the current stimulus S2 and the remembered S1 was strongly reflected in broadband LFP activity, with an early sensory-related component proportional to stimulus difference and a later choice-related component reflecting the behavioral decision buildup. Our results demonstrate that individual LFP bands reflect both sensory and cognitive processes engaged independently during different stages of the task. This activation pattern suggests that during elementary cognitive tasks, the prefrontal network transitions dynamically between states and that these transitions are characterized by the conjunction of LFP rhythms rather than by single LFP bands. Neurons in the brain communicate through electrical impulses and coordinate this activity in ensembles that pulsate rhythmically, very much like musical instruments in an orchestra. These rhythms change with "brain state," from sleep to waking, but also signal with different oscillation frequencies rapid changes between sensory and cognitive processing. Here, we studied rhythmic electrical activity in the monkey prefrontal cortex, an area implicated in working memory, decision making, and executive control. Monkeys had to identify and remember a visual motion pattern and compare it to a second pattern. We found orderly transitions between rhythmic activity where the same frequency channels were active in all ongoing prefrontal computations. This supports prefrontal circuit dynamics that transitions rapidly between complex rhythmic patterns during structured cognitive tasks. Copyright © 2016 the authors 0270-6474/16/360489-17$15.00/0.

Active photosynthetic inhibition mediated by MPK3/MPK6 is critical to effector-triggered immunity

PubMed Central

Su, Jianbin; Yang, Liuyi; Zhu, Qiankun; Wu, Hongjiao; He, Yi; Liu, Yidong; Xu, Juan; Jiang, Dean

2018-01-01

Extensive research revealed tremendous details about how plants sense pathogen effectors during effector-triggered immunity (ETI). However, less is known about downstream signaling events. In this report, we demonstrate that prolonged activation of MPK3 and MPK6, two Arabidopsis pathogen-responsive mitogen-activated protein kinases (MPKs), is essential to ETI mediated by both coiled coil-nucleotide binding site-leucine rich repeats (CNLs) and toll/interleukin-1 receptor nucleotide binding site-leucine rich repeats (TNLs) types of R proteins. MPK3/MPK6 activation rapidly alters the expression of photosynthesis-related genes and inhibits photosynthesis, which promotes the accumulation of superoxide (O2•−) and hydrogen peroxide (H2O2), two major reactive oxygen species (ROS), in chloroplasts under light. In the chemical-genetically rescued mpk3 mpk6 double mutants, ETI-induced photosynthetic inhibition and chloroplastic ROS accumulation are compromised, which correlates with delayed hypersensitive response (HR) cell death and compromised resistance. Furthermore, protection of chloroplasts by expressing a plastid-targeted cyanobacterial flavodoxin (pFLD) delays photosynthetic inhibition and compromises ETI. Collectively, this study highlights a critical role of MPK3/MPK6 in manipulating plant photosynthetic activities to promote ROS accumulation in chloroplasts and HR cell death, which contributes to the robustness of ETI. Furthermore, the dual functionality of MPK3/MPK6 cascade in promoting defense and inhibiting photosynthesis potentially allow it to orchestrate the trade-off between plant growth and defense in plant immunity. PMID:29723186

The Benefit of Directed Forgetting Persists After a Daytime Nap: The Role of Spindles and Rapid Eye Movement Sleep in the Consolidation of Relevant Memories.

PubMed

Blaskovich, Borbála; Szollosi, Ágnes; Gombos, Ferenc; Racsmány, Mihály; Simor, Péter

2017-03-01

We aimed to investigate the effect of directed forgetting instruction on memory retention after a 2-hour delay involving a daytime nap or an equivalent amount of time spent awake. We examined the associations between sleep-specific oscillations and the retention of relevant and irrelevant study materials. We applied a list-method directed forgetting paradigm manipulating the perceived relevance of previously encoded lists of words. Participants were randomly assigned to either a nap or an awake group, and to a remember or a forget subgroup. The remember and the forget subgroups were both instructed to study two consecutive lists of words, although, the forget subgroup was manipulated to forget the first list and memorize only the second one. Participants were 112 healthy individuals (44 men; Mage = 21.4 years, SD = 2.4). A significant directed forgetting effect emerged after a 2-hour delay both in the awake and sleep conditions; however, the effect was more pronounced within the sleep group. The benefit of directed forgetting, that is, relatively enhanced recall of relevant words in the forget group, was evidenced only in those participants that reached rapid eye movement (REM) phase. Non-rapid eye movement (NREM) sigma power was correlated with memory performance for the relevant (second) list, and sleep spindle amplitude was associated with the retention of both lists. These associations, however, were detected only within the forget subgroup. REM duration correlated with recall performance for the relevant (second) list within the forget subgroup, and with recall performance for the first list within the remember subgroup. A directed forgetting effect persists after a 2-hour delay spent awake or asleep. Spindle-related activity and subsequent REM sleep might selectively facilitate the processing of memories that are considered to be relevant for the future. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Rapid wall relaxation in elongating tissues.

PubMed

Matyssek, R; Maruyama, S; Boyer, J S

1988-04-01

Reported differences in the relaxation of cell walls in enlarging stem tissues of soybean (Glycine max [L.] Merr.) and pea (Pisum sativum L.) cause measurements of the yield threshold turgor, an important growth parameter, to be in doubt. Using the pressure probe and guillotine psychrometer, we investigated wall relaxation in these species by excising the elongating tissue in air to remove the water supply. We found that the rapid kinetics usually exhibited by soybean could be delayed and made similar to the slow kinetics previously reported for pea if slowly growing or mature tissue was left attached to the rapidly growing tissue when relaxation was initiated. The greater the amount of attached tissue, the slower the relaxation, suggesting that slowly growing tissue acted as a water source. Consistent with this concept was a lower water potential in the rapidly elongating tissue than in the slowly growing tissue. Previous reports of wall relaxation in pea included slowly growing tissue. If this tissue was removed from pea, relaxation became as rapid as usually exhibited by soybean. It is concluded that the true relaxation of cell walls to the yield threshold requires only a few minutes and that the yield threshold should be constant during so short a time, thus reflecting the yield threshold in the intact plant before excision. Under these conditions, the yield threshold was close to the turgor in the intact plant regardless of the species. The presence of slowly growing or mature tissue delays wall relaxation and should be avoided during such measurements. However, this delay can be used to advantage when turgor of intact growing tissues is being measured using excised tissues because turgor does not change for a considerable time after excision.

Rapid Wall Relaxation in Elongating Tissues 1

PubMed Central

Matyssek, Rainer; Maruyama, Sachio; Boyer, John S.

1988-01-01

Reported differences in the relaxation of cell walls in enlarging stem tissues of soybean (Glycine max [L.] Merr.) and pea (Pisum sativum L.) cause measurements of the yield threshold turgor, an important growth parameter, to be in doubt. Using the pressure probe and guillotine psychrometer, we investigated wall relaxation in these species by excising the elongating tissue in air to remove the water supply. We found that the rapid kinetics usually exhibited by soybean could be delayed and made similar to the slow kinetics previously reported for pea if slowly growing or mature tissue was left attached to the rapidly growing tissue when relaxation was initiated. The greater the amount of attached tissue, the slower the relaxation, suggesting that slowly growing tissue acted as a water source. Consistent with this concept was a lower water potential in the rapidly elongating tissue than in the slowly growing tissue. Previous reports of wall relaxation in pea included slowly growing tissue. If this tissue was removed from pea, relaxation became as rapid as usually exhibited by soybean. It is concluded that the true relaxation of cell walls to the yield threshold requires only a few minutes and that the yield threshold should be constant during so short a time, thus reflecting the yield threshold in the intact plant before excision. Under these conditions, the yield threshold was close to the turgor in the intact plant regardless of the species. The presence of slowly growing or mature tissue delays wall relaxation and should be avoided during such measurements. However, this delay can be used to advantage when turgor of intact growing tissues is being measured using excised tissues because turgor does not change for a considerable time after excision. PMID:16666048

A ``delayed'' counting method to determine indoor Rn-222 levels indirectly

NASA Astrophysics Data System (ADS)

Iannopollo, V.; Licandro, M.; Trimarchi, M.; Tripepi, M. G.; Vermiglio, G.

2001-08-01

A new indirect and "delayed" way is presented to determine indoor concentration of Rn-222 by best-fitting methods. If a rapid knowledge of Rn-222 levels is required and if a detection system is not available in situ, it is possible to obtain concentration of radioactive gas by determining of "delayed" counts of Po-214. The "delay" time consists of two or three hours. The method is based on the use of cellulose filters for particulate collection and on the analysis of samples by alpha spectroscopy. It is also possible to obtain concentrations of short-lived radon daughters Po-218, Pb-214, Bi-214, which are very important quantities in a medical framework.

[Effects of allitridum on rapidly delayed rectifier potassium current in HEK293 cell line].

PubMed

Zhang, Jiancheng; Lin, Kun; Wei, Zhixiong; Chen, Qian; Liu, Li; Zhao, Xiaojing; Zhao, Ying; Xu, Bin; Chen, Xi; Li, Yang

2015-08-01

To study the effect of allitridum on rapidly delayed rectifier potassium current (IKr) in HEK293 cell line. HEK293 cells were transiently transfected with HERG channel cDNA plasmid pcDNA3.1 via Lipofectamine. Allitridum was added to the extracellular solution by partial perfusion after giga seal at the final concentration of 30 µmol/L. Whole-cell patch clamp technique was used to record the HERG currents and gating kinetics before and after allitridum exposure at room temperature. The amplitude and density of IHERG were both suppressed by allitridum in a voltage-dependent manner. In the presence of allitridum, the peak current of IHERG was reduced from 73.5∓4.3 pA/pF to 42.1∓3.6 pA/pF at the test potential of +50 mV (P<0.01). Allitridum also concentration-dependently decreased the density of the IHERG. The IC50 of allitridum was 34.74 µmol/L with a Hill coefficient of 1.01. Allitridum at 30 µmol/L caused a significant positive shift of the steady-state activation curve of IHERG and a markedly negative shift of the steady-state inactivation of IHERG, and significantly shortened the slow time constants of IHERG deactivation. Allitridum can potently block IHERG in HEK293 cells, which might be the electrophysiological basis for its anti-arrhythmic action.

Switching dynamics of TaOx-based threshold switching devices

NASA Astrophysics Data System (ADS)

Goodwill, Jonathan M.; Gala, Darshil K.; Bain, James A.; Skowronski, Marek

2018-03-01

Bi-stable volatile switching devices are being used as access devices in solid-state memory arrays and as the active part of compact oscillators. Such structures exhibit two stable states of resistance and switch between them at a critical value of voltage or current. A typical resistance transient under a constant amplitude voltage pulse starts with a slow decrease followed by a rapid drop and leveling off at a low steady state value. This behavior prompted the interpretation of initial delay and fast transition as due to two different processes. Here, we show that the entire transient including incubation time, transition time, and the final resistance values in TaOx-based switching can be explained by one process, namely, Joule heating with the rapid transition due to the thermal runaway. The time, which is required for the device in the conducting state to relax back to the stable high resistance one, is also consistent with the proposed mechanism.

Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis

PubMed Central

2013-01-01

Background A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided. Methods A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed. Results Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and increased rates of vaccination further improved effectiveness and cost effectiveness. Conclusions The effectiveness and cost effectiveness consequences of the time-critical interplay of pandemic dynamics, vaccine availability and intervention timing has been quantified. For moderate and extreme pandemics, vaccination combined with rapidly activated antiviral and social distancing interventions of sufficient duration is cost effective from the perspective of life years saved. PMID:23398722

Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis.

PubMed

Kelso, Joel K; Halder, Nilimesh; Milne, George J

2013-02-11

A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided. A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed. Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and increased rates of vaccination further improved effectiveness and cost effectiveness. The effectiveness and cost effectiveness consequences of the time-critical interplay of pandemic dynamics, vaccine availability and intervention timing has been quantified. For moderate and extreme pandemics, vaccination combined with rapidly activated antiviral and social distancing interventions of sufficient duration is cost effective from the perspective of life years saved.

Delays reducing waterborne and water-related infectious diseases in China under climate change

PubMed Central

Hodges, Maggie; Belle, Jessica H.; Carlton, Elizabeth J.; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy J.; Remais, Justin V.

2014-01-01

Despite China’s rapid progress improving water, sanitation and hygiene (WSH) access, in 2011, 471 million people lacked access to improved sanitation and 401 million to household piped water. Because certain infectious diseases are sensitive to changes in both climate and WSH conditions, we projected impacts of climate change on WSH-attributable diseases in China in 2020 and 2030 by coupling estimates of the temperature sensitivity of diarrheal diseases and three vector-borne diseases, temperature projections from global climate models, WSH-infrastructure development scenarios, and projected demographic changes. By 2030, climate change is projected to delay China’s rapid progress toward reducing WSH-attributable infectious disease burden by 8–85 months. This development delay summarizes the adverse impact of climate change on WSH-attributable infectious diseases in China, and can be used in other settings where a significant health burden may accompany future changes in climate even as the total burden of disease falls due to non-climate reasons. PMID:25530812

Analysis of the Effect of Injection Pressure on Ignition Delay and Combustion Process of Biodiesel from Palm Oil, Algae and Waste Cooking Oil

NASA Astrophysics Data System (ADS)

Irham Anas, Mohd; Khalid, Amir; Hakim Zulkifli, Fathul; Jaat, Norrizam; Faisal Hushim, Mohd; Manshoor, Bukhari; Zaman, Izzuddin

2017-10-01

Biodiesel is a domestically produced, renewable fuel that can be manufactured from vegetable oils, animal fats, or recycled restaurant grease for use in diesel engines. The objective of this research is investigation the effects of the variant injection pressure on ignition delay and emission for different biodiesel using rapid compression machine. Rapid Compression Machine (RCM) is used to simulate a single compression stroke of an internal combustion engine as a real engine. Four types of biodiesel which are waste cooking oil, crude palm oil, algae and jatropha were tested at injection pressure of 80 MPa, 90 MPa and 130 MPa under constant ambient temperature at 950 K. Increased in injection pressure resulted shorter ignition delay proven by WCO5 which decreased from 1.3 ms at 80 MPa to 0.7 ms at 130 MPa. Meanwhile, emission for CO2 increased due to better fuel atomization for fuel-air mixture formation lead to completed combustion.

Delays in reducing waterborne and water-related infectious diseases in China under climate change

NASA Astrophysics Data System (ADS)

Hodges, Maggie; Belle, Jessica H.; Carlton, Elizabeth J.; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy J.; Remais, Justin V.

2014-12-01

Despite China's rapid progress in improving water, sanitation and hygiene (WSH) access, in 2011, 471 million people lacked access to improved sanitation and 401 million to household piped water. As certain infectious diseases are sensitive to changes in both climate and WSH conditions, we projected impacts of climate change on WSH-attributable diseases in China in 2020 and 2030 by coupling estimates of the temperature sensitivity of diarrhoeal diseases and three vector-borne diseases, temperature projections from global climate models, WSH-infrastructure development scenarios, and projected demographic changes. By 2030, climate change is projected to delay China's rapid progress towards reducing WSH-attributable infectious disease burden by 8-85 months. This development delay summarizes the adverse impact of climate change on WSH-attributable infectious diseases in China, and can be used in other settings where a significant health burden may accompany future changes in climate even as the total burden of disease falls owing to non-climate reasons.

Delays reducing waterborne and water-related infectious diseases in China under climate change.

PubMed

Hodges, Maggie; Belle, Jessica H; Carlton, Elizabeth J; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C; Liu, Yang; Gao, Yang; Hess, Jeremy J; Remais, Justin V

2014-12-01

Despite China's rapid progress improving water, sanitation and hygiene (WSH) access, in 2011, 471 million people lacked access to improved sanitation and 401 million to household piped water. Because certain infectious diseases are sensitive to changes in both climate and WSH conditions, we projected impacts of climate change on WSH-attributable diseases in China in 2020 and 2030 by coupling estimates of the temperature sensitivity of diarrheal diseases and three vector-borne diseases, temperature projections from global climate models, WSH-infrastructure development scenarios, and projected demographic changes. By 2030, climate change is projected to delay China's rapid progress toward reducing WSH-attributable infectious disease burden by 8-85 months. This development delay summarizes the adverse impact of climate change on WSH-attributable infectious diseases in China, and can be used in other settings where a significant health burden may accompany future changes in climate even as the total burden of disease falls due to non-climate reasons.

The imprint of rapid star formation quenching on the spectral energy distributions of galaxies

NASA Astrophysics Data System (ADS)

Ciesla, L.; Boselli, A.; Elbaz, D.; Boissier, S.; Buat, V.; Charmandaris, V.; Schreiber, C.; Béthermin, M.; Baes, M.; Boquien, M.; De Looze, I.; Fernández-Ontiveros, J. A.; Pappalardo, C.; Spinoglio, L.; Viaene, S.

2016-01-01

In high density environments, the gas content of galaxies is stripped, leading to a rapid quenching of their star formation activity. This dramatic environmental effect, which is not related to typical passive evolution, is generally not taken into account in the star formation histories (SFHs) usually assumed to perform spectral energy distribution (SED) fitting of these galaxies, yielding a poor fit of their stellar emission and, consequently, biased estimate of the star formation rate (SFR). In this work, we aim at reproducing this rapid quenching using a truncated delayed SFH that we implemented in the SED fitting code CIGALE. We show that the ratio between the instantaneous SFR and the SFR just before the quenching (rSFR) is well constrained as long as rest-frame UV data are available. This SED modeling is applied to the Herschel Reference Survey (HRS) containing isolated galaxies and sources falling in the dense environment of the Virgo cluster. The latter are Hi-deficient because of ram pressure stripping. We show that the truncated delayed SFH successfully reproduces their SED, while typical SFH assumptions fail. A good correlation is found between rSFR and Hi-def, the parameter that quantifies the gas deficiency of cluster galaxies, meaning that SED fitting results can be used to provide a tentative estimate of the gas deficiency of galaxies for which Hi observations are not available. The HRS galaxies are placed on the SFR-M∗ diagram showing that the Hi-deficient sources lie in the quiescent region, thus confirming previous studies. Using the rSFR parameter, we derive the SFR of these sources before quenching and show that they were previously on the main sequence relation. We show that the rSFR parameter is also recovered well for deeply obscured high redshift sources, as well as in the absence of IR data. SED fitting is thus a powerful tool for identifying galaxies that underwent a rapid star formation quenching.

Time and decision making: differential contribution of the posterior insular cortex and the striatum during a delay discounting task.

PubMed

Wittmann, Marc; Leland, David S; Paulus, Martin P

2007-06-01

Delay discounting refers to the fact that an immediate reward is valued more than the same reward if it occurs some time in the future. To examine the neural substrates underlying this process, we studied 13 healthy volunteers who repeatedly had to decide between an immediate and parametrically varied delayed hypothetical reward using a delay discounting task during event-related functional magnetic resonance imaging. Subject's preference judgments resulted in different discounting slopes for shorter (<1 year) and for longer (> or =1 year) delays. Neural activation associated with the shorter delays relative to the longer delays was associated with increased activation in the head of the left caudate nucleus and putamen. When individuals selected the delayed relative to the immediate reward, a strong activation was found in bilateral posterior insular cortex. Several brain areas including the left caudate nucleus showed a correlation between the behaviorally determined discounting and brain activation for the contrast of intervals with delays <1 and > or =1 year. These results suggest that (1) the posterior insula, which is a critical component of the decision-making neural network, is involved in delaying gratification and (2) the degree of neural activation in the striatum, which plays a fundamental role in reward prediction and in time estimation, may code for the time delay.

Delayed Expansion and Contraction of CD8+ T Cell Response during Infection with Virulent Salmonella typhimurium1

PubMed Central

Luu, Rachel A.; Gurnani, Komal; Dudani, Renu; Kammara, Rajagopal; van Faassen, Henk; Sirard, Jean-Claude; Krishnan, Lakshmi; Sad, Subash

2014-01-01

Ag presentation to CD8+ T cells often commences immediately after infection, which facilitates their rapid expansion and control of infection. Subsequently, the primed cells undergo rapid contraction. We report that this paradigm is not followed during infection with virulent Salmonella enterica, serovar Typhimurium (ST), an intracellular bacterium that replicates within phagosomes of infected cells. Although susceptible mice die rapidly (~7 days), resistant mice (129×1SvJ) harbor a chronic infection lasting ~60–90 days. Using rOVA-expressing ST (ST-OVA), we show that T cell priming is considerably delayed in the resistant mice. CD8+ T cells that are induced during ST-OVA infection undergo delayed expansion, which peaks around day 21, and is followed by protracted contraction. Initially, ST-OVA induces a small population of cycling central phenotype (CD62LhighIL-7RαhighCD44high) CD8+ T cells. However, by day 14–21, majority of the primed CD8+ T cells display an effector phenotype (CD62LlowIL-7RαlowCD44high). Subsequently, a progressive increase in the numbers of effector memory phenotype cells (CD62LlowIL-7RαhighCD44high) occurs. This differentiation program remained unchanged after accelerated removal of the pathogen with antibiotics, as majority of the primed cells displayed an effector memory phenotype even at 6 mo postinfection. Despite the chronic infection, CD8+ T cells induced by ST-OVA were functional as they exhibited killing ability and cytokine production. Importantly, even memory CD8+ T cells failed to undergo rapid expansion in response to ST-OVA infection, suggesting a delay in T cell priming during infection with virulent ST-OVA. Thus, phagosomal lifestyle may allow escape from host CD8+ T cell recognition, conferring a survival advantage to the pathogen. PMID:16849458

A Comparison of the Effects of Brief Rules, a Timer, and Preferred Toys on Self-Control

ERIC Educational Resources Information Center

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

2012-01-01

Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining…

Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain.

PubMed

Holmqvist, Mats H; Cao, Jie; Hernandez-Pineda, Ricardo; Jacobson, Michael D; Carroll, Karen I; Sung, M Amy; Betty, Maria; Ge, Pei; Gilbride, Kevin J; Brown, Melissa E; Jurman, Mark E; Lawson, Deborah; Silos-Santiago, Inmaculada; Xie, Yu; Covarrubias, Manuel; Rhodes, Kenneth J; Distefano, Peter S; An, W Frank

2002-01-22

The Kv4 A-type potassium currents contribute to controlling the frequency of slow repetitive firing and back-propagation of action potentials in neurons and shape the action potential in heart. Kv4 currents exhibit rapid activation and inactivation and are specifically modulated by K-channel interacting proteins (KChIPs). Here we report the discovery and functional characterization of a modular K-channel inactivation suppressor (KIS) domain located in the first 34 aa of an additional KChIP (KChIP4a). Coexpression of KChIP4a with Kv4 alpha-subunits abolishes fast inactivation of the Kv4 currents in various cell types, including cerebellar granule neurons. Kinetic analysis shows that the KIS domain delays Kv4.3 opening, but once the channel is open, it disrupts rapid inactivation and slows Kv4.3 closing. Accordingly, KChIP4a increases the open probability of single Kv4.3 channels. The net effects of KChIP4a and KChIP1-3 on Kv4 gating are quite different. When both KChIP4a and KChIP1 are present, the Kv4.3 current shows mixed inactivation profiles dependent on KChIP4a/KChIP1 ratios. The KIS domain effectively converts the A-type Kv4 current to a slowly inactivating delayed rectifier-type potassium current. This conversion is opposite to that mediated by the Kv1-specific "ball" domain of the Kv beta 1 subunit. Together, these results demonstrate that specific auxiliary subunits with distinct functions actively modulate gating of potassium channels that govern membrane excitability.

Factors associated with delay in trauma team activation and impact on patient outcomes.

PubMed

Connolly, Rory; Woo, Michael Y; Lampron, Jacinthe; Perry, Jeffrey J

2017-09-05

Trauma code activation is initiated by emergency physicians using physiological and anatomical criteria, mechanism of injury, and patient demographic factors. Our objective was to identify factors associated with delayed trauma team activation. We assessed consecutive cases from a regional trauma database from January 2008 to March 2014. We defined a delay in trauma code activation as a time greater than 30 minutes from the time of arrival. We conducted univariate analysis for factors potentially influencing trauma team activation, and we subsequently used multiple logistic regression analysis models for delayed activation in relation to mortality, length of stay, and time to operative management. Patients totalling 846 were included for our analysis; 4.1% (35/846) of trauma codes were activated after 30 minutes. Mean age was 40.8 years in the early group versus 49.2 in the delayed group (p=0.01). Patients were over age 70 years in 7.6% in the early activation group versus 17.1% in the delayed group (p=0.04). There was no significant difference in sex, type of injury, injury severity, or time from injury between the two groups. There was no significant difference in mortality, median length of stay, or median time to operative management. Delayed activation is linked with increasing age with no clear link to increased mortality. Given the severe injuries in the delayed cohort that required activation of the trauma team, further emphasis on the older trauma patient and interventions to recognize this vulnerable population should be made.

Neural correlates of sample-coding and reward-coding in the delay activity of neurons in the entopallium and nidopallium caudolaterale of pigeons (Columba livia).

PubMed

Johnston, Melissa; Anderson, Catrona; Colombo, Michael

2017-01-15

We recorded neuronal activity from the nidopallium caudolaterale, the avian equivalent of mammalian prefrontal cortex, and the entopallium, the avian equivalent of the mammalian visual cortex, in four birds trained on a differential outcomes delayed matching-to-sample procedure in which one sample stimulus was followed by reward and the other was not. Despite similar incidence of reward-specific and reward-unspecific delay cell types across the two areas, overall entopallium delay activity occurred following both rewarded and non-rewarded stimuli, whereas nidopallium caudolaterale delay activity tended to occur following the rewarded stimulus but not the non-rewarded stimulus. These findings are consistent with the view that delay activity in entopallium represents a code of the sample stimulus whereas delay activity in nidopallium caudolaterale represents a code of the possibility of an upcoming reward. However, based on the types of delay cells encountered, cells in NCL also code the sample stimulus and cells in ENTO are influenced by reward. We conclude that both areas support the retention of information, but that the activity in each area is differentially modulated by factors such as reward and attentional mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Zinc irreversibly damages major enzymes of energy production and antioxidant defense prior to mitochondrial permeability transition.

PubMed

Gazaryan, Irina G; Krasinskaya, Inna P; Kristal, Bruce S; Brown, Abraham M

2007-08-17

Recent observations point to the role played by Zn2+ as an inducer of neuronal death. Two Zn2+ targets have been identified that result in inhibition of mitochondrial respiration: the bc1 center and, more recently, alpha-ketoglutarate dehydrogenase. Zn2+ is also a mediator of oxidative stress, leading to mitochondrial failure, release of apoptotic peptides, and neuronal death. We now present evidence, by means of direct biochemical assays, that Zn2+ is imported through the Ca2+ uniporter and directly targets major enzymes of energy production (lipoamide dehydrogenase) and antioxidant defense (thioredoxin reductase and glutathione reductase). We demonstrate the following. (a) These matrix enzymes are rapidly inhibited by application of Zn2+ to intact mitochondria. (b) Delayed treatment with membrane-impermeable chelators has no effect, indicating rapid transport of biologically relevant quantities of Zn2+ into the matrix. (c) Membrane-permeable chelators stop but do not reverse enzyme inactivation. (d) Enzyme inhibition is rapid and irreversible and precedes the major changes associated with the mitochondrial permeability transition (MPT). (e) The extent and rate of enzyme inactivation linearly correlates with the MPT onset and propagation. (f) The Ca2+ uniporter blocker, Ruthenium Red, protects enzyme activities and delays pore opening up to 2 microm Zn2+. An additional, unidentified import route functions at higher Zn2+ concentrations. (g) No enzyme inactivation is observed for Ca2+-induced MPT. These observations strongly suggest that, unlike Ca2+, exogenous Zn2+ interferes with mitochondrial NADH production and directly alters redox protection in the matrix, contributing to mitochondrial dysfunction. Inactivation of these enzymes by Zn2+ is irreversible, and thus only their de novo synthesis can restore function, which may underlie persistent loss of oxidative carbohydrate metabolism following transient ischemia.

Fast fMRI can detect oscillatory neural activity in humans.

PubMed

Lewis, Laura D; Setsompop, Kawin; Rosen, Bruce R; Polimeni, Jonathan R

2016-10-25

Oscillatory neural dynamics play an important role in the coordination of large-scale brain networks. High-level cognitive processes depend on dynamics evolving over hundreds of milliseconds, so measuring neural activity in this frequency range is important for cognitive neuroscience. However, current noninvasive neuroimaging methods are not able to precisely localize oscillatory neural activity above 0.2 Hz. Electroencephalography and magnetoencephalography have limited spatial resolution, whereas fMRI has limited temporal resolution because it measures vascular responses rather than directly recording neural activity. We hypothesized that the recent development of fast fMRI techniques, combined with the extra sensitivity afforded by ultra-high-field systems, could enable precise localization of neural oscillations. We tested whether fMRI can detect neural oscillations using human visual cortex as a model system. We detected small oscillatory fMRI signals in response to stimuli oscillating at up to 0.75 Hz within single scan sessions, and these responses were an order of magnitude larger than predicted by canonical linear models. Simultaneous EEG-fMRI and simulations based on a biophysical model of the hemodynamic response to neuronal activity suggested that the blood oxygen level-dependent response becomes faster for rapidly varying stimuli, enabling the detection of higher frequencies than expected. Accounting for phase delays across voxels further improved detection, demonstrating that identifying vascular delays will be of increasing importance with higher-frequency activity. These results challenge the assumption that the hemodynamic response is slow, and demonstrate that fMRI has the potential to map neural oscillations directly throughout the brain.

Delay dynamics of neuromorphic optoelectronic nanoscale resonators: Perspectives and applications

NASA Astrophysics Data System (ADS)

Romeira, Bruno; Figueiredo, José M. L.; Javaloyes, Julien

2017-11-01

With the recent exponential growth of applications using artificial intelligence (AI), the development of efficient and ultrafast brain-like (neuromorphic) systems is crucial for future information and communication technologies. While the implementation of AI systems using computer algorithms of neural networks is emerging rapidly, scientists are just taking the very first steps in the development of the hardware elements of an artificial brain, specifically neuromorphic microchips. In this review article, we present the current state of the art of neuromorphic photonic circuits based on solid-state optoelectronic oscillators formed by nanoscale double barrier quantum well resonant tunneling diodes. We address, both experimentally and theoretically, the key dynamic properties of recently developed artificial solid-state neuron microchips with delayed perturbations and describe their role in the study of neural activity and regenerative memory. This review covers our recent research work on excitable and delay dynamic characteristics of both single and autaptic (delayed) artificial neurons including all-or-none response, spike-based data encoding, storage, signal regeneration and signal healing. Furthermore, the neural responses of these neuromorphic microchips display all the signatures of extended spatio-temporal localized structures (LSs) of light, which are reviewed here in detail. By taking advantage of the dissipative nature of LSs, we demonstrate potential applications in optical data reconfiguration and clock and timing at high-speeds and with short transients. The results reviewed in this article are a key enabler for the development of high-performance optoelectronic devices in future high-speed brain-inspired optical memories and neuromorphic computing.

Delay dynamics of neuromorphic optoelectronic nanoscale resonators: Perspectives and applications.

PubMed

Romeira, Bruno; Figueiredo, José M L; Javaloyes, Julien

2017-11-01

With the recent exponential growth of applications using artificial intelligence (AI), the development of efficient and ultrafast brain-like (neuromorphic) systems is crucial for future information and communication technologies. While the implementation of AI systems using computer algorithms of neural networks is emerging rapidly, scientists are just taking the very first steps in the development of the hardware elements of an artificial brain, specifically neuromorphic microchips. In this review article, we present the current state of the art of neuromorphic photonic circuits based on solid-state optoelectronic oscillators formed by nanoscale double barrier quantum well resonant tunneling diodes. We address, both experimentally and theoretically, the key dynamic properties of recently developed artificial solid-state neuron microchips with delayed perturbations and describe their role in the study of neural activity and regenerative memory. This review covers our recent research work on excitable and delay dynamic characteristics of both single and autaptic (delayed) artificial neurons including all-or-none response, spike-based data encoding, storage, signal regeneration and signal healing. Furthermore, the neural responses of these neuromorphic microchips display all the signatures of extended spatio-temporal localized structures (LSs) of light, which are reviewed here in detail. By taking advantage of the dissipative nature of LSs, we demonstrate potential applications in optical data reconfiguration and clock and timing at high-speeds and with short transients. The results reviewed in this article are a key enabler for the development of high-performance optoelectronic devices in future high-speed brain-inspired optical memories and neuromorphic computing.

Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses

PubMed Central

Tabor, Kathryn M.; Bergeron, Sadie A.; Horstick, Eric J.; Jordan, Diana C.; Aho, Vilma; Porkka-Heiskanen, Tarja; Haspel, Gal

2014-01-01

Rapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs). Sensitization of the Mauthner cell by genetic overexpression of the voltage-gated sodium channel SCN5 increased EFP responsiveness, whereas Mauthner ablation with an engineered variant of nitroreductase with increased activity (epNTR) eliminated the response. The reaction time to EFPs is extremely short, with many responses initiated within 2 ms of the EFP. Large neurons, such as Mauthner cells, show heightened sensitivity to extracellular voltage gradients. We therefore tested whether the rapid response to EFPs was due to direct activation of the Mauthner cells, bypassing delays imposed by stimulus detection and transmission by sensory cells. Consistent with this, calcium imaging indicated that EFPs robustly activated the Mauthner cell but only rarely fired other reticulospinal neurons. Further supporting this idea, pharmacological blockade of synaptic transmission in zebrafish did not affect Mauthner cell activity in response to EFPs. Moreover, Mauthner cells transgenically expressing a tetrodotoxin (TTX)-resistant voltage-gated sodium channel retained responses to EFPs despite TTX suppression of action potentials in the rest of the brain. We propose that EFPs directly activate Mauthner cells because of their large size, thereby driving ultrarapid escape responses in fish. PMID:24848468

AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis

PubMed Central

Concannon, Caoimhín G.; Tuffy, Liam P.; Weisová, Petronela; Bonner, Helena P.; Dávila, David; Bonner, Caroline; Devocelle, Marc C.; Strasser, Andreas; Ward, Manus W.

2010-01-01

Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for the activation of excitotoxic apoptosis. In this study, we demonstrate that even a transient decrease in cellular bioenergetics and an associated activation of adenosine monophosphate–activated protein kinase (AMPK) is necessary for the activation of excitotoxic apoptosis. We show that the Bcl-2 homology domain 3 (BH3)–only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic apoptosis, and inhibits delayed Ca2+ deregulation, mitochondrial depolarization, and apoptosis-inducing factor translocation. We demonstrate that bim activation required the activation of AMPK and that prolonged AMPK activation is sufficient to induce bim gene expression and to trigger a bim-dependent cell death. Collectively, our data demonstrate that AMPK activation and the BH3-only protein Bim couple transient energy depletion to stress-induced neuronal apoptosis. PMID:20351066

Temperature and water loss affect ADH activity and gene expression in grape berry during postharvest dehydration.

PubMed

Cirilli, Marco; Bellincontro, Andrea; De Santis, Diana; Botondi, Rinaldo; Colao, Maria Chiara; Muleo, Rosario; Mencarelli, Fabio

2012-05-01

Clusters of Aleatico wine grape were picked at 18°Brix and placed at 10, 20, or 30°C, 45% relative humidity (RH) and 1.5m/s of air flow to dehydrate the berries up to 40% of loss of initial fresh weight. Sampling was done at 0%, 10%, 20%, 30%, and 40% weight loss (wl). ADH (alcohol dehydrogenase) gene expression, enzyme activity, and related metabolites were analysed. At 10°C, acetaldehyde increased rapidly and then declined, while ethanol continued to rise. At 20°C, acetaldehyde and ethanol increased significantly with the same pattern and declined at 40%wl. At 30°C, acetaldehyde did not increase but ethanol increased rapidly already at 10%wl. At the latter temperature, a significant increase in acetic acid and ethyl acetate occurred, while at 10°C their values were low. At 30°C, the ADH activity (ethanol to acetaldehyde direction), increased rapidly but acetaldehyde did not rise because of its oxidation to acetic acid, which increased together with ethyl acetate. At 10°C, the ADH activity increased at 20%wl and continued to rise even at 40%wl, meaning that ethanol oxidation was delayed. At 20°C, the behaviour was intermediate to the other temperatures. The relative expression of the VvAdh2 gene was the highest at 10°C already at 10%wl in a synchrony with the ADH activity, indicating a rapid response likely due to low temperature. The expression subsequently declined. At 20 and 30°C, the expression was lower and increased slightly during dehydration in combination with the ADH activity. This imbalance between gene expression and ADH activity at 10°C, as well as the unexpected expression of the carotenoid cleavage dioxygenase 1 (CCD1) gene, opens the discussion on the stress sensitivity and transcription event during postharvest dehydration, and the importance of carefully monitoring temperature during dehydration. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rapid detection of urinary soluble intercellular adhesion molecule-1 for determination of lupus nephritis activity.

PubMed

Wang, Yanyun; Tao, Ye; Liu, Yi; Zhao, Yi; Song, Chao; Zhou, Bin; Wang, Tao; Gao, Linbo; Zhang, Lin; Hu, Huaizhong

2018-06-01

The current methods of monitoring the activity of lupus nephritis (LN) may cause unnecessary hospital visits or delayed immunosuppressive therapy. We aimed to find a urinary biomarker that could be developed as a home-based test for monitoring the activity of LN.Urine samples were collected immediately before a renal biopsy from patients of suspected active LN, and also from patients with inactive LN, systemic lupus erythematous without LN or healthy controls. Biomarker search was conducted on a cytokine antibody array and confirmation was done by quantitative evaluation with enzyme-linked immunosorbent assay. The Mann-Whiney test or Student t test was used to compare the levels of 9 cytokines between different groups. The sensitivity and specificity of each cytokine for diagnosis of LN was evaluated by receiver operating characteristic curve. A rapid test based on colloidal gold immunochromatography was then developed for bedside or home use. Furthermore, an experimental e-healthcare system was constructed for recording and sharing the results of the rapid test a cloud-assisted internet of things (IoT) consisting of a sensing device, an IoT device and a cloud server.Adiponectin (Acrp30), soluble intercellular cell adhesion molecule-1 (sICAM-1), neural cell adhesion molecule 1 (NCAM-1), and CD26 were significantly higher in urine samples of active LN patients. sICAM-1 appeared more sensitive and specific among these candidates. When the cut-off value of sICAM-1 was set at 1.44 ng/mL, the sensitivity reached 98.33% with a specificity at 85.71%. The sICAM-1 strip test showed comparable sensitivity of 95% and a specificity of 83.3% for assessing the LN activity. Meanwhile, the e-healthcare system was able to conveniently digitize and share the sICAM-1 rapid test results.sICAM-1 appeared to be an excellent biomarker for monitoring LN activity. The e-healthcare system with cloud-assisted IoT could assist the digitalization and sharing of the bedside or home-based sICAM-1 test results.

Automated and manual patch clamp data of human induced pluripotent stem cell-derived dopaminergic neurons.

PubMed

Franz, Denise; Olsen, Hervør Lykke; Klink, Oliver; Gimsa, Jan

2017-04-25

Human induced pluripotent stem cells can be differentiated into dopaminergic neurons (Dopa.4U). Dopa.4U neurons expressed voltage-gated Na V and K V channels and showed neuron-like spontaneous electrical activity. In automated patch clamp measurements with suspended Dopa.4U neurons, delayed rectifier K + current (delayed K V ) and rapidly inactivating A-type K + current (fast K V ) were identified. Examination of the fast K V current with inhibitors yielded IC 50 values of 0.4 mM (4-aminopyridine) and 0.1 mM (tetraethylammonium). In manual patch clamp measurements with adherent Dopa.4U neurons, fast K V current could not be detected, while the delayed K V current showed an IC 50 of 2 mM for 4-aminopyridine. The Na V channels in adherent and suspended Dopa.4U neurons showed IC 50 values for tetrodotoxin of 27 and 2.9 nM, respectively. GABA-induced currents that could be observed in adherent Dopa.4U neurons could not be detected in suspended cells. Application of current pulses induced action potentials in approx. 70 % of the cells. Our results proved the feasibility of automated electrophysiological characterization of neuronal cells.

Maintained Physical Activity Induced Changes in Delay Discounting.

PubMed

Sofis, Michael J; Carrillo, Ale; Jarmolowicz, David P

2017-07-01

Those who discount the subjective value of delayed rewards less steeply are more likely to engage in physical activity. There is limited research, however, showing whether physical activity can change rates of delay discounting. In a two-experiment series, treatment and maintenance effects of a novel, effort-paced physical activity intervention on delay discounting were evaluated with multiple baseline designs. Using a lap-based method, participants were instructed to exercise at individualized high and low effort levels and to track their own perceived effort. The results suggest that treatment-induced changes in discounting were maintained at follow-up for 13 of 16 participants. In Experiment 2, there were statistically significant group-level improvements in physical activity and delay discounting when comparing baseline with both treatment and maintenance phases. Percentage change in delay discounting was significantly correlated with session attendance and relative pace (min/mile) improvement over the course of the 7-week treatment. Implications for future research are discussed.

Do differences in inducible resistance explain the population dynamics of birch and pine defoliators?

Treesearch

Seppo Neuvonen; Pekka Niemela

1991-01-01

Damage inflicted by insects may trigger responses in their host plants resulting either in immediate effects on herbivores either rapidly or in effects upon subsequent herbivore generations. Differentiation between rapid and delayed inducible resistance is essential since the two responses affect the population dynamics of herbivores in fundamentally different ways (...

Introduction of the Concepts of Plate Tectonics into Secondary-School Earth Science Textbooks.

ERIC Educational Resources Information Center

Glenn, William Harold

1992-01-01

Secondary school earth-science textbooks in print from 1960 through 1979 were examined to determine how rapidly concepts of plate tectonics were incorporated into those texts during the period when scientists' views about these concepts were evolving most rapidly. Suggests that delays were probably due to an unwillingness to engage in speculation…

Delayed hyperbaric oxygen therapy for air emboli after open heart surgery: case report and review of a success story.

PubMed

Niyibizi, Eva; Kembi, Guillaume Elyes; Lae, Claude; Pignel, Rodrigue; Sologashvili, Tornike

2016-12-05

The current case describes a rare diagnosis of iatrogenic air emboli after elective cardiopulmonary bypass that was successfully treated with delayed hyperbaric oxygen therapy, with good clinical evolution in spite of rare complications. A 35 years old male was admitted to the intensive care unit (ICU) for post-operative management after being placed on cardiopulmonary bypass (CPB) for an elective ventricular septal defect closure and aortic valvuloplasty. The patient initially presented with pathologically late awakening and was extubated 17 h after admission. Neurologic clinical status after extubation showed global aphasia, mental slowness and spatio-temporal disorientation. The injected cerebral CT scan was normal; the EEG was inconclusive (it showed metabolic encephalopathy without epileptic activity); and the cerebral MRI done 48 h after surgery showed multiple small subcortical acute ischemic lesions, mainly on the left fronto- parieto- temporo-occipital lobes. He was taken for hyperbaric oxygen therapy (HOT) over 54 h after cardiac surgery. The first session ended abruptly after 20 min when the patient suffered a generalised tonico-clonic seizure, necessitating a moderately rapid decompression, airway management, and antiepileptic treatment. In total, the patient received 7 HOT sessions over 6 days. He demonstrated full neurological recovery at 4 weeks and GOS (Glasgow Outcome Scale) of 5 out of 5 even after a long delay in initial management. Convulsions are a rare complication of HOT either due to reperfusion syndrome or hyperoxic toxicity and can be managed. Prior imaging by MRI or tympanic paracentesis (myringotomy) should not add further delay of treatment. HOT should be initiated upon late awakening and/or neurologic symptoms after CPB heart surgery, after exclusion of formal counter-indications, even if the delay exceeds 48 h.

Effectiveness of travel restrictions in the rapid containment of human influenza: a systematic review.

PubMed

Mateus, Ana L P; Otete, Harmony E; Beck, Charles R; Dolan, Gayle P; Nguyen-Van-Tam, Jonathan S

2014-12-01

To assess the effectiveness of internal and international travel restrictions in the rapid containment of influenza. We conducted a systematic review according to the requirements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Health-care databases and grey literature were searched and screened for records published before May 2014. Data extraction and assessments of risk of bias were undertaken by two researchers independently. Results were synthesized in a narrative form. The overall risk of bias in the 23 included studies was low to moderate. Internal travel restrictions and international border restrictions delayed the spread of influenza epidemics by one week and two months, respectively. International travel restrictions delayed the spread and peak of epidemics by periods varying between a few days and four months. Travel restrictions reduced the incidence of new cases by less than 3%. Impact was reduced when restrictions were implemented more than six weeks after the notification of epidemics or when the level of transmissibility was high. Travel restrictions would have minimal impact in urban centres with dense populations and travel networks. We found no evidence that travel restrictions would contain influenza within a defined geographical area. Extensive travel restrictions may delay the dissemination of influenza but cannot prevent it. The evidence does not support travel restrictions as an isolated intervention for the rapid containment of influenza. Travel restrictions would make an extremely limited contribution to any policy for rapid containment of influenza at source during the first emergence of a pandemic virus.

Effectiveness of travel restrictions in the rapid containment of human influenza: a systematic review

PubMed Central

Mateus, Ana LP; Otete, Harmony E; Beck, Charles R; Dolan, Gayle P; Nguyen-Van-Tam, Jonathan S

2014-01-01

Abstract Objective To assess the effectiveness of internal and international travel restrictions in the rapid containment of influenza. Methods We conducted a systematic review according to the requirements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Health-care databases and grey literature were searched and screened for records published before May 2014. Data extraction and assessments of risk of bias were undertaken by two researchers independently. Results were synthesized in a narrative form. Findings The overall risk of bias in the 23 included studies was low to moderate. Internal travel restrictions and international border restrictions delayed the spread of influenza epidemics by one week and two months, respectively. International travel restrictions delayed the spread and peak of epidemics by periods varying between a few days and four months. Travel restrictions reduced the incidence of new cases by less than 3%. Impact was reduced when restrictions were implemented more than six weeks after the notification of epidemics or when the level of transmissibility was high. Travel restrictions would have minimal impact in urban centres with dense populations and travel networks. We found no evidence that travel restrictions would contain influenza within a defined geographical area. Conclusion Extensive travel restrictions may delay the dissemination of influenza but cannot prevent it. The evidence does not support travel restrictions as an isolated intervention for the rapid containment of influenza. Travel restrictions would make an extremely limited contribution to any policy for rapid containment of influenza at source during the first emergence of a pandemic virus. PMID:25552771

Dynamic analysis of a stochastic delayed rumor propagation model

NASA Astrophysics Data System (ADS)

Jia, Fangju; Lv, Guangying; Wang, Shuangfeng; Zou, Guang-an

2018-02-01

The rapid development of the Internet, especially the emergence of the social networks, has led rumor propagation into a new media era. In this paper, we are concerned with a stochastic delayed rumor propagation model. Firstly, we obtain the existence of the global solution. Secondly, sufficient conditions for extinction of the rumor are established. Lastly, the boundedness of solution is proved and some simulations are given to verify our results.

Propellant Crack Tip Ignition and Propagation under Rapid Pressurization

DTIC Science & Technology

1982-10-01

that the ignition-delay time decreases and the heat flux to the propellant surface increases as the pressurization rate is increased. The decrease in...leading to ignition. The model predicts the experimental obseriation that the ignition delay time decreases as the pressurization rate is increased...pressurization rate on both crack propagation velocity and time variation of crack shape was studied. Experimental results indicated that the crack velocity

Correspondence of presaccadic activity in the monkey primary visual cortex with saccadic eye movements

PubMed Central

Supèr, Hans; van der Togt, Chris; Spekreijse, Henk; Lamme, Victor A. F.

2004-01-01

We continuously scan the visual world via rapid or saccadic eye movements. Such eye movements are guided by visual information, and thus the oculomotor structures that determine when and where to look need visual information to control the eye movements. To know whether visual areas contain activity that may contribute to the control of eye movements, we recorded neural responses in the visual cortex of monkeys engaged in a delayed figure-ground detection task and analyzed the activity during the period of oculomotor preparation. We show that ≈100 ms before the onset of visually and memory-guided saccades neural activity in V1 becomes stronger where the strongest presaccadic responses are found at the location of the saccade target. In addition, in memory-guided saccades the strength of presaccadic activity shows a correlation with the onset of the saccade. These findings indicate that the primary visual cortex contains saccade-related responses and participates in visually guided oculomotor behavior. PMID:14970334

[Changes in the work capacity of the operators of command-measuring systems during daily duty].

PubMed

Novikov, V S; Lustin, S I; Blaginin, A A; Kozlov, V P

1997-06-01

Through 12 hours of work the operators of command-measuring complexes had initial signs of exhaustion, showed them-self by decrease of health state, activity, mood, increase of latent period of simple sensorimotor reaction. These changes of a functional condition had no effect on quality of fulfillment of target problems. At the end of daily duty exhaustion, described by deterioration of health state, increase of operators' anxiousness, rapid pulse, reduction of time of delay of breath, increase of time of instability of sensorimotor reactions, amount of faulty actions, reduction of speed of mental processes and distribution of attention were developed.

Perinatal asphyxia: CNS development and deficits with delayed onset

PubMed Central

Herrera-Marschitz, Mario; Neira-Pena, Tanya; Rojas-Mancilla, Edgardo; Espina-Marchant, Pablo; Esmar, Daniela; Perez, Ronald; Muñoz, Valentina; Gutierrez-Hernandez, Manuel; Rivera, Benjamin; Simola, Nicola; Bustamante, Diego; Morales, Paola; Gebicke-Haerter, Peter J.

2013-01-01

Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. The primary insult relates to the duration of the period lacking oxygenation, leading to death if not re-established. Re-oxygenation leads to a secondary insult, related to a cascade of biochemical events required for restoring proper function. Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated to mental and neurological diseases with delayed clinical onset, by mechanisms not yet clarified. In the experimental scenario, the effects observed long after perinatal asphyxia have been explained by overexpression of sentinel proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for NAD+ during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. Asphyxia induces transcriptional activation of pro-inflammatory factors, in tandem with PARP-1 overactivation, and pharmacologically induced PARP-1 inhibition also down-regulates the expression of proinflammatory cytokines. Nicotinamide has been proposed as a suitable PARP-1 inhibitor. Its effect has been studied in an experimental model of global hypoxia in rats. In that model, the insult is induced by immersing rat fetus into a water bath for various periods of time. Following asphyxia, the pups are delivered, treated, and nursed by surrogate dams, pending further experiments. Nicotinamide rapidly distributes into the brain following systemic administration, reaching steady state concentrations sufficient to inhibit PARP-1 activity for several hours, preventing several of the long-term consequences of perinatal asphyxia, supporting the idea that nicotinamide constitutes a lead for exploring compounds with similar or better pharmacological profiles. PMID:24723845

A nontranscriptional role for Oct4 in the regulation of mitotic entry

PubMed Central

Zhao, Rui; Deibler, Richard W.; Lerou, Paul H.; Ballabeni, Andrea; Heffner, Garrett C.; Cahan, Patrick; Unternaehrer, Juli J.; Kirschner, Marc W.; Daley, George Q.

2014-01-01

Rapid progression through the cell cycle and a very short G1 phase are defining characteristics of embryonic stem cells. This distinct cell cycle is driven by a positive feedback loop involving Rb inactivation and reduced oscillations of cyclins and cyclin-dependent kinase (Cdk) activity. In this setting, we inquired how ES cells avoid the potentially deleterious consequences of premature mitotic entry. We found that the pluripotency transcription factor Oct4 (octamer-binding transcription factor 4) plays an unappreciated role in the ES cell cycle by forming a complex with cyclin–Cdk1 and inhibiting Cdk1 activation. Ectopic expression of Oct4 or a mutant lacking transcriptional activity recapitulated delayed mitotic entry in HeLa cells. Reduction of Oct4 levels in ES cells accelerated G2 progression, which led to increased chromosomal missegregation and apoptosis. Our data demonstrate an unexpected nontranscriptional function of Oct4 in the regulation of mitotic entry. PMID:25324523

Impulsive choice and pre-exposure to delays: iv. effects of delay- and immediacy-exposure training relative to maturational changes in impulsivity.

PubMed

Renee Renda, C; Rung, Jillian M; Hinnenkamp, Jay E; Lenzini, Stephanie N; Madden, Gregory J

2018-04-23

Impulsive choice describes preference for smaller, sooner rewards over larger, later rewards. Excessive delay discounting (i.e., rapid devaluation of delayed rewards) underlies some impulsive choices, and is observed in many maladaptive behaviors (e.g., substance abuse, gambling). Interventions designed to reduce delay discounting may provide therapeutic gains. One such intervention provides rats with extended training with delayed reinforcers. When compared to a group given extended training with immediate reinforcers, delay-exposed rats make significantly fewer impulsive choices. To what extent is this difference due to delay-exposure training shifting preference toward self-control or immediacy-exposure training (the putative control group) shifting preference toward impulsivity? The current study compared the effects of delay- and immediacy-exposure training to a no-training control group and evaluated within-subject changes in impulsive choice across 51 male Wistar rats. Delay-exposed rats made significantly fewer impulsive choices than immediacy-exposed and control rats. Between-group differences in impulsive choice were not observed in the latter two groups. While delay-exposed rats showed large, significant pre- to posttraining reductions in impulsive choice, immediacy-exposed and control rats showed small reductions in impulsive choice. These results suggest that extended training with delayed reinforcers reduces impulsive choice, and that extended training with immediate reinforcers does not increase impulsive choice. © 2018 Society for the Experimental Analysis of Behavior.

DECISION-MAKING ALIGNED WITH RAPID-CYCLE EVALUATION IN HEALTH CARE.

PubMed

Schneeweiss, Sebastian; Shrank, William H; Ruhl, Michael; Maclure, Malcolm

2015-01-01

Availability of real-time electronic healthcare data provides new opportunities for rapid-cycle evaluation (RCE) of health technologies, including healthcare delivery and payment programs. We aim to align decision-making processes with stages of RCE to optimize the usefulness and impact of rapid results. Rational decisions about program adoption depend on program effect size in relation to externalities, including implementation cost, sustainability, and likelihood of broad adoption. Drawing on case studies and experience from drug safety monitoring, we examine how decision makers have used scientific evidence on complex interventions in the past. We clarify how RCE alters the nature of policy decisions; develop the RAPID framework for synchronizing decision-maker activities with stages of RCE; and provide guidelines on evidence thresholds for incremental decision-making. In contrast to traditional evaluations, RCE provides early evidence on effectiveness and facilitates a stepped approach to decision making in expectation of future regularly updated evidence. RCE allows for identification of trends in adjusted effect size. It supports adapting a program in midstream in response to interim findings, or adapting the evaluation strategy to identify true improvements earlier. The 5-step RAPID approach that utilizes the cumulating evidence of program effectiveness over time could increase policy-makers' confidence in expediting decisions. RCE enables a step-wise approach to HTA decision-making, based on gradually emerging evidence, reducing delays in decision-making processes after traditional one-time evaluations.

Prehospital delay, contributing aspects and responses to symptoms among Norwegian women and men with first time acute myocardial infarction.

PubMed

Løvlien, M; Schei, B; Hole, T

2007-12-01

In patients with acute myocardial infarction (AMI), the delay between the onset of symptoms and hospital admission is a critical factor in reducing morbidity and mortality. To assess gender differences in prehospital delay among women and men with first time AMI, generate more knowledge about aspects influencing this delay and investigate responses to acute symptoms. Of 738 eligible patients, 149 women and 384 men responded to a questionnaire (72%). Over half of both women and men waited over one hour before they called for medical assistance and more than half the patients had a total prehospital delay exceeding two hours. Rapid development of symptoms and symptoms matching expectations reduced, self medication and consulting the spouse increased patient delay in both genders. Calling the Emergency Medical Service (EMS) reduced and calling a general practitioner increased total prehospital delay in both genders. ST-ELEVATION: (STEMI), symptoms experienced as unbearable and attributed as cardiac reduced patient delay, and symptoms from the back, shoulders or between scapulae increased prehospital delay, only in men. How patients responded to symptoms had vital impact on prehospital delay among both genders, but the experience and interpretation of symptoms had more influence in men than in women.

Singular Hopf bifurcation in a differential equation with large state-dependent delay

PubMed Central

Kozyreff, G.; Erneux, T.

2014-01-01

We study the onset of sustained oscillations in a classical state-dependent delay (SDD) differential equation inspired by control theory. Owing to the large delays considered, the Hopf bifurcation is singular and the oscillations rapidly acquire a sawtooth profile past the instability threshold. Using asymptotic techniques, we explicitly capture the gradual change from nearly sinusoidal to sawtooth oscillations. The dependence of the delay on the solution can be either linear or nonlinear, with at least quadratic dependence. In the former case, an asymptotic connection is made with the Rayleigh oscillator. In the latter, van der Pol’s equation is derived for the small-amplitude oscillations. SDD differential equations are currently the subject of intense research in order to establish or amend general theorems valid for constant-delay differential equation, but explicit analytical construction of solutions are rare. This paper illustrates the use of singular perturbation techniques and the unusual way in which solvability conditions can arise for SDD problems with large delays. PMID:24511255

Singular Hopf bifurcation in a differential equation with large state-dependent delay.

PubMed

Kozyreff, G; Erneux, T

2014-02-08

We study the onset of sustained oscillations in a classical state-dependent delay (SDD) differential equation inspired by control theory. Owing to the large delays considered, the Hopf bifurcation is singular and the oscillations rapidly acquire a sawtooth profile past the instability threshold. Using asymptotic techniques, we explicitly capture the gradual change from nearly sinusoidal to sawtooth oscillations. The dependence of the delay on the solution can be either linear or nonlinear, with at least quadratic dependence. In the former case, an asymptotic connection is made with the Rayleigh oscillator. In the latter, van der Pol's equation is derived for the small-amplitude oscillations. SDD differential equations are currently the subject of intense research in order to establish or amend general theorems valid for constant-delay differential equation, but explicit analytical construction of solutions are rare. This paper illustrates the use of singular perturbation techniques and the unusual way in which solvability conditions can arise for SDD problems with large delays.

Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome.

PubMed

Griffin, Aliesha; Hamling, Kyla R; Knupp, Kelly; Hong, SoonGweon; Lee, Luke P; Baraban, Scott C

2017-03-01

Dravet syndrome is a catastrophic childhood epilepsy with early-onset seizures, delayed language and motor development, sleep disturbances, anxiety-like behaviour, severe cognitive deficit and an increased risk of fatality. It is primarily caused by de novo mutations of the SCN1A gene encoding a neuronal voltage-activated sodium channel. Zebrafish with a mutation in the SCN1A homologue recapitulate spontaneous seizure activity and mimic the convulsive behavioural movements observed in Dravet syndrome. Here, we show that phenotypic screening of drug libraries in zebrafish scn1 mutants rapidly and successfully identifies new therapeutics. We demonstrate that clemizole binds to serotonin receptors and its antiepileptic activity can be mimicked by drugs acting on serotonin signalling pathways e.g. trazodone and lorcaserin. Coincident with these zebrafish findings, we treated five medically intractable Dravet syndrome patients with a clinically-approved serotonin receptor agonist (lorcaserin, Belviq®) and observed some promising results in terms of reductions in seizure frequency and/or severity. Our findings demonstrate a rapid path from preclinical discovery in zebrafish, through target identification, to potential clinical treatments for Dravet syndrome. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-01-01

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

A Novel Adaptive H∞ Filtering Method with Delay Compensation for the Transfer Alignment of Strapdown Inertial Navigation Systems.

PubMed

Lyu, Weiwei; Cheng, Xianghong

2017-11-28

Transfer alignment is always a key technology in a strapdown inertial navigation system (SINS) because of its rapidity and accuracy. In this paper a transfer alignment model is established, which contains the SINS error model and the measurement model. The time delay in the process of transfer alignment is analyzed, and an H∞ filtering method with delay compensation is presented. Then the H∞ filtering theory and the robust mechanism of H∞ filter are deduced and analyzed in detail. In order to improve the transfer alignment accuracy in SINS with time delay, an adaptive H∞ filtering method with delay compensation is proposed. Since the robustness factor plays an important role in the filtering process and has effect on the filtering accuracy, the adaptive H∞ filter with delay compensation can adjust the value of robustness factor adaptively according to the dynamic external environment. The vehicle transfer alignment experiment indicates that by using the adaptive H∞ filtering method with delay compensation, the transfer alignment accuracy and the pure inertial navigation accuracy can be dramatically improved, which demonstrates the superiority of the proposed filtering method.

System for sensing droplet formation time delay in a flow cytometer

DOEpatents

Van den Engh, Ger; Esposito, Richard J.

1997-01-01

A droplet flow cytometer system which includes a system to optimize the droplet formation time delay based on conditions actually experienced includes an automatic droplet sampler which rapidly moves a plurality of containers stepwise through the droplet stream while simultaneously adjusting the droplet time delay. Through the system sampling of an actual substance to be processed can be used to minimize the effect of the substances variations or the determination of which time delay is optimal. Analysis such as cell counting and the like may be conducted manually or automatically and input to a time delay adjustment which may then act with analysis equipment to revise the time delay estimate actually applied during processing. The automatic sampler can be controlled through a microprocessor and appropriate programming to bracket an initial droplet formation time delay estimate. When maximization counts through volume, weight, or other types of analysis exists in the containers, the increment may then be reduced for a more accurate ultimate setting. This may be accomplished while actually processing the sample without interruption.

T Cell Dynamic Activation and Functional Analysis in Nanoliter Droplet Microarray.

PubMed

Sarkar, Saheli; Motwani, Vinny; Sabhachandani, Pooja; Cohen, Noa; Konry, Tania

2015-06-01

Characterization of the heterogeneity in immune reactions requires assessing dynamic single cell responses as well as interactions between the various immune cell subsets. Maturation and activation of effector cells is regulated by cell contact-dependent and soluble factor-mediated paracrine signalling. Currently there are few methods available that allow dynamic investigation of both processes simultaneously without physically constraining non-adherent cells and eliminating crosstalk from neighboring cell pairs. We describe here a microfluidic droplet microarray platform that permits rapid functional analysis of single cell responses and co-encapsulation of heterotypic cell pairs, thereby allowing us to evaluate the dynamic activation state of primary T cells. The microfluidic droplet platform enables generation and docking of monodisperse nanoliter volume (0.523 nl) droplets, with the capacity of monitoring a thousand droplets per experiment. Single human T cells were encapsulated in droplets and stimulated on-chip with the calcium ionophore ionomycin. T cells were also co-encapsulated with dendritic cells activated by ovalbumin peptide, followed by dynamic calcium signal monitoring. Ionomycin-stimulated cells depicted fluctuation in calcium signalling compared to control. Both cell populations demonstrated marked heterogeneity in responses. Calcium signalling was observed in T cells immediately following contact with DCs, suggesting an early activation signal. T cells further showed non-contact mediated increase in calcium level, although this response was delayed compared to contact-mediated signals. Our results suggest that this nanoliter droplet array-based microfluidic platform is a promising technique for assessment of heterogeneity in various types of cellular responses, detection of early/delayed signalling events and live cell phenotyping of immune cells.

CHIP−/−-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications

PubMed Central

Kim, Sung-Mi; Grenert, James P.; Patterson, Cam; Correia, Maria Almira

2016-01-01

Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin-ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) production, triggering oxidative/proteotoxic stress associated with sustained activation of c-Jun NH2-terminal kinase (JNK)-signaling cascades, pro-inflammatory effectors/cytokines, insulin resistance, progressive hepatocellular ballooning and microvesicular steatosis. Despite this, little evidence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) was found in CHIP−/−-mice over the first 8–9-months of life. We herein document that this lack of tissue injury is largely due to the concurrent up-regulation and/or activation of the adiponectin-5′-AMP-activated protein kinase (AMPK)-forkhead box O (FOXO)-signaling axis stemming from at the least three synergistic features: Up-regulated expression of adipose tissue adiponectin and its hepatic adipoR1/adipoR2 receptors, stabilization of hepatic AMPKα1-isoform, identified herein for the first time as a CHIP-ubiquitination substrate (unlike its AMPKα2-isoform), as well as nuclear stabilization of FOXOs, well-known CHIP-ubiquitination targets. Such beneficial predominance of the adiponectin-AMPK-FOXO-signaling axis over the sustained JNK-elevation and injurious insulin resistance in CHIP−/−-livers apparently counteracts/delays rapid progression of the hepatic microvesicular steatosis to the characteristic macrovesicular steatosis observed in clinical NASH and/or rodent NASH-models. PMID:27406999

Nosepiece respiration monitor

NASA Technical Reports Server (NTRS)

Lavery, A. L.; Long, L. E.; Rice, N. E.

1968-01-01

Comfortable, inexpensive nosepiece respiration monitor produces rapid response signals to most conventional high impedance medical signal conditioners. The monitor measures respiration in a manner that produces a large signal with minimum delay.

Priors Engaged in Long-Latency Responses to Mechanical Perturbations Suggest a Rapid Update in State Estimation

PubMed Central

Crevecoeur, Frédéric; Scott, Stephen H.

2013-01-01

In every motor task, our brain must handle external forces acting on the body. For example, riding a bike on cobblestones or skating on irregular surface requires us to appropriately respond to external perturbations. In these situations, motor predictions cannot help anticipate the motion of the body induced by external factors, and direct use of delayed sensory feedback will tend to generate instability. Here, we show that to solve this problem the motor system uses a rapid sensory prediction to correct the estimated state of the limb. We used a postural task with mechanical perturbations to address whether sensory predictions were engaged in upper-limb corrective movements. Subjects altered their initial motor response in ∼60 ms, depending on the expected perturbation profile, suggesting the use of an internal model, or prior, in this corrective process. Further, we found trial-to-trial changes in corrective responses indicating a rapid update of these perturbation priors. We used a computational model based on Kalman filtering to show that the response modulation was compatible with a rapid correction of the estimated state engaged in the feedback response. Such a process may allow us to handle external disturbances encountered in virtually every physical activity, which is likely an important feature of skilled motor behaviour. PMID:23966846

Anger in brain and body: the neural and physiological perturbation of decision-making by emotion.

PubMed

Garfinkel, Sarah N; Zorab, Emma; Navaratnam, Nakulan; Engels, Miriam; Mallorquí-Bagué, Núria; Minati, Ludovico; Dowell, Nicholas G; Brosschot, Jos F; Thayer, Julian F; Critchley, Hugo D

2016-01-01

Emotion and cognition are dynamically coupled to bodily arousal: the induction of anger, even unconsciously, can reprioritise neural and physiological resources toward action states that bias cognitive processes. Here we examine behavioural, neural and bodily effects of covert anger processing and its influence on cognition, indexed by lexical decision-making. While recording beat-to-beat blood pressure, the words ANGER or RELAX were presented subliminally just prior to rapid word/non-word reaction-time judgements of letter-strings. Subliminal ANGER primes delayed the time taken to reach rapid lexical decisions, relative to RELAX primes. However, individuals with high trait anger were speeded up by subliminal anger primes. ANGER primes increased systolic blood pressure and the magnitude of this increase predicted reaction time prolongation. Within the brain, ANGER trials evoked an enhancement of activity within dorsal pons and an attenuation of activity within visual occipitotemporal and attentional parietal cortices. Activity within periaqueductal grey matter, occipital and parietal regions increased linearly with evoked blood pressure changes, indicating neural substrates through which covert anger impairs semantic decisions, putatively through its expression as visceral arousal. The behavioural and physiological impact of anger states compromises the efficiency of cognitive processing through action-ready changes in autonomic response that skew regional neural activity. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

Gilat, E.; Kadar, T.; Levy, A.

Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 {+-} 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsantmore » effect (53 {+-} 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in brain damage. The addition of scopolamine to midazolam did not alter the above observation. In summary, nasal midazolam treatment briefly after initiation of OP-induced seizure leads to cessation of EGSA and prevented brain lesions and behavioral deficiencies in the rat model.« less

Time delays in the response to the Neisseria meningitidis serogroup C outbreak in Nigeria - 2017.

PubMed

Hassan, Assad; Mustapha, G U; Lawal, Bola B; Na'uzo, Aliyu M; Ismail, Raji; Womi-Eteng Oboma, Eteng; Oyebanji, Oyeronke; Agenyi, Jeremiah; Thomas, Chima; Balogun, Muhammad Shakir; Dalhat, Mahmood M; Nguku, Patrick; Ihekweazu, Chikwe

2018-01-01

Nigeria reports high rates of mortality linked with recurring meningococcal meningitis outbreaks within the African meningitis belt. Few studies have thoroughly described the response to these outbreaks to provide strong and actionable public health messages. We describe how time delays affected the response to the 2016/2017 meningococcal meningitis outbreak in Nigeria. Using data from Nigeria Centre for Disease Control (NCDC), National Primary Health Care Development Agency (NPHCDA), World Health Organisation (WHO), and situation reports of rapid response teams, we calculated attack and death rates of reported suspected meningococcal meningitis cases per week in Zamfara, Sokoto and Yobe states respectively, between epidemiological week 49 in 2016 and epidemiological week 25 in 2017. We identified when alert and epidemic thresholds were crossed and determined when the outbreak was detected and notified in each state. We examined response activities to the outbreak. There were 12,535 suspected meningococcal meningitis cases and 877 deaths (CFR: 7.0%) in the three states. It took an average time of three weeks before the outbreaks were detected and notified to NCDC. Four weeks after receiving notification, an integrated response coordinating centre was set up by NCDC and requests for vaccines were sent to International Coordinating Group (ICG) on vaccine provision. While it took ICG one week to approve the requests, it took an average of two weeks for approximately 41% of requested vaccines to arrive. On the average, it took nine weeks from the date the epidemic threshold was crossed to commencement of reactive vaccination in the three states. There were delays in detection and notification of the outbreak, in coordinating response activities, in requesting for vaccines and their arrival from ICG, and in initiating reactive vaccination. Reducing these delays in future outbreaks could help decrease the morbidity and mortality linked with meningococcal meningitis outbreaks.

Test-retest reliability and practice effects of a rapid screen of mild traumatic brain injury.

PubMed

De Monte, Veronica Eileen; Geffen, Gina Malke; Kwapil, Karleigh

2005-07-01

Test-retest reliabilities and practice effects of measures from the Rapid Screen of Concussion (RSC), in addition to the Digit Symbol Substitution Test (Digit Symbol), were examined. Twenty five male participants were tested three times; each testing session scheduled a week apart. The test-retest reliability estimates for most measures were reasonably good, ranging from .79 to .97. An exception was the delayed word recall test, which has had a reliability estimate of .66 for the first retest, and .59 for the second retest. Practice effects were evident from Times 1 to 2 on the sentence comprehension and delayed recall subtests of the RSC, Digit Symbol and a composite score. There was also a practice effect of the same magnitude found from Time 2 to Time 3 on Digit Symbol, delayed recall and the composite score. Statistics on measures for both the first and second retest intervals, with associated practice effects, are presented to enable the calculation of reliable change indices (RCI). The RCI may be used to assess any improvement in cognitive functioning after mild Traumatic Brain Injury.

Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

PubMed

Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

2016-01-01

India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Delay Discounting as an Index of Sustainable Behavior: Devaluation of Future Air Quality and Implications for Public Health.

PubMed

Berry, Meredith S; Nickerson, Norma P; Odum, Amy L

2017-09-01

Poor air quality and resulting annual deaths represent significant public health concerns. Recently, rapid delay discounting (the devaluation of future outcomes) of air quality has been considered a potential barrier for engaging in long term, sustainable behaviors that might help to reduce emissions (e.g., reducing private car use, societal support for clean air initiatives). Delay discounting has been shown to be predictive of real world behavior outside of laboratory settings, and therefore may offer an important framework beyond traditional variables thought to measure sustainable behavior such as importance of an environmental issue, or environmental attitudes/values, although more research is needed in this area. We examined relations between discounting of air quality, respiratory health, and monetary gains and losses. We also examined, relations between discounting and self-reported importance of air quality and respiratory health, and nature relatedness. Results showed rapid delay discounting of all outcomes across the time frames assessed, and significant positive correlations between delay discounting of air quality, respiratory health, and monetary outcomes. Steeper discounting of monetary outcomes relative to air quality and respiratory health outcomes was observed in the context of gains; however, no differences in discounting were observed across losses of monetary, air quality, and respiratory health. Replicating the sign effect, monetary outcomes were discounted more steeply than monetary losses. Importance of air quality, respiratory health and nature relatedness were significantly and positively correlated with one another, but not with degree of delay discounting of any outcome, demonstrating the need for more comprehensive measures that predict pro-environmental behaviors that might benefit individuals and public health over time. These results add to our understanding of decision-making, and demonstrate alarming rates of delay discounting of air quality and health. These results implicate a major public health concern and potential barriers to individual and societal behavior that reduce pollution and emissions for conservation of clean air.

Delay Discounting as an Index of Sustainable Behavior: Devaluation of Future Air Quality and Implications for Public Health

PubMed Central

Berry, Meredith S.; Nickerson, Norma P.; Odum, Amy L.

2017-01-01

Poor air quality and resulting annual deaths represent significant public health concerns. Recently, rapid delay discounting (the devaluation of future outcomes) of air quality has been considered a potential barrier for engaging in long term, sustainable behaviors that might help to reduce emissions (e.g., reducing private car use, societal support for clean air initiatives). Delay discounting has been shown to be predictive of real world behavior outside of laboratory settings, and therefore may offer an important framework beyond traditional variables thought to measure sustainable behavior such as importance of an environmental issue, or environmental attitudes/values, although more research is needed in this area. We examined relations between discounting of air quality, respiratory health, and monetary gains and losses. We also examined, relations between discounting and self-reported importance of air quality and respiratory health, and nature relatedness. Results showed rapid delay discounting of all outcomes across the time frames assessed, and significant positive correlations between delay discounting of air quality, respiratory health, and monetary outcomes. Steeper discounting of monetary outcomes relative to air quality and respiratory health outcomes was observed in the context of gains; however, no differences in discounting were observed across losses of monetary, air quality, and respiratory health. Replicating the sign effect, monetary outcomes were discounted more steeply than monetary losses. Importance of air quality, respiratory health and nature relatedness were significantly and positively correlated with one another, but not with degree of delay discounting of any outcome, demonstrating the need for more comprehensive measures that predict pro-environmental behaviors that might benefit individuals and public health over time. These results add to our understanding of decision-making, and demonstrate alarming rates of delay discounting of air quality and health. These results implicate a major public health concern and potential barriers to individual and societal behavior that reduce pollution and emissions for conservation of clean air. PMID:28862671

Churg-Strauss syndrome associated with rapid deterioration of left ventricular diastolic dysfunction and conduction disturbance.

PubMed

Chin, Jung Yeon; Yi, Jeong Eun; Youn, Ho-Joong

2013-10-01

Cardiac involvement in Churg-Strauss syndrome (CSS) is a major cause of mortality. Here we report a case of a 75-year-old woman with eosinophilic endomyocarditis due to CSS. An electrocardiogram showed intraventricular conduction delay, and echocardiography showed an impaired relaxation pattern and biventricular apical thickening. Magnetic resonance imaging revealed subendocardial delayed enhancement with biventricular apical thrombi. Endomyocardial biopsy showed perivascular eosinophilic infiltration. Despite resolution of the hypereosinophilia after steroid therapy, her left ventricular (LV) diastolic function worsened into a restrictive pattern and she died with a ventricular escape rhythm on her 14th day in the hospital. This case is unusual in that there was rapid progression of the LV diastolic dysfunction and conduction disturbance due to CSS. © 2013, Wiley Periodicals, Inc.

Rapid diagnosis of sexually transmitted infections.

PubMed

Otero-Guerra, Luis; Fernández-Blázquez, Ana; Vazquez, Fernando

Sexually transmitted infections (STIs) are responsible for an enormous burden of morbidity and mortality. Worldwide, millions of cases of STIs, such as syphilis, chlamydia, or gonorrhoea occur every year, and there is now an increase in antimicrobial resistance in pathogens, such as gonococcus. Delay in diagnosis is one of the factors that justifies the difficulty in controlling these infections. Rapid diagnostic tests allow the introduction of aetiological treatment at the first visit, and also leads to treating symptomatic and asymptomatic patients more effectively, as well as to interrupt the epidemiological transmission chain without delay. The World Health Organisation includes these tests in its global strategy against STIs. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Auto-ignitions of a methane/air mixture at high and intermediate temperatures

NASA Astrophysics Data System (ADS)

Leschevich, V. V.; Martynenko, V. V.; Penyazkov, O. G.; Sevrouk, K. L.; Shabunya, S. I.

2016-09-01

A rapid compression machine (RCM) and a shock tube (ST) have been employed to study ignition delay times of homogeneous methane/air mixtures at intermediate-to-high temperatures. Both facilities allow measurements to be made at temperatures of 900-2000 K, at pressures of 0.38-2.23 MPa, and at equivalence ratios of 0.5, 1.0, and 2.0. In ST experiments, nitrogen served as a diluent gas, whereas in RCM runs the diluent gas composition ranged from pure nitrogen to pure argon. Recording pressure, UV, and visible emissions identified the evolution of chemical reactions. Correlations of ignition delay time were generated from the data for each facility. At temperatures below 1300 K, a significant reduction of average activation energy from 53 to 15.3 kcal/mol was obtained. Moreover, the RCM data showed significant scatter that dramatically increased with decreasing temperature. An explanation for the abnormal scatter in the data was proposed based on the high-speed visualization of auto-ignition phenomena and experiments performed with oxygen-free and fuel-free mixtures. It is proposed that the main reason for such a significant reduction of average activation energy is attributable to the premature ignition of ultrafine particles in the reactive mixture.

Determinants of Motion Sickness in Tilting Trains: Coriolis/Cross-Coupling Stimuli and Tilt Delay

PubMed Central

Bertolini, Giovanni; Durmaz, Meek Angela; Ferrari, Kim; Küffer, Alexander; Lambert, Charlotte; Straumann, Dominik

2017-01-01

Faster trains require tilting of the cars to counterbalance the centrifugal forces during curves. Motion sensitive passengers, however, complain of discomfort and overt motion sickness. A recent study comparing different control systems in a tilting train, suggested that the delay of car tilts relative to the curve of the track contributes to motion sickness. Other aspects of the motion stimuli, like the lateral accelerations and the car jitters, differed between the tested conditions and prevented a final conclusion on the role of tilt delay. Nineteen subjects were tested on a motorized 3D turntable that simulated the roll tilts during yaw rotations experienced on a tilting train, isolating them from other motion components. Each session was composed of two consecutive series of 12 ideal curves that were defined on the bases of recordings during an actual train ride. The simulated car tilts started either at the beginning of the curve acceleration phase (no-delay condition) or with 3 s of delay (delay condition). Motion sickness was self-assessed by each subject at the end of each series using an analog motion sickness scale. All subjects were tested in both conditions. Significant increases of motion sickness occurred after the first sequence of 12 curves in the delay condition, but not in the no-delay condition. This increase correlated with the sensitivity of motion sickness, which was self-assessed by each subject before the experiment. The second sequence of curve did not lead to a significant further increase of motion sickness in any condition. Our results demonstrate that, even if the speed and amplitude are as low as those experienced on tilting trains, a series of roll tilts with a delay relative to the horizontal rotations, isolated from other motion stimuli occurring during a travel, generate Coriolis/cross-coupling stimulations sufficient to rapidly induce motion sickness in sensitive individuals. The strength and the rapid onset of the motion sickness reported confirm that, even if the angular velocity involved are low, the Coriolis/cross-coupling resulting from the delay is a major factor in causing sickness that can be resolved by improving the tilt timing relative to the horizontal rotation originating from the curve. PMID:28555125

Direct real-time measurement of intra-oocyte nitric oxide concentration in vivo.

PubMed

Goud, Pravin T; Goud, Anuradha P; Najafi, Tohid; Gonik, Bernard; Diamond, Michael P; Saed, Ghassan M; Zhang, Xueji; Abu-Soud, Husam M

2014-01-01

Nitric oxide (NO) is reported to play significant a role in oocyte activation and maturation, implantation, and early embryonic development. Previously we have shown that NO forms an important component of the oocyte microenvironment, and functions effectively to delay oocyte aging. Thus, precise information about intra-oocyte NO concentrations [NO] will result in designing more accurate treatment plans in assisted reproduction. In this work, the direct, real-time and quantitative intra-oocyte [NO] was measured utilizing an L-shaped amperometric integrated NO-selective electrode. This method not only provides an elegant and convenient approach to real-time the measurement of NO in physiological environments, but also mimics the loss of NO caused by rapid NO diffusion combined with its reactivity in the biological milieu. This experiment suggests that the NO levels of oocytes obtained from young animals are significantly higher than those of oocytes obtained from old animals. Additionally the NO levels stay constant during the measurements; however, the intra-oocyte [NO] is reduced significantly (70-75% reduction) in response to L-NAME incubation, suggesting that NO measurements are truly NOS based rather than caused by an unknown interfering substance in our system. We believe this first demonstration of the direct quantitative measurement of [NO] in situ in an intact cellular complex should be useful in tracking real-time and rapid changes at nanomolar levels. Moreover, this finding confirms and extends our previous work showing that supplementation with NO delays the oocyte aging process.

Direct Real-Time Measurement of Intra-Oocyte Nitric Oxide Concentration In Vivo

PubMed Central

Goud, Pravin T.; Goud, Anuradha P.; Najafi, Tohid; Gonik, Bernard; Diamond, Michael P.; Saed, Ghassan M.; Zhang, Xueji; Abu-Soud, Husam M.

2014-01-01

Nitric oxide (NO) is reported to play significant a role in oocyte activation and maturation, implantation, and early embryonic development. Previously we have shown that NO forms an important component of the oocyte microenvironment, and functions effectively to delay oocyte aging. Thus, precise information about intra-oocyte NO concentrations [NO] will result in designing more accurate treatment plans in assisted reproduction. In this work, the direct, real-time and quantitative intra-oocyte [NO] was measured utilizing an L-shaped amperometric integrated NO-selective electrode. This method not only provides an elegant and convenient approach to real-time the measurement of NO in physiological environments, but also mimics the loss of NO caused by rapid NO diffusion combined with its reactivity in the biological milieu. This experiment suggests that the NO levels of oocytes obtained from young animals are significantly higher than those of oocytes obtained from old animals. Additionally the NO levels stay constant during the measurements; however, the intra-oocyte [NO] is reduced significantly (70–75% reduction) in response to L-NAME incubation, suggesting that NO measurements are truly NOS based rather than caused by an unknown interfering substance in our system. We believe this first demonstration of the direct quantitative measurement of [NO] in situ in an intact cellular complex should be useful in tracking real-time and rapid changes at nanomolar levels. Moreover, this finding confirms and extends our previous work showing that supplementation with NO delays the oocyte aging process. PMID:24887331

Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

PubMed

Geelen, P; Drolet, B; Rail, J; Bérubé, J; Daleau, P; Rousseau, G; Cardinal, R; O'Hara, G E; Turgeon, J

2000-07-18

BACKGROUND-Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. METHODS AND RESULTS-Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 mcmol/L. Action potential duration increased 15% from baseline 117+/-3 to 134+/-2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99+/-2 to 105+/-2 ms was seen with pacing at 150 ms cycle length. Experiments in human ether-a-go-go-related gene (HERG)-transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current: activating current was 50% decreased at 100 mcmol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I(K)-like current. CONCLUSIONS-Sildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment.

Tolerance and immunity in mice infected with herpes simplex virus: simultaneous induction of protective immunity and tolerance to delayed-type hypersensitivity.

PubMed

Nash, A A; Gell, P G; Wildy, P

1981-05-01

Unresponsiveness to delayed type hypersensitivity was induced in mice following an intravenous injection of herpes simplex virus. The principal tolerogens used were thymidine kinase-deficient virus mutants which grow poorly in vivo; u.v.-inactivated and to a lesser extent formalin-inactivated virus were also tolerogenic. The tolerance induced was specific for the virus type. Despite the tolerance to delayed hypersensitivity, anti-viral immunity is present as determined by the rapid inactivation of infectious virus. The mechanism of tolerance to herpes virus and the importance of these observations for the pathogenesis of viral disease is discussed.

Tolerance and immunity in mice infected with herpes simplex virus: simultaneous induction of protective immunity and tolerance to delayed-type hypersensitivity.

PubMed Central

Nash, A A; Gell, P G; Wildy, P

1981-01-01

Unresponsiveness to delayed type hypersensitivity was induced in mice following an intravenous injection of herpes simplex virus. The principal tolerogens used were thymidine kinase-deficient virus mutants which grow poorly in vivo; u.v.-inactivated and to a lesser extent formalin-inactivated virus were also tolerogenic. The tolerance induced was specific for the virus type. Despite the tolerance to delayed hypersensitivity, anti-viral immunity is present as determined by the rapid inactivation of infectious virus. The mechanism of tolerance to herpes virus and the importance of these observations for the pathogenesis of viral disease is discussed. PMID:7251047

Delay activity of saccade-related neurons in the caudal dentate nucleus of the macaque cerebellum

PubMed Central

Sommer, Marc A.

2013-01-01

The caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum: the frontal eye field and lateral intraparietal cortex. Many neurons in frontal eye field and lateral intraparietal cortex produce “delay activity” between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that caudal DN neurons would have prominent delay activity as well. From lesion studies, we predicted that this activity would be related to self-timing, i.e., the triggering of saccades based on the internal monitoring of time. We recorded from neurons in the caudal DN of monkeys (Macaca mulatta) that made delayed saccades with or without a self-timing requirement. Most (84%) of the caudal DN neurons had delay activity. These neurons conveyed at least three types of information. First, their activity was often correlated, trial by trial, with saccade initiation. Correlations were found more frequently in a task that required self-timing of saccades (53% of neurons) than in a task that did not (27% of neurons). Second, the delay activity was often tuned for saccade direction (in 65% of neurons). This tuning emerged continuously during a trial. Third, the time course of delay activity associated with self-timed saccades differed significantly from that associated with visually guided saccades (in 71% of neurons). A minority of neurons had sensory-related activity. None had presaccadic bursts, in contrast to DN neurons recorded more rostrally. We conclude that caudal DN neurons convey saccade-related delay activity that may contribute to the motor preparation of when and where to move. PMID:23365182

Successive contractile periods activate mitochondria at the onset of contractions in intact rat cardiac trabeculae.

PubMed

Wüst, Rob C I; Stienen, Ger J M

2018-04-01

The rate of oxidative phosphorylation depends on the contractile activity of the heart. Cardiac mitochondrial oxidative phosphorylation is determined by free ADP concentration, mitochondrial Ca 2+ accumulation, mitochondrial enzyme activities, and Krebs cycle intermediates. The purpose of the present study was to examine the factors that limit oxidative phosphorylation upon rapid changes in contractile activity in cardiac muscle. We tested the hypotheses that prior contractile performance enhances the changes in NAD(P)H and FAD concentration upon an increase in contractile activity and that this mitochondrial "priming" depends on pyruvate dehydrogenase activity. Intact rat cardiac trabeculae were electrically stimulated at 0.5 Hz for at least 30 min. Thereafter, two equal bouts at elevated stimulation frequency of 1, 2, or 3 Hz were applied for 3 min with 3 min of 0.5-Hz stimulation in between. No discernible time delay was observed in the changes in NAD(P)H and FAD fluorescence upon rapid changes in contractile activity. The amplitudes of the rapid changes in fluorescence upon an increase in stimulation frequency (the on-transients) were smaller than upon a decrease in stimulation frequency (the off-transients). A first bout in glucose-containing superfusion solution resulted, during the second bout, in an increase in the amplitudes of the on-transients, but the off-transients remained the same. No such priming effect was observed after addition of 10 mM pyruvate. These results indicate that mitochondrial priming can be observed in cardiac muscle in situ and that pyruvate dehydrogenase activity is critically involved in the mitochondrial adaptation to increases in contractile performance. NEW & NOTEWORTHY Mitochondrial respiration increases with increased cardiac contractile activity. Similar to mitochondrial "priming" in skeletal muscle, we hypothesized that cardiac mitochondrial activity is altered upon successive bouts of contractions and depends on pyruvate dehydrogenase activity. We found altered bioenergetics upon repeated contractile periods, indicative of mitochondrial priming in rat myocardium. No effect was seen when pyruvate was added to the perfusate. As such, pyruvate dehydrogenase activity is involved in the mitochondrial adaptation to increased contractile performance.

Digital signaling decouples activation probability and population heterogeneity.

PubMed

Kellogg, Ryan A; Tian, Chengzhe; Lipniacki, Tomasz; Quake, Stephen R; Tay, Savaş

2015-10-21

Digital signaling enhances robustness of cellular decisions in noisy environments, but it is unclear how digital systems transmit temporal information about a stimulus. To understand how temporal input information is encoded and decoded by the NF-κB system, we studied transcription factor dynamics and gene regulation under dose- and duration-modulated inflammatory inputs. Mathematical modeling predicted and microfluidic single-cell experiments confirmed that integral of the stimulus (or area, concentration × duration) controls the fraction of cells that activate NF-κB in the population. However, stimulus temporal profile determined NF-κB dynamics, cell-to-cell variability, and gene expression phenotype. A sustained, weak stimulation lead to heterogeneous activation and delayed timing that is transmitted to gene expression. In contrast, a transient, strong stimulus with the same area caused rapid and uniform dynamics. These results show that digital NF-κB signaling enables multidimensional control of cellular phenotype via input profile, allowing parallel and independent control of single-cell activation probability and population heterogeneity.

Rapid disinhibition by adjustment of PV intrinsic excitability during whisker map plasticity in mouse S1.

PubMed

Gainey, Melanie A; Aman, Joseph W; Feldman, Daniel E

2018-04-20

Rapid plasticity of layer (L) 2/3 inhibitory circuits is an early step in sensory cortical map plasticity, but its cellular basis is unclear. We show that, in mice of either sex, 1 day whisker deprivation drives rapid loss of L4-evoked feedforward inhibition and more modest loss of feedforward excitation in L2/3 pyramidal (PYR) cells, increasing E-I conductance ratio. Rapid disinhibition was due to reduced L4-evoked spiking by L2/3 parvalbumin (PV) interneurons, caused by reduced PV intrinsic excitability. This included elevated PV spike threshold, associated with an increase in low-threshold, voltage activated delayed rectifier (presumed Kv1) and A-type potassium currents. Excitatory synaptic input and unitary inhibitory output of PV cells were unaffected. Functionally, the loss of feedforward inhibition and excitation were precisely coordinated in L2/3 PYR cells, so that peak feedforward synaptic depolarization remained stable. Thus, rapid plasticity of PV intrinsic excitability offsets early weakening of excitatory circuits to homeostatically stabilize synaptic potentials in PYR cells of sensory cortex. SIGNIFICANCE STATEMENT Inhibitory circuits in cerebral cortex are highly plastic, but the cellular mechanisms and functional importance of this plasticity are incompletely understood. We show that brief (1-day) sensory deprivation rapidly weakens parvalbumin (PV) inhibitory circuits by reducing the intrinsic excitability of PV neurons. This involved a rapid increase in voltage-gated potassium conductances that control near-threshold spiking excitability. Functionally, the loss of PV-mediated feedforward inhibition in L2/3 pyramidal cells was precisely balanced with the separate loss of feedforward excitation, resulting in a net homeostatic stabilization of synaptic potentials. Thus, rapid plasticity of PV intrinsic excitability implements network-level homeostasis to stabilize synaptic potentials in sensory cortex. Copyright © 2018 the authors.

Patient and health system delay among patients with pulmonary tuberculosis in Beira city, Mozambique.

PubMed

Saifodine, Abuchahama; Gudo, Paula Samo; Sidat, Mohsin; Black, James

2013-06-07

TB control is based on the rapid identification of cases and their effective treatment. However, many studies have shown that there are important delays in diagnosis and treatment of patients with TB. The purpose of this study was to assess the prevalence of and identify risk factors associated with patient delay and health system delay among newly diagnosed patients with pulmonary TB. A cross sectional study was carried out in Beira city, Mozambique between September 2009 and February 2010. Patients in the first month of treatment were consecutively selected to this study if they had a diagnosis of pulmonary TB, had no history of previous TB treatment, and were 18 years or older and provided informed consent. Data was obtained through a questionnaire administered to the patients and from patients' files. Among the 622 patients included in the study the median age was 32 years (interquartile range, 26-40) and 272 (43.7%) were females. The median total delay, patient delay and health system delay was 150 days (interquartile range, 91-240), 61 days (28-113) and 62 days (37-120), respectively. The contribution of patient delay and health system delay to total delay was similar. Farming, visiting first a traditional healer, low TB knowledge and coexistence of a chronic disease were associated with increased patient delay. More than two visits to a health facility, farming and coexistence of a chronic disease were associated with increased health system delay. This study revealed a long total delay with a similar contribution of patient delay and health system delay. To reduce the total delay in this setting we need a combination of interventions to encourage patients to seek appropriate health care earlier and to expedite TB diagnosis within the health care system.

Resistance evolution to the first generation of genetically modified Diabrotica-active Bt-maize events by western corn rootworm: management and monitoring considerations.

PubMed

Devos, Yann; Meihls, Lisa N; Kiss, József; Hibbard, Bruce E

2013-04-01

Western corn rootworm (Diabrotica virgifera virgifera; WCR) is a major coleopteran maize pest in North America and the EU, and has traditionally been managed through crop rotation and broad-spectrum soil insecticides. Genetically modified Bt-maize offers an additional management tool for WCR and has been valuable in reducing insecticide use and increasing farm income. A concern is that the widespread, repeated, and exclusive deployment of the same Bt-maize transformation event will result in the rapid evolution of resistance in WCR. This publication explores the potential of WCR to evolve resistance to plant-produced Bt-toxins from the first generation of Diabrotica-active Bt-maize events (MON 863 and MON 88017, DAS-59122-7 and MIR604), and whether currently implemented risk management strategies to delay and monitor resistance evolution are appropriate. In twelve of the twelve artificial selection experiments reported, resistant WCR populations were yielded rapidly. Field-selected resistance of WCR to Cry3Bb1 is documented in some US maize growing areas, where an increasing number of cases of unexpected damage of WCR larvae to Bt-maize MON 88017 has been reported. Currently implemented insect resistance management measures for Bt-crops usually rely on the high dose/refuge (HDR) strategy. Evidence (including laboratory, greenhouse and field data) indicates that several conditions contributing to the success of the HDR strategy may not be met for the first generation of Bt-maize events and WCR: (1) the Bt-toxins are expressed heterogeneously at a low-to-moderate dose in roots; (2) resistance alleles may be present at a higher frequency than initially assumed; (3) WCR may mate in a non-random manner; (4) resistance traits could have non-recessive inheritance; and (5) fitness costs may not necessarily be associated with resistance evolution. However, caution must be exercised when extrapolating laboratory and greenhouse results to field conditions. Model predictions suggest that a 20 % refuge of non-Diabrotica-active Bt-maize can delay resistance evolution in WCR under certain conditions. This publication concludes that further research is needed to resolve the remaining scientific uncertainty related to the appropriateness of the HDR in delaying resistance evolution in WCR, resistance monitoring is essential to detect early warning signs indicating resistance evolution in the field, and that integrated pest management reliant on multiple tactics should be deployed to ensure effective long-term corn rootworm management and sustainable use of Bt-maize.

White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy.

PubMed

Wang, B; Armstrong, J S; Reyes, M; Kulikowicz, E; Lee, J-H; Spicer, D; Bhalala, U; Yang, Z-J; Koehler, R C; Martin, L J; Lee, J K

2016-03-01

Therapeutic hypothermia is widely used to treat neonatal hypoxic ischemic (HI) brain injuries. However, potentially deleterious effects of delaying the induction of hypothermia and of rewarming on white matter injury remain unclear. We used a piglet model of HI to assess the effects of delayed hypothermia and rewarming on white matter apoptosis. Piglets underwent HI injury or sham surgery followed by normothermic or hypothermic recovery at 2h. Hypothermic groups were divided into those with no rewarming, slow rewarming at 0.5°C/h, or rapid rewarming at 4°C/h. Apoptotic cells in the subcortical white matter of the motor gyrus, corpus callosum, lateral olfactory tract, and internal capsule at 29h were identified morphologically and counted by hematoxylin & eosin staining. Cell death was verified by terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay. White matter neurons were also counted, and apoptotic cells were immunophenotyped with the oligodendrocyte marker 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). Hypothermia, slow rewarming, and rapid rewarming increased apoptosis in the subcortical white matter relative to normothermia (p<0.05). The number of white matter neurons was not lower in groups with more apoptosis after hypothermia or rapid rewarming, indicating that the apoptosis occurred among glial cells. Hypothermic piglets had more apoptosis in the lateral olfactory tract than those that were rewarmed (p<0.05). The promotion of apoptosis by hypothermia and rewarming in these regions was independent of HI. In the corpus callosum, HI piglets had more apoptosis than shams after normothermia, slow rewarming, and rapid rewarming (p<0.05). Many apoptotic cells were myelinating oligodendrocytes identified by CNPase positivity. Our results indicate that delaying the induction of hypothermia and rewarming are associated with white matter apoptosis in a piglet model of HI; in some regions these temperature effects are independent of HI. Vulnerable cells include myelinating oligodendrocytes. This study identifies a deleterious effect of therapeutic hypothermia in the developing brain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Delayed recolonization of foraminifera in a suddenly flooded tidal (former freshwater) marsh in Oregon (USA): Implications for relative sea-level reconstructions

NASA Astrophysics Data System (ADS)

Milker, Yvonne; Horton, Benjamin P.; Khan, Nicole S.; Nelson, Alan R.; Witter, Robert C.; Engelhart, Simon E.; Ewald, Michael; Brophy, Laura; Bridgeland, William T.

2016-04-01

Stratigraphic sequences beneath salt marshes along the U.S. Pacific Northwest coast preserve 7000 years of plate-boundary earthquakes at the Cascadia subduction zone. The sequences record rapid rises in relative sea level during regional coseismic subsidence caused by great earthquakes and gradual falls in relative sea level during interseismic uplift between earthquakes. These relative sea-level changes are commonly quantified using foraminiferal transfer functions with the assumption that foraminifera rapidly recolonize salt marshes and adjacent tidal flats following coseismic subsidence. The restoration of tidal inundation in the Ni-les'tun unit (NM unit) of the Bandon Marsh National Wildlife Refuge (Oregon), following extensive dike removal in August 2011, allowed us to directly observe changes in foraminiferal assemblages that occur during rapid "coseismic" (simulated by dike removal with sudden tidal flooding) and "interseismic" (stabilization of the marsh following flooding) relative sea-level changes analogous to those of past earthquake cycles. We analyzed surface sediment samples from 10 tidal stations at the restoration site (NM unit) from mudflat to high marsh, and 10 unflooded stations in the Bandon Marsh control site. Samples were collected shortly before and at 1- to 6-month intervals for 3 years after tidal restoration of the NM unit. Although tide gauge and grain-size data show rapid restoration of tides during approximately the first 3 months after dike removal, recolonization of the NM unit by foraminifera was delayed at least 10 months. Re-establishment of typical tidal foraminiferal assemblages, as observed at the control site, required 31 months after tidal restoration, with Miliammina fusca being the dominant pioneering species. If typical of past recolonizations, this delayed foraminiferal recolonization affects the accuracy of coseismic subsidence estimates during past earthquakes because significant postseismic uplift may shortly follow coseismic subsidence at subduction zones. Depending on the location and dimensions of past plate-boundary earthquake ruptures, delayed recolonization of foraminifera may result in an underestimation of coseismic subsidence for past earthquakes at Cascadia.

Growing Pains from Rapid Growth: A Historical Case Study of George Fox University from 1983 to 2003

ERIC Educational Resources Information Center

Railsback, Gary L.

2007-01-01

This article is a historical case study of George Fox University (GFU) in Newberg, Oregon. Using organizational lifecycle as a theoretical framework, George Fox University had a long and delayed childhood in that it remained a small and struggling institution for most of the 20th century, and then experienced rapid growth in the late 1980s. This…

Phasic and tonic fluctuations in brain, muscle, and skin temperatures during motivated drinking behavior in rats: physiological correlates of motivation and reward.

PubMed

Smirnov, Michael S; Kiyatkin, Eugene A

2010-01-15

Since brain metabolism is accompanied by heat production, measurement of brain temperature offers a method for assessing global alterations in metabolic neural activity. This approach, high-resolution (5-s bin) temperature recording from the nucleus accumbens (NAcc), temporal muscle, and facial skin, was used to study motivated drinking behavior in rats. Experienced animals were presented with a cup containing 5-ml of Coca-Cola(R) (Coke) beverage that resulted, within certain latencies, in initiation of a continuous chain of licking until all liquid was fully consumed. While cup presentation induced rapid, gradual NAcc temperature increase peaking at the start of drinking, temperatures slowly decreased during Coke consumption, but phasically increased again in the post-consumption period when rats were hyperactive, showing multiple interactions with an empty cup. Muscle temperatures followed a similar pattern, but the changes were weaker and delayed compared to those in the brain. Skin temperature rapidly dropped after cup presentation, steadily maintained at low levels during consumption, and slowly restored during the post-consumption period. Substitution of the expected Coke with either sugar-free Diet Coke(R) or water resulted in numerous drinking attempts but ultimately no consumption. During these tests, locomotor activation was much greater and more prolonged, brain and muscle temperatures increased monophasically, and their elevation was significantly greater than that with regular Coke tests. Food deprivation decreased drinking latencies, did not change the pattern of temperature fluctuations during Coke consumption, but temperature elevations were greater than in controls. Our data suggest sustained neural activation triggered by appetitive stimuli and associated with activational (seeking) aspects of appetitive motivated behavior. This seeking-related activation is rapidly ceased following consumption, suggesting this change as a neural correlate of reward. In contrast, inability to obtain an expected reward maintains neural activation and seeking behavior, resulting in larger deviations in physiological parameters. Published by Elsevier B.V.

Phasic and tonic fluctuations in brain, muscle and skin temperatures during motivated drinking behavior in rats: physiological correlates of motivation and reward

PubMed Central

Smirnov, Michael S.; Kiyatkin, Eugene A.

2009-01-01

Since brain metabolism is accompanied by heat production, measurement of brain temperature offers a method for assessing global alterations in metabolic neural activity. This approach, high-resolution (5-s bin) temperature recording from the nucleus accumbens (NAcc), temporal muscle, and facial skin, was used to study motivated drinking behavior in rats. Experienced animals were presented with a cup containing 5-ml of Coca-Cola® (Coke) beverage that resulted, within certain latencies, in initiation of a continuous chain of licking until all liquid was fully consumed. While cup presentation induced rapid, gradual NAcc temperature increase peaking at the start of drinking, temperatures slowly decreased during Coke consumption, but phasically increased again in the post-consumption period when rats were hyperactive, showing multiple interactions with an empty cup. Muscle temperatures followed a similar pattern, but the changes were weaker and delayed compared to those in the brain. Skin temperature rapidly dropped after cup presentation, steadily maintained at low levels during consumption, and slowly restored during the post-consumption period. Substitution of the expected Coke with either sugar-free Diet Coke® or water resulted in numerous drinking attempts but ultimately no consumption. During these tests, locomotor activation was much greater and more prolonged, brain and muscle temperatures increased monophasically, and their elevation was significantly greater than that with regular Coke tests. Food deprivation decreased drinking latencies, did not change the pattern of temperature fluctuations during Coke consumption, but temperature elevations were greater than in controls. Our data suggest sustained neural activation triggered by appetitive stimuli and associated with activational (seeking) aspects of appetitive motivated behavior. This seeking-related activation is rapidly ceased following consumption, suggesting this change as a neural correlate of reward. In contrast, inability to obtain an expected reward maintains neural activation and seeking behavior, resulting in larger deviations in physiological parameters. PMID:19932691

An iteration algorithm for optimal network flows

NASA Astrophysics Data System (ADS)

Woong, C. J.

1983-09-01

A packet switching network has the desirable feature of rapidly handling short (bursty) messages of the type often found in computer communication systems. In evaluating packet switching networks, the average time delay per packet is one of the most important measures of performance. The problem of message routing to minimize time delay is analyzed here using two approaches, called "successive saturation' and "max-slack', for various traffic requirement matrices and networks with fixed topology and link capacities.

Suppression of reaction during rapid compression and its effect on ignition delay

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

Mohamed, C.

1998-02-01

A single-shot, rapid compression machine has been used to investigate the effect of diethylamine (5 mol%) on the spontaneous ignition (or autoignition) of n-heptane and n-pentane in stoichiometric proportion in air ({psi} = 1.0). Autoignition delays were measured at compressed gas temperatures and pressures in the range 659--950 K and 9--11 atm, respectively. In addition to pressure-time data, the total light output from the chamber was recorded as a function of time using a photomultiplier positioned at the end window. Diethylamine retards the first stage of the two-stage ignition of n-heptane and n-pentane, causing a reduction in both the pressuremore » rise and the light intensity associated with the first (cool flame) stage. A longer duration of the second stage of ignition was measured. Consequently, an increase in ignition delay was observed for n-heptane throughout the temperature range 650--950 K, for which first-stage reactions persist in the compression stroke at temperatures above 850 K. The ignition delay of n-pentane was increased in the range 650--850 K by the addition of diethylamine, but was decreased at compressed gas temperatures greater than 850 K. The possible mechanisms of the inhibition of the first stage of autoignition and promotion of the second stage by diethylamine are outlined.« less

A Cooperative Traffic Control of Vehicle–Intersection (CTCVI) for the Reduction of Traffic Delays and Fuel Consumption

PubMed Central

Li, Jinjian; Dridi, Mahjoub; El-Moudni, Abdellah

2016-01-01

The problem of reducing traffic delays and decreasing fuel consumption simultaneously in a network of intersections without traffic lights is solved by a cooperative traffic control algorithm, where the cooperation is executed based on the connection of Vehicle-to-Infrastructure (V2I). This resolution of the problem contains two main steps. The first step concerns the itinerary of which intersections are chosen by vehicles to arrive at their destination from their starting point. Based on the principle of minimal travel distance, each vehicle chooses its itinerary dynamically based on the traffic loads in the adjacent intersections. The second step is related to the following proposed cooperative procedures to allow vehicles to pass through each intersection rapidly and economically: on one hand, according to the real-time information sent by vehicles via V2I in the edge of the communication zone, each intersection applies Dynamic Programming (DP) to cooperatively optimize the vehicle passing sequence with minimal traffic delays so that the vehicles may rapidly pass the intersection under the relevant safety constraints; on the other hand, after receiving this sequence, each vehicle finds the optimal speed profiles with the minimal fuel consumption by an exhaustive search. The simulation results reveal that the proposed algorithm can significantly reduce both travel delays and fuel consumption compared with other papers under different traffic volumes. PMID:27999333

The role of early detection and treatment in malaria elimination.

PubMed

Landier, Jordi; Parker, Daniel M; Thu, Aung Myint; Carrara, Verena I; Lwin, Khin Maung; Bonnington, Craig A; Pukrittayakamee, Sasithon; Delmas, Gilles; Nosten, François H

2016-07-15

Falciparum malaria persists in hard-to-reach areas or demographic groups that are missed by conventional healthcare systems but could be reached by trained community members in a malaria post (MP). The main focus of a MP is to provide uninterrupted and rapid access to rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT) too all inhabitants of a village. RDTs allow trained community members to perform malaria diagnosis accurately and prescribe appropriate treatment, reducing as much as possible any delay between the onset of fever and treatment. Early treatment with ACT and with a low-dose of primaquine prevents further transmission from human to mosquito. A functioning MP represents an essential component of any malaria elimination strategy. Implementing large-scale, high-coverage, community-based early diagnosis and treatment through MPs requires few technological innovations but relies on a very well structured organization able to train, supervise and supply MPs, to monitor activity and to perform strict malaria surveillance.

The future of rapid bridge deck replacement.

DOT National Transportation Integrated Search

2015-06-01

Replacing aging, deteriorated infrastructure often requires road closures and traffic detours which impose : inconvenience and delay on commerce and members of the motoring public. Accelerated bridge construction : techniques often use precast member...

Wheat miR9678 Affects Seed Germination by Generating Phased siRNAs and Modulating Abscisic Acid/Gibberellin Signaling[OPEN

PubMed Central

Sun, Fenglong; Cao, Jie; Huo, Na; Wuda, Bala; Du, Jinkun; Peng, Huiru; Ni, Zhongfu; Sun, Qixin

2018-01-01

Seed germination is important for grain yield and quality and rapid, near-simultaneous germination helps in cultivation; however, cultivars that germinate too readily can undergo preharvest sprouting (PHS), which causes substantial losses in areas that tend to get rain around harvest time. Moreover, our knowledge of mechanisms regulating seed germination in wheat (Triticum aestivum) remains limited. In this study, we analyzed function of a wheat-specific microRNA 9678 (miR9678), which is specifically expressed in the scutellum of developing and germinating seeds. Overexpression of miR9678 delayed germination and improved resistance to PHS in wheat through reducing bioactive gibberellin (GA) levels; miR9678 silencing enhanced germination rates. We provide evidence that miR9678 targets a long noncoding RNA (WSGAR) and triggers the generation of phased small interfering RNAs that play a role in the delay of seed germination. Finally, we found that abscisic acid (ABA) signaling proteins bind the promoter of miR9678 precursor and activate its expression, indicating that miR9678 affects germination by modulating the GA/ABA signaling. PMID:29567662

Finite-time robust stabilization of uncertain delayed neural networks with discontinuous activations via delayed feedback control.

PubMed

Wang, Leimin; Shen, Yi; Sheng, Yin

2016-04-01

This paper is concerned with the finite-time robust stabilization of delayed neural networks (DNNs) in the presence of discontinuous activations and parameter uncertainties. By using the nonsmooth analysis and control theory, a delayed controller is designed to realize the finite-time robust stabilization of DNNs with discontinuous activations and parameter uncertainties, and the upper bound of the settling time functional for stabilization is estimated. Finally, two examples are provided to demonstrate the effectiveness of the theoretical results. Copyright © 2016 Elsevier Ltd. All rights reserved.

HAMLET treatment delays bladder cancer development.

PubMed

Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

2010-04-01

HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Visual short-term memory load modulates the early attention and perception of task-irrelevant emotional faces

PubMed Central

Yang, Ping; Wang, Min; Jin, Zhenlan; Li, Ling

2015-01-01

The ability to focus on task-relevant information, while suppressing distraction, is critical for human cognition and behavior. Using a delayed-match-to-sample (DMS) task, we investigated the effects of emotional face distractors (positive, negative, and neutral faces) on early and late phases of visual short-term memory (VSTM) maintenance intervals, using low and high VSTM loads. Behavioral results showed decreased accuracy and delayed reaction times (RTs) for high vs. low VSTM load. Event-related potentials (ERPs) showed enhanced frontal N1 and occipital P1 amplitudes for negative faces vs. neutral or positive faces, implying rapid attentional alerting effects and early perceptual processing of negative distractors. However, high VSTM load appeared to inhibit face processing in general, showing decreased N1 amplitudes and delayed P1 latencies. An inverse correlation between the N1 activation difference (high-load minus low-load) and RT costs (high-load minus low-load) was found at left frontal areas when viewing negative distractors, suggesting that the greater the inhibition the lower the RT cost for negative faces. Emotional interference effect was not found in the late VSTM-related parietal P300, frontal positive slow wave (PSW) and occipital negative slow wave (NSW) components. In general, our findings suggest that the VSTM load modulates the early attention and perception of emotional distractors. PMID:26388763

Delay in breast cancer: implications for stage at diagnosis and survival.

PubMed

Caplan, Lee

2014-01-01

Breast cancer continues to be a disease with tremendous public health significance. Primary prevention of breast cancer is still not available, so efforts to promote early detection continue to be the major focus in fighting breast cancer. Since early detection is associated with decreased mortality, one would think that it is important to minimize delays in detection and diagnosis. There are two major types of delay. Patient delay is delay in seeking medical attention after self-discovering a potential breast cancer symptom. System delay is delay within the health care system in getting appointments, scheduling diagnostic tests, receiving a definitive diagnosis, and initiating therapy. Earlier studies of the consequences of delay on prognosis tended to show that increased delay is associated with more advanced stage cancers at diagnosis, thus resulting in poorer chances for survival. More recent studies have had mixed results, with some studies showing increased survival with longer delays. One hypothesis is that diagnostic difficulties could perhaps account for this survival paradox. A rapidly growing lump may suggest cancer to both doctors and patients, while a slow growing lump or other symptoms could be less obvious to them. If this is the case, then the shorter delays would be seen with the more aggressive tumors for which the prognosis is worse leading to reduced survival. It seems logical that a tumor that is more advanced at diagnosis would lead to shorter survival but the several counter-intuitive studies in this review show that it is dangerous to make assumptions.

Measuring and improving performance in incident management.

DOT National Transportation Integrated Search

2010-03-01

Traffic incidents account for about 25 percent of traffic congestion and delay. Clearing incidents rapidly is crucial in : minimizing congestion, reducing secondary crashes and improving safety for both emergency responders and : travelers. Especiall...

The clinical benefit of cardiac resynchronization therapy optimization using a device-based hemodynamic sensor in a patient with dilated cardiomyopathy: a case report.

PubMed

Volpicelli, Mario; Covino, Gregorio; Capogrosso, Paolo

2015-12-19

Results on the evolution of the clinical status of patients undergoing cardiac resynchronization therapy with a defibrillator after automatic optimization of their cardiac resynchronization therapy are scarce. We observed a rapid and important change in the clinical status of our non-responding patient following activation of a sensor capable of weekly atrioventricular and interventricular delays' optimization. A 78-year-old Caucasian man presented with dilated cardiomyopathy, left bundle branch block, a left ventricular ejection fraction of 35 %, New York Heart Association class III/IV heart failure, and paroxysmal atrial fibrillation. Our patient was implanted with a cardiac resynchronization device with a defibrillator and the SonRtip atrial lead. Right ventricular and left ventricular leads were also implanted. Because of the recurrence of atrial fibrillation, the automatic optimization was set off at discharge. Consequently, the device did not optimize atrioventricular and interventricular delays (programming at discharge: 125 ms for the atrioventricular delay and 0 ms for the interventriculardelay). Our patient was treated with an anti-arrhythmic drug. Five months after implantation, his clinical status remained impaired (left ventricular ejection fraction = 30 %). The SonR signal amplitude had also decreased from 0.52 g to 0.29 g. Nevertheless, because our patient was no longer presenting with atrial fibrillation, the anti-arrhythmic treatment was stopped and the SonR optimization system was activated. After 2 months of automatic cardiac resynchronization therapy with defibrillator optimization, our patient's clinical status had significantly improved (left ventricular ejection fraction = 60 %, New York Heart Association class II) and the SonR signal amplitude had doubled shortly after the first weekly automatic optimization. In this non-responding patient, device-based automatic cardiac resynchronization therapy optimization was shown to significantly improve his clinical status.

Enhanced Reactive Oxygen Species Scavenging by Overproduction of Superoxide Dismutase and Catalase Delays Postharvest Physiological Deterioration of Cassava Storage Roots1[C][W][OA

PubMed Central

Xu, Jia; Duan, Xiaoguang; Yang, Jun; Beeching, John R.; Zhang, Peng

2013-01-01

Postharvest physiological deterioration (PPD) of cassava (Manihot esculenta) storage roots is the result of a rapid oxidative burst, which leads to discoloration of the vascular tissues due to the oxidation of phenolic compounds. In this study, coexpression of the reactive oxygen species (ROS)-scavenging enzymes copper/zinc superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) in transgenic cassava was used to explore the intrinsic relationship between ROS scavenging and PPD occurrence. Transgenic cassava plants integrated with the expression cassette p54::MeCu/ZnSOD-35S::MeCAT1 were confirmed by Southern-blot analysis. The expression of MeCu/ZnSOD and MeCAT1 was verified by quantitative reverse transcription-polymerase chain reaction and enzymatic activity analysis both in the leaves and storage roots. Under exposure to the ROS-generating reagent methyl viologen or to hydrogen peroxide (H2O2), the transgenic plants showed higher enzymatic activities of SOD and CAT than the wild-type plants. Levels of malondialdehyde, chlorophyll degradation, lipid peroxidation, and H2O2 accumulation were dramatically reduced in the transgenic lines compared with the wild type. After harvest, the storage roots of transgenic cassava lines show a delay in their PPD response of at least 10 d, accompanied by less mitochondrial oxidation and H2O2 accumulation, compared with those of the wild type. We hypothesize that this is due to the combined ectopic expression of Cu/ZnSOD and CAT leading to an improved synergistic ROS-scavenging capacity of the roots. Our study not only sheds light on the mechanism of the PPD process but also develops an effective approach for delaying the occurrence of PPD in cassava. PMID:23344905

Enhanced reactive oxygen species scavenging by overproduction of superoxide dismutase and catalase delays postharvest physiological deterioration of cassava storage roots.

PubMed

Xu, Jia; Duan, Xiaoguang; Yang, Jun; Beeching, John R; Zhang, Peng

2013-03-01

Postharvest physiological deterioration (PPD) of cassava (Manihot esculenta) storage roots is the result of a rapid oxidative burst, which leads to discoloration of the vascular tissues due to the oxidation of phenolic compounds. In this study, coexpression of the reactive oxygen species (ROS)-scavenging enzymes copper/zinc superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) in transgenic cassava was used to explore the intrinsic relationship between ROS scavenging and PPD occurrence. Transgenic cassava plants integrated with the expression cassette p54::MeCu/ZnSOD-35S::MeCAT1 were confirmed by Southern-blot analysis. The expression of MeCu/ZnSOD and MeCAT1 was verified by quantitative reverse transcription-polymerase chain reaction and enzymatic activity analysis both in the leaves and storage roots. Under exposure to the ROS-generating reagent methyl viologen or to hydrogen peroxide (H2O2), the transgenic plants showed higher enzymatic activities of SOD and CAT than the wild-type plants. Levels of malondialdehyde, chlorophyll degradation, lipid peroxidation, and H2O2 accumulation were dramatically reduced in the transgenic lines compared with the wild type. After harvest, the storage roots of transgenic cassava lines show a delay in their PPD response of at least 10 d, accompanied by less mitochondrial oxidation and H2O2 accumulation, compared with those of the wild type. We hypothesize that this is due to the combined ectopic expression of Cu/ZnSOD and CAT leading to an improved synergistic ROS-scavenging capacity of the roots. Our study not only sheds light on the mechanism of the PPD process but also develops an effective approach for delaying the occurrence of PPD in cassava.

Sonic hedgehog signaling in spinal cord contributes to morphine-induced hyperalgesia and tolerance through upregulating brain-derived neurotrophic factor expression

PubMed Central

Song, Zhi-Jing; Miao, Shuai; Zhao, Ye; Wang, Xiu-Li; Liu, Yue-Peng

2018-01-01

Purpose Preventing opioid-induced hyperalgesia and tolerance continues to be a major clinical challenge, and the underlying mechanisms of hyperalgesia and tolerance remain elusive. Here, we investigated the role of sonic hedgehog (Shh) signaling in opioid-induced hyperalgesia and tolerance. Methods Shh signaling expression, behavioral changes, and neurochemical alterations induced by morphine were analyzed in male adult CD-1 mice with repeated administration of morphine. To investigate the contribution of Shh to morphine-induced hyperalgesia (MIH) and tolerance, Shh signaling inhibitor cyclopamine and Shh small interfering RNA (siRNA) were used. To explore the mechanisms of Shh signaling in MIH and tolerance, brain-derived neurotrophic factor (BDNF) inhibitor K252 and anti-BDNF antibody were used. Results Repeated administration of morphine produced obvious hyperalgesia and tolerance. The behavioral changes were correlated with the upregulation and activation of morphine treatment-induced Shh signaling. Pharmacologic and genetic inhibition of Shh signaling significantly delayed the generation of MIH and tolerance and associated neurochemical changes. Chronic morphine administration also induced upregulation of BDNF. Inhibiting BDNF effectively delayed the generation of MIH and tolerance. The upregulation of BDNF induced by morphine was significantly suppressed by inhibiting Shh signaling. In naïve mice, exogenous activation of Shh signaling caused a rapid increase of BDNF expression, as well as thermal hyperalgesia. Inhibiting BDNF significantly suppressed smoothened agonist-induced hyperalgesia. Conclusion These findings suggest that Shh signaling may be a critical mediator for MIH and tolerance by regulating BDNF expression. Inhibiting Shh signaling, especially during the early phase, may effectively delay or suppress MIH and tolerance. PMID:29662325

Human dendritic cell DC-SIGN and TLR-2 mediate complementary immune regulatory activities in response to Lactobacillus rhamnosus JB-1.

PubMed

Konieczna, Patrycja; Schiavi, Elisa; Ziegler, Mario; Groeger, David; Healy, Selena; Grant, Ray; O'Mahony, Liam

2015-01-01

The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses.

Human Dendritic Cell DC-SIGN and TLR-2 Mediate Complementary Immune Regulatory Activities in Response to Lactobacillus rhamnosus JB-1

PubMed Central

Konieczna, Patrycja; Schiavi, Elisa; Ziegler, Mario; Groeger, David; Healy, Selena; Grant, Ray; O’Mahony, Liam

2015-01-01

The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses. PMID:25816321

Measurement of the heaviest β-delayed 2-neutron emitter: 136Sb

NASA Astrophysics Data System (ADS)

Caballero-Folch, R.; Dillmann, I.; Taín, J. L.; Agramunt, J.; Domingo-Pardo, C.; Algora, A.; Äystö, J.; Calviño, F.; Canete, L.; Cortès, G.; Eronen, T.; Ganioglu, E.; Gelletly, W.; Gorelov, D.; Guadilla, V.; Hakala, J.; Jokinen, A.; Kankainen, A.; Kolhinen, V.; Koponen, J.; Marta, M.; Mendoza, E.; Montaner-Pizá, A.; Moore, I.; Nobs, Ch.; Orrigo, S.; Penttilä, H.; Pohjalainen, I.; Reinikainen, J.; Riego, A.; Rinta-Antila, S.; Rubio, B.; Salvador-Castiñeira, P.; Simutkin, V.; Voss, A.

2017-09-01

The β-delayed neutron emission probability, Pn, of very exotic nuclei is crucial for the understanding of nuclear structure properties of many isotopes and astrophysical processes such as the rapid neutron capture process (r-process). In addition β-delayed neutrons are important in a nuclear power reactor operated in a prompt sub-critical, delayed critical condition, as they contribute to the decay heat inducing fission reactions after a shut down. The study of neutron-rich isotopes and the measurement of β-delayed one-neutron emitters (β1n) is possible thanks to the Rare Isotope Beam (RIB) facilities, where radioactive beams allow the production of exotic nuclei of interest, which can be studied and analyzed using specific detection systems. This contribution reports two recent measurements of β-delayed neutron emitters which allowed the determination of half-lives and the neutron branching ratio of isotopes in the mass region above A = 200 and N > 126, and a second experiment which confirmed 136Sb as the heaviest double neutron emitter (β2n) measured so far.

Ergodic properties of spiking neuronal networks with delayed interactions

NASA Astrophysics Data System (ADS)

Palmigiano, Agostina; Wolf, Fred

The dynamical stability of neuronal networks, and the possibility of chaotic dynamics in the brain pose profound questions to the mechanisms underlying perception. Here we advance on the tractability of large neuronal networks of exactly solvable neuronal models with delayed pulse-coupled interactions. Pulse coupled delayed systems with an infinite dimensional phase space can be studied in equivalent systems of fixed and finite degrees of freedom by introducing a delayer variable for each neuron. A Jacobian of the equivalent system can be analytically obtained, and numerically evaluated. We find that depending on the action potential onset rapidness and the level of heterogeneities, the asynchronous irregular regime characteristic of balanced state networks loses stability with increasing delays to either a slow synchronous irregular or a fast synchronous irregular state. In networks of neurons with slow action potential onset, the transition to collective oscillations leads to an increase of the exponential rate of divergence of nearby trajectories and of the entropy production rate of the chaotic dynamics. The attractor dimension, instead of increasing linearly with increasing delay as reported in many other studies, decreases until eventually the network reaches full synchrony

Engineering fluidic delays in paper-based devices using laser direct-writing.

PubMed

He, P J W; Katis, I N; Eason, R W; Sones, C L

2015-10-21

We report the use of a new laser-based direct-write technique that allows programmable and timed fluid delivery in channels within a paper substrate which enables implementation of multi-step analytical assays. The technique is based on laser-induced photo-polymerisation, and through adjustment of the laser writing parameters such as the laser power and scan speed we can control the depth and/or the porosity of hydrophobic barriers which, when fabricated in the fluid path, produce controllable fluid delay. We have patterned these flow delaying barriers at pre-defined locations in the fluidic channels using either a continuous wave laser at 405 nm, or a pulsed laser operating at 266 nm. Using this delay patterning protocol we generated flow delays spanning from a few minutes to over half an hour. Since the channels and flow delay barriers can be written via a common laser-writing process, this is a distinct improvement over other methods that require specialist operating environments, or custom-designed equipment. This technique can therefore be used for rapid fabrication of paper-based microfluidic devices that can perform single or multistep analytical assays.

A comparison of pecking generated by serial, delay, and trace autoshaping procedures1

PubMed Central

Newlin, Robert J.; LoLordo, Vincent M.

1976-01-01

Pigeons were exposed to serial, delay, and trace autoshaping procedures. In Experiment I, all conditioned stimuli (CSs) were changes in illumination of the response key. The number of trials to acquisition of the keypeck increased from serial, to 4-sec delay, 8-sec delay, and 8-sec trace procedures, in that order. In Experiment II, which used a longer intertrial interval, trials to criterion increased from 8-sec delay, to 28-sec delay, 8-sec trace, and 28-sec trace procedures, in that order. In Experiment III, two groups received serial procedures in which the first CS was either a tone or a houselight, and the second was a keylight. The tone group acquired the key peck more rapidly than the houselight group. Early in conditioning in these experiments, and when the conditioned stimulus was a change in the keylight, there was a short latency to the onset of pecking and pecking was directed at the CS. After extensive conditioning, or when the CS was relatively diffuse, pecking still occurred, but had a longer latency and was not reliably directed toward the conditioned stimulus. PMID:16811907

A Novel Adaptive H∞ Filtering Method with Delay Compensation for the Transfer Alignment of Strapdown Inertial Navigation Systems

PubMed Central

Lyu, Weiwei

2017-01-01

Transfer alignment is always a key technology in a strapdown inertial navigation system (SINS) because of its rapidity and accuracy. In this paper a transfer alignment model is established, which contains the SINS error model and the measurement model. The time delay in the process of transfer alignment is analyzed, and an H∞ filtering method with delay compensation is presented. Then the H∞ filtering theory and the robust mechanism of H∞ filter are deduced and analyzed in detail. In order to improve the transfer alignment accuracy in SINS with time delay, an adaptive H∞ filtering method with delay compensation is proposed. Since the robustness factor plays an important role in the filtering process and has effect on the filtering accuracy, the adaptive H∞ filter with delay compensation can adjust the value of robustness factor adaptively according to the dynamic external environment. The vehicle transfer alignment experiment indicates that by using the adaptive H∞ filtering method with delay compensation, the transfer alignment accuracy and the pure inertial navigation accuracy can be dramatically improved, which demonstrates the superiority of the proposed filtering method. PMID:29182592

Emergency department patient perceptions and preferences on opt-in rapid HIV screening program components

PubMed Central

Merchant, Roland C.; Clark, Melissa A.; Seage, George R.; Mayer, Kenneth H.; DeGruttola, Victor G.; Becker, Bruce M.

2011-01-01

The aim of this investigation was to assess emergency department (ED) patients’ perceptions and preferences about an opt-in, universal, rapid HIV screening program and identify patient groups who expressed stronger beliefs about components of the testing program. From July 2005 to July 2006, ED patients in the opt-in, universal, rapid HIV screening program were interviewed in person. Multivariable regression models were used to compare participants on their beliefs about the program components. Of the 561 participants, 62.0% had previously been tested for HIV. The majority of participants (58.8%) believed the rapid and standard/conventional HIV tests to be equally accurate, 27.7% believed the rapid test to be less or much less accurate, and 8.7% believed the rapid test to be more or much more accurate. Almost two-thirds (65.1%) favored having a rapid instead of a standard/conventional HIV test, 94.6% wanted the test results within one hour, and 61.3% would be likely or very likely to undergo testing in the ED if it prolonged their ED visit. Almost all (92.5%) believed that their medical care was “not at all” delayed because of being tested, 94.1% believed that testing did “not at all” divert attention from the reason for their ED visit, and 80.9% thought that testing in the ED was “not at all” stressful. In multivariable logistic regression models, males and those with more than 12 years of formal education showed greater concerns about the rapid HIV test’s accuracy. Hispanic/Latinos, participants with governmental insurance, and those previously HIV tested were more apt to be screened for HIV even if testing delayed their ED departure. Overall, participants were highly accepting of the components of this opt-in rapid HIV screening program. However, concerns regarding the accuracy of the rapid HIV test might limit test acceptance and should be addressed during pre-test information procedures. PMID:19283644

[Benefits of using rapid HIV testing at the PMU-FLON walk-in clinic in Lausanne].

PubMed

Gilgien, W; Aubert, J; Bischoff, T; Herzig, L; Perdrix, J

2012-05-16

Lab tests are frequently used in primary care to guide patient care. This is particularly the case when a severe disorder, or one that will affect patients' initial care, needs to be excluded rapidly. At the PMU-FLON walk-in clinic the use of HIV testing as recommended by the Swiss Office of Public Health was hampered by the delay in obtaining test results. This led us to introduce rapid HIV testing which provides results within 30 minutes. Following the first 250 tests the authors discuss the results as well as the benefits of rapid HIV testing in an urban walk-in clinic.

ARABIDOPSIS TRITHORAX-RELATED3/SET DOMAIN GROUP2 is Required for the Winter-Annual Habit of Arabidopsis thaliana

PubMed Central

Yun, Jae-Young; Tamada, Yosuke; Kang, Ye Eun; Amasino, Richard M.

2012-01-01

The winter-annual habit of Arabidopsis thaliana requires active alleles of FLOWERING LOCUS C (FLC), which encodes a potent flowering repressor, and FRIGIDA (FRI), an activator of FLC. FLC activation by FRI is accompanied by an increase in specific histone modifications, such as tri-methylation of histone H3 at lysine 4 (H3K4me3), and requires three H3K4 methyltransferases, the Drosophila Trithorax-class ARABIDOPSIS TRITHORAX1 (ATX1) and ATX2, and yeast Set1-class ATX-RELATED7/SET DOMAIN GROUP25 (ATXR7/SDG25). However, lesions in all of these genes failed to suppress the enhanced FLC expression caused by FRI completely, suggesting that another H3K4 methyltransferase may participate in the FLC activation. Here, we show that ATXR3/SDG2, which is a member of a novel class of H3K4 methyltransferases, also contributes to FLC activation. An ATXR3 lesion suppressed the enhanced FLC expression and delayed flowering caused by an active allele of FRI in non-vernalized plants. The decrease in FLC expression in atxr3 mutants was accompanied by reduced H3K4me3 levels at FLC chromatin. We also found that the rapid flowering of atxr3 was epistatic to that of atxr7, suggesting that ATXR3 functions in FLC activation in sequence with ATXR7. Our results indicate that the novel-class H3K4 methyltransferase, ATXR3, is a transcriptional activator that plays a role in the FLC activation and establishing the winter-annual habit. In addition, ATXR3 also contributes to the activation of other FLC clade members, such as FLOWERING LOCUS M/MADS AFFECTING FLOWERING1 (FLM/MAF1) and MAF5, at least partially explaining the ATXR3 function in delayed flowering caused by non-inductive photoperiods. PMID:22378382

Effect of immediate or delayed light activation on curing kinetics and shrinkage stress of dual-cure resin cements.

PubMed

Faria-e-Silva, Andre; Boaro, Leticia; Braga, Roberto; Piva, Evandro; Arias, Vanessa; Martins, Luis

2011-01-01

This study evaluated the effect of light activation (absence, immediate, or delayed) on conversion kinetics and polymerization stress of three commercial dual-cured resin cements (Enforce, RelyX ARC, and Panavia F). Degree of conversion (DC) was monitored for 30 minutes using real-time near–Fourier transform infrared spectroscopy. The cement was mixed, placed on the spectrometer sample holder, and light activated either immediately or after five minutes (delayed light activation). When no light activation was performed, the materials were protected from light exposure (control). DC was evaluated at five and 30 minutes postmixture. Maximum rates of polymerization (Rp(max)) were obtained from the first derivative of the DC vs time curve. Polymerization stress was monitored for 30 minutes in 1-mm-thick specimens inserted between two cylinders attached to a universal testing machine. Data were submitted to analysis of variance/Tukey tests (α=0.05). Immediate light activation promoted the highest DC at five minutes. At 30 minutes, only RelyX ARC did not present a significant difference in DC between activation modes. Enforce and Panavia F presented higher Rp(max) for immediate and delayed light-activation, respectively. RelyX ARC showed similar Rp(max) for all activation modes. The absence of light activation resulted in the lowest stress followed by delayed light activation, while immediate light activation led to the highest values. RelyX ARC showed higher stress than Enforce, while the stress of Panavia F was similar to that of the others. Delayed light activation reduced the polymerization stress of the resin cements tested without jeopardizing DC.

Induction of a G1-S checkpoint in fission yeast.

PubMed

Bøe, Cathrine A; Krohn, Marit; Rødland, Gro Elise; Capiaghi, Christoph; Maillard, Olivier; Thoma, Fritz; Boye, Erik; Grallert, Beáta

2012-06-19

Entry into S phase is carefully regulated and, in most organisms, under the control of a G(1)-S checkpoint. We have previously described a G(1)-S checkpoint in fission yeast that delays formation of the prereplicative complex at chromosomal replication origins after exposure to UV light (UVC). This checkpoint absolutely depends on the Gcn2 kinase. Here, we explore the signal for activation of the Gcn2-dependent G(1)-S checkpoint in fission yeast. If some form of DNA damage can activate the checkpoint, deficient DNA repair should affect the length of the checkpoint-induced delay. We find that the cell-cycle delay differs in repair-deficient mutants from that in wild-type cells. However, the duration of the delay depends not only on the repair capacity of the cells, but also on the nature of the repair deficiency. First, the delay is abolished in cells that are deficient in the early steps of repair. Second, the delay is prolonged in repair mutants that fail to complete repair after the incision stage. We conclude that the G(1)-S delay depends on damage to the DNA and that the activating signal derives not from the initial DNA damage, but from a repair intermediate(s). Surprisingly, we find that activation of Gcn2 does not depend on the processing of DNA damage and that activated Gcn2 alone is not sufficient to delay entry into S phase in UVC-irradiated cells. Thus, the G(1)-S delay depends on at least two different inputs.

Molecular and Cellular Mechanisms of Rapid-Acting Antidepressants Ketamine and Scopolamine

PubMed Central

Wohleb, Eric S.; Gerhard, Danielle; Thomas, Alex; Duman, Ronald S.

2017-01-01

Major depressive disorder (MDD) is a prevalent neuropsychiatric disease that causes profound social and economic burdens. The impact of MDD is compounded by the limited therapeutic efficacy and delay of weeks to months of currently available medications. These issues highlight the need for more efficacious and faster-acting treatments to alleviate the burdens of MDD. Recent breakthroughs demonstrate that certain drugs, including ketamine and scopolamine, produce rapid and long-lasting antidepressant effects in MDD patients. Moreover, preclinical work has shown that the antidepressant actions of ketamine and scopolamine in rodent models are caused by an increase of extracellular glutamate, elevated BDNF, activation of the mammalian target of rapamycin complex 1 (mTORC1) cascade, and increased number and function of spine synapses in the prefrontal cortex (PFC). Here we review studies showing that both ketamine and scopolamine elicit rapid antidepressant effects through converging molecular and cellular mechanisms in the PFC. In addition, we discuss evidence that selective antagonists of NMDA and muscarinic acetylcholine (mACh) receptor subtypes (i.e., NR2B and M1-AChR) in the PFC produce comparable antidepressant responses. Furthermore, we discuss evidence that ketamine and scopolamine antagonize inhibitory interneurons in the PFC leading to disinhibition of pyramidal neurons and increased extracellular glutamate that promotes the rapid antidepressant responses to these agents. Collectively, these studies indicate that specific NMDA and mACh receptor subtypes on GABAergic interneurons are promising targets for novel rapid-acting antidepressant therapies. PMID:26955968

Neural activation during delay discounting is associated with 6-month change in risky sexual behavior in adolescents.

PubMed

Gardiner, Casey K; Karoly, Hollis C; Thayer, Rachel E; Gillman, Arielle S; Sabbineni, Amithrupa; Bryan, Angela D

2018-04-19

Identifying cognitive and neural mechanisms of decision making in adolescence can enhance understanding of, and interventions to reduce, risky health behaviors in adolescence. Delay discounting, or the propensity to discount the magnitude of temporally distal rewards, has been associated with diverse health risk behaviors, including risky sex. This cognitive process involves recruitment of reward and cognitive control brain regions, which develop on different trajectories in adolescence and are also implicated in real-world risky decision making. However, no extant research has examined how neural activation during delay discounting is associated with adolescents' risky sexual behavior. To determine whether a relationship exists between adolescents' risky sexual behavior and neural activation during delay discounting. Adolescent participants completed a delay discounting paradigm during functional magnetic resonance imaging (fMRI) scanning, and they reported risky sexual behavior at baseline, 3-, 6-, 9-, and 12-month follow-up time points. Latent growth curve models were employed to determine relationships between brain activation during delay discounting and change in risky sexual behavior over time. Greater activation in brain regions associated with reward and cognitive control (caudate, putamen, nucleus accumbens, anterior cingulate, insula, orbitofrontal cortex, inferior frontal gyrus, dorsolateral prefrontal cortex) during delay discounting was associated with lower mean levels of risky sexual behavior but greater growth over the period from baseline to 6 months. Neural activation during delay discounting is cross-sectionally and prospectively associated with risky sexual behavior in adolescence, highlighting a neural basis of risky decision-making as well as opportunities for early identification and intervention.

Enterprise Information System Integration Technology

NASA Astrophysics Data System (ADS)

Tanaka, Tetsuo; Yumoto, Masaki; Itsuki, Rei

In the current rapidly changing business environment, companies need to be efficient and agile to survive and thrive. That is why flexible systems integration is urgent and crucial concern for any enterprise. For the meanwhile, systems integration technology is getting more complicated, and middleware types are beginning blur for decades. We sort system integration into four different types, “Delayed Federation", “Real-time Federation", “Delayed Integration", and “Real-time Integration". We also outline appropriate technology and architecture for each type.

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)

PubMed Central

Saver, Jeffrey L.; Zaidat, Osama O.; Jahan, Reza; Aziz-Sultan, Mohammad Ali; Klucznik, Richard P.; Haussen, Diogo C.; Hellinger, Frank R.; Yavagal, Dileep R.; Yao, Tom L.; Liebeskind, David S.; Jadhav, Ashutosh P.; Gupta, Rishi; Hassan, Ameer E.; Martin, Coleman O.; Bozorgchami, Hormozd; Kaushal, Ritesh; Nogueira, Raul G.; Gandhi, Ravi H.; Peterson, Eric C.; Dashti, Shervin R.; Given, Curtis A.; Mehta, Brijesh P.; Deshmukh, Vivek; Starkman, Sidney; Linfante, Italo; McPherson, Scott H.; Kvamme, Peter; Grobelny, Thomas J.; Hussain, Muhammad S.; Thacker, Ike; Vora, Nirav; Chen, Peng Roc; Monteith, Stephen J.; Ecker, Robert D.; Schirmer, Clemens M.; Sauvageau, Eric; Abou-Chebl, Alex; Derdeyn, Colin P.; Maidan, Lucian; Badruddin, Aamir; Siddiqui, Adnan H.; Dumont, Travis M.; Alhajeri, Abdulnasser; Taqi, M. Asif; Asi, Khaled; Carpenter, Jeffrey; Boulos, Alan; Jindal, Gaurav; Puri, Ajit S.; Chitale, Rohan; Deshaies, Eric M.; Robinson, David H.; Kallmes, David F.; Baxter, Blaise W.; Jumaa, Mouhammad A.; Sunenshine, Peter; Majjhoo, Aniel; English, Joey D.; Suzuki, Shuichi; Fessler, Richard D.; Delgado Almandoz, Josser E.; Martin, Jerry C.; Mueller-Kronast, Nils H.

2017-01-01

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640. PMID:28943516

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

PubMed

Froehler, Michael T; Saver, Jeffrey L; Zaidat, Osama O; Jahan, Reza; Aziz-Sultan, Mohammad Ali; Klucznik, Richard P; Haussen, Diogo C; Hellinger, Frank R; Yavagal, Dileep R; Yao, Tom L; Liebeskind, David S; Jadhav, Ashutosh P; Gupta, Rishi; Hassan, Ameer E; Martin, Coleman O; Bozorgchami, Hormozd; Kaushal, Ritesh; Nogueira, Raul G; Gandhi, Ravi H; Peterson, Eric C; Dashti, Shervin R; Given, Curtis A; Mehta, Brijesh P; Deshmukh, Vivek; Starkman, Sidney; Linfante, Italo; McPherson, Scott H; Kvamme, Peter; Grobelny, Thomas J; Hussain, Muhammad S; Thacker, Ike; Vora, Nirav; Chen, Peng Roc; Monteith, Stephen J; Ecker, Robert D; Schirmer, Clemens M; Sauvageau, Eric; Abou-Chebl, Alex; Derdeyn, Colin P; Maidan, Lucian; Badruddin, Aamir; Siddiqui, Adnan H; Dumont, Travis M; Alhajeri, Abdulnasser; Taqi, M Asif; Asi, Khaled; Carpenter, Jeffrey; Boulos, Alan; Jindal, Gaurav; Puri, Ajit S; Chitale, Rohan; Deshaies, Eric M; Robinson, David H; Kallmes, David F; Baxter, Blaise W; Jumaa, Mouhammad A; Sunenshine, Peter; Majjhoo, Aniel; English, Joey D; Suzuki, Shuichi; Fessler, Richard D; Delgado Almandoz, Josser E; Martin, Jerry C; Mueller-Kronast, Nils H

2017-12-12

Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640. © 2017 The Authors.

A novel live cell imaging system reveals a reversible hydrostatic pressure impact on cell cycle progression.

PubMed

Brooker, Holly R; Gyamfi, Irene A; Wieckowska, Agnieszka; Brooks, Nicholas J; Mulvihill, Daniel P; Geeves, Michael A

2018-06-21

Life is dependent upon the ability of a cell to rapidly respond to changes in environment. Small perturbations in local environments change the ability of molecules to interact and hence communicate. Hydrostatic pressure provides a rapid non-invasive, fully-reversible method for modulating affinities between molecules both in vivo and in vitro We have developed a simple fluorescence imaging chamber that allows intracellular protein dynamics and molecular events to be followed at pressures up to 200 bar in living cells. Using yeast we investigate the impact of hydrostatic pressure upon cell growth and cell cycle progression. While 100 bar has no affect upon viability, it induces a delay in chromosome segregation, resulting in the accumulation of long-undivided-bent cells, consistent with disruption of the cytoskeletons. This delay is independent of stress signalling and induces synchronisation of cell-cycle progression. Equivalent affects were observed in Candida albicans , with pressure inducing a reversible cell-cycle delay and hyphal growth. We present a simple novel non-invasive fluorescence microscopy based approach to transiently impact molecular dynamics to visualise, dissect and study signalling pathways and cellular processes in living cells. © 2018. Published by The Company of Biologists Ltd.

Experiencing leisure in later life: a study of retirees and activity in Singapore.

PubMed

Thang, Leng Leng

2005-12-01

In a society faced with rapid aging and extended life expectancy, older persons in Singapore are just beginning to see retirement as a new era in their lives that can be quite different from the later life experiences of their own parents. Presenting an ethnographic case study of one of the first retiree activity centers in Singapore, this article will examine (a) how older persons cope with retirement, social, and cultural norms, and (b) the strategies older adults adopt in order to stay relevant in a fast-paced society. The ethnographic study shows that extrafamilial social support and opportunities for new experiences in learning and leisure contribute significantly to positive and active living in old age. Although the discussion of aging in Asia usually focuses on the problems of health, finances, and caregiving, the present study suggests the need for policy makers to pay equal attention to issues such as activity participation in old age. Participation in leisure activities may act as a preventive measure to delay the onset of aging-related problems, while at the same time enhancing life satisfaction among seniors.

Bubbling in delay-coupled lasers.

PubMed

Flunkert, V; D'Huys, O; Danckaert, J; Fischer, I; Schöll, E

2009-06-01

We theoretically study chaos synchronization of two lasers which are delay coupled via an active or a passive relay. While the lasers are synchronized, their dynamics is identical to a single laser with delayed feedback for a passive relay and identical to two delay-coupled lasers for an active relay. Depending on the coupling parameters the system exhibits bubbling, i.e., noise-induced desynchronization, or on-off intermittency. We associate the desynchronization dynamics in the coherence collapse and low-frequency fluctuation regimes with the transverse instability of some of the compound cavity's antimodes. Finally, we demonstrate how, by using an active relay, bubbling can be suppressed.

Ablation of the Ferroptosis Inhibitor Glutathione Peroxidase 4 in Neurons Results in Rapid Motor Neuron Degeneration and Paralysis.

PubMed

Chen, Liuji; Hambright, William Sealy; Na, Ren; Ran, Qitao

2015-11-20

Glutathione peroxidase 4 (GPX4), an antioxidant defense enzyme active in repairing oxidative damage to lipids, is a key inhibitor of ferroptosis, a non-apoptotic form of cell death involving lipid reactive oxygen species. Here we show that GPX4 is essential for motor neuron health and survival in vivo. Conditional ablation of Gpx4 in neurons of adult mice resulted in rapid onset and progression of paralysis and death. Pathological inspection revealed that the paralyzed mice had a dramatic degeneration of motor neurons in the spinal cord but had no overt neuron degeneration in the cerebral cortex. Consistent with the role of GPX4 as a ferroptosis inhibitor, spinal motor neuron degeneration induced by Gpx4 ablation exhibited features of ferroptosis, including no caspase-3 activation, no TUNEL staining, activation of ERKs, and elevated spinal inflammation. Supplementation with vitamin E, another inhibitor of ferroptosis, delayed the onset of paralysis and death induced by Gpx4 ablation. Also, lipid peroxidation and mitochondrial dysfunction appeared to be involved in ferroptosis of motor neurons induced by Gpx4 ablation. Taken together, the dramatic motor neuron degeneration and paralysis induced by Gpx4 ablation suggest that ferroptosis inhibition by GPX4 is essential for motor neuron health and survival in vivo. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice.

PubMed

Liu, Karen J; Arron, Joseph R; Stankunas, Kryn; Crabtree, Gerald R; Longaker, Michael T

2007-03-01

Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interacts with many different pathways, its specific developmental roles remain unclear. We have discovered a genetic requirement for GSK-3beta in midline development. Homozygous null mice display cleft palate, incomplete fusion of the ribs at the midline and bifid sternum as well as delayed sternal ossification. Using a chemically regulated allele of GSK-3beta (ref. 6), we have defined requirements for GSK-3beta activity during discrete temporal windows in palatogenesis and skeletogenesis. The rapamycin-dependent allele of GSK-3beta produces GSK-3beta fused to a tag, FRB* (FKBP/rapamycin binding), resulting in a rapidly destabilized chimaeric protein. In the absence of drug, GSK-3beta(FRB)*(/FRB)* mutants appear phenotypically identical to GSK-3beta-/- mutants. In the presence of drug, GSK-3betaFRB* is rapidly stabilized, restoring protein levels and activity. Using this system, mutant phenotypes were rescued by restoring endogenous GSK-3beta activity during two distinct periods in gestation. This technology provides a powerful tool for defining windows of protein function during development.

New exponential synchronization criteria for time-varying delayed neural networks with discontinuous activations.

PubMed

Cai, Zuowei; Huang, Lihong; Zhang, Lingling

2015-05-01

This paper investigates the problem of exponential synchronization of time-varying delayed neural networks with discontinuous neuron activations. Under the extended Filippov differential inclusion framework, by designing discontinuous state-feedback controller and using some analytic techniques, new testable algebraic criteria are obtained to realize two different kinds of global exponential synchronization of the drive-response system. Moreover, we give the estimated rate of exponential synchronization which depends on the delays and system parameters. The obtained results extend some previous works on synchronization of delayed neural networks not only with continuous activations but also with discontinuous activations. Finally, numerical examples are provided to show the correctness of our analysis via computer simulations. Our method and theoretical results have a leading significance in the design of synchronized neural network circuits involving discontinuous factors and time-varying delays. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Unifying Mechanism for Cancer Cell Death through Ion Channel Activation by HAMLET

PubMed Central

Storm, Petter; Kjaer Klausen, Thomas; Trulsson, Maria; Ho CS, James; Dosnon, Marion; Westergren, Tomas; Chao, Yinxia; Rydström, Anna; Yang, Henry; Pedersen, Stine Falsig; Svanborg, Catharina

2013-01-01

Ion channels and ion fluxes control many aspects of tissue homeostasis. During oncogenic transformation, critical ion channel functions may be perturbed but conserved tumor specific ion fluxes remain to be defined. Here we used the tumoricidal protein-lipid complex HAMLET as a probe to identify ion fluxes involved in tumor cell death. We show that HAMLET activates a non-selective cation current, which reached a magnitude of 2.74±0.88 nA within 1.43±0.13 min from HAMLET application. Rapid ion fluxes were essential for HAMLET-induced carcinoma cell death as inhibitors (amiloride, BaCl2), preventing the changes in free cellular Na+ and K+ concentrations also prevented essential steps accompanying carcinoma cell death, including changes in morphology, uptake, global transcription, and MAP kinase activation. Through global transcriptional analysis and phosphorylation arrays, a strong ion flux dependent p38 MAPK response was detected and inhibition of p38 signaling delayed HAMLET-induced death. Healthy, differentiated cells were resistant to HAMLET challenge, which was accompanied by innate immunity rather than p38-activation. The results suggest, for the first time, a unifying mechanism for the initiation of HAMLET’s broad and rapid lethal effect on tumor cells. These findings are particularly significant in view of HAMLET’s documented therapeutic efficacy in human studies and animal models. The results also suggest that HAMLET offers a two-tiered therapeutic approach, killing cancer cells while stimulating an innate immune response in surrounding healthy tissues. PMID:23505537

A unifying mechanism for cancer cell death through ion channel activation by HAMLET.

PubMed

Storm, Petter; Klausen, Thomas Kjaer; Trulsson, Maria; Ho C S, James; Dosnon, Marion; Westergren, Tomas; Chao, Yinxia; Rydström, Anna; Yang, Henry; Pedersen, Stine Falsig; Svanborg, Catharina

2013-01-01

Ion channels and ion fluxes control many aspects of tissue homeostasis. During oncogenic transformation, critical ion channel functions may be perturbed but conserved tumor specific ion fluxes remain to be defined. Here we used the tumoricidal protein-lipid complex HAMLET as a probe to identify ion fluxes involved in tumor cell death. We show that HAMLET activates a non-selective cation current, which reached a magnitude of 2.74±0.88 nA within 1.43±0.13 min from HAMLET application. Rapid ion fluxes were essential for HAMLET-induced carcinoma cell death as inhibitors (amiloride, BaCl2), preventing the changes in free cellular Na(+) and K(+) concentrations also prevented essential steps accompanying carcinoma cell death, including changes in morphology, uptake, global transcription, and MAP kinase activation. Through global transcriptional analysis and phosphorylation arrays, a strong ion flux dependent p38 MAPK response was detected and inhibition of p38 signaling delayed HAMLET-induced death. Healthy, differentiated cells were resistant to HAMLET challenge, which was accompanied by innate immunity rather than p38-activation. The results suggest, for the first time, a unifying mechanism for the initiation of HAMLET's broad and rapid lethal effect on tumor cells. These findings are particularly significant in view of HAMLET's documented therapeutic efficacy in human studies and animal models. The results also suggest that HAMLET offers a two-tiered therapeutic approach, killing cancer cells while stimulating an innate immune response in surrounding healthy tissues.

High-precision coseismic displacement estimation with a single-frequency GPS receiver

NASA Astrophysics Data System (ADS)

Guo, Bofeng; Zhang, Xiaohong; Ren, Xiaodong; Li, Xingxing

2015-07-01

To improve the performance of Global Positioning System (GPS) in the earthquake/tsunami early warning and rapid response applications, minimizing the blind zone and increasing the stability and accuracy of both the rapid source and rupture inversion, the density of existing GPS networks must be increased in the areas at risk. For economic reasons, low-cost single-frequency receivers would be preferable to make the sparse dual-frequency GPS networks denser. When using single-frequency GPS receivers, the main problem that must be solved is the ionospheric delay, which is a critical factor when determining accurate coseismic displacements. In this study, we introduce a modified Satellite-specific Epoch-differenced Ionospheric Delay (MSEID) model to compensate for the effect of ionospheric error on single-frequency GPS receivers. In the MSEID model, the time-differenced ionospheric delays observed from a regional dual-frequency GPS network to a common satellite are fitted to a plane rather than part of a sphere, and the parameters of this plane are determined by using the coordinates of the stations. When the parameters are known, time-differenced ionospheric delays for a single-frequency GPS receiver could be derived from the observations of those dual-frequency receivers. Using these ionospheric delay corrections, coseismic displacements of a single-frequency GPS receiver can be accurately calculated based on time-differenced carrier-phase measurements in real time. The performance of the proposed approach is validated using 5 Hz GPS data collected during the 2012 Nicoya Peninsula Earthquake (Mw 7.6, 2012 September 5) in Costa Rica. This shows that the proposed approach improves the accuracy of the displacement of a single-frequency GPS station, and coseismic displacements with an accuracy of a few centimetres are achieved over a 10-min interval.

Time Delay of CGM Sensors

PubMed Central

Schmelzeisen-Redeker, Günther; Schoemaker, Michael; Kirchsteiger, Harald; Freckmann, Guido; Heinemann, Lutz; del Re, Luigi

2015-01-01

Background: Continuous glucose monitoring (CGM) is a powerful tool to support the optimization of glucose control of patients with diabetes. However, CGM systems measure glucose in interstitial fluid but not in blood. Rapid changes in one compartment are not accompanied by similar changes in the other, but follow with some delay. Such time delays hamper detection of, for example, hypoglycemic events. Our aim is to discuss the causes and extent of time delays and approaches to compensate for these. Methods: CGM data were obtained in a clinical study with 37 patients with a prototype glucose sensor. The study was divided into 5 phases over 2 years. In all, 8 patients participated in 2 phases separated by 8 months. A total number of 108 CGM data sets including raw signals were used for data analysis and were processed by statistical methods to obtain estimates of the time delay. Results: Overall mean (SD) time delay of the raw signals with respect to blood glucose was 9.5 (3.7) min, median was 9 min (interquartile range 4 min). Analysis of time delays observed in the same patients separated by 8 months suggests a patient dependent delay. No significant correlation was observed between delay and anamnestic or anthropometric data. The use of a prediction algorithm reduced the delay by 4 minutes on average. Conclusions: Prediction algorithms should be used to provide real-time CGM readings more consistent with simultaneous measurements by SMBG. Patient specificity may play an important role in improving prediction quality. PMID:26243773

A Computer Simulation Analysis of Conventional and Trunked Land Mobile Radio Systems at Wright Patterson Air Force Base

DTIC Science & Technology

1988-11-01

ATRIB(1) .EQ.21,CD20; ACTIVITY,ND,ATRIB(1) .EQ.22, CD22 ; ACTIVITY,MD,ATRIB(l) .EQ.23,CD23; ACTIVITY,MD,ATRIB(1).EQ.24,CD24; ACTIVITY,MD,ATRIB(1) .EQ.25...TCD; CD20 COLCT,INT(5),FLT 20 CH DELAY; ACT,, ,TCD; CD21 COLCT,INT(5),FLT 21 CH DELAY; ACT,, ,TCD; CD22 COLCT,INT(5),FLT 22 CH DELAY; ACT,, ,TCD

Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier K+ current of human atria by inhibiting EGF receptor tyrosine kinase.

PubMed

Xiao, Guo-Sheng; Zhang, Yan-Hui; Wu, Wei; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong

2017-03-01

The ultra-rapidly activating delayed rectifier K + current I Kur (encoded by K v 1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). Whole-cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial I Kur and hKv1.5 channels stably expressed in HEK 293 cells. Human atrial I Kur was decreased by genistein (a broad-spectrum PTK inhibitor) and AG556 (a highly selective EGFR TK inhibitor) in a concentration-dependent manner. Inhibition of I Kur induced by 30 μM genistein or 10 μM AG556 was significantly reversed by 1 mM orthovanadate (a protein tyrosine phosphatase inhibitor). Similar results were observed in HEK 293 cells stably expressing hK v 1.5 channels. On the other hand, the Src family kinase inhibitor PP2 (1 μM) slightly enhanced I Kur and hK v 1.5 current, and the current increase was also reversed by orthovanadate. Immunoprecipitation and Western blotting analysis showed that genistein, AG556, and PP2 decreased tyrosine phosphorylation of hK v 1.5 channels and that the decrease was countered by orthovanadate. The PTK inhibitors genistein and AG556 decrease human atrial I Kur and cloned hK v 1.5 channels by inhibiting EGFR TK, whereas the Src kinase inhibitor PP2 increases I Kur and hK v 1.5 current. These results imply that EGFR TK and the soluble Src kinases may have opposite effects on human atrial I Kur . © 2017 The British Pharmacological Society.

People Use their Knowledge of Common Events to Understand Language, and Do So as Quickly as Possible

PubMed Central

McRae, Ken; Matsuki, Kazunaga

2011-01-01

People possess a great deal of knowledge about how the world works, and it is undoubtedly true that adults use this knowledge when understanding and producing language. However, psycholinguistic theories differ regarding whether this extra-linguistic pragmatic knowledge can be activated and used immediately, or only after a delay. The authors present research that investigates whether people immediately use their generalized knowledge of common events when understanding language. This research demonstrates that (i) individual isolated words immediately activate event-based knowledge; (ii) combinations of words in sentences immediately constrain people’s event-based expectations for concepts that are upcoming in language; (iii) syntax modulates people’s expectations for ensuing concepts; and (iv) event-based knowledge can produce expectations for ensuing syntactic structures. It is concluded that theories of sentence comprehension must allow for the rapid dynamic interplay among these sources of information. PMID:22125574

Sequential biodegradation of TNT, RDX and HMX in a mixture.

PubMed

Sagi-Ben Moshe, S; Ronen, Z; Dahan, O; Weisbrod, N; Groisman, L; Adar, E; Nativ, R

2009-01-01

We describe TNT's inhibition of RDX and HMX anaerobic degradation in contaminated soil containing indigenous microbial populations. Biodegradation of RDX or HMX alone was markedly faster than their degradation in a mixture with TNT, implying biodegradation inhibition by the latter. The delay caused by the presence of TNT continued even after its disappearance and was linked to the presence of its intermediate, tetranitroazoxytoluene. PCR-DGGE analysis of cultures derived from the soil indicated a clear reduction in microbial biomass and diversity with increasing TNT concentration. At high-TNT concentrations (30 and 90 mg/L), only a single band, related to Clostridium nitrophenolicum, was observed after 3 days of incubation. We propose that the mechanism of TNT inhibition involves a cytotoxic effect on the RDX- and HMX-degrading microbial population. TNT inhibition in the top active soil can therefore initiate rapid transport of RDX and HMX to the less active subsurface and groundwater.

Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes

PubMed Central

Glennie, Nelson D.; Volk, Susan W.

2017-01-01

Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells. This protection occurs rapidly after challenge, and requires the recruitment and activation of inflammatory monocytes, which limit parasites by production of both reactive oxygen species and nitric oxide. Overall, these data highlight a novel role for tissue-resident memory cells in recruiting and activating inflammatory monocytes, and underscore the central role that skin-resident T cells play in immunity to cutaneous leishmaniasis. PMID:28419151

Ferroelectric switch for a high-power Ka-band active pulse compressor

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

Hirshfield, Jay L.

2013-12-18

Results are presented for design of a high-power microwave switch for operation at 34.3 GHz, intended for use in an active RF pulse compressor. The active element in the switch is a ring of ferroelectric material, whose dielectric constant can be rapidly changed by application of a high-voltage pulse. As envisioned, two of these switches would be built into a pair of delay lines, as in SLED-II at SLAC, so as to allow 30-MW μs-length Ka-band pulses to be compressed in time by a factor-of-9 and multiplied in amplitude to generate 200 MW peak power pulses. Such high-power pulses couldmore » be used for testing and evaluation of high-gradient mm-wave accelerator structures, for example. Evaluation of the switch design was carried out with an X-band (11.43 GHz) prototype, built to incorporate all the features required for the Ka-band version.« less

Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

PubMed Central

Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

Implementation of a national anti-tuberculosis drug resistance survey in Tanzania.

PubMed

Chonde, Timothy M; Doulla, Basra; van Leth, Frank; Mfinanga, Sayoki G M; Range, Nyagosya; Lwilla, Fred; Mfaume, Saidi M; van Deun, Armand; Zignol, Matteo; Cobelens, Frank G; Egwaga, Saidi M

2008-12-30

A drug resistance survey is an essential public health management tool for evaluating and improving the performance of National Tuberculosis control programmes. The current manuscript describes the implementation of the first national drug resistance survey in Tanzania. Description of the implementation process of a national anti-tuberculosis drug resistance survey in Tanzania, in relation to the study protocol and Standard Operating Procedures. Factors contributing positively to the implementation of the survey were a continuous commitment of the key stakeholders, the existence of a well organized National Tuberculosis Programme, and a detailed design of cluster-specific arrangements for rapid sputum transportation. Factors contributing negatively to the implementation were a long delay between training and actual survey activities, limited monitoring of activities, and an unclear design of the data capture forms leading to difficulties in form-filling. Careful preparation of the survey, timing of planned activities, a strong emphasis on data capture tools and data management, and timely supervision are essential for a proper implementation of a national drug resistance survey.

Reactivation in Working Memory: An Attractor Network Model of Free Recall

PubMed Central

Lansner, Anders; Marklund, Petter; Sikström, Sverker; Nilsson, Lars-Göran

2013-01-01

The dynamic nature of human working memory, the general-purpose system for processing continuous input, while keeping no longer externally available information active in the background, is well captured in immediate free recall of supraspan word-lists. Free recall tasks produce several benchmark memory phenomena, like the U-shaped serial position curve, reflecting enhanced memory for early and late list items. To account for empirical data, including primacy and recency as well as contiguity effects, we propose here a neurobiologically based neural network model that unifies short- and long-term forms of memory and challenges both the standard view of working memory as persistent activity and dual-store accounts of free recall. Rapidly expressed and volatile synaptic plasticity, modulated intrinsic excitability, and spike-frequency adaptation are suggested as key cellular mechanisms underlying working memory encoding, reactivation and recall. Recent findings on the synaptic and molecular mechanisms behind early LTP and on spiking activity during delayed-match-to-sample tasks support this view. PMID:24023690

Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.

PubMed

Araya, Romina E; Jury, Jennifer; Bondar, Constanza; Verdu, Elena F; Chirdo, Fernando G

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.

Reactivation in working memory: an attractor network model of free recall.

PubMed

Lansner, Anders; Marklund, Petter; Sikström, Sverker; Nilsson, Lars-Göran

2013-01-01

The dynamic nature of human working memory, the general-purpose system for processing continuous input, while keeping no longer externally available information active in the background, is well captured in immediate free recall of supraspan word-lists. Free recall tasks produce several benchmark memory phenomena, like the U-shaped serial position curve, reflecting enhanced memory for early and late list items. To account for empirical data, including primacy and recency as well as contiguity effects, we propose here a neurobiologically based neural network model that unifies short- and long-term forms of memory and challenges both the standard view of working memory as persistent activity and dual-store accounts of free recall. Rapidly expressed and volatile synaptic plasticity, modulated intrinsic excitability, and spike-frequency adaptation are suggested as key cellular mechanisms underlying working memory encoding, reactivation and recall. Recent findings on the synaptic and molecular mechanisms behind early LTP and on spiking activity during delayed-match-to-sample tasks support this view.

Fibroblasts from long-lived species of mammals and birds show delayed, but prolonged, phosphorylation of ERK.

PubMed

Elbourkadi, Najoua; Austad, Steven N; Miller, Richard A

2014-04-01

Fibroblasts from long-lived mutant mice show diminished phosphorylation of the stress-activated protein kinases ERK1/2 after exposure to peroxide, cadmium, or paraquat. We have now evaluated the kinetics of ERK phosphorylation in fibroblasts from long-lived and short-lived species of mammals and birds in response to stress by cadmium or hydrogen peroxide. Fibroblasts from the shorter-lived species of rodents and birds showed rapid induction of ERK phosphorylation, with a decline to basal level within 60 min. In contrast, cells from longer-lived species showed slower and more prolonged activation of ERK phosphorylation. These results suggest that fibroblasts from long-lived species may be less susceptible to the early phases of damage from cadmium or peroxide and suggest that altered kinetics of ERK activity may contribute to their stress resistance properties. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Comparison of delayed versus immediate pushing during second stage of labor for nulliparous women with epidural anesthesia.

PubMed

Gillesby, Erica; Burns, Suzan; Dempsey, Amy; Kirby, Shirley; Mogensen, Kami; Naylor, Kelly; Petrella, Joann; Vanicelli, Rebecca; Whelan, Breon

2010-01-01

To determine if the use of delayed pushing after the onset of the second stage of labor decreases the time of active pushing and decreases maternal fatigue. Randomized clinical trial. Labor and delivery unit of a not-for-profit community hospital. Convenience sample of nulliparous laboring women with epidural anesthesia. Immediate or delayed pushing (2 hours) during the second stage of labor at the time of complete cervical dilatation. The length of pushing, total length of the second stage, and maternal fatigue. A total of 77 women were studied (immediate pushing group=39; delayed pushing=38). The immediate pushing group averaged 94 (± 57) minutes in active pushing, while the delayed pushing group averaged 68 (± 46) minutes, a statistically significant difference (p=.04). No significant differences were found in fatigue scores between the immediate and delayed pushing groups (p>.05). We found that by delaying the onset of active pushing for 2 hours after the beginning of the second stage of labor, the time that nulliparous women with epidural anesthesia spent in active pushing was significantly decreased by 27%. Although the delayed pushing group rested for up to 2 hours, the total time in the second stage of labor averaged only 59 minutes longer than the immediate pushing group. © 2010 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Oxalate exposure provokes HSP 70 response in LLC-PK1 cells, a line of renal epithelial cells: protective role of HSP 70 against oxalate toxicity.

PubMed

Koul, Sweaty; Huang, Meiyi; Bhat, Sidarth; Maroni, Paul; Meacham, Randall B; Koul, Hari K

2008-02-01

We investigated the effects of oxalate on immediate early genes (IEGs) and stress protein HSP 70, commonly induced genes in response to a variety of stresses. LLC-PK1 cells were exposed to oxalate. Gene transcription and translation were monitored by Northern and Western blot analysis. RNA and DNA synthesis were assessed by [(3)H]-uridine and [(3)H]-thymidine incorporation, respectively. Oxalate exposure selectively increased the levels of mRNA encoding IEGs c-myc and c-jun as well as stress protein HSP 70. While expression of c-myc and c-jun was rapid (within 15 min to 2 h) and transient, HSP 70 expression was delayed (approximately 8 h) and stable. Furthermore, oxalate exposure resulted in delayed induction of generalized transcription by 18 h and reinitiation of the DNA synthesis by 24 h of oxalate exposure. Moreover, we show that prior induction of HSP 70 by mild hypertonic exposure protected the cells from oxalate toxicity. To the best of our knowledge this is the first study to demonstrate rapid IEG response and delayed heat-shock response to oxalate toxicity and protective role of HSP 70 against oxalate toxicity to renal epithelial cells. Oxalate, a metabolic end product, induces IEGs c-myc and c-jun and a delayed HSP 70 expression; While IEG expression may regulate additional genetic responses to oxalate, increased HSP 70 expression would serve an early protective role during oxalate stress.

0-6723 : development of rapid, cement-based repair materials for transportation structures.

DOT National Transportation Integrated Search

2014-08-01

The state of Texas has been plagued by various : durability-related issues in recent years, : including deterioration from alkali-silica : reaction, delayed ettringite formation, corrosion : of reinforcing steel, volume changes (plastic : shrinkage, ...

An On-Demand Emergency Packet Transmission Scheme for Wireless Body Area Networks.

PubMed

Al Ameen, Moshaddique; Hong, Choong Seon

2015-12-04

The rapid developments of sensor devices that can actively monitor human activities have given rise to a new field called wireless body area network (BAN). A BAN can manage devices in, on and around the human body. Major requirements of such a network are energy efficiency, long lifetime, low delay, security, etc. Traffic in a BAN can be scheduled (normal) or event-driven (emergency). Traditional media access control (MAC) protocols use duty cycling to improve performance. A sleep-wake up cycle is employed to save energy. However, this mechanism lacks features to handle emergency traffic in a prompt and immediate manner. To deliver an emergency packet, a node has to wait until the receiver is awake. It also suffers from overheads, such as idle listening, overhearing and control packet handshakes. An external radio-triggered wake up mechanism is proposed to handle prompt communication. It can reduce the overheads and improve the performance through an on-demand scheme. In this work, we present a simple-to-implement on-demand packet transmission scheme by taking into considerations the requirements of a BAN. The major concern is handling the event-based emergency traffic. The performance analysis of the proposed scheme is presented. The results showed significant improvements in the overall performance of a BAN compared to state-of-the-art protocols in terms of energy consumption, delay and lifetime.

An On-Demand Emergency Packet Transmission Scheme for Wireless Body Area Networks

PubMed Central

Al Ameen, Moshaddique; Hong, Choong Seon

2015-01-01

The rapid developments of sensor devices that can actively monitor human activities have given rise to a new field called wireless body area network (BAN). A BAN can manage devices in, on and around the human body. Major requirements of such a network are energy efficiency, long lifetime, low delay, security, etc. Traffic in a BAN can be scheduled (normal) or event-driven (emergency). Traditional media access control (MAC) protocols use duty cycling to improve performance. A sleep-wake up cycle is employed to save energy. However, this mechanism lacks features to handle emergency traffic in a prompt and immediate manner. To deliver an emergency packet, a node has to wait until the receiver is awake. It also suffers from overheads, such as idle listening, overhearing and control packet handshakes. An external radio-triggered wake up mechanism is proposed to handle prompt communication. It can reduce the overheads and improve the performance through an on-demand scheme. In this work, we present a simple-to-implement on-demand packet transmission scheme by taking into considerations the requirements of a BAN. The major concern is handling the event-based emergency traffic. The performance analysis of the proposed scheme is presented. The results showed significant improvements in the overall performance of a BAN compared to state-of-the-art protocols in terms of energy consumption, delay and lifetime. PMID:26690161

Ultrafast isomerization initiated by X-ray core ionization

NASA Astrophysics Data System (ADS)

Liekhus-Schmaltz, Chelsea E.; Tenney, Ian; Osipov, Timur; Sanchez-Gonzalez, Alvaro; Berrah, Nora; Boll, Rebecca; Bomme, Cedric; Bostedt, Christoph; Bozek, John D.; Carron, Sebastian; Coffee, Ryan; Devin, Julien; Erk, Benjamin; Ferguson, Ken R.; Field, Robert W.; Foucar, Lutz; Frasinski, Leszek J.; Glownia, James M.; Gühr, Markus; Kamalov, Andrei; Krzywinski, Jacek; Li, Heng; Marangos, Jonathan P.; Martinez, Todd J.; McFarland, Brian K.; Miyabe, Shungo; Murphy, Brendan; Natan, Adi; Rolles, Daniel; Rudenko, Artem; Siano, Marco; Simpson, Emma R.; Spector, Limor; Swiggers, Michele; Walke, Daniel; Wang, Song; Weber, Thorsten; Bucksbaum, Philip H.; Petrovic, Vladimir S.

2015-09-01

Rapid proton migration is a key process in hydrocarbon photochemistry. Charge migration and subsequent proton motion can mitigate radiation damage when heavier atoms absorb X-rays. If rapid enough, this can improve the fidelity of diffract-before-destroy measurements of biomolecular structure at X-ray-free electron lasers. Here we study X-ray-initiated isomerization of acetylene, a model for proton dynamics in hydrocarbons. Our time-resolved measurements capture the transient motion of protons following X-ray ionization of carbon K-shell electrons. We Coulomb-explode the molecule with a second precisely delayed X-ray pulse and then record all the fragment momenta. These snapshots at different delays are combined into a `molecular movie' of the evolving molecule, which shows substantial proton redistribution within the first 12 fs. We conclude that significant proton motion occurs on a timescale comparable to the Auger relaxation that refills the K-shell vacancy.

TSaT-MUSIC: a novel algorithm for rapid and accurate ultrasonic 3D localization

NASA Astrophysics Data System (ADS)

Mizutani, Kyohei; Ito, Toshio; Sugimoto, Masanori; Hashizume, Hiromichi

2011-12-01

We describe a fast and accurate indoor localization technique using the multiple signal classification (MUSIC) algorithm. The MUSIC algorithm is known as a high-resolution method for estimating directions of arrival (DOAs) or propagation delays. A critical problem in using the MUSIC algorithm for localization is its computational complexity. Therefore, we devised a novel algorithm called Time Space additional Temporal-MUSIC, which can rapidly and simultaneously identify DOAs and delays of mul-ticarrier ultrasonic waves from transmitters. Computer simulations have proved that the computation time of the proposed algorithm is almost constant in spite of increasing numbers of incoming waves and is faster than that of existing methods based on the MUSIC algorithm. The robustness of the proposed algorithm is discussed through simulations. Experiments in real environments showed that the standard deviation of position estimations in 3D space is less than 10 mm, which is satisfactory for indoor localization.

From starburst to quiescence: testing active galactic nucleus feedback in rapidly quenching post-starburst galaxies

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

Yesuf, Hassen M.; Faber, S. M.; Trump, Jonathan R.

Post-starbursts are galaxies in transition from the blue cloud to the red sequence. Although they are rare today, integrated over time they may be an important pathway to the red sequence. This work uses Sloan Digital Sky Survey, the Galaxy Evolution Explorer, and Wide-field Infrared Survey Explorer observations to identify the evolutionary sequence from starbursts to fully quenched post-starbursts (QPSBs) in the narrow mass range log M(M {sub ☉}) = 10.3-10.7, and identifies 'transiting' post-starbursts (TPSBs) which are intermediate between these two populations. In this mass range, ∼0.3% of galaxies are starbursts, ∼0.1% are QPSBs, and ∼0.5% are the transitingmore » types in between. The TPSBs have stellar properties that are predicted for fast-quenching starbursts and morphological characteristics that are already typical of early-type galaxies. The active galactic nucleus (AGN) fraction, as estimated from optical line ratios, of these post-starbursts is about three times higher (≳ 36% ± 8%) than that of normal star forming galaxies of the same mass, but there is a significant delay between the starburst phase and the peak of nuclear optical AGN activity (median age difference of ≳ 200 ± 100 Myr), in agreement with previous studies. The time delay is inferred by comparing the broadband near-NUV-to-optical photometry with stellar population synthesis models. We also find that starbursts and post-starbursts are significantly more dust obscured than normal star forming galaxies in the same mass range. About 20% of the starbursts and 15% of the TPSBs can be classified as 'dust-obscured galaxies' (DOGs), with a near-UV-to-mid-IR flux ratio of ≳ 900, while only 0.8% of normal galaxies are DOGs. The time delay between the starburst phase and AGN activity suggests that AGNs do not play a primary role in the original quenching of starbursts but may be responsible for quenching later low-level star formation by removing gas and dust during the post-starburst phase.« less

Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat.

PubMed

Hurteau, Marie-France; Thibaudier, Yann; Dambreville, Charline; Danner, Simon M; Rybak, Ilya A; Frigon, Alain

2018-04-25

When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response. SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the contacted limb and opposite homologous limb help maintain balance and forward progression. Here, we investigated reflexes during quadrupedal locomotion in the cat by electrically stimulating cutaneous nerves in each of the four limbs. Functionally, responses appear to modify the trajectory or stabilize the movement of the stimulated limb while modifying the support phase of the other limbs. Reflexes between limbs are mediated by fast-conducting pathways that involve excitatory and inhibitory circuits controlling each limb. The comparatively stronger descending pathways from cervical to lumbar circuits controlling the forelimbs and hindlimbs, respectively, could serve a protective function. Copyright © 2018 the authors 0270-6474/18/384104-19$15.00/0.

YneA, an SOS-induced inhibitor of cell division in Bacillus subtilis, is regulated posttranslationally and requires the transmembrane region for activity.

PubMed

Mo, Allison H; Burkholder, William F

2010-06-01

Cell viability depends on the stable transmission of genetic information to each successive generation. Therefore, in the event of intrinsic or extrinsic DNA damage, it is important that cell division be delayed until DNA repair has been completed. In Bacillus subtilis, this is accomplished in part by YneA, an inhibitor of division that is induced as part of the SOS response. We sought to gain insight into the mechanism by which YneA blocks cell division and the processes involved in shutting off YneA activity. Our data suggest that YneA is able to inhibit daughter cell separation as well as septum formation. YneA contains a LysM peptidoglycan binding domain and is predicted to be exported. We established that the YneA signal peptide is rapidly cleaved, resulting in secretion of YneA into the medium. Mutations within YneA affect both the rate of signal sequence cleavage and the activity of YneA. YneA does not stably associate with the cell wall and is rapidly degraded by extracellular proteases. Based on these results, we hypothesize that exported YneA is active prior to signal peptide cleavage and that proteolysis contributes to the inactivation of YneA. Finally, we identified mutations in the transmembrane segment of YneA that abolish the ability of YneA to inhibit cell division, while having little or no effect on YneA export or stability. These data suggest that protein-protein interactions mediated by the transmembrane region may be required for YneA activity.

Positive parenting mitigates the effects of poor self-regulation on body mass index trajectories from ages 4-15 years.

PubMed

Connell, Lauren E; Francis, Lori A

2014-08-01

This study sought to determine whether parenting style moderates the effects of delay of gratification on body mass index (BMI) trajectories from ages 4-15 years. Longitudinal data were analyzed for 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (i.e., authoritative, authoritarian, permissive, and neglectful) was created from measures of mothers' sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4-15 years. There was a significant interaction effect of parenting and ability to delay on BMI growth from 4-15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting by delay group. Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles.

Positive parenting mitigates the effects of poor self-regulation on BMI trajectories from age 4 to 15 years

PubMed Central

Connell, Lauren E.; Francis, Lori A.

2014-01-01

Objective This study sought to determine whether parenting style moderated the effects of delay of gratification on BMI trajectories from age 4 to 15 years. Methods Longitudinal data were analyzed on 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (authoritative, authoritarian, permissive, neglectful) was created from measures of mothers’ sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4 to 15 years. Results There was a significant interaction effect of parenting and ability to delay on BMI growth from 4 to 15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting x delay group. Conclusions Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles. PMID:23977874

Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting-a pilot study.

PubMed

Wong, E; Pulenzas, N; Bedard, G; DeAngelis, C; Zhang, L; Tsao, M; Danjoux, C; Thavarajah, N; Lechner, B; McDonald, R; Cheon, P M; Chow, E

2015-06-01

The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. Ondansetron rdf is effective for the prophylaxis of rinv.

Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy

PubMed Central

Stuart, Sarah A; Butler, Paul; Munafò, Marcus R; Nutt, David J; Robinson, Emma SJ

2015-01-01

The biochemical targets for antidepressants are relatively well established, but we lack a clear understanding of how actions at these proteins translate to clinical benefits. This study used a novel rodent assay to investigate how different antidepressant drugs act to modify affective biases that have been implicated in depression. In this bowl-digging task, rats encounter two equal value learning experiences on separate days (one during an affective manipulation and the other during control conditions). This induces an affective bias that is quantified using a preference test in which both digging substrates are presented together and the individual rats’ choices recorded. The assay can be used to measure affective biases associated with learning (when the treatment is given at the time of the experience) or examine the modification of previously acquired biases (when the treatment is administered before the preference test). The rapid-onset antidepressant ketamine, but not the delayed-onset antidepressant, venlafaxine, attenuated the previously acquired FG7142-induced negative bias following systemic administration. Venlafaxine but not ketamine induced a positive bias when administered before learning. We then used local drug infusions and excitotoxic lesions to localize the effects of ketamine to the medial prefrontal cortex and venlafaxine to the amygdala. Using a modified protocol we also showed that positive and negative biases amplified further when the numbers of substrate–reinforcer associations are increased. We propose that this pattern of results could explain the delayed onset of action of venlafaxine and the rapid onset of action but lack of long-term efficacy seen with ketamine. PMID:25740288

Antibacterial activity of lichen secondary metabolite usnic acid is primarily caused by inhibition of RNA and DNA synthesis.

PubMed

Maciąg-Dorszyńska, Monika; Węgrzyn, Grzegorz; Guzow-Krzemińska, Beata

2014-04-01

Usnic acid, a compound produced by various lichen species, has been demonstrated previously to inhibit growth of different bacteria and fungi; however, mechanism of its antimicrobial activity remained unknown. In this report, we demonstrate that usnic acid causes rapid and strong inhibition of RNA and DNA synthesis in Gram-positive bacteria, represented by Bacillus subtilis and Staphylococcus aureus, while it does not inhibit production of macromolecules (DNA, RNA, and proteins) in Escherichia coli, which is resistant to even high doses of this compound. However, we also observed slight inhibition of RNA synthesis in a Gram-negative bacterium, Vibrio harveyi. Inhibition of protein synthesis in B. subtilis and S. aureus was delayed, which suggest indirect action (possibly through impairment of transcription) of usnic acid on translation. Interestingly, DNA synthesis was halted rapidly in B. subtilis and S. aureus, suggesting interference of usnic acid with elongation of DNA replication. We propose that inhibition of RNA synthesis may be a general mechanism of antibacterial action of usnic acid, with additional direct mechanisms, such as impairment of DNA replication in B. subtilis and S. aureus. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Determinants of PDT-induced apoptosis

NASA Astrophysics Data System (ADS)

Kessel, David; Luo, Yu; Kim, Hyeong-Reh C.

2000-03-01

Photodynamic therapy can initiate cell death by apoptosis or necrosis. Using agents with known patterns of sub-cellular localization, we examined the correlation between sites of photodamage and the mode of cell death, using murine leukemia cells in vitro. Mitochondrial or mitochondrial/lysosomal photodamage caused the rapid release of cytochrome c. This effect was not temperature sensitive, and could be demonstrated immediately after irradiation of photosensitized cells at 10 degrees C. Subsequent warming to 37 degrees C led to a rapid apoptotic response, consistent with the known ability of cytochrome c to trigger the activation of caspase-3. In contrast, lysosomal or lysosomal/membrane photodamage resulted in the release of cathepsins and other proteolytic enzymes. A subsequent incubation at 37 degrees C resulted in mitochondrial degradation, leading to loss of cytochrome c within 30 min. The apoptotic response was both delayed and incomplete, with many dead cells not exhibiting an apoptotic morphology. The latter outcome was traced to photodamage to procaspase-3, an effect not observed with sensitizers that caused mainly mitochondrial photodamage. Studies in a cell-free system demonstrated that agents with lysosomal and/or membrane targets could bring about photoinactivation of caspase-3. These result are consistent with the proposal that photodynamic therapy can both activate and inactivate components of the apoptotic process.

The impact of physicochemical property interactions of iso -octane/ethanol blends on ignition timescales

DOE PAGES

Barraza-Botet, Cesar L.; Luecke, Jon; Zigler, Bradley T.; ...

2018-03-20

This work presents new measurements of liquid fuel ignition delay times of iso-octane and ethanol fuel blends obtained from an ignition quality tester at the National Renewable Energy Laboratory (NREL IQT), which are compared to previous ignition delay data from the University of Michigan rapid compression facility (UM RCF), at the same experimental conditions. Pressure-time histories were used to determine liquid fuel ignition delays at global stoichiometric non-premixed conditions for iso-octane, ethanol and iso-octane/ethanol blends of 25, 50, 75% by volume in mixtures of 10% oxygen diluted in nitrogen. Temperatures ranging from 880 to 970 K were studied at amore » pressure of 10 atm. By comparing total ignition delay times from the NREL IQT with chemical ignition delay times from the UM RCF, the contributions of physical phenomena were quantified as representative time scales for spray injection, breakup and evaporation processes, and for gas-phase turbulent mixing. Regression analyses were developed for ignition time scales as function of blend level and charge temperature. Non-dimensional analyses were also carried out to determine the relative effects of physical time scales with respect to chemical ignition delay times.« less

The impact of physicochemical property interactions of iso -octane/ethanol blends on ignition timescales

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

Barraza-Botet, Cesar L.; Luecke, Jon; Zigler, Bradley T.

This work presents new measurements of liquid fuel ignition delay times of iso-octane and ethanol fuel blends obtained from an ignition quality tester at the National Renewable Energy Laboratory (NREL IQT), which are compared to previous ignition delay data from the University of Michigan rapid compression facility (UM RCF), at the same experimental conditions. Pressure-time histories were used to determine liquid fuel ignition delays at global stoichiometric non-premixed conditions for iso-octane, ethanol and iso-octane/ethanol blends of 25, 50, 75% by volume in mixtures of 10% oxygen diluted in nitrogen. Temperatures ranging from 880 to 970 K were studied at amore » pressure of 10 atm. By comparing total ignition delay times from the NREL IQT with chemical ignition delay times from the UM RCF, the contributions of physical phenomena were quantified as representative time scales for spray injection, breakup and evaporation processes, and for gas-phase turbulent mixing. Regression analyses were developed for ignition time scales as function of blend level and charge temperature. Non-dimensional analyses were also carried out to determine the relative effects of physical time scales with respect to chemical ignition delay times.« less

Visual search guidance is best after a short delay

PubMed Central

Schmidt, Joseph; Zelinsky, Gregory J.

2011-01-01

Search displays are typically presented immediately after a target cue, but in the real-world, delays often exist between target designation and search. Experiments 1 and 2 asked how search guidance changes with delay. Targets were cued using a picture or text label, each for 3000ms, followed by a delay up to 9000ms before the search display. Search stimuli were realistic objects, and guidance was quantified using multiple eye movement measures. Text-based cues showed a non-significant trend towards greater guidance following any delay relative to a no-delay condition. However, guidance from a pictorial cue increased sharply 300–600 msec after preview offset. Experiment 3 replicated this guidance enhancement using shorter preview durations while equating the time from cue onset to search onset, demonstrating that the guidance benefit is linked to preview offset rather than a more complete encoding of the target. Experiment 4 showed that enhanced guidance persists even with a mask flashed at preview offset, suggesting an explanation other than visual priming. We interpret our findings as evidence for the rapid consolidation of target information into a guiding representation, which attains its maximum effectiveness shortly after preview offset. PMID:21295053

Visual search guidance is best after a short delay.

PubMed

Schmidt, Joseph; Zelinsky, Gregory J

2011-03-25

Search displays are typically presented immediately after a target cue, but in the real-world, delays often exist between target designation and search. Experiments 1 and 2 asked how search guidance changes with delay. Targets were cued using a picture or text label, each for 3000ms, followed by a delay up to 9000ms before the search display. Search stimuli were realistic objects, and guidance was quantified using multiple eye movement measures. Text-based cues showed a non-significant trend towards greater guidance following any delay relative to a no-delay condition. However, guidance from a pictorial cue increased sharply 300-600ms after preview offset. Experiment 3 replicated this guidance enhancement using shorter preview durations while equating the time from cue onset to search onset, demonstrating that the guidance benefit is linked to preview offset rather than a more complete encoding of the target. Experiment 4 showed that enhanced guidance persists even with a mask flashed at preview offset, suggesting an explanation other than visual priming. We interpret our findings as evidence for the rapid consolidation of target information into a guiding representation, which attains its maximum effectiveness shortly after preview offset. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prospective associations between measures of gross and fine motor coordination in infants and objectively measured physical activity and sedentary behavior in childhood

PubMed Central

Sánchez, Guillermo F López; Williams, Genevieve; Aggio, Daniel; Vicinanza, Domenico; Stubbs, Brendon; Kerr, Catherine; Johnstone, James; Roberts, Justine; Smith, Lee

2017-01-01

Abstract One important determinant of childhood physical activity and sedentary behavior may be that of motor development in infancy. The present analyses aimed to investigate whether gross and fine motor delays in infants were associated with objective and self-reported activity in childhood. Data were from the UK Millennium Cohort Study, a prospective cohort study, involving UK children born on or around the millennium (September 2000 and January 2002). When children were 9 months old, parents reported children's fine and gross motor-coordination, and at 7 years, sports club attendance and daily TV viewing time. Children's physical activity was measured using accelerometers at 7 years. Adjusted regression models were used to examine associations between delayed motor development and accelerometry measured moderate-to-vigorous physical activity and sedentary behavior, and parent-reported sport club attendance and TV viewing time. In this sample (n = 13,021), gross motor delay in infancy was associated with less time in moderate-to-vigorous physical activity (B −5.0 95% confidence interval [CI] −6.8, −3.2) and more time sedentary (B 13.5 95% CI 9.3, 17.8) in childhood. Gross and fine motor delays during infancy were associated with a reduced risk of having high attendance at sports clubs in childhood (both relative risk [RR] 0.7, 95% CI 0.6, 0.9). Fine motor delays, but not gross delays, were also associated with an increased risk of having high TV viewing time (RR 1.3 95% CI 1.0, 1.6). Findings from the present study suggest that delays in motor development in infancy are associated with physical activity and sedentary time in childhood. PMID:29145249

Prospective associations between measures of gross and fine motor coordination in infants and objectively measured physical activity and sedentary behavior in childhood.

PubMed

Sánchez, Guillermo F López; Williams, Genevieve; Aggio, Daniel; Vicinanza, Domenico; Stubbs, Brendon; Kerr, Catherine; Johnstone, James; Roberts, Justin; Smith, Lee

2017-11-01

One important determinant of childhood physical activity and sedentary behavior may be that of motor development in infancy. The present analyses aimed to investigate whether gross and fine motor delays in infants were associated with objective and self-reported activity in childhood. Data were from the UK Millennium Cohort Study, a prospective cohort study, involving UK children born on or around the millennium (September 2000 and January 2002). When children were 9 months old, parents reported children's fine and gross motor-coordination, and at 7 years, sports club attendance and daily TV viewing time. Children's physical activity was measured using accelerometers at 7 years. Adjusted regression models were used to examine associations between delayed motor development and accelerometry measured moderate-to-vigorous physical activity and sedentary behavior, and parent-reported sport club attendance and TV viewing time. In this sample (n = 13,021), gross motor delay in infancy was associated with less time in moderate-to-vigorous physical activity (B -5.0 95% confidence interval [CI] -6.8, -3.2) and more time sedentary (B 13.5 95% CI 9.3, 17.8) in childhood. Gross and fine motor delays during infancy were associated with a reduced risk of having high attendance at sports clubs in childhood (both relative risk [RR] 0.7, 95% CI 0.6, 0.9). Fine motor delays, but not gross delays, were also associated with an increased risk of having high TV viewing time (RR 1.3 95% CI 1.0, 1.6). Findings from the present study suggest that delays in motor development in infancy are associated with physical activity and sedentary time in childhood.

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

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Tolerance in Nonhuman Primates by Delayed Mixed Chimerism

DTIC Science & Technology

2014-10-01

swelling at the surgical site was noted, associated with cellulitis tracking proximally in the recipient forearm and purulent discharge from the...antibiotic sensitivity screening and empirical antibiotic therapy started. This treatment resulted in rapid improvement, with relief of cellulitis

Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes

PubMed Central

1991-01-01

Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of the patch-clamp recording technique. During brief depolarizations to potentials positive to -40 mV, Ca(2+)-independent outward K+ currents in these cells rise to a transient peak, followed by a slower decay to an apparent plateau. The analyses completed here reveal that the observed outward current waveforms result from the activation of two kinetically distinct voltage-dependent K+ currents: one that activates and inactivates rapidly, and one that activates and inactivates slowly, on membrane depolarization. These currents are referred to here as Ito (transient outward) and IK (delayed rectifier), respectively, because their properties are similar (although not identical) to these K+ current types in other cells. Although the voltage dependences of Ito and IK activation are similar, Ito activates approximately 10-fold and inactivates approximately 30-fold more rapidly than IK at all test potentials. In the composite current waveforms measured during brief depolarizations, therefore, the peak current predominantly reflects Ito, whereas IK is the primary determinant of the plateau. There are also marked differences in the voltage dependences of steady-state inactivation of these two K+ currents: IK undergoes steady-state inactivation at all potentials positive to -120 mV, and is 50% inactivated at -69 mV; Ito, in contrast, is insensitive to steady-state inactivation at membrane potentials negative to -50 mV. In addition, Ito recovers from steady-state inactivation faster than IK: at -90 mV, for example, approximately 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers approximately 25-fold more slowly. The pharmacological properties of Ito and IK are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly IK. The voltage- and time- dependent properties of these currents are interpreted here in terms of a model in which Ito underlies the initial, rapid repolarization phase of the action potential (AP), and IK is responsible for the slower phase of AP repolarization back to the resting membrane potential, in adult rat ventricular myocytes. PMID:1865177

Excimer laser phototherapeutic keratectomy for shield ulcers and corneal plaques in vernal keratoconjunctivitis.

PubMed

Cameron, J A; Antonios, S R; Badr, I A

1995-01-01

Shield-shaped corneal ulcers and corneal plaques in vernal keratoconjunctivitis are associated with delayed epithelial healing, as well as the risks of infectious keratitis and sterile stromal ulceration. Significant visual impairment due to scarring and irregular astigmatism may result from central corneal lesions. Three eyes with central corneal lesions resulting from vernal keratoconjunctivitis were treated by excimer laser after active vernal keratoconjunctivitis was controlled and inflammatory plaque overlying the shield ulcers was removed. All three eyes showed rapid reepithelialization within 1 week. Spectacle-corrected visual acuity of 20/30 or better was obtained in each eye. In selected patients, excimer laser phototherapeutic keratectomy may be a useful adjunct in the treatment of shield-shaped corneal ulcers and plaques in vernal keratoconjunctivitis.

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay

PubMed Central

Strickland, Justin C.; Feinstein, Max A.; Lacy, Ryan T.; Smith, Mark A.

2016-01-01

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-second delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. PMID:26964905

Working Memory Delay Activity Predicts Individual Differences in Cognitive Abilities

PubMed Central

Unsworth, Nash; Fukuda, Keisuke; Awh, Edward; Vogel, Edward K.

2015-01-01

A great deal of prior research has examined the relation between estimates of working memory and cognitive abilities. Yet, the neural mechanisms that account for these relations are still not very well understood. The current study explored whether individual differences in working memory delay activity would be a significant predictor of cognitive abilities. A large number of participants performed multiple measures of capacity, attention control, long-term memory, working memory span, and fluid intelligence, and latent variable analyses were used to examine the data. During two working memory change detection tasks, we acquired EEG data and examined the contra-lateral delay activity. The results demonstrated that the contralateral delay activity was significantly related to cognitive abilities, and importantly these relations were because of individual differences in both capacity and attention control. These results suggest that individual differences in working memory delay activity predict individual differences in a broad range of cognitive abilities, and this is because of both differences in the number of items that can be maintained and the ability to control access to working memory. PMID:25436671

Working memory delay activity predicts individual differences in cognitive abilities.

PubMed

Unsworth, Nash; Fukuda, Keisuke; Awh, Edward; Vogel, Edward K

2015-05-01

A great deal of prior research has examined the relation between estimates of working memory and cognitive abilities. Yet, the neural mechanisms that account for these relations are still not very well understood. The current study explored whether individual differences in working memory delay activity would be a significant predictor of cognitive abilities. A large number of participants performed multiple measures of capacity, attention control, long-term memory, working memory span, and fluid intelligence, and latent variable analyses were used to examine the data. During two working memory change detection tasks, we acquired EEG data and examined the contralateral delay activity. The results demonstrated that the contralateral delay activity was significantly related to cognitive abilities, and importantly these relations were because of individual differences in both capacity and attention control. These results suggest that individual differences in working memory delay activity predict individual differences in a broad range of cognitive abilities, and this is because of both differences in the number of items that can be maintained and the ability to control access to working memory.

The New Tropospheric Product of the International GNSS Service

NASA Technical Reports Server (NTRS)

Byun, Sung H.; Bar-Sever, Yoaz E.; Gendt, Gerd

2005-01-01

We compare this new approach for generating the IGS tropospheric products with the previous approach, which was based on explicit combination of total zenith delay contributions from the IGS ACs. The new approach enables the IGS to rapidly generate highly accurate and highly reliable total zenith delay time series for many hundreds of sites, thus increasing the utility of the products to weather modelers, climatologists, and GPS analysts. In this paper we describe this new method, and discuss issues of accuracy, quality control, utility of the new products and assess its benefits.

Cell-mediated immunity in herpes simplex virus-infected mice: H-2 mapping of the delayed-type hypersensitivity response and the antiviral T cell response.

PubMed

Nash, A A; Phelan, J; Wildy, P

1981-04-01

An adoptive transfer system was used to investigate the H-2 restriction of delayed-type hypersensitivity (DTH) to herpes simplex virus. A successful DTH transfer was achieved when donor and recipient were compatible at the I-A region, with K and D region compatibility unnecessary. However, the rapid clearance of infectious virus from the inoculation site was found only when the donor and recipients were compatible at H-2K (and presumably D) and I-A regions.

Exacerbated Glial Response in the Aged Mouse Hippocampus Following Controlled Cortical Impact Injury

PubMed Central

Sandhir, Rajat; Onyszchuk, Gregory; Berman, Nancy E. J.

2008-01-01

Old age is associated with enhanced susceptibility to and poor recovery from brain injury. An exacerbated microglial and astrocyte response to brain injury might be involved in poor outcomes observed in the elderly. The present study was therefore designed to quantitate the expression of markers of microglia and astrocyte activation using real-time RT-PCR, immunoblot and immunohistochemical analysis in aging brain in response to brain injury. We examined the hippocampus, a region that undergoes secondary neuron death, in aged (21–24 month) and adult (5–6 month) mice following controlled cortical impact (CCI) injury to the sensorimotor cortex. Basal mRNA expression of CD11b and Iba1, markers of activated microglia, was higher in aged hippocampus as compared to the adult. The mRNA expression of microglial markers increased and reached maximum 3 days post injury in both adult and aged mice, but was higher in the aged mice at all time points studied, and in the aged mice the return to baseline levels was delayed. Basal mRNA expression of GFAP and S100B, markers of activated astrocytes, was higher in aged mice. Both markers increased and reached maximum 7 days post injury. The mRNA expression of astrocyte markers returned to near basal levels rapidly after injury in the adult mice, whereas again in the aged mice return to baseline was delayed. Immunochemical analysis using Iba1 and GFAP antibodies indicate accentuated glial responses in the aged hippocampus after injury. The pronounced and prolonged activation of microglia and astrocytes in hippocampus may contribute to worse cognitive outcomes in the elderly following TBI. PMID:18692046

Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone

PubMed Central

Shuhaibar, Leia C.; Egbert, Jeremy R.; Edmund, Aaron B.; Uliasz, Tracy F.; Dickey, Deborah M.; Yee, Siu-Pok; Potter, Lincoln R.; Jaffe, Laurinda A.

2016-01-01

The meiotic cell cycle of mammalian oocytes starts during embryogenesis and then pauses until luteinizing hormone (LH) acts on the granulosa cells of the follicle surrounding the oocyte to restart the cell cycle. An essential event in this process is a decrease in cyclic GMP in the granulosa cells, and part of the cGMP decrease results from dephosphorylation and inactivation of the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase, also known as guanylyl cyclase B. However, it is unknown whether NPR2 dephosphorylation is essential for LH-induced meiotic resumption. Here, we prevented NPR2 dephosphorylation by generating a mouse line in which the seven regulatory serines and threonines of NPR2 were changed to the phosphomimetic amino acid glutamate (Npr2–7E). Npr2–7E/7E follicles failed to show a decrease in enzyme activity in response to LH, and the cGMP decrease was attenuated; correspondingly, LH-induced meiotic resumption was delayed. Meiotic resumption in response to EGF receptor activation was likewise delayed, indicating that NPR2 dephosphorylation is a component of the pathway by which EGF receptor activation mediates LH signaling. We also found that most of the NPR2 protein in the follicle was present in the mural granulosa cells. These findings indicate that NPR2 dephosphorylation in the mural granulosa cells is essential for the normal progression of meiosis in response to LH and EGF receptor activation. In addition, these studies provide the first demonstration that a change in phosphorylation of a transmembrane guanylyl cyclase regulates a physiological process, a mechanism that may also control other developmental events. PMID:26522847

Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons.

PubMed

Yang, Yoon-Sil; Jeon, Sang-Chan; Kim, Dong-Kwan; Eun, Su-Yong; Jung, Sung-Cherl

2017-03-01

Excessive influx and the subsequent rapid cytosolic elevation of Ca 2+ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca 2+ level in normal as well as pathological conditions. Delayed rectifier K + channels (I DR channels) play a role to suppress membrane excitability by inducing K + outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca 2+ -mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of I DR channels to hyperexcitable conditions induced by high Ca 2+ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca 2+ -treatment significantly increased the amplitude of I DR without changes of gating kinetics. Nimodipine but not APV blocked Ca 2+ -induced I DR enhancement, confirming that the change of I DR might be targeted by Ca 2+ influx through voltage-dependent Ca 2+ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I DR enhancement was not affected by either Ca 2+ -induced Ca 2+ release (CICR) or small conductance Ca 2+ -activated K + channels (SK channels). Furthermore, PP2 but not H89 completely abolished I DR enhancement under high Ca 2+ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca 2+ -mediated I DR enhancement. Thus, SFKs may be sensitive to excessive Ca 2+ influx through VDCCs and enhance I DR to activate a neuroprotective mechanism against Ca 2+ -mediated hyperexcitability in neurons.

IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained IGF signaling.

PubMed

Yoneyama, Yosuke; Lanzerstorfer, Peter; Niwa, Hideaki; Umehara, Takashi; Shibano, Takashi; Yokoyama, Shigeyuki; Chida, Kazuhiro; Weghuber, Julian; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

2018-04-11

Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long-term IGF activities including growth and metabolism. Kinetics of ligand-dependent IGF-IR endocytosis determines how IGF induces such downstream signaling outputs. Here, we find that the insulin receptor substrate (IRS)-1 modulates how long ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1, but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis after the ligand stimulation. Mechanistically, IRS-1 inhibits the recruitment of IGF-IR into clathrin-coated structures; for this reason, IGF-IR avoids rapid endocytosis and prolongs its activity on the cell surface. Accelerating IGF-IR endocytosis via IRS-1 depletion induces the shift from sustained to transient Akt activation and augments FoxO-mediated transcription. Our study establishes a new role for IRS-1 as an endocytic regulator of IGF-IR that ensures sustained IGF bioactivity, independent of its classic role as an adaptor in IGF-IR signaling. © 2018, Yoneyama et al.

RESPIRATORY MODULATION OF LINGUAL MUSCLE ACTIVITY ACROSS SLEEP-WAKE STATES IN RATS

PubMed Central

Stettner, Georg M.; Rukhadze, Irma; Mann, Graziella L.; Lei, Yanlin; Kubin, Leszek

2013-01-01

In obstructive sleep apnea (OSA) patients, inspiratory activation (IA) of lingual muscles protects the upper airway from collapse. We aimed to determine when rats’ lingual muscles exhibit IA. In 5 Sprague-Dawley and 3 Wistar rats, we monitored cortical EEG and lingual, diaphragmatic and nuchal electromyograms (EMGs), and identified segments of records when lingual EMG exhibited IA. Individual segments lasted 2.4–269 s (median: 14.5 s), most (89%) occurred during slow-wave sleep (SWS), and they collectively occupied 0.3–6.1% of the total recording time. IA usually started to increase with a delay after SWS onset and ended with an arousal, or declined prior to rapid eye movement sleep. IA of lingual EMG was not accompanied by increased diaphragmatic activity or respiratory rate changes, but occurred when cortical EEG power was particularly low in a low beta-1 frequency range (12.5–16.4 Hz). A deep SWS-related activation of upper airway muscles may be an endogenous phenomenon designed to protect the upper airway against collapse. PMID:23732510

IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained IGF signaling

PubMed Central

Yoneyama, Yosuke; Lanzerstorfer, Peter; Niwa, Hideaki; Umehara, Takashi; Shibano, Takashi; Yokoyama, Shigeyuki; Chida, Kazuhiro; Weghuber, Julian

2018-01-01

Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long-term IGF activities including growth and metabolism. Kinetics of ligand-dependent IGF-IR endocytosis determines how IGF induces such downstream signaling outputs. Here, we find that the insulin receptor substrate (IRS)−1 modulates how long ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1, but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis after the ligand stimulation. Mechanistically, IRS-1 inhibits the recruitment of IGF-IR into clathrin-coated structures; for this reason, IGF-IR avoids rapid endocytosis and prolongs its activity on the cell surface. Accelerating IGF-IR endocytosis via IRS-1 depletion induces the shift from sustained to transient Akt activation and augments FoxO-mediated transcription. Our study establishes a new role for IRS-1 as an endocytic regulator of IGF-IR that ensures sustained IGF bioactivity, independent of its classic role as an adaptor in IGF-IR signaling. PMID:29661273

CK1/Doubletime activity delays transcription activation in the circadian clock

PubMed Central

O'Neil, Jenna L; Merz, Gregory E; Dusad, Kritika; Crane, Brian R; Young, Michael W

2018-01-01

In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex. Our results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence. The role of DBT in regulating PER activity, stabilization and degradation ensures that these events are chronologically and biochemically linked, and contributes to the timing of an essential delay that influences the period of the circadian clock. PMID:29611807

Cenozoic lithospheric deformation in Northeast Asia and the rapidly-aging Pacific Plate

NASA Astrophysics Data System (ADS)

Yang, Ting; Moresi, Louis; Zhao, Dapeng; Sandiford, Dan; Whittaker, Joanne

2018-06-01

Northeast Asia underwent widespread rifting and magmatic events during the Cenozoic. The geodynamic origins of these tectonic events are often linked to Pacific plate subduction beneath Northeast Asia. However, the Japan Sea did not open until the late Oligocene, tens of millions of years after Pacific Plate subduction initiation in the Paleocene. Moreover, it is still not clear why the Baikal Rift Zone extension rate increased significantly after the late Miocene, while the Japan Sea opening ceased at the same time. Geodynamic models suggest these enigmatic events are related to the rapidly-aging Pacific Plate at the trench after Izanagi-Pacific spreading ridge subduction. Subduction of the young Pacific Plate delayed the Japan Sea opening during the Eocene while advection of the old Pacific Plate towards the trench increases seafloor age rapidly, allowing the Japan Sea to open after the early Miocene. The Japan Sea opening promotes fast trench retreat and slab stagnation, with subduction-induced wedge zone convection gradually increasing its extent during this process. The active rifting center associated with wedge zone convection upwelling also shifts inland-ward during slab stagnation, preventing further Japan Sea spreading while promoting the Baikal Rift Zone extension. Our geodynamic model provides a good explanation for the temporal-spatial patterns of the Cenozoic tectonic and magmatic events in Northeast Asia.

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence

PubMed Central

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C.

2015-01-01

A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1 mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05 mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition. PMID:26234588

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence.

PubMed

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C

2015-11-01

A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

Migratory behavior of adult sea lamprey and cumulative passage performance through four fishways

USGS Publications Warehouse

Castro-Santos, Theodore R.; Shi, Xiaotao; Haro, Alexander

2017-01-01

This article describes a study of PIT-tagged sea lamprey (Petromyzon marinus) ascending four fishways comprising three designs at two dams on the Connecticut River, USA. Migration between dams was rapid (median migration rate = 23 km·day−1). Movement through the fishways was much slower, however (median = 0.02–0.33 km·day−1). Overall delay at dams was substantial (median = 13.6–14.6 days); many fish failed to pass (percent passage ranged from 29% to 55%, depending on fishway), and repeated passage attempts compounded delay for both passers and failers. Cox regression revealed that fishway entry rates were influenced by flow, temperature, and diel cycle, with most lampreys entering at night and at elevated flows, but with no apparent effect of sex or length. Overall delay was influenced by slow movement through the fishways, but repeated failures were the primary factor determining delay. These data suggest that although some lamprey were able to pass fishways, they did so with difficulty, and delays incurred as they attempted to pass may act to limit their distribution within their native range.

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

PubMed Central

Wenstrup, Jeffrey J.; Portfors, Christine V.

2011-01-01

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

Exploring the daily activities associated with delayed bedtime of Japanese university students.

PubMed

Asaoka, Shoichi; Komada, Yoko; Fukuda, Kazuhiko; Sugiura, Tatsuki; Inoue, Yuichi; Yamazaki, Katuo

2010-07-01

University students show delayed sleep-wake patterns, i.e., later bed- and rise-times, and this pattern is known to be associated with various malfunctions. There may be a variety of daily activities associated with their delayed sleep patterns, such as watching TV. However, it is unclear to what extent each activity possesses an impact on their sleep patterns. The purpose of this study was to determine the daily activities associated with delayed bedtime in Japanese university students who live with or without their families. Three hundred and thirty-one participants were required to record the timing and duration of their sleep and daily activities, and the data from the 275 students (160 men and 115 women; 19.01 +/- 1.66 years) who completely filled forms were used for analysis. The results of multiple regression analyses suggested that interpersonal communication late at night is one of the major factors leading to the delayed bedtime of students living away from home. Among those living with their families, indoor activities such as watching TV and using the Internet were related to their delayed bedtimes. Attending classes and having a morning meal were related to the earlier bedtimes of the students living away from home, but there were no activities associated with those of the students living with their families. These results suggest that ensuring attendance at morning classes and having appropriate mealtimes, as well as restricting the use of visual media and socializing activities at night, are necessary for preventing late bedtimes in university students.

Rapid shape detection signals in area V4

PubMed Central

Weiner, Katherine F.; Ghose, Geoffrey M.

2014-01-01

Vision in foveate animals is an active process that requires rapid and constant decision-making. For example, when a new object appears in the visual field, we can quickly decide to inspect it by directing our eyes to the object's location. We studied the contribution of primate area V4 to these types of rapid foveation decisions. Animals performed a reaction time task that required them to report when any shape appeared within a peripherally-located noisy stimulus by making a saccade to the stimulus location. We found that about half of the randomly sampled V4 neurons not only rapidly and precisely represented the appearance of this shape, but they were also predictive of the animal's saccades. A neuron's ability to predict the animal's saccades was not related to the specificity with which the cell represented a single type of shape but rather to its ability to signal whether any shape was present. This relationship between sensory sensitivity and behavioral predictiveness was not due to global effects such as alertness, as it was equally likely to be observed for cells with increases and decreases in firing rate. Careful analysis of the timescales of reliability in these neurons implies that they reflect both feedforward and feedback shape detecting processes. In approximately 7% of our recorded sample, individual neurons were able to predict both the delay and precision of the animal's shape detection performance. This suggests that a subset of V4 neurons may have been directly and causally contributing to task performance and that area V4 likely plays a critical role in guiding rapid, form-based foveation decisions. PMID:25278828

Compromised genomic integrity impedes muscle growth after Atrx inactivation

PubMed Central

Huh, Michael S.; Price O’Dea, Tina; Ouazia, Dahmane; McKay, Bruce C.; Parise, Gianni; Parks, Robin J.; Rudnicki, Michael A.; Picketts, David J.

2012-01-01

ATR-X syndrome is a severe intellectual disability disorder caused by mutations in the ATRX gene. Many ancillary clinical features are attributed to CNS deficiencies, yet most patients have muscle hypotonia, delayed ambulation, or kyphosis, pointing to an underlying skeletal muscle defect. Here, we identified a cell-intrinsic requirement for Atrx in postnatal muscle growth and regeneration in mice. Mice with skeletal muscle–specific Atrx conditional knockout (Atrx cKO mice) were viable, but by 3 weeks of age presented hallmarks of underdeveloped musculature, including kyphosis, 20% reduction in body mass, and 34% reduction in muscle fiber caliber. Atrx cKO mice also demonstrated a marked regeneration deficit that was not due to fewer resident satellite cells or their inability to terminally differentiate. However, activation of Atrx-null satellite cells from isolated muscle fibers resulted in a 9-fold reduction in myoblast expansion, caused by delayed progression through mid to late S phase. While in S phase, Atrx colocalized specifically to late-replicating chromatin, and its loss resulted in rampant signs of genomic instability. These observations support a model in which Atrx maintains chromatin integrity during the rapid developmental growth of a tissue. PMID:23114596

Working memory and decision processes in visual area v4.

PubMed

Hayden, Benjamin Y; Gallant, Jack L

2013-01-01

Recognizing and responding to a remembered stimulus requires the coordination of perception, working memory, and decision-making. To investigate the role of visual cortex in these processes, we recorded responses of single V4 neurons during performance of a delayed match-to-sample task that incorporates rapid serial visual presentation of natural images. We found that neuronal activity during the delay period after the cue but before the images depends on the identity of the remembered image and that this change persists while distractors appear. This persistent response modulation has been identified as a diagnostic criterion for putative working memory signals; our data thus suggest that working memory may involve reactivation of sensory neurons. When the remembered image reappears in the neuron's receptive field, visually evoked responses are enhanced; this match enhancement is a diagnostic criterion for decision. One model that predicts these data is the matched filter hypothesis, which holds that during search V4 neurons change their tuning so as to match the remembered cue, and thus become detectors for that image. More generally, these results suggest that V4 neurons participate in the perceptual, working memory, and decision processes that are needed to perform memory-guided decision-making.

Compact continuum brain model for human electroencephalogram

NASA Astrophysics Data System (ADS)

Kim, J. W.; Shin, H.-B.; Robinson, P. A.

2007-12-01

A low-dimensional, compact brain model has recently been developed based on physiologically based mean-field continuum formulation of electric activity of the brain. The essential feature of the new compact model is a second order time-delayed differential equation that has physiologically plausible terms, such as rapid corticocortical feedback and delayed feedback via extracortical pathways. Due to its compact form, the model facilitates insight into complex brain dynamics via standard linear and nonlinear techniques. The model successfully reproduces many features of previous models and experiments. For example, experimentally observed typical rhythms of electroencephalogram (EEG) signals are reproduced in a physiologically plausible parameter region. In the nonlinear regime, onsets of seizures, which often develop into limit cycles, are illustrated by modulating model parameters. It is also shown that a hysteresis can occur when the system has multiple attractors. As a further illustration of this approach, power spectra of the model are fitted to those of sleep EEGs of two subjects (one with apnea, the other with narcolepsy). The model parameters obtained from the fittings show good matches with previous literature. Our results suggest that the compact model can provide a theoretical basis for analyzing complex EEG signals.

Impact of Rapid Susceptibility Testing and Antibiotic Selection Strategy on the Emergence and Spread of Antibiotic Resistance in Gonorrhea

PubMed Central

Tuite, Ashleigh R; Gift, Thomas L; Chesson, Harrell W; Hsu, Katherine; Salomon, Joshua A; Grad, Yonatan H

2017-01-01

Abstract Background Increasing antibiotic resistance limits treatment options for gonorrhea. We examined the impact of a hypothetical point-of-care (POC) test reporting antibiotic susceptibility profiles on slowing resistance spread. Methods A mathematical model describing gonorrhea transmission incorporated resistance emergence probabilities and fitness costs associated with resistance based on characteristics of ciprofloxacin (A), azithromycin (B), and ceftriaxone (C). We evaluated time to 1% and 5% prevalence of resistant strains among all isolates with the following: (1) empiric treatment (B and C), and treatment guided by POC tests determining susceptibility to (2) A only and (3) all 3 antibiotics. Results Continued empiric treatment without POC testing was projected to result in >5% of isolates being resistant to both B and C within 15 years. Use of either POC test in 10% of identified cases delayed this by 5 years. The 3 antibiotic POC test delayed the time to reach 1% prevalence of triply-resistant strains by 6 years, whereas the A-only test resulted in no delay. Results were less sensitive to assumptions about fitness costs and test characteristics with increasing test uptake. Conclusions Rapid diagnostics reporting antibiotic susceptibility may extend the usefulness of existing antibiotics for gonorrhea treatment, but ongoing monitoring of resistance patterns will be critical. PMID:28968710

Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum.

PubMed

Inouye, M; Yamamura, H; Nakano, A

1995-09-01

Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 mumol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 micrograms/g at the time of irradiation and remaining at more than 40 micrograms/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositidemediated signaling systems regulate radiation-induced apoptosis.

Delay-slope-dependent stability results of recurrent neural networks.

PubMed

Li, Tao; Zheng, Wei Xing; Lin, Chong

2011-12-01

By using the fact that the neuron activation functions are sector bounded and nondecreasing, this brief presents a new method, named the delay-slope-dependent method, for stability analysis of a class of recurrent neural networks with time-varying delays. This method includes more information on the slope of neuron activation functions and fewer matrix variables in the constructed Lyapunov-Krasovskii functional. Then some improved delay-dependent stability criteria with less computational burden and conservatism are obtained. Numerical examples are given to illustrate the effectiveness and the benefits of the proposed method.

Synchronization and anti-synchronization of a fractional order delayed memristor-based chaotic system using active control

NASA Astrophysics Data System (ADS)

Ding, Dawei; Qian, Xin; Wang, Nian; Liang, Dong

2018-05-01

In this paper, the issue of synchronization and anti-synchronization for fractional-delayed memristor-based chaotic system is studied by using active control strategy. Firstly, some explicit conditions are proposed to guarantee the synchronization and anti-synchronization of the proposed system. Secondly, the influence of order and time delay on the synchronization (anti-synchronization) is discussed. It reveals that synchronization (anti-synchronization) is faster as the order increases or the time delay decreases. Finally, some numerical simulations are presented to verify the validity of our theoretical analysis.

Rapid Tachyphylaxis of the Glucagon-Like Peptide 1–Induced Deceleration of Gastric Emptying in Humans

PubMed Central

Nauck, Michael A.; Kemmeries, Guido; Holst, Jens J.; Meier, Juris J.

2011-01-01

OBJECTIVE Glucagon-like peptide (GLP)-1 lowers postprandial glycemia primarily through inhibition of gastric emptying. We addressed whether the GLP-1–induced deceleration of gastric emptying is subject to rapid tachyphylaxis and if so, how this would alter postprandial glucose control. RESEARCH DESIGN AND METHODS Nine healthy volunteers (25 ± 4 years old, BMI: 24.6 ± 4.7 kg/m2) were examined with intravenous infusion of GLP-1 (0.8 pmol · kg−1 . min−1) or placebo over 8.5 h. Two liquid mixed meals were administered at a 4-h interval. Gastric emptying was determined, and blood samples were drawn frequently. RESULTS GLP-1 decelerated gastric emptying significantly more after the first meal compared with the second meal (P = 0.01). This was associated with reductions in pancreatic polypeptide levels (marker of vagal activation) after the first but not the second meal (P < 0.05). With GLP-1, glucose concentrations declined after the first meal but increased after the second meal (P < 0.05). The GLP-1–induced reductions in postprandial insulin and C-peptide levels were stronger during the first meal course (P < 0.05). Likewise, glucagon levels were lowered by GLP-1 after the first meal but increased after the second test meal (P < 0.05). CONCLUSIONS The GLP-1–induced delay in gastric emptying is subject to rapid tachyphylaxis at the level of vagal nervous activation. As a consequence, postprandial glucose control by GLP-1 is attenuated after its chronic administration. PMID:21430088

Dreaming and electroencephalographic changes during anesthesia maintained with propofol or desflurane.

PubMed

Leslie, Kate; Sleigh, Jamie; Paech, Michael J; Voss, Logan; Lim, Chiew Woon; Sleigh, Callum

2009-09-01

Dream recall is reportedly more common after propofol than after volatile anesthesia, but this may be due to delayed emergence or more amnesia after longer-acting volatiles. The electroencephalographic signs of dreaming during anesthesia and the differences between propofol and desflurane also are unknown. The authors therefore compared dream recall after propofol- or desflurane-maintained anesthesia and analyzed electroencephalographic patterns in dreamers and nondreamers and in propofol and desflurane patients for similarities to rapid eye movement and non-rapid eye movement sleep. Three hundred patients presenting for noncardiac surgery were randomized to receive propofol- or desflurane-maintained anesthesia. The raw electroencephalogram was recorded from induction until patients were interviewed about dreaming when they became first oriented postoperatively. Using spectral and ordinal methods, the authors quantified the amount of sleep spindle-like activity and high-frequency power in the electroencephalogram. The incidence of dream recall was similar for propofol (27%) and desflurane (28%) patients. Times to interview were similar (median 20 [range 4-114] vs. 17 [7-86] min; P = 0.1029), but bispectral index values at interview were lower (85 [69-98] vs. 92 [40-98]; P < 0.0001) in propofol than in desflurane patients. During surgery, the raw electroencephalogram of propofol patients showed more and faster spindle activity than in desflurane patients (P < 0.001). The raw electroencephalogram of dreamers showed fewer spindles and more high-frequency power than in nondreamers in the 5 min before interview (P < 0.05). Anesthetic-related dreaming seems to occur just before awakening and is associated with a rapid eye movement-like electroencephalographic pattern.

Molecular basis of slow activation of the human ether-á-go-go related gene potassium channel

PubMed Central

Subbiah, Rajesh N; Clarke, Catherine E; Smith, David J; Zhao, JingTing; Campbell, Terence J; Vandenberg, Jamie I

2004-01-01

The human ether-á-go-go related gene (HERG) encodes the pore forming α-subunit of the rapid delayed rectifier K+ channel which is central to the repolarization phase of the cardiac action potential. HERG K+ channels have unusual kinetics characterized by slow activation and deactivation, yet rapid inactivation. The fourth transmembrane domain (S4) of HERG, like other voltage-gated K+ channels, contains multiple positive charges and is the voltage sensor for activation. In this study, we mutated each of the positively charged residues in this region to glutamine (Q), expressed the mutant and wild-type (WT) channels in Xenopus laevis oocytes and studied them using two-electrode voltage clamp methods. K525Q channels activated at more hyperpolarized potentials than WT, whereas all the other mutant channels activated at more depolarized potentials. All mutants except for R531Q also had a reduction in apparent gating charge associated with activation. Mutation of K525 to cysteine (C) resulted in a less dramatic phenotype than K525Q. The addition of the positively charged MTSET to K525C altered the phenotype to one more similar to K525Q than to WT. Therefore it is not charge per se, but the specific lysine side chain at position 525, that is crucial for stabilizing the closed state. When rates of activation and deactivation for WT and mutant channels were compared at equivalent total (chemical + electrostatic) driving forces, K525Q and R528Q accelerated activation but had no effect on deactivation, R531Q slowed activation and deactivation, R534Q accelerated activation but slowed deactivation and R537Q accelerated deactivation but had no effect on activation. The main conclusions we can draw from these data are that in WT channels K525 stabilizes the closed state, R531 stabilizes the open state and R534 participates in interactions that stabilize pre-open closed states. PMID:15181157

An active balance board system with real-time control of stiffness and time-delay to assess mechanisms of postural stability.

PubMed

Cruise, Denise R; Chagdes, James R; Liddy, Joshua J; Rietdyk, Shirley; Haddad, Jeffrey M; Zelaznik, Howard N; Raman, Arvind

2017-07-26

Increased time-delay in the neuromuscular system caused by neurological disorders, concussions, or advancing age is an important factor contributing to balance loss (Chagdes et al., 2013, 2016a,b). We present the design and fabrication of an active balance board system that allows for a systematic study of stiffness and time-delay induced instabilities in standing posture. Although current commercial balance boards allow for variable stiffness, they do not allow for manipulation of time-delay. Having two controllable parameters can more accurately determine the cause of balance deficiencies, and allows us to induce instabilities even in healthy populations. An inverted pendulum model of human posture on such an active balance board predicts that reduced board rotational stiffness destabilizes upright posture through board tipping, and limit cycle oscillations about the upright position emerge as feedback time-delay is increased. We validate these two mechanisms of instability on the designed balance board, showing that rotational stiffness and board time-delay induced the predicted postural instabilities in healthy, young adults. Although current commercial balance boards utilize control of rotational stiffness, real-time control of both stiffness and time-delay on an active balance board is a novel and innovative manipulation to reveal balance deficiencies and potentially improve individualized balance training by targeting multiple dimensions contributing to standing balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

The interhemispheric CA1 circuit governs rapid generalisation but not fear memory.

PubMed

Zhou, Heng; Xiong, Gui-Jing; Jing, Liang; Song, Ning-Ning; Pu, De-Lin; Tang, Xun; He, Xiao-Bing; Xu, Fu-Qiang; Huang, Jing-Fei; Li, Ling-Jiang; Richter-Levin, Gal; Mao, Rong-Rong; Zhou, Qi-Xin; Ding, Yu-Qiang; Xu, Lin

2017-12-19

Encoding specificity theory predicts most effective recall by the original conditions at encoding, while generalization endows recall flexibly under circumstances which deviate from the originals. The CA1 regions have been implicated in memory and generalization but whether and which locally separated mechanisms are involved is not clear. We report here that fear memory is quickly formed, but generalization develops gradually over 24 h. Generalization but not fear memory is impaired by inhibiting ipsilateral (ips) or contralateral (con) CA1, and by optogenetic silencing of the ipsCA1 projections onto conCA1. By contrast, in vivo fEPSP recordings reveal that ipsCA1-conCA1 synaptic efficacy is increased with delay over 24 h when generalization is formed but it is unchanged if generalization is disrupted. Direct excitation of ipsCA1-conCA1 synapses using chemogenetic hM3Dq facilitates generalization formation. Thus, rapid generalization is an active process dependent on bilateral CA1 regions, and encoded by gradual synaptic learning in ipsCA1-conCA1 circuit.

Rotifer neuropharmacology--III. Adrenergic drug effects on Brachionus plicatilis.

PubMed

Keshmirian, J; Nogrady, T

1987-01-01

Norepinephrine (NE) induces three pharmacological effects in Brachionus plicatilis. As a result of excitation the rate of ciliary motion and swimming increases, and the animals flip their foot constantly at a rapid rate. This rapid foot flipping was used as a specific model to measure adrenergic effects in B. plicatilis. Phenylephrine induces the same effect at identical efficacy, while isoproterenol and salbutamol, two beta-agonists, show one-half and one-tenth NE efficacy. The beta blocker propranolol and the alpha blocker tolazoline both antagonize foot flipping induced by NE. However, propranolol shows antagonism because it causes foot paralysis by itself. Timolol, another beta blocker but without the membrane effect of propranolol, does not antagonize the alpha receptor mediated NE effect, nor does it cause foot paralysis. Propranolol, timolol and tolazoline also show agonist activity, inducing foot flipping. NE does not antagonize the foot paralysis induced by propranolol, only its anesthetic effect by delaying its onset. These results indicate that the foot flipping induced by NE is a receptor-mediated alpha adrenergic effect, while the foot paralysis is caused by membrane phenomena.

Impairment of Swimming Motility by Antidiarrheic Lactobacillus acidophilus Strain LB Retards Internalization of Salmonella enterica Serovar Typhimurium within Human Enterocyte-Like Cells▿

PubMed Central

Liévin-Le Moal, Vanessa; Amsellem, Raymonde; Servin, Alain L.

2011-01-01

We report that both culture and the cell-free culture supernatant (CFCS) of Lactobacillus acidophilus strain LB (Lactéol Boucard) have the ability (i) to delay the appearance of Salmonella enterica serovar Typhimurium strain SL1344-induced mobilization of F-actin and, subsequently, (ii) to retard cell entry by S. Typhimurium SL1344. Time-lapse imaging and Western immunoblotting showed that S. Typhimurium SL1344 swimming motility, as represented by cell tracks of various types, was rapidly but temporarily blocked without affecting the expression of FliC flagellar propeller protein. We show that the product(s) secreted by L. acidophilus LB that supports the inhibitory activity is heat stable and of low molecular weight. The product(s) caused rapid depolarization of the S. Typhimurium SL1344 cytoplasmic membrane without affecting bacterial viability. We identified inhibition of swimming motility as a newly discovered mechanism by which the secreted product(s) of L. acidophilus strain LB retards the internalization of the diarrhea-associated pathogen S. enterica serovar Typhimurium within cultured human enterocyte-like cells. PMID:21825295

SPEEDY babies: A putative new behavioral syndrome of unbalanced motor-speech development

PubMed Central

Haapanen, Marja-Leena; Aro, Tuomo; Isotalo, Elina

2008-01-01

Even though difficulties in motor development in children with speech and language disorders are widely known, hardly any attention is paid to the association between atypically rapidly occurring unassisted walking and delayed speech development. The four children described here presented with a developmental behavioral triad: 1) atypically speedy motor development, 2) impaired expressive speech, and 3) tongue carriage dysfunction resulting in related misarticulations. Those characteristics might be phenotypically or genetically clustered. These children didn’t have impaired cognition, neurological or mental disease, defective sense organs, craniofacial dysmorphology or susceptibility to upper respiratory infections, particularly recurrent otitis media. Attention should be paid on discordant and unbalanced achievement of developmental milestones. Present children are termed SPEEDY babies, where SPEEDY refers to rapid independent walking, SPEE and DY to dyspractic or dysfunctional speech development and lingual dysfunction resulting in linguoalveolar misarticulations. SPEEDY babies require health care that recognizes and respects their motor skills and supports their needs for motor activities and on the other hand include treatment for impaired speech. The parents may need advice and support with these children. PMID:19337462

Relations among Temperament, Self-regulatory Strategies and Gender in Predicting Delay of Gratification.

PubMed

Hong, Fang; Doan, Stacey N; Lopez, Angelica; Evans, Gary W

2017-01-01

Self-regulation is associated with many positive outcomes, but there is limited information about individual difference regarding children's spontaneous use of strategies to self-regulate and the relative success of those strategies. In the current study, we examined whether temperament and gender are associated with self-regulation and explored the types of spontaneous strategies children use during Mischel's delay of gratification protocol. In addition, we investigated whether spontaneous strategy use during the task could moderate the effects of temperament on self-regulation and whether temperament would mediate the effect of gender on self-regulation. Participants were 349 9-year-olds (182 boys, M age = 9.18, SD = 1.17). Mothers reported on children's temperament and the Delay of Gratification task was used to assess self-regulation. Both temperament and child's gender were significantly associated with children's delay time. Girls were able to delay longer than boys, and children scoring high on activity level were less able to delay. Activity level also mediated the relationship between gender and delay time. Finally, we found an interaction effect between activity level and certain strategies in relation to self-regulatory behavior.

Relations among Temperament, Self-regulatory Strategies and Gender in Predicting Delay of Gratification

PubMed Central

Hong, Fang; Doan, Stacey N.; Lopez, Angelica; Evans, Gary W.

2017-01-01

Self-regulation is associated with many positive outcomes, but there is limited information about individual difference regarding children’s spontaneous use of strategies to self-regulate and the relative success of those strategies. In the current study, we examined whether temperament and gender are associated with self-regulation and explored the types of spontaneous strategies children use during Mischel’s delay of gratification protocol. In addition, we investigated whether spontaneous strategy use during the task could moderate the effects of temperament on self-regulation and whether temperament would mediate the effect of gender on self-regulation. Participants were 349 9-year-olds (182 boys, Mage = 9.18, SD = 1.17). Mothers reported on children’s temperament and the Delay of Gratification task was used to assess self-regulation. Both temperament and child’s gender were significantly associated with children’s delay time. Girls were able to delay longer than boys, and children scoring high on activity level were less able to delay. Activity level also mediated the relationship between gender and delay time. Finally, we found an interaction effect between activity level and certain strategies in relation to self-regulatory behavior. PMID:29163300

Caudate responses to reward anticipation associated with delay discounting behavior in healthy youth

PubMed Central

Benningfield, Margaret M.; Blackford, Jennifer U.; Ellsworth, Melissa E.; Samanez-Larkin, Gregory R.; Martin, Peter R.; Cowan, Ronald L.; Zald, David H.

2014-01-01

Background Choices requiring delay of gratification made during adolescence can have significant impact on life trajectory. Willingness to delay gratification can be measured using delay discounting tasks that require a choice between a smaller immediate reward and a larger delayed reward. Individual differences in the subjective value of delayed rewards are associated with risk for development of psychopathology including substance abuse. The neurobiological underpinnings related to these individual differences early in life are not fully understood. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that individual differences in delay discounting behavior in healthy youth are related to differences in responsiveness to potential reward. Method Nineteen 10 to 14 year-olds performed a monetary incentive delay task to assess neural sensitivity to potential reward and a questionnaire to measure discounting of future monetary rewards. Results Left ventromedial caudate activation during anticipation of potential reward was negatively correlated with delay discounting behavior. There were no regions where brain responses during notification of reward outcome were associated with discounting behavior. Conclusions Brain activation during anticipation of potential reward may serve as a marker for individual differences in ability or willingness to delay gratification in healthy youth. PMID:24309299

MRS evidence of adequate O2 supply in human skeletal muscle at the onset of exercise

PubMed Central

Richardson, Russell S.; Wary, Claire; Wray, D. Walter; Hoff, Jan; Rossiter, Harry; Layec, Gwenael; Carlier, Pierre G.

2015-01-01

Purpose At exercise onset, intramuscular oxidative energy production responds relatively slowly in comparison to the change in ATP demand. To determine if the slow kinetics of oxidative ATP production is due to inadequate O2 supply or metabolic inertia we studied the kinetics of intramyocellular deoxygenation (deoxy-myoglobin, Mb) and metabolism (phosphocreatine, PCr), using proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) in 6 healthy subjects (33 ± 5 yrs). Methods Specifically, utilizing dynamic plantar flexion exercise, rest to exercise and recovery was assessed at both 60% of maximum work rate (WRmax) (moderate intensity) and 80% of WRmax (heavy intensity). Results At exercise onset [PCr] fell without delay and with a similar time constant (τ) at both exercise intensities (~33 s). In contrast, the increase in deoxy-Mb was delayed at exercise onset by 5–7 s, after which it increased with kinetics (moderate τ = 37 ± 9 s, and heavy τ = 29 ± 6 s) that were not different from τPCr (p > 0.05). At cessation, deoxy-Mb recovered without a time delay and more rapidly (τ ~20 s) than PCr (τ ~33 s) (p < 0.05). Conclusion using a unique combination of in vivo MRS techniques with high time-resolution, this study revealed a delay in intramuscular de-oxygenation at the onset of exercise, and rapid re-oxygenation kinetics upon cessation. Together these data imply that intramuscular substrate-enzyme interactions, and not O2 availability, determine the exercise onset kinetics of oxidative metabolism in healthy human skeletal muscle. PMID:25830362

Electrochemical sensors for identifying pyocyanin production in clinical Pseudomonas aeruginosa isolates.

PubMed

Sismaet, Hunter J; Pinto, Ameet J; Goluch, Edgar D

2017-11-15

In clinical practice, delays in obtaining culture results impact patient care and the ability to tailor antibiotic therapy. Despite the advancement of rapid molecular diagnostics, the use of plate cultures inoculated from swab samples continues to be the standard practice in clinical care. Because the inoculation culture process can take between 24 and 48h before a positive identification test can be run, there is an unmet need to develop rapid throughput methods for bacterial identification. Previous work has shown that pyocyanin can be used as a rapid, redox-active biomarker for identifying Pseudomonas aeruginosa in clinical infections. However, further validation is needed to confirm pyocyanin production occurs in all clinical strains of P. aeruginosa. Here, we validate this electrochemical detection strategy using clinical isolates obtained from patients with hospital-acquired infections or with cystic fibrosis. Square-wave voltammetric scans of 94 different clinical P. aeruginosa isolates were taken to measure the concentration of pyocyanin. The results showed that all isolates produced measureable concentrations of pyocyanin with production rates correlated with patient symptoms and comorbidity. Further bioinformatics analysis confirmed that 1649 genetically sequenced strains (99.9%) of P. aeruginosa possess the two genes (PhzM and PhzS) necessary to produce pyocyanin, supporting the specificity of this biomarker. Confirming the production of pyocyanin by all clinically-relevant strains of P. aeruginosa is a significant step towards validating this strategy for rapid, point-of-care diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Vibrotactile masking experiments reveal accelerated somatosensory processing in congenitally blind braille readers.

PubMed

Bhattacharjee, Arindam; Ye, Amanda J; Lisak, Joy A; Vargas, Maria G; Goldreich, Daniel

2010-10-27

Braille reading is a demanding task that requires the identification of rapidly varying tactile patterns. During proficient reading, neighboring characters impact the fingertip at ∼100 ms intervals, and adjacent raised dots within a character at 50 ms intervals. Because the brain requires time to interpret afferent sensorineural activity, among other reasons, tactile stimuli separated by such short temporal intervals pose a challenge to perception. How, then, do proficient Braille readers successfully interpret inputs arising from their fingertips at such rapid rates? We hypothesized that somatosensory perceptual consolidation occurs more rapidly in proficient Braille readers. If so, Braille readers should outperform sighted participants on masking tasks, which demand rapid perceptual processing, but would not necessarily outperform the sighted on tests of simple vibrotactile sensitivity. To investigate, we conducted two-interval forced-choice vibrotactile detection, amplitude discrimination, and masking tasks on the index fingertips of 89 sighted and 57 profoundly blind humans. Sighted and blind participants had similar unmasked detection (25 ms target tap) and amplitude discrimination (compared with 100 μm reference tap) thresholds, but congenitally blind Braille readers, the fastest readers among the blind participants, exhibited significantly less masking than the sighted (masker, 50 Hz, 50 μm; target-masker delays, ±50 and ±100 ms). Indeed, Braille reading speed correlated significantly and specifically with masking task performance, and in particular with the backward masking decay time constant. We conclude that vibrotactile sensitivity is unchanged but that perceptual processing is accelerated in congenitally blind Braille readers.

Vibrotactile masking experiments reveal accelerated somatosensory processing in congenitally blind Braille readers

PubMed Central

Bhattacharjee, Arindam; Ye, Amanda J.; Lisak, Joy A.; Vargas, Maria G.; Goldreich, Daniel

2010-01-01

Braille reading is a demanding task that requires the identification of rapidly varying tactile patterns. During proficient reading, neighboring characters impact the fingertip at about 100-ms intervals, and adjacent raised dots within a character at 50-ms intervals. Because the brain requires time to interpret afferent sensorineural activity, among other reasons, tactile stimuli separated by such short temporal intervals pose a challenge to perception. How, then, do proficient Braille readers successfully interpret inputs arising from their fingertips at such rapid rates? We hypothesized that somatosensory perceptual consolidation occurs more rapidly in proficient Braille readers. If so, Braille readers should outperform sighted participants on masking tasks, which demand rapid perceptual processing, but would not necessarily outperform the sighted on tests of simple vibrotactile sensitivity. To investigate, we conducted two-interval forced-choice vibrotactile detection, amplitude discrimination, and masking tasks on the index fingertips of 89 sighted and 57 profoundly blind humans. Sighted and blind participants had similar unmasked detection (25-ms target tap) and amplitude discrimination (compared to 100-micron reference tap) thresholds, but congenitally blind Braille readers, the fastest readers among the blind participants, exhibited significantly less masking than the sighted (masker: 50-Hz, 50-micron; target-masker delays ±50 and ±100 ms). Indeed, Braille reading speed correlated significantly and specifically with masking task performance, and in particular with the backward masking decay time constant. We conclude that vibrotactile sensitivity is unchanged, but that perceptual processing is accelerated in congenitally blind Braille readers. PMID:20980584

Macrophage triggering by aggregated immunoglobulins. II. Comparison of IgE and IgG aggregates or immune complexes.

PubMed Central

Pestel, J; Dessaint, J P; Joseph, M; Bazin, H; Capron, A

1984-01-01

Macrophages incubated with complexed or aggregated IgE released beta-glucuronidase (beta-G) within 30 min. In contrast in the presence of aggregated or complexed IgG, macrophages liberated equivalent amount of beta-G only after 6 h incubation. In addition the rapid macrophage stimulation induced by aggregated IgE was also followed by a faster 3H-glucosamine incorporation when compared to the delayed activation caused by aggregated IgG. However, macrophages stimulated either by IgG or by IgE oligomers produced the same percentage of plasminogen activator at 24 h. In contrast, while the interaction between macrophages and aggregated IgE was only followed by a peak of cyclic GMP and a beta-G release during the first 30 min of incubation, the interaction between macrophages and IgG oligomers was accompanied by a simultaneous increase of cyclic GMP and AMP nucleotides and by an absence of beta-G exocytosis. Moreover, the beta-G release induced by aggregated IgE was increased when macrophages were preincubated with aggregated IgG. This additive effect was not observed in the reverse situation. Finally macrophages activated by IgG oligomers were demonstrated to exert a cytotoxic effect on tumour cells and to kill schistosomula in the presence of a low level of complement. Taken together these results underline the peculiar ability of aggregated or complexed IgE to trigger rapidly the macrophage activation compared to aggregated IgG and can explain the important role of complexed IgE in some macrophage dependent cytotoxicity mechanisms (i.e. in parasitic diseases). PMID:6088135

Pediatric Status Epilepticus Management

PubMed Central

Abend, Nicholas S; Loddenkemper, Tobias

2014-01-01

Purpose of Review This review discusses management of status epilepticus in children including both anticonvulsant medications and overall management approaches. Recent Findings Rapid management of status epilepticus is associated with a greater likelihood of seizure termination and better outcomes, yet data indicate there are often management delays. This review discusses an overall management approach aiming to simultaneously identify and manage underlying precipitant etiologies, administer anticonvulsants in rapid succession until seizures have terminated, and identify and manage systemic complications. An example management pathway is provided. Summary Status epilepticus is a common neurologic emergency in children and requires rapid intervention. Having a predetermined status epilepticus management pathway can expedite management. PMID:25304961

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay.

PubMed

Strickland, Justin C; Feinstein, Max A; Lacy, Ryan T; Smith, Mark A

2016-05-01

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-s delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

34 CFR 303.420 - Due process procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... infant's or toddler's development is so rapid that undue delay could be potentially harmful. [58 FR 40959... AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND... Children § 303.420 Due process procedures. Each system must include written procedures including procedures...

34 CFR 303.420 - Due process procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... infant's or toddler's development is so rapid that undue delay could be potentially harmful. [58 FR 40959... AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND... Children § 303.420 Due process procedures. Each system must include written procedures including procedures...

Rapid Functional Decline of Activated and Memory Graft-vs-Host-Reactive T Cells Encountering Host Antigens in the Absence of Inflammation

PubMed Central

Li, Hao Wei; Andreola, Giovanna; Carlson, Alicia; Shao, Steven; Lin, Charles; Zhao, Guiling; Sykes, Megan

2015-01-01

Inflammation in the priming host environment has critical effects on the graft-vs-host (GVH) responses mediated by naïve donor T cells. However, it is unclear how a quiescent or inflammatory environment impacts the activity of GVH-reactive primed T and memory cells. We show here that GVH-reactive primed donor T cells generated in irradiated recipients had diminished ability compared to naïve T cells to increase donor chimerism when transferred to quiescent mixed allogeneic chimeras. GVH-reactive primed T cells showed marked loss of cytotoxic function and activation and delayed but not decreased proliferation or accumulation in lymphoid tissues when transferred to quiescent mixed chimeras compared to freshly irradiated secondary recipients. Primed CD4 and CD8 T cells provided mutual help to sustain these functions in both subsets. CD8 help for CD4 cells was largely IFN-γ-dependent. Toll-like receptor (TLR) stimulation following transfer of GVH-reactive primed T cells to mixed chimeras restored their cytotoxic effector function and permitted the generation of more effective T cell memory in association with reduced PD-1 expression on CD4 memory cells. Our data indicate that an inflammatory host environment is required for the maintenance of GVH-reactive primed T cell functions and the generation of memory T cells that can rapidly acquire effector functions. These findings have important implications for GVHD and T cell-mediated immunotherapies. PMID:26085679

Visual Reliance for Balance Control in Older Adults Persists When Visual Information Is Disrupted by Artificial Feedback Delays

PubMed Central

Balasubramaniam, Ramesh

2014-01-01

Sensory information from our eyes, skin and muscles helps guide and correct balance. Less appreciated, however, is that delays in the transmission of sensory information between our eyes, limbs and central nervous system can exceed several 10s of milliseconds. Investigating how these time-delayed sensory signals influence balance control is central to understanding the postural system. Here, we investigate how delayed visual feedback and cognitive performance influence postural control in healthy young and older adults. The task required that participants position their center of pressure (COP) in a fixed target as accurately as possible without visual feedback about their COP location (eyes-open balance), or with artificial time delays imposed on visual COP feedback. On selected trials, the participants also performed a silent arithmetic task (cognitive dual task). We separated COP time series into distinct frequency components using low and high-pass filtering routines. Visual feedback delays affected low frequency postural corrections in young and older adults, with larger increases in postural sway noted for the group of older adults. In comparison, cognitive performance reduced the variability of rapid center of pressure displacements in young adults, but did not alter postural sway in the group of older adults. Our results demonstrate that older adults prioritize vision to control posture. This visual reliance persists even when feedback about the task is delayed by several hundreds of milliseconds. PMID:24614576

Delay in Seeking Care for Sexually Transmitted Diseases in Young Men and Women Attending a Public STD Clinic.

PubMed

Malek, Angela M; Chang, Chung-Chou H; Clark, Duncan B; Cook, Robert L

2013-01-01

Delay in seeking care for sexually transmitted diseases (STDs) has adverse consequences for both the individual and population. We sought to identify factors associated with delay in seeking care for STDs. Subjects included 300 young men and women (aged 15-24) attending an urban STD clinic for a new STD-related problem due to symptoms or referral for an STD screening. Subjects completed a structured interview that evaluated STD history, attitudes and beliefs about STDs, depression, substance use, and other factors possibly associated with delay. Delay was defined as waiting > 7 days to seek and obtain care for STDs. Nearly one-third of participants delayed seeking care for > 7 days. Significant predictors for delay included self-referral for symptoms as the reason for visit (OR 5.3, 95% CI: 2.58 - 10.98), and the beliefs "my partner would blame me if I had an STD" (OR 2.44, 95% CI: 1.30 - 4.60) and "it's hard to find time to get checked for STDs" (OR 3.62, 95% CI: 1.95 - 6.69), after adjusting for age, race, sex, and other factors. Agreeing with the statement "would use a STD test at home if one were available" was associated with a decrease in delay (OR 0.24, 95% CI: 0.09 - 0.60). Many young persons delay seeking care for STDs for a number of reasons. Strategies to improve STD care-seeking include encouragement of symptomatic persons to seek medical care more rapidly, reduction of social stigmas, and improved access to testing options.

A statistical frame based TDMA protocol for human body communication.

PubMed

Nie, Zedong; Li, Zhao; Huang, Renwei; Liu, Yuhang; Li, Jingzhen; Wang, Lei

2015-07-09

Human body communication (HBC) using the human body as the transmission medium, which has been regarded as one of the most promising short-range communications in wireless body area networks (WBAN). Compared to the traditional wireless networks, two challenges are existed in HBC based WBAN. (1) Its sensor nodes should be energy saving since it is inconvenient to replace or recharge the battery on these sensor nodes; (2) the coordinator should be able to react dynamically and rapidly to the burst traffic triggered by sensing events. Those burst traffic conditions include vital physical signal (electrocardiogram, electroencephalogram etc.) monitoring, human motion detection (fall detection, activity monitoring, gesture recognition, motion sensing etc.) and so on. To cope with aforementioned challenges, a statistical frame based TDMA (S-TDMA) protocol with multi-constrained (energy, delay, transmission efficiency and emergency management) service is proposed in this paper. The scenarios where burst traffic is often triggered rapidly with low power consumption and low delay is handled in our proposed S-TDMA. A beacon frame with the contained synchronous and poll information is designed to reduce the possibility of collisions of request frames. A statistical frame which broadcasts the unified scheduling information is adopted to avoid packet collisions, idle listening and overhearing. Dynamic time slot allocation mechanism is presented to manage the burst traffic and reduce the active period in each beacon period. An emergency mechanism is proposed for vital signals to be transmitted. The theory analysis is proceed and the result is evaluated in the hardware platform. To verify its feasibility, S-TDMA was fully implemented on our independently-developed HBC platform where four sensor nodes and a coordinator are fastened on a human body. Experiment results show that S-TDMA costs 89.397 mJ every 20 s when the payload size is 122 bytes, 9.51% lower than Lightweight MAC (LMAC); the average data latency of S-TDMA is 6.3 ms, 7.02% lower than Preamble-based TDMA (PB-TDMA); the transmission efficiency of S-TDMA is 93.67%, 4.83% higher than IEEE 802.15.6 carrier sense multiple access/collision avoidance (CSMA/CA) protocol. With respect to the challenges of HBC based WBANs, a novel S-TDMA protocol was proposed in this paper. Compared to the traditional protocols, the results demonstrate that S-TDMA successfully meets the delay and transmission efficiency requirements of HBC while keeping a low energy consumption. We also believe that our S-TDMA protocol will promote development of HBC in wearable applications.

Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line?

PubMed

Lawrence, Yaacov Richard; Blumenthal, Deborah T; Matceyevsky, Diana; Kanner, Andrew A; Bokstein, Felix; Corn, Benjamin W

2011-10-01

Glioblastoma is a malignant tumor characterized by a rapid proliferation rate. Contemporary multi-modality treatment consists of maximal surgical resection followed by radiation therapy (RT) combined with cytotoxic chemotherapy. The optimal timing of these different steps is not known. Four studies from the pre-temozolomide era, encompassing a total of 4,584 subjects, have examined the consequences of a delay between resection and starting RT. Whereas the two small single-institution studies found this delay to be detrimental, two large multi-institutional studies found delay to be either slightly beneficial or at least not harmful. Here, we critically compare the methodologies and results presented in these studies, and include a novel analysis of the combined datasets. We conclude that moderate wait periods (up to 4-6 weeks post-operatively) are safe and may be modestly beneficial. Conversely, there is no evidence to justify waiting longer than 6 weeks. Underlying radiobiological principles are discussed.

Delayed Surgical Debridement and Use of Semiocclusive Dressings for Salvage of Fingers After Purpura Fulminans.

PubMed

Pino, Paula A; Román, Javier A; Fernández, Felipe

2016-12-01

Background: Purpura fulminans is a condition characterized by rapidly evolving skin necrosis and disseminated intravascular coagulation. Early recognition and aggressive supportive management has led to a decrease in its mortality rate, but most of these patients must undergo extensive soft tissue debridement and partial or total limb amputation. There is controversial evidence about the timing of surgery, suggesting that some patients may benefit from delayed debridement with limb preservation. Methods: We present a case of an 86-year-old patient who developed skin necrosis of his four limbs after infectious purpura fulminans. He was treated in the ICU with supportive measures and antibiotic treatment. Surgical debridement was delayed for 4 weeks until necrosis delimitation. Results: Only upper extremity debridement was necessary. Four fingers, including one thumb, were salvaged and successfully treated with semi-occlusive dressing without complications. Conclusion: Early recognition of infectious PF and timely supportive management are important pillars of its treatment. Delayed surgical debridement allows for less aggressive resection and good functional outcome.

Differential regulation of the slow and rapid components of guinea-pig cardiac delayed rectifier K+ channels by hypoxia

PubMed Central

Hool, Livia C

2004-01-01

The aim of this study was to examine the effects of acute hypoxia on the slow (IKs) and rapid (IKr) components of the native delayed rectifier K+ channel in the absence and presence of the β-adrenergic receptor agonist isoproterenol (isoprenaline; Iso) using the whole-cell configuration of the patch-clamp technique. Hypoxia reversibly inhibited basal IKs. The effect could be mimicked by exposing the cells to the thiol-specific reducing agent dithiothreitol (DTT) and attenuated upon exposure of cells to the membrane-impermeant thiol-specific oxidizing compound 5,5′-dithio-bis[2-nitrobenzoic acid] (DTNB). In the presence of hypoxia, the K0.5 for activation of IKs by Iso was significantly decreased from 18.3 to 1.9 nm. DTT mimicked the effect of hypoxia on the sensitivity of IKs to Iso while DTNB had no effect. Hypoxia increased the sensitivity of IKs to histamine and forskolin suggesting that the effect of hypoxia is not occurring at the β-adrenergic receptor. The increase in sensitivity of IKs to Iso could be attenuated with addition of PKCβ peptide to the pipette solution. While hypoxia and DTT inhibited basal IKs they were without effect on IKr. In addition, Iso did not appear to alter the magnitude of IKr in the absence or presence of hypoxia. These data suggest that hypoxia regulates native IKs through two distinct mechanisms: direct inhibition of basal IKs and an increase in sensitivity to Iso that occurs downstream from the β-adrenergic receptor. Both mechanisms appear to involve redox modification of thiol groups. In contrast native IKr does not appear to be regulated by Iso, hypoxia or redox state. PMID:14634203

Source motion detection, estimation, and compensation for underwater acoustics inversion by wideband ambiguity lag-Doppler filtering.

PubMed

Josso, Nicolas F; Ioana, Cornel; Mars, Jérôme I; Gervaise, Cédric

2010-12-01

Acoustic channel properties in a shallow water environment with moving source and receiver are difficult to investigate. In fact, when the source-receiver relative position changes, the underwater environment causes multipath and Doppler scale changes on the transmitted signal over low-to-medium frequencies (300 Hz-20 kHz). This is the result of a combination of multiple paths propagation, source and receiver motions, as well as sea surface motion or water column fast changes. This paper investigates underwater acoustic channel properties in a shallow water (up to 150 m depth) and moving source-receiver conditions using extracted time-scale features of the propagation channel model for low-to-medium frequencies. An average impulse response of one transmission is estimated using the physical characteristics of propagation and the wideband ambiguity plane. Since a different Doppler scale should be considered for each propagating signal, a time-warping filtering method is proposed to estimate the channel time delay and Doppler scale attributes for each propagating path. The proposed method enables the estimation of motion-compensated impulse responses, where different Doppler scaling factors are considered for the different time delays. It was validated for channel profiles using real data from the BASE'07 experiment conducted by the North Atlantic Treaty Organization Undersea Research Center in the shallow water environment of the Malta Plateau, South Sicily. This paper provides a contribution to many field applications including passive ocean tomography with unknown natural sources position and movement. Another example is active ocean tomography where sources motion enables to rapidly cover one operational area for rapid environmental assessment and hydrophones may be drifting in order to avoid additional flow noise.

A 5-trial adjusting delay discounting task: Accurate discount rates in less than 60 seconds

PubMed Central

Koffarnus, Mikhail N.; Bickel, Warren K.

2014-01-01

Individuals who discount delayed rewards at a high rate are more likely to engage in substance abuse, overeating, or problem gambling. Findings such as these suggest the value of methods to obtain an accurate and fast measurement of discount rate that can be easily deployed in variety of settings. In the present study, we developed and evaluated the 5-trial adjusting delay task, a novel method of obtaining discount rate in less than one minute. We hypothesized that discount rates from the 5-trial adjusting delay task would be similar and correlated with discount rates from a lengthier task we have used previously, and that four known effects relating to delay discounting would be replicable with this novel task. To test these hypotheses, the 5-trial adjusting delay task was administered to 111 college students six times to obtain discount rates for six different commodities, along with a lengthier adjusting amount discounting task. We found that discount rates were similar and correlated between the 5-trial adjusting delay task and the adjusting amount task. Each of the four known effects relating to delay discounting was replicated with the 5-trial adjusting delay task to varying degrees. First, discount rates were inversely correlated with amount. Second, discount rates between past and future outcomes were correlated. Third, discount rates were greater for consumable rewards than with money, although we did not control for amount in this comparison. Fourth, discount rates were lower when zero amounts opposing the chosen time point were explicitly described. Results indicate that the 5-trial adjusting delay task is a viable, rapid method to assess discount rate. PMID:24708144

A 5-trial adjusting delay discounting task: accurate discount rates in less than one minute.

PubMed

Koffarnus, Mikhail N; Bickel, Warren K

2014-06-01

Individuals who discount delayed rewards at a high rate are more likely to engage in substance abuse, overeating, or problem gambling. Such findings suggest the value of methods to obtain an accurate and fast measurement of discount rate that can be easily deployed in variety of settings. In the present study, we developed and evaluated the 5-trial adjusting delay task, a novel method of obtaining a discount rate in less than 1 min. We hypothesized that discount rates from the 5-trial adjusting delay task would be similar and would correlate with discount rates from a lengthier task we have used previously, and that 4 known effects relating to delay discounting would be replicable with this novel task. To test these hypotheses, the 5-trial adjusting delay task was administered to 111 college students 6 times to obtain discount rates for 6 different commodities, along with a lengthier adjusting amount discounting task. We found that discount rates were similar and correlated between the 5-trial adjusting delay task and the adjusting amount task. Each of the 4 known effects relating to delay discounting was replicated with the 5-trial adjusting delay task to varying degrees. First, discount rates were inversely correlated with amount. Second, discount rates between past and future outcomes were correlated. Third, discount rates were greater for consumable rewards than with money, although we did not control for amount in this comparison. Fourth, discount rates were lower when $0 amounts opposing the chosen time point were explicitly described. Results indicate that the 5-trial adjusting delay task is a viable, rapid method to assess discount rate. PsycINFO Database Record (c) 2014 APA, all rights reserved.

REM Theta Activity Enhances Inhibitory Control in Typically Developing Children but not Children with ADHD Symptoms

PubMed Central

Cremone, Amanda; Lugo-Candelas, Claudia I.; Harvey, Elizabeth A.; McDermott, Jennifer M.; Spencer, Rebecca M. C.

2017-01-01

Sleep disturbances impair cognitive functioning in typically developing populations. Children with attention-deficit/hyperactivity disorder (ADHD), a disorder characterized by impaired inhibitory control and attention, commonly experience sleep disturbances. Whether inhibitory impairments are related to sleep deficits in children with ADHD is unknown. Children with ADHD (n = 18; Mage = 6.70 years) and typically developing controls (n = 15; Mage = 6.73 years) completed a Go/No-Go task to measure inhibitory control and sustained attention before and after polysomnography-monitored overnight sleep. Inhibitory control and sustained attention were improved following overnight sleep in typically developing children. Moreover, morning inhibitory control was positively correlated with rapid eye movement (REM) theta activity in this group. Although REM theta activity was greater in children with ADHD compared to typically developing children, it was functionally insignificant. Neither inhibitory control nor sustained attention were improved following overnight sleep in children with ADHD symptoms, and neither of these behaviors was associated with REM theta activity in this group. Taken together, these results indicate that elevated REM theta activity may be functionally related to ADHD symptomology, possibly reflecting delayed cortical maturation. PMID:28246970

Use of blood-pool imaging in evaluation of diffuse activity patterns in technetium-99m pyrophosphate myocardial scintigraphy.

PubMed

Cowley, M J; Mantle, J A; Rogers, W J; Russell, R O; Rackley, C E; Logic, J R

1979-06-01

It has been suggested that diffuse Tc-99m pyrophosphate precordial activity may be due to persistent blood-pool activity in routine delayed views during myocardial imaging. To answer this question, we reviewed myocardial scintigrams recorded 60--90 min following the injection of 12--15 mCi of Tc-99m pyrophosphate for the presence of diffuse precordial activity, and compared these with early images of the blood pool in 265 patients. Diffuse activity in the delayed images was identified in 48 patients: in 20 with acute myocardial infarction and in 28 with no evidence of it. Comparison of these routine delayed images with early views of the blood pool revealed two types of patterns. In patients with acute infarction, 95% had delayed images that were distinguishable from blood pool either because the activity was smaller than the early blood pool, or by the presence of localized activity superimposed on diffuse activity identical to blood pool. In those without infarction, 93% had activity distribution in routine delayed views matching that in the early blood-pool images. The usefulness of the diffuse TcPPi precordial activity in myocardial infarction is improved when early blood-pool imaging is used to exclude persistence of blood-pool activity as its cause. Moreover, it does not require additional amounts of radioactivity nor complex computer processing, a feature that may be of value in the community hospital using the technique to "rule out" infarction 24--72 hr after onset of suggestive symptoms.

Study on validity of a rapid diagnostic test kit versus light microscopy for malaria diagnosis in Ahmedabad city, India.

PubMed

Vyas, S; Puwar, B; Patel, V; Bhatt, G; Kulkarni, S; Fancy, M

2014-05-01

Light microscopy of blood smears for diagnosis of malaria in the field has several limitations, notably delays in diagnosis. This study in Ahmedabad in Gujarat State, India, evaluated the diagnostic performance of a rapid diagnostic test for malaria (SD Bioline Malaria Ag P.f/Pan) versus blood smear examination as the gold standard. All fever cases presenting at 13 urban health centres were subjected to rapid diagnostic testing and thick and thin blood smears. A total of 677 cases with fever were examined; 135 (20.0%) tested positive by rapid diagnostic test and 86 (12.7%) by blood smear. The sensitivity of the rapid diagnostic test for malaria was 98.8%, specificity was 91.5%, positive predictive value 63.0% and negative predictive value 99.8%. For detection of Plasmodium falciparum the sensitivity of rapid diagnostic test was 100% and specificity was 97.3%. The results show the acceptability of the rapid test as an alternative to light microscopy in the field setting.

Vision Problems and Reduced Reading Outcomes in Queensland Schoolchildren.

PubMed

Hopkins, Shelley; Sampson, Geoff P; Hendicott, Peter L; Wood, Joanne M

2017-03-01

To assess the relationship between vision and reading outcomes in Indigenous and non-Indigenous schoolchildren to determine whether vision problems are associated with lower reading outcomes in these populations. Vision testing and reading assessments were performed on 508 Indigenous and non-Indigenous schoolchildren in Queensland, Australia divided into two age groups: Grades 1 and 2 (6-7 years of age) and Grades 6 and 7 (12-13 years of age). Vision parameters measured included cycloplegic refraction, near point of convergence, heterophoria, fusional vergence range, rapid automatized naming, and visual motor integration. The following vision conditions were then classified based on the vision findings: uncorrected hyperopia, convergence insufficiency, reduced rapid automatized naming, and delayed visual motor integration. Reading accuracy and reading comprehension were measured with the Neale reading test. The effect of uncorrected hyperopia, convergence insufficiency, reduced rapid automatized naming, and delayed visual motor integration on reading accuracy and reading comprehension were investigated with ANCOVAs. The ANCOVAs explained a significant proportion of variance in both reading accuracy and reading comprehension scores in both age groups, with 40% of the variation in reading accuracy and 33% of the variation in reading comprehension explained in the younger age group, and 27% and 10% of the variation in reading accuracy and reading comprehension, respectively, in the older age group. The vision parameters of visual motor integration and rapid automatized naming were significant predictors in all ANCOVAs (P < .01). The direction of the relationship was such that reduced reading results were explained by reduced visual motor integration and rapid automatized naming results. Both reduced rapid automatized naming and visual motor integration were associated with poorer reading outcomes in Indigenous and non-Indigenous children. This is an important finding given the recent emphasis placed on Indigenous children's reading skills and the fact that reduced rapid automatized naming and visual motor integration skills are more common in this group.

Re‐estimated effects of deep episodic slip on the occurrence and probability of great earthquakes in Cascadia

USGS Publications Warehouse

Beeler, Nicholas M.; Roeloffs, Evelyn A.; McCausland, Wendy

2013-01-01

Mazzotti and Adams (2004) estimated that rapid deep slip during typically two week long episodes beneath northern Washington and southern British Columbia increases the probability of a great Cascadia earthquake by 30–100 times relative to the probability during the ∼58 weeks between slip events. Because the corresponding absolute probability remains very low at ∼0.03% per week, their conclusion is that though it is more likely that a great earthquake will occur during a rapid slip event than during other times, a great earthquake is unlikely to occur during any particular rapid slip event. This previous estimate used a failure model in which great earthquakes initiate instantaneously at a stress threshold. We refine the estimate, assuming a delayed failure model that is based on laboratory‐observed earthquake initiation. Laboratory tests show that failure of intact rock in shear and the onset of rapid slip on pre‐existing faults do not occur at a threshold stress. Instead, slip onset is gradual and shows a damped response to stress and loading rate changes. The characteristic time of failure depends on loading rate and effective normal stress. Using this model, the probability enhancement during the period of rapid slip in Cascadia is negligible (<10%) for effective normal stresses of 10 MPa or more and only increases by 1.5 times for an effective normal stress of 1 MPa. We present arguments that the hypocentral effective normal stress exceeds 1 MPa. In addition, the probability enhancement due to rapid slip extends into the interevent period. With this delayed failure model for effective normal stresses greater than or equal to 50 kPa, it is more likely that a great earthquake will occur between the periods of rapid deep slip than during them. Our conclusion is that great earthquake occurrence is not significantly enhanced by episodic deep slip events.

SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram.

PubMed

Waldinger, M D; Zwinderman, A H; Olivier, B

2001-12-01

Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it.

Mitigating delay and non-payment in the Malaysian construction industry

NASA Astrophysics Data System (ADS)

Mohamad, N.; Suman, A. S.; Harun, H.; Hashim, H.

2018-02-01

Construction industry is one of the industries that have contributed towards the rapid growth of development and economics in Malaysia. However, the industry is inundated with delay and non-payment issues between the two parties in contract that is the clients and contractors Even though there are contractual and administrative provisions in the standard forms of contract in Malaysia regarding payments, delay and non-payment issues still occur between them. The aim of the study is to develop measures to mitigate delay and non-payment issues between contractors and clients in the Malaysian construction industry. Questionnaire survey was conducted with clients and contractors in Klang Valley. Results from data analysis identified significant measures to mitigate delay and non-payment issues between contractors and clients which include contractors should submit their progress work invoicing with adequate documents; contractors should follow up constantly with client regarding payment; proper understanding of requirements with regards to payment; mutual discussion of problems with client to address problems in a timely manner and proper use of payment provisions in the standard form of contract. This study is significant to contractors and clients and to other construction players in order to reduce and minimise delay and non-payment issues for the growth of economy in the Malaysian construction industry.

Serotonin delays habituation of leech swim response to touch.

PubMed

Alkatout, Bilal A; Marvin, Nicole M; Crisp, Kevin M

2007-08-22

Serotonin, acting through a cAMP-signaling pathway, delayed habituation to criterion of the leech's swim response to touch. This delay was reversed by crushing the connective between serotonin-exposed and serotonin-naive ganglia, and correlated with an increase in spontaneous impulse activity in this connective. We suggest that increased activity in intersegmental interneurons may play a role in maintaining swim responsiveness when concentrations of serotonin are elevated.

Effect of the antitumoral alkylating agent 3-bromopyruvate on mitochondrial respiration: role of mitochondrially bound hexokinase.

PubMed

Rodrigues-Ferreira, Clara; da Silva, Ana Paula Pereira; Galina, Antonio

2012-02-01

The alkylating agent 3-Bromopyruvate (3-BrPA) has been used as an anti-tumoral drug due to its anti-proliferative property in hepatomas cells. This propriety is believed to disturb glycolysis and respiration, which leads to a decreased rate of ATP synthesis. In this study, we evaluated the effects of the alkylating agent 3-BrPA on the respiratory states and the metabolic steps of the mitochondria of mice liver, brain and in human hepatocarcinoma cell line HepG2. The mitochondrial membrane potential (ΔΨ(m)), O(2) consumption and dehydrogenase activities were rapidly dissipated/or inhibited by 3-BrPA in respiration medium containing ADP and succinate as respiratory substrate. 3-BrPA inhibition was reverted by reduced glutathione (GSH). Respiration induced by yeast soluble hexokinase (HK) was rapidly inhibited by 3-BrPA. Similar results were observed using mice brain mitochondria that present HK naturally bound to the outer mitochondrial membrane. When the adenine nucleotide transporter (ANT) was blocked by the carboxyatractiloside, the 3-BrPA effect was significantly delayed. In permeabilized human hepatoma HepG2 cells that present HK type II bound to mitochondria (mt-HK II), the inhibiting effect occurred faster when the endogenous HK activity was activated by 2-deoxyglucose (2-DOG). Inhibition of mt-HK II by glucose-6-phosphate retards the mitochondria to react with 3-BrPA. The HK activities recovered in HepG2 cells treated or not with 3-BrPA were practically the same. These results suggest that mitochondrially bound HK supporting the ADP/ATP exchange activity levels facilitates the 3-BrPA inhibition reaction in tumors mitochondria by a proton motive force-dependent dynamic equilibrium between sensitive and less sensitive SDH in the electron transport system.

Phospholipase B activity and organophosphorus compound toxicity in cultured neural cells

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

Read, David J.; Langford, Lynda; Barbour, Helen R.

2007-03-15

Organophosphorus compounds (OP) such as phenyl saligenin phosphate (PSP) and mipafox (MPX) which cause delayed neuropathy, inhibit neuropathy target esterase (NTE), while OPs such as paraoxon (PXN) react more readily with acetylcholinesterase. In yeast and mammalian cell lines, NTE has been shown to have phospholipase B (PLB) activity which deacylates intracellular phosphatidylcholine to glycerophosphocholine (GroPCho) and can be detected by metabolic labeling with [{sup 14}C]choline. Here we investigated PLB activity in primary cultures of mouse neural cells. In cortical and cerebellar granule neurons and astrocytes, [{sup 14}C]GroPCho labeling was inhibited by PSP and MPX: phenyl dipentylphosphinate (PDPP), a non-neuropathic NTEmore » inhibitor, was more potent, while PXN, was substantially less so. In all three cell types, conversion of [{sup 14}C]phosphatidylcholine to [{sup 14}C]GroPCho over 24 h was relatively small (2.3-14%). Consequently, even with > 80% inhibition of [{sup 14}C]GroPCho production, increased [{sup 14}C]phosphatidylcholine was not detected. At concentrations of 1-10 {mu}M, only PSP was cytotoxic to cortical and cerebellar granule neurons after 24-h exposure. Moreover, dramatic changes in glial cell morphology were induced by PSP, but not PDPP or MPX, with rapid (2-3 h) rounding up of astrocytes and of Schwann cells in cultures of dissociated mouse dorsal root ganglia. We conclude that PLB activity is present in a variety of cultured mouse neural cell types but that acute loss of this activity is not cytotoxic. Conversely, the rapid toxic effects of PSP in vitro suggest that a serine hydrolase distinct from NTE is required continuously by neurons and glia.« less

Active caspase-1 induces plasma membrane pores that precede pyroptotic lysis and are blocked by lanthanides#

PubMed Central

Russo, Hana M.; Rathkey, Joseph; Boyd-Tressler, Andrea; Katsnelson, Michael A.; Abbott, Derek W.; Dubyak, George R.

2016-01-01

Canonical inflammasome activation induces a caspase-1/gasdermin D (Gsdmd) dependent lytic cell death called pyroptosis which promotes anti-microbial host defense but may contribute to sepsis. The nature of the caspase-1-dependent change in plasma membrane (PM) permeability during pyroptotic progression remains incompletely defined. We assayed propidium2+ (Pro2+) influx kinetics during NLRP3 or Pyrin inflammasome activation in murine bone marrow-derived macrophages (BMDM) as an indicator of this PM permeabilization. BMDM were characterized by rapid Pro2+ influx after initiation of NLRP3 or Pyrin inflammasomes by nigericin or C. difficile toxin B (TcdB), respectively. No Pro2+ uptake in response to nigericin or TcdB was observed in Caspase-1−/− or ASC−/− BMDM. The cytoprotectant glycine profoundly suppressed nigericin and TcdB-induced lysis but not Pro2+ influx. The absence of Gsdmd expression resulted in suppression of nigericin-stimulated Pro2+ influx and pyroptotic lysis. Extracellular La3+ and Gd3+ rapidly and reversibly blocked the induced Pro2+ influx and markedly delayed pyroptotic lysis without limiting upstream inflammasome assembly and caspase-1 activation. Thus, caspase-1 driven pyroptosis requires induction of initial pre-lytic pores in the PM that are dependent on Gsdmd expression. These PM pores also facilitated the efflux of cytosolic ATP and influx of extracellular Ca2+. Although lanthanides and Gsdmd deletion both suppressed PM pore activity and pyroptotic lysis, robust IL-1β release was observed in lanthanide-treated BMDM but not in Gsdmd-deficient cells. This suggests roles for Gsdmd in both passive IL-1β release secondary to pyroptotic lysis and in non-lytic/non-classical IL-1β export. PMID:27385778

A new method for the noninvasive determination of abdominal muscle feedforward activity based on tissue velocity information from tissue Doppler imaging.

PubMed

Mannion, A F; Pulkovski, N; Schenk, P; Hodges, P W; Gerber, H; Loupas, T; Gorelick, M; Sprott, H

2008-04-01

Rapid arm movements elicit anticipatory activation of the deep-lying abdominal muscles; this appears modified in back pain, but the invasive technique used for its assessment [fine-wire electromyography (EMG)] has precluded its widespread investigation. We examined whether tissue-velocity changes recorded with ultrasound (M-mode) tissue Doppler imaging (TDI) provided a viable noninvasive alternative. Fourteen healthy subjects rapidly flexed, extended, and abducted the shoulder; recordings were made of medial deltoid (MD) surface EMG and of fine-wire EMG and TDI tissue-velocity changes of the contralateral transversus abdominis, obliquus internus, and obliquus externus. Muscle onsets were determined by blinded visual analysis of EMG and TDI data. TDI could not distinguish between the relative activation of the three muscles, so in subsequent analyses only the onset of the earliest abdominal muscle activity was used. The latter occurred <50 ms after the onset of medial deltoid EMG (i.e., was feedforward) and correlated with the corresponding EMG onsets (r = 0.47, P < 0.0001). The mean difference between methods was 20 ms and was likely explained by electromechanical delay; limits of agreement were wide (-40 to +80 ms) but no greater than those typical of repeated measurements using either technique. The between-day standard error of measurement of the TDI onsets (examined in 16 further subjects) was 16 ms. TDI yielded reliable and valid measures of the earliest onset of feedforward activity within the anterolateral abdominal muscle group. The method can be used to assess muscle dysfunction in large groups of back-pain patients and may also be suitable for the noninvasive analysis of other deep-lying or small/thin muscles.

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

PubMed Central

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-01-01

Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action. PMID:23610573

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction.

PubMed

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-03-01

To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I to), the rapidly activated omponent of delayed rectifier potassium current (I Kr), the slowly activated component of delayed rectifier potassium current (I Ks), and the L-type calcium current (I CaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.

Rapid genetic restoration of a keystone species exhibiting delayed demographic response

USDA-ARS?s Scientific Manuscript database

Genetic founder effects are often expected when animals colonize restored habitat in fragmented landscapes, but empirical data on genetic responses to restoration are limited. We examined the genetic response of banner-tailed kangaroo rats (Dipodomys spectabilis) to landscape-scale grassland restor...

Overload protection for switching regulators

NASA Technical Reports Server (NTRS)

Lachochi, E.

1980-01-01

Circuit protects all output lines of switching regulator against overloads without requiring current sensors on every line. If overload is sensed, device short circuits bias on switching transistor so that power is rapidly cut off from loads. Circuit also includes delay network to inhibit erroneous operation during startup.

Critical capacity, travel time delays and travel time distribution of rapid mass transit systems

NASA Astrophysics Data System (ADS)

Legara, Erika Fille; Monterola, Christopher; Lee, Kee Khoon; Hung, Gih Guang

2014-07-01

We set up a mechanistic agent-based model of a rapid mass transit system. Using empirical data from Singapore's unidentifiable smart fare card, we validate our model by reconstructing actual travel demand and duration of travel statistics. We subsequently use this model to investigate two phenomena that are known to significantly affect the dynamics within the RTS: (1) overloading in trains and (2) overcrowding in the RTS platform. We demonstrate that by varying the loading capacity of trains, a tipping point emerges at which an exponential increase in the duration of travel time delays is observed. We also probe the impact on the rail system dynamics of three types of passenger growth distribution across stations: (i) Dirac delta, (ii) uniform and (iii) geometric, which is reminiscent of the effect of land use on transport. Under the assumption of a fixed loading capacity, we demonstrate the dependence of a given origin-destination (OD) pair on the flow volume of commuters in station platforms.

Golf-course and funnel energy landscapes: Protein folding concepts in martensites

NASA Astrophysics Data System (ADS)

Shankaraiah, N.

2017-06-01

We use protein folding energy landscape concepts such as golf course and funnel to study re-equilibration in athermal martensites under systematic temperature quench Monte Carlo simulations. On quenching below a transition temperature, the seeded high-symmetry parent-phase austenite that converts to the low-symmetry product-phase martensite, through autocatalytic twinning or elastic photocopying, has both rapid conversions and incubation delays in the temperature-time-transformation phase diagram. We find the rapid (incubation delays) conversions at low (high) temperatures arises from the presence of large (small) size of golf-course edge that has the funnel inside for negative energy states. In the incubating state, the strain structure factor enters into the Brillouin-zone golf course through searches for finite transitional pathways which close off at the transition temperature with Vogel-Fulcher divergences that are insensitive to Hamiltonian energy scales and log-normal distributions, as signatures of dominant entropy barriers. The crossing of the entropy barrier is identified through energy occupancy distributions, Monte Carlo acceptance fractions, heat emission, and internal work.

A microwave-mediated saponification of galactosylceramide and galactosylceramide I3-sulfate and identification of their lyso-compounds by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

PubMed

Taketomi, T; Hara, A; Uemura, K; Kurahashi, H; Sugiyama, E

1996-07-16

Small amounts of galactosylceramide (cerebroside) and galactosylceramide I3-sulfate (sulfatide) obtained from porcine spinal cord and equine kidney were deacylated by a rapid method of microwave-mediated saponification to prepare their lyso-compounds. Mass spectra of their protonated or deprotonated molecular ion peaks were detected by recently developed new technology of a delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometer with reflector detector in positive or negative ion mode. Long chain bases of lysocerebroside and lysosulfatide were different between porcine spinal cord and equine kidney, but similar to each other in the same organ, suggesting their common synthetic pathway. It is noted that the new rapid method can be similarly applied to the deacylation of both cerebroside and sulfatide in contrast to our classical method which was able to be applied to cerebroside, but not to sulfatide.

Probing ultrafast dynamics of solid-density plasma generated by high-contrast intense laser pulses

NASA Astrophysics Data System (ADS)

Jana, Kamalesh; Blackman, David R.; Shaikh, Moniruzzaman; Lad, Amit D.; Sarkar, Deep; Dey, Indranuj; Robinson, Alex P. L.; Pasley, John; Ravindra Kumar, G.

2018-01-01

We present ultrafast dynamics of solid-density plasma created by high-contrast (picosecond contrast ˜10-9), high-intensity (˜4 × 1018 W/cm2) laser pulses using time-resolved pump-probe Doppler spectrometry. Experiments show a rapid rise in blue-shift at early time delay (2-4.3 ps) followed by a rapid fall (4.3-8.3 ps) and then a slow rise in blue-shift at later time delays (>8.3 ps). Simulations show that the early-time observations, specifically the absence of any red-shifting of the reflected probe, can only be reproduced if the front surface is unperturbed by the laser pre-pulse at the moment that the high intensity pulse arrives. A flexible diagnostic which is capable of diagnosing the presence of low-levels of pre-plasma formation would be useful for potential applications in laser-produced proton and ion production, such as cancer therapy and security imaging.

Effects of gas-wall partitioning in Teflon tubing and instrumentation on time-resolved measurements of gas-phase organic compounds

NASA Astrophysics Data System (ADS)

Pagonis, Demetrios; Krechmer, Jordan E.; de Gouw, Joost; Jimenez, Jose L.; Ziemann, Paul J.

2017-12-01

Recent studies have demonstrated that organic compounds can partition from the gas phase to the walls in Teflon environmental chambers and that the process can be modeled as absorptive partitioning. Here these studies were extended to investigate gas-wall partitioning of organic compounds in Teflon tubing and inside a proton-transfer-reaction mass spectrometer (PTR-MS) used to monitor compound concentrations. Rapid partitioning of C8-C14 2-ketones and C11-C16 1-alkenes was observed for compounds with saturation concentrations (c∗) in the range of 3 × 104 to 1 × 107 µg m-3, causing delays in instrument response to step-function changes in the concentration of compounds being measured. These delays vary proportionally with tubing length and diameter and inversely with flow rate and c∗. The gas-wall partitioning process that occurs in tubing is similar to what occurs in a gas chromatography column, and the measured delay times (analogous to retention times) were accurately described using a linear chromatography model where the walls were treated as an equivalent absorbing mass that is consistent with values determined for Teflon environmental chambers. The effect of PTR-MS surfaces on delay times was also quantified and incorporated into the model. The model predicts delays of an hour or more for semivolatile compounds measured under commonly employed conditions. These results and the model can enable better quantitative design of sampling systems, in particular when fast response is needed, such as for rapid transients, aircraft, or eddy covariance measurements. They may also allow estimation of c∗ values for unidentified organic compounds detected by mass spectrometry and could be employed to introduce differences in time series of compounds for use with factor analysis methods. Best practices are suggested for sampling organic compounds through Teflon tubing.

Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells.

PubMed

Yuan, X J; Wang, J; Juhaszova, M; Golovina, V A; Rubin, L J

1998-04-01

K(+)-channel activity-mediated alteration of the membrane potential and cytoplasmic free Ca2+ concentration ([Ca2+]cyt) is a pivotal mechanism in controlling pulmonary vasomotor tone. By using combined approaches of patch clamp, imaging fluorescent microscopy, and molecular biology, we examined the electrophysiological properties of K+ channels and the role of different K+ currents in regulating [Ca2+]cyt and explored the molecular identification of voltage-gated K+ (KV)- and Ca(2+)-activated K+ (KCa)-channel genes expressed in pulmonary arterial smooth muscle cells (PASMC). Two kinetically distinct KV currents [IK(V)], a rapidly inactivating (A-type) and a noninactivating delayed rectifier, as well as a slowly activated KCa current [IK(Ca)] were identified. IK(V) was reversibly inhibited by 4-aminopyridine (5 mM), whereas IK(Ca) was significantly inhibited by charybdotoxin (10-20 nM). K+ channels are composed of pore-forming alpha-subunits and auxiliary beta-subunits. Five KV-channel alpha-subunit genes from the Shaker subfamily (KV1.1, KV1.2, KV1.4, KV1.5, and KV1.6), a KV-channel alpha-subunit gene from the Shab subfamily (KV2.1), a KV-channel modulatory alpha-subunit (KV9.3), and a KCa-channel alpha-subunit gene (rSlo), as well as three KV-channel beta-subunit genes (KV beta 1.1, KV beta 2, and KV beta 3) are expressed in PASMC. The data suggest that 1) native K+ channels in PASMC are encoded by multiple genes; 2) the delayed rectifier IK(V) may be generated by the KV1.1, KV1.2, KV1.5, KV1.6, KV2.1, and/or KV2.1/KV9.3 channels; 3) the A-type IK(V) may be generated by the KV1.4 channel and/or the delayed rectifier KV channels (KV1 subfamily) associated with beta-subunits; and 4) the IK(Ca) may be generated by the rSlo gene product. The function of the KV channels plays an important role in the regulation of membrane potential and [Ca2+]cyt in PASMC.

Solar wind electron densities from Viking dual-frequency radio measurements

NASA Technical Reports Server (NTRS)

Muhleman, D. O.; Anderson, J. D.

1981-01-01

Simultaneous phase coherent, two-frequency measurements of the time delay between the earth station and the Viking spacecraft have been analyzed in terms of the electron density profiles from 4 solar radii to 200 solar radii. The measurements were made during a period of solar activity minimum (1976-1977) and show a strong solar latitude effect. The data were analyzed with both a model independent, direct numerical inversion technique and with model fitting, yielding essentially the same results. It is shown that the solar wind density can be represented by two power laws near the solar equator proportional to r exp -2.7 and r exp -2.04. However, the more rapidly falling term quickly disappears at moderate latitudes (approximately 20 deg) leaving only the inverse-square behavior.

Bi-frontal direct current stimulation affects delay discounting choices.

PubMed

Hecht, David; Walsh, Vincent; Lavidor, Michal

2013-01-01

In delay discounting tasks, participants decide between receiving a certain amount of money now or a larger sum sometime in the future. This study investigated the effects of transcranial direct current stimulation on delay discounting. Participants made delay discounting choices while receiving a bi-frontal stimulation of right-hemisphere anodal/left-hemisphere cathodal, left-hemisphere anodal/right-hemisphere cathodal, and sham stimulation, in three separate sessions. When the difference between the alternatives was 10% or more, participants generally preferred to wait for the larger sum. Nevertheless, there were more choices of smaller "immediate" gains, instead of the larger delayed options, when the left dorsolateral prefrontal cortex (DLPFC) was facilitated and the right DLPFC inhibited, compared to the sham stimulation. These observations indicate the significant role of the prefrontal cortex in delay discounting choices, and demonstrate that increased left frontal activation combined with decreased right frontal activation can alter decision-making by intensifying a tendency to choose immediate gains.

Reduced Plasminogen Binding and Delayed Activation Render γ′-Fibrin More Resistant to Lysis than γA-Fibrin*

PubMed Central

Kim, Paul Y.; Vu, Trang T.; Leslie, Beverly A.; Stafford, Alan R.; Fredenburgh, James C.; Weitz, Jeffrey I.

2014-01-01

Fibrin (Fn) clots formed from γ′-fibrinogen (γ′-Fg), a variant with an elongated γ-chain, are resistant to lysis when compared with clots formed from the predominant γA-Fg, a finding previously attributed to differences in clot structure due to delayed thrombin-mediated fibrinopeptide (FP) B release or impaired cross-linking by factor XIIIa. We investigated whether slower lysis of γ′-Fn reflects delayed plasminogen (Pg) binding and/or activation by tissue plasminogen activator (tPA), reduced plasmin-mediated proteolysis of γ′-Fn, and/or altered cross-linking. Clots formed from γ′-Fg lysed more slowly than those formed from γA-Fg when lysis was initiated with tPA/Pg when FPA and FPB were both released, but not when lysis was initiated with plasmin, or when only FPA was released. Pg bound to γ′-Fn with an association rate constant 22% lower than that to γA-Fn, and the lag time for initiation of Pg activation by tPA was longer with γ′-Fn than with γA-Fn. Once initiated, however, Pg activation kinetics were similar. Factor XIIIa had similar effects on clots formed from both Fg isoforms. Therefore, slower lysis of γ′-Fn clots reflects delayed FPB release, which results in delayed binding and activation of Pg. When clots were formed from Fg mixtures containing more than 20% γ′-Fg, the upper limit of the normal level, the delay in lysis was magnified. These data suggest that circulating levels of γ′-Fg modulate the susceptibility of clots to lysis by slowing Pg activation by tPA and provide another example of the intimate connections between coagulation and fibrinolysis. PMID:25128532

Local Immediate versus Long-Range Delayed Changes in Functional Connectivity Following rTMS on the Visual Attention Network.

PubMed

Battelli, Lorella; Grossman, Emily D; Plow, Ela B

The interhemispheric competition hypothesis attributes the distribution of selective attention to a balance of mutual inhibition between homotopic, interhemispheric connections in parietal cortex (Kinsbourne 1977; Battelli et al., 2009). In support of this hypothesis, repetitive inhibitory TMS over right parietal cortex in healthy individuals rapidly induces interhemispheric imbalance in cortical activity that spreads beyond the site of stimulation (Plow et al., 2014). Behaviorally, the impacts of inhibitory rTMS may be long delayed from the onset of stimulation, as much as 30 minutes (Agosta et al., 2014; Hubl et al., 2008). In this study, we examine the temporal dynamics of inhibitory rTMS on cortical network integrity that supports sustained visual attention. Healthy individuals received 15 min of 1 Hz offline, inhibitory rTMS (or sham) over left parietal cortex, and then immediately engaged in a bilateral visual tracking task while we recorded brain activity with fMRI. We computed functional connectivity (FC) between three nodes of the attention network engaged by visual tracking: the intraparietal sulcus (IPS), frontal eye fields (FEF) and human MT+ (hMT+). FC immediately and significantly decreased between the stimulation site (left IPS) and all other regions, then recovered to normal levels within 30 minutes. rTMS increased FC between left and right FEF at approximately 36 min following stimulation, and between sites in the unstimulated hemisphere approximately 48 min after stimulation. These findings demonstrate large-scale changes in cortical organization following inhibitory rTMS. The immediate impact of rTMS on connectivity to the stimulation site dovetails with the putative role of interhemispheric balance for bilateral visual sustained attention. The delayed, compensatory increases in functional connectivity have implications for models of dynamic reorganization in networks supporting spatial and nonspatial selective attention, and compensatory mechanisms within these networks that may be stabilized in chronic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

The effectiveness of graded activity for low back pain in occupational healthcare.

PubMed

Steenstra, I A; Anema, J R; Bongers, P M; de Vet, H C W; Knol, D L; van Mechelen, W

2006-11-01

Low back pain is a common medical and social problem associated with disability and absence from work. Knowledge on effective return to work (RTW) interventions is scarce. To determine the effectiveness of graded activity as part of a multistage RTW programme. Randomised controlled trial. Occupational healthcare. 112 workers absent from work for more than eight weeks due to low back pain were randomised to either graded activity (n = 55) or usual care (n = 57). Graded activity, a physical exercise programme aimed at RTW based on operant-conditioning behavioural principles. The number of days off work until first RTW for more then 28 days, total number of days on sick leave during follow up, functional status, and severity of pain. Follow up was 26 weeks. Graded activity prolonged RTW. Median time until RTW was equal to the total number of days on sick leave and was 139 (IQR = 69) days in the graded activity group and 111 (IQR = 76) days in the usual care group (hazard ratio = 0.52, 95% CI 0.32 to 0.86). An interaction between a prior workplace intervention and graded activity, together with a delay in the start of the graded activity intervention, explained most of the delay in RTW (hazard ratio = 0.86, 95% CI 0.40 to 1.84 without prior intervention and 0.39, 95% CI 0.19 to 0.81 with prior intervention). Graded activity did not improve pain or functional status clinically significantly. Graded activity was not effective for any of the outcome measures. Different interventions combined can lead to a delay in RTW. Delay in referral to graded activity delays RTW. In implementing graded activity special attention should be paid to the structure and process of care.

Positive and negative modulation of circadian activity rhythms by mGluR5 and mGluR2/3 metabotropic glutamate receptors.

PubMed

Gannon, Robert L; Millan, Mark J

2011-01-01

Glutamate released from retinal ganglion cells conveys information about the daily light:dark cycle to master circadian pacemaker neurons within the suprachiasmatic nucleus that then synchronize internal circadian rhythms with the external day-length. Glutamate activation of ionotropic glutamate receptors in the suprachiasmatic nucleus is well established, but the function of the metabotropic glutamate receptors that are also located in this nucleus is not known. Therefore, in this study we evaluated agonists and antagonists acting at orthosteric or allosteric sites for mGluR5 and mGluR2/3 metabotropic glutamate receptors for their ability to modulate light-induced phase advances and delays of hamster circadian activity rhythms. mGluR5 allosteric antagonists fenobam, MPEP and MTEP, each 10 mg/kg, potentiated light-induced phase advances of hamster circadian activity rhythms, while the mGluR5 agonists CHPG, (S)-3,5-DHPG or positive allosteric modulator CDPPB had no effect. Neither mGluR5 agonists nor antagonists had any effect on light-induced phase delays of activity rhythms. The competitive mGluR2/3 antagonist LY341495, 10 mg/kg, also potentiated light-induced phase advances, but inhibited light-induced phase delays. The mGluR2/3 agonists LY354740 and LY404039 were without effect on phase advances while a third agonist LY379268, 10 mg/kg, inhibited both light-induced advances and delays. Finally, mGluR2/3 agonists LY379268 and LY404039 also inhibited light-induced phase delays of activity rhythms. These results suggest that during light-induced phase advances, mGluR2/3 and mGluR5 receptors act to negatively modulate the effects of light on the circadian pacemaker or its output(s). mGluR5 receptors do not appear to be involved during light-induced phase delays. In contrast, the role for mGluR2/3 receptors during phase delays is more complicated as both agonists and antagonists inhibit light-induced phase delays. Dysfunctions in human circadian rhythms have been implicated in some forms of depression, and metabotropic glutamate receptor ligands, which are also being evaluated for antidepressant activity, are shown here to be capable of modifying light-induced phase shifts of circadian activity rhythms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Does Early Versus Delayed Active Range of Motion Affect Rotator Cuff Healing After Surgical Repair? A Systematic Review and Meta-analysis.

PubMed

Kluczynski, Melissa A; Isenburg, Maureen M; Marzo, John M; Bisson, Leslie J

2016-03-01

The timing of passive range of motion (ROM) after surgical repair of the rotator cuff (RC) has been shown to affect healing. However, it is unknown if early or delayed active ROM affects healing. To determine whether early versus delayed active ROM affects structural results of RC repair surgery. Systematic review and meta-analysis. A systematic review of articles published between January 2004 and April 2014 was conducted. Structural results were compared for early (<6 weeks after surgery) versus delayed (≥6 weeks after surgery) active ROM using chi-square and Fisher exact tests, as well as relative risks (RRs) and 95% CIs. The analyses were stratified by tear size and repair method. A total of 37 studies (2251 repairs) were included in the analysis, with 10 (649 repairs) in the early group and 27 (1602 repairs) in the delayed group. For tears ≤3 cm, the risk of a structural tendon defect was higher in the early versus delayed group for transosseous plus single-row suture anchor repairs (39.7% vs 24.3%; RR, 1.63 [95% CI, 1.28-2.08]). For tears >3 cm, the risk of a structural tendon defect was higher in the early versus delayed group for suture bridge repairs (48% vs 17.5%; RR, 2.74 [95% CI, 1.59-4.73]) and all repair methods combined (40.5% vs 26.7%; RR, 1.52 [95% CI, 1.17-1.97]). For tears >5 cm, the risk of structural tendon defect was higher in the early versus delayed group for suture bridge repairs (100% vs 16.7%; RR, 6.00 [95% CI, 1.69-21.26]). There were no statistically significant associations for tears measuring ≤1, 1-3, or 3-5 cm. Early active ROM was associated with increased risk of a structural defect for small and large RC tears, and thus might not be advisable after RC repair. © 2015 The Author(s).

Delaying the international spread of pandemic influenza.

PubMed

Cooper, Ben S; Pitman, Richard J; Edmunds, W John; Gay, Nigel J

2006-06-01

The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected. Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.

Gravitational lensing, time delay, and gamma-ray bursts

NASA Technical Reports Server (NTRS)

Mao, Shude

1992-01-01

The probability distributions of time delay in gravitational lensing by point masses and isolated galaxies (modeled as singular isothermal spheres) are studied. For point lenses (all with the same mass) the probability distribution is broad, and with a peak at delta(t) of about 50 S; for singular isothermal spheres, the probability distribution is a rapidly decreasing function with increasing time delay, with a median delta(t) equals about 1/h month, and its behavior depends sensitively on the luminosity function of galaxies. The present simplified calculation is particularly relevant to the gamma-ray bursts if they are of cosmological origin. The frequency of 'recurrent' bursts due to gravitational lensing by galaxies is probably between 0.05 and 0.4 percent. Gravitational lensing can be used as a test of the cosmological origin of gamma-ray bursts.

It's about time: Earlier rewards increase intrinsic motivation.

PubMed

Woolley, Kaitlin; Fishbach, Ayelet

2018-06-01

Can immediate (vs. delayed) rewards increase intrinsic motivation? Prior research compared the presence versus absence of rewards. By contrast, this research compared immediate versus delayed rewards, predicting that more immediate rewards increase intrinsic motivation by creating a perceptual fusion between the activity and its goal (i.e., the reward). In support of the hypothesis, framing a reward from watching a news program as more immediate (vs. delayed) increased intrinsic motivation to watch the program (Study 1), and receiving more immediate bonus (vs. delayed, Study 2; and vs. delayed and no bonus, Study 3) increased intrinsic motivation in an experimental task. The effect of reward timing was mediated by the strength of the association between an activity and a reward, and was specific to intrinsic (vs. extrinsic) motivation-immediacy influenced the positive experience of an activity, but not perceived outcome importance (Study 4). In addition, the effect of the timing of rewards was independent of the effect of the magnitude of the rewards (Study 5). (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Involvement of cannabinoid system in the nucleus accumbens on delay-based decision making in the rat.

PubMed

Fatahi, Zahra; Sadeghi, Bahman; Haghparast, Abbas

2018-01-30

The nucleus accumbens (NAc) plays a fundamental role in decision making and anticipation of reward. In addition, exogenous cannabinoids affect the behavior of humans and animals including disruption of short-term memory and cognitive impairments. Therefore, in this study, cannabinoid agonist and antagonist were administrated into the NAc to determine the effect of cannabinoid activation in the entire NAc on delay-based decision making. Rats were trained on a cost-benefit T-maze decision making task in which the animals were well-trained to choose between a small/immediate reward and a large/delay reward. After training, the animals were implanted with guide cannulae in the NAc. On test day, they received cannabinoid agonist (Win 55,212-2; 10, 50 and 100μM) and/or antagonist (AM251; 45μM) into the NAc. Percentage of high reward choice and latency of reward achievement were evaluated. Results showed that cannabinoid agonist administration caused a decrease in high reward choice such that rats selected small/immediate reward instead of large/delay reward. Moreover, in agonist-treated animals latency of reward achievement increased. Effects of cannabinoid activation on delay-based decision making with equivalent delays demonstrated that if the delay was equated on both arm goals, animals still had a preference for the high/delay reward, showing the results was not caused by an impairment of spatial preference or memory. These finding clarified that cannabinoid system activation in the entire NAc plays a critical role in the regulation of delay-based decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

Implementation of a national anti-tuberculosis drug resistance survey in Tanzania

PubMed Central

Chonde, Timothy M; Doulla, Basra; van Leth, Frank; Mfinanga, Sayoki GM; Range, Nyagosya; Lwilla, Fred; Mfaume, Saidi M; van Deun, Armand; Zignol, Matteo; Cobelens, Frank G; Egwaga, Saidi M

2008-01-01

Background A drug resistance survey is an essential public health management tool for evaluating and improving the performance of National Tuberculosis control programmes. The current manuscript describes the implementation of the first national drug resistance survey in Tanzania. Methods Description of the implementation process of a national anti-tuberculosis drug resistance survey in Tanzania, in relation to the study protocol and Standard Operating Procedures. Results Factors contributing positively to the implementation of the survey were a continuous commitment of the key stakeholders, the existence of a well organized National Tuberculosis Programme, and a detailed design of cluster-specific arrangements for rapid sputum transportation. Factors contributing negatively to the implementation were a long delay between training and actual survey activities, limited monitoring of activities, and an unclear design of the data capture forms leading to difficulties in form-filling. Conclusion Careful preparation of the survey, timing of planned activities, a strong emphasis on data capture tools and data management, and timely supervision are essential for a proper implementation of a national drug resistance survey. PMID:19116022

Coding of visual object features and feature conjunctions in the human brain.

PubMed

Martinovic, Jasna; Gruber, Thomas; Müller, Matthias M

2008-01-01

Object recognition is achieved through neural mechanisms reliant on the activity of distributed coordinated neural assemblies. In the initial steps of this process, an object's features are thought to be coded very rapidly in distinct neural assemblies. These features play different functional roles in the recognition process--while colour facilitates recognition, additional contours and edges delay it. Here, we selectively varied the amount and role of object features in an entry-level categorization paradigm and related them to the electrical activity of the human brain. We found that early synchronizations (approx. 100 ms) increased quantitatively when more image features had to be coded, without reflecting their qualitative contribution to the recognition process. Later activity (approx. 200-400 ms) was modulated by the representational role of object features. These findings demonstrate that although early synchronizations may be sufficient for relatively crude discrimination of objects in visual scenes, they cannot support entry-level categorization. This was subserved by later processes of object model selection, which utilized the representational value of object features such as colour or edges to select the appropriate model and achieve identification.

The Tropospheric Products of the International VLBI Service for Geodesy and Astrometry

NASA Technical Reports Server (NTRS)

Heinkelmann, Robert; Schwatke, Christian

2010-01-01

The IVS runs two tropospheric products: The IVS tropospheric parameter rapid combination monitors the zenith wet delay (ZWD) and zenith total delay (ZTD) of the rapid turnaround sessions R1 and R4. Goal of the combination is the identification and the exclusion of outliers by comparison and the assessment of the precision of current VLBI solutions in terms of tropospheric parameters. The rapid combination is done on a weekly basis four weeks after the observation files are released on IVS Data Centers. Since tropospheric and geodetic parameters, such as vertical station components, can significantly correlate, the consistency of the ZTD can be a measure of the consistency of the corresponding TRF as well. The ZWD mainly rely on accurate atmospheric pressure data. Thus, besides estimation techniques, modeling and analyst s noise, ZWD reflects differences in the atmospheric pressure data applied to the VLBI analysis. The second product, called tropospheric parameter long-term combination, aims for an accurate determination of climatological signals, such as trends of the atmospheric water vapor observed by VLBI. Therefore, the long-term homogeneity of atmospheric pressure data plays a crucial role for this product. The paper reviews the methods applied and results achieved so far and describes the new maintenance through DGFI.

77 FR 11137 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... nonspecific, and the diagnosis is frequently difficult and delayed. The inventors established a rapid ELISA assay to evaluate biomarker levels in serum. The ELISA assay tests a novel combination of two biomarkers...-invasive ELISA serum assay. Potential for high sensitivity. Cost effective. Development Stage: Pilot. Early...

Intraluminal polyethylene glycol stabilizes tight junctions and improves intestinal preservation in the rat.

PubMed

Oltean, M; Joshi, M; Björkman, E; Oltean, S; Casselbrant, A; Herlenius, G; Olausson, M

2012-08-01

Rapidly progressing mucosal breakdown limits the intestinal preservation time below 10 h. Recent studies indicate that intraluminal solutions containing polyethylene glycol (PEG) alleviate preservation injury of intestines stored in UW-Viaspan. We investigated whether a low-sodium PEG solution is beneficial for intestines stored in histidine-tryptophane-ketoglutarate (HTK) preservation solution. Rat intestines used as control tissue (group 1) were perfused with HTK, groups 2 and 3 received either a customized PEG-3350 (group 2) or an electrolyte solution (group 3) intraluminally before cold storage. Tissue injury, brush-border maltase activity, zonula occludens-1 (ZO-1) and claudin-3 expression in the tight junctions (TJ) were analyzed after 8, 14 and 20 h. We measured epithelial resistance and permeability (Ussing chamber) after 8 and 14 h. Group 2 had superior morphology while maltase activity was similar in all groups. TJ proteins rapidly decreased and decolocalized in groups 1 3; these negative events were delayed in group 2, where colocalization persisted for about 14 h. Intestines in group 2 had higher epithelial resistance and lower permeability than the other groups. These results suggest that a customized PEG solution intraluminally reduces the intestinal preservation injury by improving several major epithelial characteristics without negatively affecting the brush-border enzymes or promoting edema. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Neurotoxic and teratogenic effects of an organophosphorus insecticide (phenyl phosphonothioic acid-O-ethyl -O-[4-nitrophenyl] ester) on mallard development

USGS Publications Warehouse

Hoffman, D.J.; Sileo, L.

1984-01-01

Phenyl phosphonothioic acid-O-ethyl-O-[4-nitrophenyl] ester (EPN) is one of the 10 most frequently used organophosphorus insecticides and causes delayed neurotoxicity in adult chickens and mallards. Small amounts of organophosphorus insecticides placed on birds' eggs are embryotoxic and teratogenic. For this reason, the effects of topical egg application on EPN were examined on mallard (Anas platyrhynchos) embryo development. Mallard eggs were treated topically at 72 hr of incubation with 25 microliter of a nontoxic oil vehicle or with EPN in the vehicle at concentrations of approximately 12, 36, or 108 micrograms/g egg, equivalent to one, three, and nine times the agricultural level of application used to spray crops. Treatment with EPN resulted in 22 to 44% mortality over this dose range by 18 days of development compared with 4 and 5% for untreated and vehicle-treated controls. EPN impaired embryonic growth and was highly teratogenic: 37-42% of the surviving embryos at 18 days were abnormal with cervical and axial scoliosis as well as severe edema. Brain weights were significantly lower in EPN-treated groups at different stages of development including hatchlings. Brain neurotoxic esterase (NTE) activity was inhibited by as much as 91% at 11 days, 81% at 18 days, and 79% in hatchlings. Examination of brain NTE activity during the course of normal development revealed an increase of nearly sixfold from Day 11 through hatching. The most rapid increase occurred between Day 20 and hatching. Brain acetylcholinesterase (AChE) activity was inhibited by as much as 41% at 11 days, 47% at 18 days, and 20% in hatchlings. Plasma cholinesterase and alkaline phosphatase activities were inhibited and plasma aspartate aminotransferase activity was increased at one or more stages of development. Hatchlings from EPN-treated eggs were weaker and slower to right themselves. Histopathological examination did not reveal demyelination and axonopathy of the spinal cord that was characteristic of delayed neurotoxicity in adult birds.

Cloning and Expression Analysis of Litchi (Litchi Chinensis Sonn.) Polyphenol Oxidase Gene and Relationship with Postharvest Pericarp Browning

PubMed Central

Wang, Jiabao; Liu, Baohua; Xiao, Qian; Li, Huanling; Sun, Jinhua

2014-01-01

Polyphenol oxidase (PPO) plays a key role in the postharvest pericarp browning of litchi fruit, but its underlying mechanism remains unclear. In this study, we cloned the litchi PPO gene (LcPPO, JF926153), and described its expression patterns. The LcPPO cDNA sequence was 2120 bps in length with an open reading frame (ORF) of 1800 bps. The ORF encoded a polypeptide with 599 amino acid residues, sharing high similarities with other plant PPO. The DNA sequence of the ORF contained a 215-bp intron. After carrying out quantitative RT-PCR, we proved that the LcPPO expression was tissue-specific, exhibiting the highest level in the flower and leaf. In the pericarp of newly-harvested litchi fruits, the LcPPO expression level was relatively high compared with developing fruits. Regardless of the litchi cultivar and treatment conditions, the LcPPO expression level and the PPO activity in pericarp of postharvest fruits exhibited the similar variations. When the fruits were stored at room temperature without packaging, all the pericarp browning index, PPO activity and the LcPPO expression level of litchi pericarps were reaching the highest in Nandaowuhe (the most rapid browning cultivar), but the lowest in Ziniangxi (the slowest browning cultivar) within 2 d postharvest. Preserving the fruits of Feizixiao in 0.2-μm plastic bag at room temperature would decrease the rate of pericarp water loss, delay the pericarp browning, and also cause the reduction of the pericarp PPO activity and LcPPO expression level within 3 d postharvest. In addition, postharvest storage of Feizixiao fruit stored at 4°C delayed the pericarp browning while decreasing the pericarp PPO activity and LcPPO expression level within 2 d after harvest. Thus, we concluded that the up-regulation of LcPPO expression in pericarp at early stage of postharvest storage likely enhanced the PPO activity and further accelerated the postharvest pericarp browning of litchi fruit. PMID:24763257

Greater impulsivity is associated with decreased brain activation in obese women during a delay discounting task.

PubMed

Stoeckel, Luke E; Murdaugh, Donna L; Cox, James E; Cook, Edwin W; Weller, Rosalyn E

2013-06-01

Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD), or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual's 'indifference point', or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain.

Using time-delay to improve social play skills with peers for children with autism.

PubMed

Liber, Daniella B; Frea, William D; Symon, Jennifer B G

2008-02-01

Interventions that teach social communication and play skills are crucial for the development of children with autism. The time delay procedure is effective in teaching language acquisition, social use of language, discrete behaviors, and chained activities to individuals with autism and developmental delays. In this study, three boys with autism, attending a non-public school, were taught play activities that combined a play sequence with requesting peer assistance, using a graduated time delay procedure. A multiple-baseline across subjects design demonstrated the success of this procedure to teach multiple-step social play sequences. Results indicated an additional gain of an increase in pretend play by one of the participants. Two also demonstrated a generalization of the skills learned through the time delay procedure.

Flying Drosophila stabilize their vision-based velocity controller by sensing wind with their antennae

PubMed Central

Fuller, Sawyer Buckminster; Straw, Andrew D.; Peek, Martin Y.; Murray, Richard M.; Dickinson, Michael H.

2014-01-01

Flies and other insects use vision to regulate their groundspeed in flight, enabling them to fly in varying wind conditions. Compared with mechanosensory modalities, however, vision requires a long processing delay (~100 ms) that might introduce instability if operated at high gain. Flies also sense air motion with their antennae, but how this is used in flight control is unknown. We manipulated the antennal function of fruit flies by ablating their aristae, forcing them to rely on vision alone to regulate groundspeed. Arista-ablated flies in flight exhibited significantly greater groundspeed variability than intact flies. We then subjected them to a series of controlled impulsive wind gusts delivered by an air piston and experimentally manipulated antennae and visual feedback. The results show that an antenna-mediated response alters wing motion to cause flies to accelerate in the same direction as the gust. This response opposes flying into a headwind, but flies regularly fly upwind. To resolve this discrepancy, we obtained a dynamic model of the fly’s velocity regulator by fitting parameters of candidate models to our experimental data. The model suggests that the groundspeed variability of arista-ablated flies is the result of unstable feedback oscillations caused by the delay and high gain of visual feedback. The antenna response drives active damping with a shorter delay (~20 ms) to stabilize this regulator, in exchange for increasing the effect of rapid wind disturbances. This provides insight into flies’ multimodal sensory feedback architecture and constitutes a previously unknown role for the antennae. PMID:24639532

Continuous light affects mineralization and delays osteoid incorporation in vertebral bone of Atlantic salmon (Salmo salar L.).

PubMed

Wargelius, Anna; Fjelldal, Per Gunnar; Nordgarden, Ulla; Hansen, Tom

2009-03-01

In order to study the effects of photoperiod on fish bone, Atlantic salmon (Salmo salar L.) were exposed to two light regimes (natural and continuous light) from January until June. During the experimental period, several parameters related to the inorganic (minerals) and organic (osteoid) phases were measured. Changes in the organic phase were related to mechanical strength (yield-load) and the expression of the genes sonic hedgehog (shh) and collagen type I alpha 2 (col I). Co-variation between yield-load and the expression of both shh and col I were detected in both groups. It was also shown that fish on the continuous light regime had delayed activation of osteoid incorporation. Mineralization properties were measured with stiffness, mineral incorporation per day and expression of alkaline phosphatase (alp) and matrix Gla protein (mgp). Stiffness, mineral incorporation and gene expression followed the same trend in both light groups in late spring, whereas an increase in the expression of mgp and alp was detected in April, followed by significantly higher stiffness at last sampling in both light groups. These results indicate that constant light affects mineralization and delays osteoid incorporation in Atlantic salmon during the spring. However, in this experiment light treatment did not promote the development of vertebral deformities. Our results also suggest that shh can be used as a marker of osteoblast proliferation and col I a marker of osteoid incorporation, and that both alp and mgp expression could be associated with a rapid increase in mineralization in Atlantic salmon vertebrae.

Acetazolamide on the ventral medulla of the cat increases phrenic output and delays the ventilatory response to CO2.

PubMed Central

Coates, E L; Li, A H; Nattie, E E

1991-01-01

1. Acetazolamide (0.1 mM) applied to the surface of the rostral ventrolateral medulla or microinjected beneath the medullary surface in chloralose-urethane-anaesthetized, vagotomized, carotid-denervated, paralysed, servo-ventilated cats produced a long-lasting increase in integrated phrenic nerve activity. 2. Extracellular pH measured beneath the rostral ventrolateral medulla exhibited a long-lasting decrease after surface acetazolamide but was not a good predictor, in each individual animal, of changes in phrenic activity. 3. Medullary carbonic anhydrase inhibition reduced the slope and the half-time of the phrenic response to rapid step CO2 increases. Conversely, acetazolamide did not affect the phrenic response to steady-state CO2 increases. 4. These data indicate that localized inhibition of medullary carbonic anhydrase causes a centrally mediated increase in ventilation that we attribute to medullary tissue hypercapnia and acidosis. In addition, these data indicate that medullary carbonic anhydrase may play a role in central CO2 chemotransduction. Images Fig. 8 PMID:1816381

Smad Signaling Dynamics: Insights from a Parsimonious Model

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

Wiley, H. S.; Shankaran, Harish

2008-09-09

The molecular mechanisms that transmit information from cell surface receptors to the nucleus are exceedingly complex; thus, much effort has been expended in developing computational models to understand these processes. A recent study on modeling the nuclear-cytoplasmic shuttling of Smad2-Smad4 complexes in response to transforming growth factor β (TGF-β) receptor activation has provided substantial insight into how this signaling network translates the degree of TGF-β receptor activation (input) into the amount of nuclear Smad2-Smad4 complexes (output). The study addressed this question by combining a simple, mechanistic model with targeted experiments, an approach that proved particularly powerful for exploring the fundamentalmore » properties of a complex signaling network. The mathematical model revealed that Smad nuclear-cytoplasmic dynamics enables a proportional, but time-delayed coupling between the input and the output. As a result, the output can faithfully track gradual changes in the input, while the rapid input fluctuations that constitute signaling noise are dampened out.« less

Nuclear reactor with internal thimble-type delayed neutron detection system

DOEpatents

Gross, Kenny C.; Poloncsik, John; Lambert, John D. B.

1990-01-01

This invention teaches improved apparatus for the method of detecting a breach in cladded fuel used in a nuclear reactor. The detector apparatus is located in the primary heat exchanger which conveys part of the reactor coolant past at least three separate delayed-neutron detectors mounted in this heat exchanger. The detectors are spaced apart such that the coolant flow time from the core to each detector is different, and these differences are known. The delayed-neutron activity at the detectors is a function of the delay time after the reaction in the fuel until the coolant carrying the delayed-neutron emitter passes the respective detector. This time delay is broken down into separate components including an isotopic holdup time required for the emitter to move through the fuel from the reaction to the coolant at the breach, and two transit times required for the emitter now in the coolant to flow from the breach to the detector loop and then via the loop to the detector. At least two of these time components are determined during calibrated operation of the reactor. Thereafter during normal reactor operation, repeated comparisons are made by the method of regression approximation of the third time component for the best-fit line correlating measured delayed-neutron activity against activity that is approximated according to specific equations. The equations use these time-delay components and known parameter values of the fuel and of the part and emitting daughter isotopes.

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Controlled copper ion release from phosphate-based glasses improves human umbilical vein endothelial cell survival in a reduced nutrient environment.

PubMed

Stähli, Christoph; Muja, Naser; Nazhat, Showan N

2013-02-01

The success of tissue engineering is dependent on rapid scaffold vascularization after engraftment. Copper ions are well known to be angiogenic but exhibit cytotoxicity at elevated doses. The high sensitivity to copper concentration underlines the need of a controlled release mechanism. This study investigated the effect of copper ions released from phosphate-based glasses (PGs) on human umbilical vein endothelial cells (HUVECs) under standard growth conditions (SGC), as well as in a reduced nutrient environment (RNE) with decreased bovine serum and growth factor concentrations to approximate conditions in the core of large volume scaffolds where nutrient diffusion is limited. Initially, HUVECs were exposed to a range of CuCl(2) concentrations in order to identify an optimal response in terms of their metabolism, viability, and apoptotic activity. Under SGC, HUVEC metabolic activity and viability were reduced in a dose-dependent manner in the presence of 0.44-12 ppm Cu(2+). In contrast, HUVEC death induced by the RNE was delayed by an optimal dose of 4 ppm Cu(2+), which was associated with a down-regulation of apoptosis as evidenced by caspase-3/7 activity. Copper ion release from soluble PGs of the formulation 50P(2)O(5)-30CaO-(20-x)Na(2)O-xCuO [mol%] (x=0, 1, 5 and 10) demonstrated a controllable increase with CuO content. The presence of 4 ppm copper ions released from the 10% CuO PG composition reproduced the delay in HUVEC death in the RNE, suggesting the potential of these materials to extend survival of transplanted endothelial cells in large volume scaffolds.

Plasmin-clipped beta(2)-glycoprotein-I inhibits endothelial cell growth by down-regulating cyclin A, B and D1 and up-regulating p21 and p27.

PubMed

Beecken, Wolf-Dietrich C; Ringel, Eva Maria; Babica, Jan; Oppermann, Elsie; Jonas, Dietger; Blaheta, Roman A

2010-10-28

beta(2)-Glycoprotein-I (beta(2)gpI), an abundant plasma glycoprotein, functions as a regulator of thrombosis. Previously, we demonstrated that plasmin-clipped beta(2)gpI (cbeta(2)gpI) exerts an anti-angiogenic effect on human umbilical vein endothelial cells (HUVEC). The present study was focused on the molecular background responsible for this phenomenon. cbeta(2)gpI strongly reduced HUVEC growth and proliferation as evidenced by the MTT and BrdU assay and delayed cell cycle progression arresting HUVEC in the S-and G2/M-phase. Western blot analysis indicated that cbeta(2)gpI inhibited cyclin A, B and D1, and enhanced p21 and p27 expression. Activity of p38 was down-regulated independently from the cbeta(2)gpI incubation time. Phosphorylation of ERK1/2 was not changed early (30 and 60 min) but became enhanced later (90 min, 4h). JNK activity was reduced rapidly after cbeta(2)gpI treatment but compared to controls, increased thereafter. Annexin II blockade prevented growth inhibition and cell cycle delay evoked by cbeta(2)gpI. We assume that cbeta(2)gpI's effects on HUVEC growth is mediated via cyclin A, B and D1 suppression, up-regulation of p21 and p27 and coupled to modifications of the mitogen-activated protein (MAP) kinase signalling pathway. cbeta(2)gpI may represent a potential endogenous angiogenesis-targeted compound, opening the possibility of a novel tool to treat cancer. 2010 Elsevier Ireland Ltd. All rights reserved.

Effects on subjective and objective alertness and sleep in response to evening light exposure in older subjects

PubMed Central

Münch, M; Scheuermaier, KD; Zhang, R; Dunne, SP; Guzik, AM; Silva, EJ; Ronda, JM; Duffy, JF

2011-01-01

Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages. Ten healthy older adults with sleep complaints (mean age=63.3 yrs; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5–8 the subjects were exposed for 2 h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed. Subjective alertness and wake EEG activity in the alpha range (9.75–11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p<0.05). The light exposures produced circadian phase shifts and significantly prolonged latency to rapid eye-movement (REM) sleep for both light groups (p<0.05). The increase in wake EEG alpha activity during the light exposures was negatively correlated with REM sleep duration (p<0.05). Evening light exposure could benefit older adults with early evening sleepiness, without negatively impacting the subsequent sleep episode. PMID:21664380

Bepridil differentially inhibits two delayed rectifier K+ currents, IKr and IKs, in guinea-pig ventricular myocytes

PubMed Central

Wang, Jin-Cheng; Kiyosue, Tatsuto; Kiriyama, Kuninori; Arita, Makoto

1999-01-01

We investigated the effects of bepridil on the two components of the delayed rectifier K+ current, i.e., the rapidly activating (IKr) and the slowly activating (IKs) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca2+ current with nitrendipine (5 μM) or D600 (1 μM).Bepridil decreased IKs under blockade of IKr with E4031 (5 μM), in a concentration-dependent manner. The concentration-dependent inhibition of IKs by bepridil was fitted by a curve, assuming one-to-one interactions between the channel and the drug molecule. The concentration of half-maximal inhibition (IC50) was found to be 6.2 μM.The effect of bepridil on IKr was assessed using an envelope-of-tails test. In the control condition, a ratio of the tail current to the time-dependent current measured during depolarization was large (>1) at shorter pulses (<200 ms), and it decreased to a steady state value of ∼0.4 with increases in the pulse duration. Bepridil at a concentration of 2 μM did not decrease this ratio at shorter pulses.In a short-pulse (duration=50 ms) experiment that largely activates IKr, the drug was found to block IKr in a cooperative manner (Hill coefficient=3.03) and the IC50 was 13.2 μM.These results suggest that bepridil at a clinical therapeutic concentration (∼2 μM) selectively blocks IKs but does not inhibit IKr. This may relate to the characteristic frequency-dependent effects of bepridil on the action potential duration (APD), e.g., the non-reverse use-dependent prolongation of APD. PMID:10588929

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

PubMed

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

2017-04-01

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

Choice-impulsivity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD): A meta-analytic review.

PubMed

Patros, Connor H G; Alderson, R Matt; Kasper, Lisa J; Tarle, Stephanie J; Lea, Sarah E; Hudec, Kristen L

2016-02-01

Impulsive behavior is a core DSM-5 diagnostic feature of attention-deficit/hyperactivity disorder (ADHD) that is associated with several pejorative outcomes. Impulsivity is multidimensional, consisting of two sub-constructs: rapid-response impulsivity and reward-delay impulsivity (i.e., choice-impulsivity). While previous research has extensively examined the presence and implications of rapid-response impulsivity in children with ADHD, reviews of choice-impulsive behavior have been both sparse and relatively circumscribed. This review used meta-analytic methods to comprehensively examine between-group differences in choice-impulsivity among children and adolescents with and without ADHD. Twenty-eight tasks (from 26 studies), consisting of 4320 total children (ADHD=2360, TD=1,960), provided sufficient information to compute an overall between-group effect size for choice-impulsivity performance. Results revealed a medium-magnitude between-group effect size (g=.47), suggesting that children and adolescents with ADHD exhibited moderately increased impulsive decision-making compared to TD children and adolescents. Further, relative to the TD group, children and adolescents with ADHD exhibited similar patterns of impulsive decision-making across delay discounting and delay of gratification tasks. However, the use of single-informant diagnostic procedures relative to multiple informants yielded larger between-group effects, and a similar pattern was observed across samples that excluded females relative to samples that included females. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamics of the Coupled Human-climate System Resulting from Closed-loop Control of Solar Geoengineering

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

MacMartin, Douglas; Kravitz, Benjamin S.; Keith, David

2014-07-08

If solar radiation management (SRM) were ever implemented, feedback of the observed climate state might be used to adjust the radiative forcing of SRM, in order to compensate for uncertainty in either the forcing or the climate response; this would also compensate for unexpected changes in the system, e.g. a nonlinear change in climate sensitivity. This feedback creates an emergent coupled human-climate system, with entirely new dynamics. In addition to the intended response to greenhouse-gas induced changes, the use of feedback would also result in a geoengineering response to natural climate variability. We use a simple box-diffusion dynamic model tomore » understand how changing feedback-control parameters and time delay affect the behavior of this coupled natural-human system, and verify these predictions using the HadCM3L general circulation model. In particular, some amplification of natural variability is unavoidable; any time delay (e.g., to average out natural variability, or due to decision-making) exacerbates this amplification, with oscillatory behavior possible if there is a desire for rapid correction (high feedback gain), but a delayed response needed for decision making. Conversely, the need for feedback to compensate for uncertainty, combined with a desire to avoid excessive amplification, results in a limit on how rapidly SRM could respond to uncertain changes.« less

Controlled patterns of daytime light exposure improve circadian adjustment in simulated night work.

PubMed

Dumont, Marie; Blais, Hélène; Roy, Joanie; Paquet, Jean

2009-10-01

Circadian misalignment between the endogenous circadian signal and the imposed rest-activity cycle is one of the main sources of sleep and health troubles in night shift workers. Timed bright light exposure during night work can reduce circadian misalignment in night workers, but this approach is limited by difficulties in incorporating bright light treatment into most workplaces. Controlled light and dark exposure during the daytime also has a significant impact on circadian phase and could be easier to implement in real-life situations. The authors previously described distinctive light exposure patterns in night nurses with and without circadian adaptation. In the present study, the main features of these patterns were used to design daytime light exposure profiles. Profiles were then tested in a laboratory simulation of night work to evaluate their efficacy in reducing circadian misalignment in night workers. The simulation included 2 day shifts followed by 4 consecutive night shifts (2400-0800 h). Healthy subjects (15 men and 23 women; 20-35 years old) were divided into 3 groups to test 3 daytime light exposure profiles designed to produce respectively a phase delay (delay group, n=12), a phase advance (advance group, n=13), or an unchanged circadian phase (stable group, n=13). In all 3 groups, light intensity was set at 50 lux during the nights of simulated night work. Salivary dim light melatonin onset (DLMO) showed a significant phase advance of 2.3 h (+/-1.3 h) in the advance group and a significant phase delay of 4.1 h (+/-1.3 h) in the delay group. The stable group showed a smaller but significant phase delay of 1.7 h (+/-1.6 h). Urinary 6-sulfatoxymelatonin (aMT6s) acrophases were highly correlated to salivary DLMOs. Urinary aMT6s acrophases were used to track daily phase shifts. They showed that phase shifts occurred rapidly and differed between the 3 groups by the 3rd night of simulated night work. These results show that significant phase shifts can be achieved in night workers by controlling daytime light exposure, with no nighttime intervention.

MILITARY PAY: Processes for Retaining Injured Army National Guard and Reserve Soldiers on Active Duty Have Been Improved, but Some Challenges Remain

DTIC Science & Technology

2007-05-01

Active Duty Have Been Improved, but Some Challenges Remain The Army’s MRP program has largely resolved the widespread delays in order processing that...interviewed confirmed that they did not experience gaps in pay and associated benefits because of order processing delays. However, some of the...and injured reserve component soldiers we interviewed, these improvements have virtually eliminated the widespread delays in order processing that

Note: Large active area solid state photon counter with 20 ps timing resolution and 60 fs detection delay stability

NASA Astrophysics Data System (ADS)

Prochazka, Ivan; Kodet, Jan; Eckl, Johann; Blazej, Josef

2017-10-01

We are reporting on the design, construction, and performance of a photon counting detector system, which is based on single photon avalanche diode detector technology. This photon counting device has been optimized for very high timing resolution and stability of its detection delay. The foreseen application of this detector is laser ranging of space objects, laser time transfer ground to space and fundamental metrology. The single photon avalanche diode structure, manufactured on silicon using K14 technology, is used as a sensor. The active area of the sensor is circular with 200 μm diameter. Its photon detection probability exceeds 40% in the wavelength range spanning from 500 to 800 nm. The sensor is operated in active quenching and gating mode. A new control circuit was optimized to maintain high timing resolution and detection delay stability. In connection to this circuit, timing resolution of the detector is reaching 20 ps FWHM. In addition, the temperature change of the detection delay is as low as 70 fs/K. As a result, the detection delay stability of the device is exceptional: expressed in the form of time deviation, detection delay stability of better than 60 fs has been achieved. Considering the large active area aperture of the detector, this is, to our knowledge, the best timing performance reported for a solid state photon counting detector so far.

Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.

PubMed

Navarro-Polanco, Ricardo A; Aréchiga-Figueroa, Iván A; Salazar-Fajardo, Pedro D; Benavides-Haro, Dora E; Rodríguez-Elías, Julio C; Sachse, Frank B; Tristani-Firouzi, Martin; Sánchez-Chapula, José A; Moreno-Galindo, Eloy G

2013-09-01

Choline (Ch) is a precursor and metabolite of the neurotransmitter acetylcholine (ACh). In canine and guinea pig atrial myocytes, Ch was shown to activate an outward K(+) current in a delayed rectifier fashion. This current has been suggested to modulate cardiac electrical activity and to play a role in atrial fibrillation pathophysiology. However, the exact nature and identity of this current has not been convincingly established. We recently described the unique ligand- and voltage-dependent properties of muscarinic activation of ACh-activated K(+) current (IKACh) and showed that, in contrast to ACh, pilocarpine induces a current with delayed rectifier-like properties with membrane depolarization. Here, we tested the hypothesis that Ch activates IKACh in feline atrial myocytes in a voltage-dependent manner similar to pilocarpine. Single-channel recordings, biophysical profiles, specific pharmacological inhibition and computational data indicate that the current activated by Ch is IKACh. Moreover, we show that membrane depolarization increases the potency and efficacy of IKACh activation by Ch and thus gives the appearance of a delayed rectifier activating K(+) current at depolarized potentials. Our findings support the emerging concept that IKACh modulation is both voltage- and ligand-specific and reinforce the importance of these properties in understanding cardiac physiology.

Validation of an antibody-based biosensor for rapid quantification of 2,4,6-trinitrotoluene (TNT) contamination in ground water and river water.

PubMed

Bromage, Erin S; Vadas, George G; Harvey, Ellen; Unger, Michael A; Kaattari, Stephen L

2007-10-15

Nitroaromatics are common pollutants of soil and groundwater at military installations because of their manufacture, storage, and use at these sites. Long-term monitoring of these pollutants comprise a significant percentage of restoration costs. Further, remediation activities often have to be delayed, while the samples are processed via traditional chemical assessment protocols. Here we describe a rapid (<5 min), cost-effective, accurate method using a KinExA Inline Biosensor for monitoring of 2,4,6-trinitrotoluene (TNT) in field water samples. The biosensor, which is based on KinExA technology, accurately estimated the concentration of TNT in double-blind comparisons with similar accuracy to traditional high-performance liquid chromatography(HPLC). In the assessment of field samples, the biosensor accurately predicted the concentration of TNT over the range of 1-30,000 microg/L when compared to either HPLC or quantitative gas chromatography-mass spectrometry (GC-MS). Various pre-assessment techniques were explored to examine whether field samples could be assessed untreated, without the removal of particulates or the use of solvents. In most cases, the KinExA Inline Biosensor gave a uniform assessment of TNT concentration independent of pretreatment method. This indicates that this sensor possesses significant promise for rapid, on-site assessment of TNT pollution in environmental water samples.

Rapid corticosteroid actions on synaptic plasticity in the mouse basolateral amygdala: relevance of recent stress history and β-adrenergic signaling.

PubMed

Sarabdjitsingh, R A; Joëls, M

2014-07-01

The rodent stress hormone corticosterone rapidly enhances long-term potentiation in the CA1 hippocampal area, but leads to a suppression when acting in a more delayed fashion. Both actions are thought to contribute to stress effects on emotional memory. Emotional memory formation also involves the basolateral amygdala, an important target area for corticosteroid actions. We here (1) investigated the rapid effects of corticosterone on amygdalar synaptic potentiation, (2) determined to what extent these effects depend on the mouse's recent stress history or (3) on prior β-adrenoceptor activation; earlier studies at the single cell level showed that especially a recent history of stress changes the responsiveness of basolateral amygdala neurons to corticosterone. We report that, unlike the hippocampus, stress enhances amygdalar synaptic potentiation in a slow manner. In vitro exposure to 100 nM corticosterone quickly decreases synaptic potentiation, and causes only transient potentiation in tissue from stressed mice. This transient type of potentiation is also seen when β-adrenoceptors are blocked during stress and this is further exacerbated by subsequent in vitro administered corticosterone. We conclude that stress and corticosterone change synaptic potentiation in the basolateral amygdala in a manner opposite to that seen in the hippocampus and that renewed exposure to corticosterone only allows induction of non-persistent forms of synaptic potentiation. Copyright © 2013 Elsevier Inc. All rights reserved.

Facilitating tolerance of delayed reinforcement during functional communication training.

PubMed

Fisher, W W; Thompson, R H; Hagopian, L P; Bowman, L G; Krug, A

2000-01-01

Few clinical investigations have addressed the problem of delayed reinforcement. In this investigation, three individuals whose destructive behavior was maintained by positive reinforcement were treated using functional communication training (FCT) with extinction (EXT). Next, procedures used in the basic literature on delayed reinforcement and self-control (reinforcer delay fading, punishment of impulsive responding, and provision of an alternative activity during reinforcer delay) were used to teach participants to tolerate delayed reinforcement. With the first case, reinforcer delay fading alone was effective at maintaining low rates of destructive behavior while introducing delayed reinforcement. In the second case, the addition of a punishment component reduced destructive behavior to near-zero levels and facilitated reinforcer delay fading. With the third case, reinforcer delay fading was associated with increases in masturbation and head rolling, but prompting and praising the individual for completing work during the delay interval reduced all problem behaviors and facilitated reinforcer delay fading.

Different Molecular Mechanisms Mediate Direct or Glia-Dependent Prion Protein Fragment 90-231 Neurotoxic Effects in Cerebellar Granule Neurons.

PubMed

Thellung, Stefano; Gatta, Elena; Pellistri, Francesca; Villa, Valentina; Corsaro, Alessandro; Nizzari, Mario; Robello, Mauro; Florio, Tullio

2017-10-01

Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP Sc ). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca ++ ] i increase. Indeed, while in "pure" cerebellar granule neuron cultures, PrP90-231 causes a delayed intracellular Ca ++ entry mediated by the activation of NMDA receptors; when neuron and glia are co-cultured, a transient increase of [Ca ++ ] i occurs within seconds after treatment in both granule neurons and glial cells, then followed by a delayed and sustained [Ca ++ ] i raise, associated with the induction of the expression of inducible nitric oxide synthase and phagocytic NADPH oxidase. [Ca ++ ] i fast increase in neurons is dependent on the activation of multiple pathways since it is not only inhibited by the blockade of voltage-gated channel activity and NMDA receptors but also prevented by the inhibition of nitric oxide and PGE 2 release from glial cells. Thus, Ca ++ homeostasis alteration, directly induced by PrP90-231 in cerebellar granule cells, requires the activation of NMDA receptors, but is greatly enhanced by soluble molecules released by activated glia. In glia-enriched cerebellar granule cultures, the activation of inducible nitric oxide (iNOS) and NADPH oxidase represents the main mechanism of toxicity since their pharmacological inhibition prevented PrP90-231 neurotoxicity, whereas NMDA blockade by D(-)-2-amino-5-phosphonopentanoic acid is ineffective; conversely, in pure cerebellar granule cultures, NMDA blockade but not iNOS inhibition strongly reduced PrP90-231 neurotoxicity. These data indicate that amyloidogenic peptides induce neurotoxic signals via both direct neuron interaction and glia activation through different mechanisms responsible of calcium homeostasis disruption in neurons and potentiating each other: the activation of excitotoxic pathways via NMDA receptors and the release of radical species that establish an oxidative milieu.

BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells

PubMed Central

Gu, Ning; Vervaeke, Koen; Storm, Johan F

2007-01-01

Neuronal potassium (K+) channels are usually regarded as largely inhibitory, i.e. reducing excitability. Here we show that BK-type calcium-activated K+ channels enhance high-frequency firing and cause early spike frequency adaptation in neurons. By combining slice electrophysiology and computational modelling, we investigated functions of BK channels in regulation of high-frequency firing in rat CA1 pyramidal cells. Blockade of BK channels by iberiotoxin (IbTX) selectively reduced the initial discharge frequency in response to strong depolarizing current injections, thus reducing the early spike frequency adaptation. IbTX also blocked the fast afterhyperpolarization (fAHP), slowed spike rise and decay, and elevated the spike threshold. Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits activation of slower K+ channels (in particular the delayed rectifier potassium current (IDR)) and Na+ channel inactivation, whereas M-, sAHP- or SK-channels seem not to be important for the early facilitating effect. Since the BK current rapidly inactivates, its facilitating effect diminishes during the initial discharge, thus producing early spike frequency adaptation by an unconventional mechanism. This mechanism is highly frequency dependent. Thus, IbTX had virtually no effect at spike frequencies < 40 Hz. Furthermore, extracellular field recordings demonstrated (and model simulations supported) that BK channels contribute importantly to high-frequency burst firing in response to excitatory synaptic input to distal dendrites. These results strongly support the idea that BK channels play an important role for early high-frequency, rapidly adapting firing in hippocampal pyramidal neurons, thus promoting the type of bursting that is characteristic of these cells in vivo, during behaviour. PMID:17303637

Convergent mechanisms underlying rapid antidepressant action

PubMed Central

Zanos, Panos; Thompson, Scott M.; Duman, Ronald S.; Zarate, Carlos A.; Gould, Todd D.

2018-01-01

Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal and anti-anhedonic actions following a single administration to depressed patients. Proposed mechanisms of ketamine’s antidepressant action include N-methyl-D-aspartate receptor (NMDAR) modulation, GABAergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites. Downstream actions include activation of mechanistic target of rapamycin (mTOR), deactivation of glycogen synthase kinase-3 and eukaryotic elongation factor 2 (eEF2), enhanced brain-derived neurotrophic factor (BDNF) signaling, and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs). These putative mechanisms of ketamine action are not mutually exclusive and may complement each other to induce potentiation of excitatory synapses in affective-regulating brain circuits, which results in amelioration of depression symptoms. We review these proposed mechanisms of ketamine action in the context of how such mechanisms are informing the development of novel putative rapid-acting antidepressant drugs. Such drugs that have undergoing pre-clinical, and in some cases clinical, testing include the muscarinic acetylcholine receptor antagonist scopolamine, GluN2B-NMDAR antagonists (i.e., CP-101,606, MK-0657), (2R,6R)-HNK, NMDAR glycine site modulators (i.e., 4-chlorokynurenine - pro-drug of the glycineB NMDAR antagonist 7-chlorokynurenic acid), NMDAR agonists (i.e. GLYX-13 (rapastinel)), metabotropic glutamate receptor 2/3 (mGluR2/3) antagonists, GABAA receptor modulators, and drugs acting on various serotonin receptor subtypes. These ongoing studies suggest that the future acute treatment of depression will typically occur within hours, rather than months, of treatment initiation. PMID:29516301

Methods of Muscle Activation Onset Timing Recorded During Spinal Manipulation.

PubMed

Currie, Stuart J; Myers, Casey A; Krishnamurthy, Ashok; Enebo, Brian A; Davidson, Bradley S

2016-05-01

The purpose of this study was to determine electromyographic threshold parameters that most reliably characterize the muscular response to spinal manipulation and compare 2 methods that detect muscle activity onset delay: the double-threshold method and cross-correlation method. Surface and indwelling electromyography were recorded during lumbar side-lying manipulations in 17 asymptomatic participants. Muscle activity onset delays in relation to the thrusting force were compared across methods and muscles using a generalized linear model. The threshold combinations that resulted in the lowest Detection Failures were the "8 SD-0 milliseconds" threshold (Detection Failures = 8) and the "8 SD-10 milliseconds" threshold (Detection Failures = 9). The average muscle activity onset delay for the double-threshold method across all participants was 149 ± 152 milliseconds for the multifidus and 252 ± 204 milliseconds for the erector spinae. The average onset delay for the cross-correlation method was 26 ± 101 for the multifidus and 67 ± 116 for the erector spinae. There were no statistical interactions, and a main effect of method demonstrated that the delays were higher when using the double-threshold method compared with cross-correlation. The threshold parameters that best characterized activity onset delays were an 8-SD amplitude and a 10-millisecond duration threshold. The double-threshold method correlated well with visual supervision of muscle activity. The cross-correlation method provides several advantages in signal processing; however, supervision was required for some results, negating this advantage. These results help standardize methods when recording neuromuscular responses of spinal manipulation and improve comparisons within and across investigations. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Working memory for social cues recruits orbitofrontal cortex and amygdala: a functional magnetic resonance imaging study of delayed matching to sample for emotional expressions.

PubMed

LoPresti, Matthew L; Schon, Karin; Tricarico, Marisa D; Swisher, Jascha D; Celone, Kim A; Stern, Chantal E

2008-04-02

During everyday interactions, we continuously monitor and maintain information about different individuals and their changing emotions in memory. Yet to date, working memory (WM) studies have primarily focused on mechanisms for maintaining face identity, but not emotional expression, and studies investigating the neural basis of emotion have focused on transient activity, not delay related activity. The goal of this functional magnetic resonance imaging study was to investigate WM for two critical social cues: identity and emotion. Subjects performed a delayed match-to-sample task that required them to match either the emotional expression or the identity of a face after a 10 s delay. Neuroanatomically, our predictions focused on the orbitofrontal cortex (OFC) and the amygdala, as these regions have previously been implicated in emotional processing and long-term memory, and studies have demonstrated sustained OFC and medial temporal lobe activity during visual WM. Consistent with previous studies, transient activity during the sample period representing emotion and identity was found in the superior temporal sulcus and inferior occipital cortex, respectively. Sustained delay-period activity was evident in OFC, amygdala, and hippocampus, for both emotion and identity trials. These results suggest that, although initial processing of emotion and identity is accomplished in anatomically segregated temporal and occipital regions, sustained delay related memory for these two critical features is held by the OFC, amygdala and hippocampus. These regions share rich connections, and have been shown previously to be necessary for binding features together in long-term memory. Our results suggest a role for these regions in active maintenance as well.

An App for Every Psychological Problem: Vision for the Future

ERIC Educational Resources Information Center

Brown, Alicia M.

2016-01-01

Innovations in mobile technology are occurring at a rapid pace. Mobile phone software applications (apps) in particular have great potential within the field of mental health. Lack of organizational oversight and hesitancy from providers to utilize mobile technology has delayed technological advancement--consequently limiting the ability of the…

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

ERIC Educational Resources Information Center

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

2012-01-01

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

U.S. Women at Work.

ERIC Educational Resources Information Center

Waite, Linda J.

1981-01-01

Women comprised 43% of the United States labor force in 1980, up from 29% in 1950. The surge in women's employment is linked to more delayed marriage, divorce, separation, women's increased education, lower fertility, rapid growth in clerical and service jobs, inflation, and changed attitudes toward "women's place." Employment has risen…

Prolonging microtubule dysruption enhances the immunogenicity of chronic lymphocytic leukaemia cells

PubMed Central

Shaha, S P; Tomic, J; Shi, Y; Pham, T; Mero, P; White, D; He, L; Baryza, J L; Wender, P A; Booth, J W; Spaner, D E

2009-01-01

Cytotoxic chemotherapies do not usually mediate the expression of an immunogenic gene programme in tumours, despite activating many of the signalling pathways employed by highly immunogenic cells. Concomitant use of agents that modulate and complement stress-signalling pathways activated by chemotherapeutic agents may then enhance the immunogenicity of cancer cells, increase their susceptibility to T cell-mediated controls and lead to higher clinical remission rates. Consistent with this hypothesis, the microtubule inhibitor, vincristine, caused chronic lymphocytic leukaemia (CLL) cells to die rapidly, without increasing their immunogenicity. Protein kinase C (PKC) agonists (such as bryostatin) delayed the death of vincristine-treated CLL cells and made them highly immunogenic, with increased stimulatory abilities in mixed lymphocyte responses, production of proinflammatory cytokines, expression of co-stimulatory molecules and activation of c-Jun N-terminal kinase (JNK), p38 and nuclear factor kappa B (NF-κB) signalling pathways. This phenotype was similar to the result of activating CLL cells through Toll-like receptors (TLRs), which communicate ‘danger’ signals from infectious pathogens. Use of PKC agonists and microtubule inhibitors to mimic TLR-signalling, and increase the immunogenicity of CLL cells, has implications for the design of chemo-immunotherapeutic strategies. PMID:19737143

Working memory is not fixed-capacity: More active storage capacity for real-world objects than for simple stimuli

PubMed Central

Brady, Timothy F.; Störmer, Viola S.; Alvarez, George A.

2016-01-01

Visual working memory is the cognitive system that holds visual information active to make it resistant to interference from new perceptual input. Information about simple stimuli—colors and orientations—is encoded into working memory rapidly: In under 100 ms, working memory ‟fills up,” revealing a stark capacity limit. However, for real-world objects, the same behavioral limits do not hold: With increasing encoding time, people store more real-world objects and do so with more detail. This boost in performance for real-world objects is generally assumed to reflect the use of a separate episodic long-term memory system, rather than working memory. Here we show that this behavioral increase in capacity with real-world objects is not solely due to the use of separate episodic long-term memory systems. In particular, we show that this increase is a result of active storage in working memory, as shown by directly measuring neural activity during the delay period of a working memory task using EEG. These data challenge fixed-capacity working memory models and demonstrate that working memory and its capacity limitations are dependent upon our existing knowledge. PMID:27325767

Working memory is not fixed-capacity: More active storage capacity for real-world objects than for simple stimuli.

PubMed

Brady, Timothy F; Störmer, Viola S; Alvarez, George A

2016-07-05

Visual working memory is the cognitive system that holds visual information active to make it resistant to interference from new perceptual input. Information about simple stimuli-colors and orientations-is encoded into working memory rapidly: In under 100 ms, working memory ‟fills up," revealing a stark capacity limit. However, for real-world objects, the same behavioral limits do not hold: With increasing encoding time, people store more real-world objects and do so with more detail. This boost in performance for real-world objects is generally assumed to reflect the use of a separate episodic long-term memory system, rather than working memory. Here we show that this behavioral increase in capacity with real-world objects is not solely due to the use of separate episodic long-term memory systems. In particular, we show that this increase is a result of active storage in working memory, as shown by directly measuring neural activity during the delay period of a working memory task using EEG. These data challenge fixed-capacity working memory models and demonstrate that working memory and its capacity limitations are dependent upon our existing knowledge.

Distinct roles for multiple Src family kinases at fertilization.

PubMed

O'Neill, Forest J; Gillett, Jessica; Foltz, Kathy R

2004-12-01

Egg activation at fertilization requires the release of Ca2+ from the endoplasmic reticulum of the egg. Recent evidence indicates that Src family kinases (SFKs) function in the signaling pathway that initiates this Ca2+ release in the eggs of many deuterostomes. We have identified three SFKs expressed in starfish (Asterina miniata) eggs, designated AmSFK1, AmSFK2 and AmSFK3. Antibodies made against the unique domains of each AmSFK protein revealed that all three are expressed in eggs and localized primarily to the membrane fraction. Both AmSFK1 and AmSFK3 (but not AmSFK2) are necessary for egg activation, as determined by injection of starfish oocytes with dominant-interfering Src homology 2 (SH2) domains, which specifically delay and reduce the initial release of Ca2+ at fertilization. AmSFK3 exhibits a very rapid and transient kinase activity in response to fertilization, peaking at 30 seconds post sperm addition. AmSFK1 kinase activity also increases transiently at fertilization, but peaks later, at 2 minutes. These results indicate that there are multiple SFKs present in starfish eggs with distinct, perhaps sequential, signaling roles.

On-line and Mobil Learning Activities

NASA Astrophysics Data System (ADS)

Ackerman, S. A.; Whittaker, T. M.; Jasmin, T.; Mooney, M. E.

2012-12-01

Introductory college-level science courses for non-majors are critical gateways to imparting not only discipline-specific information, but also the basics of the scientific method and how science influences society. They are also indispensable for student success to degree. On-line, web-based homework (whether on computers or mobile devices) is a rapidly growing use of the Internet and is becoming a major component of instruction in science, replacing delayed feedback from a few major exams. Web delivery and grading of traditional textbook-type questions is equally effective as having students write them out for hand grading, as measured by student performance on conceptual and problem solving exams. During this presentation we will demonstrate some of the interactive on-line activities used to teach concepts and how scientists approach problem solving, and how these activities have impacted student learning. Evaluation of the activities, including formative and summative, will be discussed and provide evidence that these interactive activities significantly enhance understanding of introductory meteorological concepts in a college-level science course. More advanced interactive activities are also used in our courses for department majors, some of these will be discussed and demonstrated. Bring your mobile devices to play along! Here is an example on teaching contouring: http://profhorn.aos.wisc.edu/wxwise/contour/index.html

Local conduction during acute myocardial infarction in rats: Interplay between central sympathetic activation and endothelin.

PubMed

Kolettis, Theofilos M; Kontonika, Marianthi; La Rocca, Vassilios; Vlahos, Antonios P; Baltogiannis, Giannis G; Kyriakides, Zenon S

2017-04-01

We investigated the effects of autonomic dysfunction and endothelin on local conduction and arrhythmogenesis during myocardial infarction. We recorded ventricular tachyarrhythmias, monophasic action potentials, and activation sequences in wild-type and ET B -deficient rats displaying high endothelin levels. Central sympathetic inputs were examined after clonidine administration. Clonidine mitigated early and delayed arrhythmogenesis in ET B -deficient and wild-type rats, respectively. The right ventricular activation delay increased in clonidine-treated ET B -deficient rats and slightly decreased in wild-type rats. The left ventricular voltage rise decreased in all groups, whereas the activation delay increased mainly in clonidine-treated ET B -deficient rats. Central sympathetic activation and endothelin modulate ischemia-induced arrhythmogenesis. Ischemia alters excitability, whereas endothelin impairs local conduction, an action partly counterbalanced by central sympathetic activity.

Altered entrainment to the day/night cycle attenuates the daily rise in circulating corticosterone in the mouse.

PubMed

Sollars, Patricia J; Weiser, Michael J; Kudwa, Andrea E; Bramley, Jayne R; Ogilvie, Malcolm D; Spencer, Robert L; Handa, Robert J; Pickard, Gary E

2014-01-01

The suprachiasmatic nucleus (SCN) is a circadian oscillator entrained to the day/night cycle via input from the retina. Serotonin (5-HT) afferents to the SCN modulate retinal signals via activation of 5-HT1B receptors, decreasing responsiveness to light. Consequently, 5-HT1B receptor knockout (KO) mice entrain to the day/night cycle with delayed activity onsets. Since circulating corticosterone levels exhibit a robust daily rhythm peaking around activity onset, we asked whether delayed entrainment of activity onsets affects rhythmic corticosterone secretion. Wheel-running activity and plasma corticosterone were monitored in mice housed under several different lighting regimens. Both duration of the light:dark cycle (T cycle) and the duration of light within that cycle was altered. 5-HT1B KO mice that entrained to a 9.5L:13.5D (short day in a T = 23 h) cycle with activity onsets delayed more than 4 h after light offset exhibited a corticosterone rhythm in phase with activity rhythms but reduced 50% in amplitude compared to animals that initiated daily activity <4 h after light offset. Wild type mice in 8L:14D (short day in a T = 22 h) conditions with highly delayed activity onsets also exhibited a 50% reduction in peak plasma corticosterone levels. Exogenous adrenocorticotropin (ACTH) stimulation in animals exhibiting highly delayed entrainment suggested that the endogenous rhythm of adrenal responsiveness to ACTH remained aligned with SCN-driven behavioral activity. Circadian clock gene expression in the adrenal cortex of these same animals suggested that the adrenal circadian clock was also aligned with SCN-driven behavior. Under T cycles <24 h, altered circadian entrainment to short day (winter-like) conditions, manifest as long delays in activity onset after light offset, severely reduces the amplitude of the diurnal rhythm of plasma corticosterone. Such a pronounced reduction in the glucocorticoid rhythm may alter rhythmic gene expression in the central nervous system and in peripheral organs contributing to an array of potential pathophysiologies.

Altered Entrainment to the Day/Night Cycle Attenuates the Daily Rise in Circulating Corticosterone in the Mouse

PubMed Central

Sollars, Patricia J.; Weiser, Michael J.; Kudwa, Andrea E.; Bramley, Jayne R.; Ogilvie, Malcolm D.; Spencer, Robert L.; Handa, Robert J.; Pickard, Gary E.

2014-01-01

The suprachiasmatic nucleus (SCN) is a circadian oscillator entrained to the day/night cycle via input from the retina. Serotonin (5-HT) afferents to the SCN modulate retinal signals via activation of 5-HT1B receptors, decreasing responsiveness to light. Consequently, 5-HT1B receptor knockout (KO) mice entrain to the day/night cycle with delayed activity onsets. Since circulating corticosterone levels exhibit a robust daily rhythm peaking around activity onset, we asked whether delayed entrainment of activity onsets affects rhythmic corticosterone secretion. Wheel-running activity and plasma corticosterone were monitored in mice housed under several different lighting regimens. Both duration of the light∶dark cycle (T cycle) and the duration of light within that cycle was altered. 5-HT1B KO mice that entrained to a 9.5L:13.5D (short day in a T = 23 h) cycle with activity onsets delayed more than 4 h after light offset exhibited a corticosterone rhythm in phase with activity rhythms but reduced 50% in amplitude compared to animals that initiated daily activity <4 h after light offset. Wild type mice in 8L:14D (short day in a T = 22 h) conditions with highly delayed activity onsets also exhibited a 50% reduction in peak plasma corticosterone levels. Exogenous adrenocorticotropin (ACTH) stimulation in animals exhibiting highly delayed entrainment suggested that the endogenous rhythm of adrenal responsiveness to ACTH remained aligned with SCN-driven behavioral activity. Circadian clock gene expression in the adrenal cortex of these same animals suggested that the adrenal circadian clock was also aligned with SCN-driven behavior. Under T cycles <24 h, altered circadian entrainment to short day (winter-like) conditions, manifest as long delays in activity onset after light offset, severely reduces the amplitude of the diurnal rhythm of plasma corticosterone. Such a pronounced reduction in the glucocorticoid rhythm may alter rhythmic gene expression in the central nervous system and in peripheral organs contributing to an array of potential pathophysiologies. PMID:25365210

Evaluation of takayasu arteritis with delayed contrast-enhanced MR imaging by a free-breathing 3D IR turbo FLASH.

PubMed

Liu, Min; Liu, Weifang; Li, Haoyuan; Shu, Xiaoming; Tao, Xincao; Zhai, Zhenguo

2017-12-01

The primary aim of our case-control study was to observe delayed contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with Takayasu arteritis (TA) in comparison with magnetic resonance angiography (MRA). Twenty-seven patients including 15 with active TA and 12 with stable TA who underwent both aortic MRA and DCE-MRI were included. A total of 27 sex- and age-matched healthy volunteers were enrolled as the control group. MRA were obtained with T1WI-volume-interpolated breath-hold examination sequence or fast low-angle shot (FLASH) sequence. DCE-MRI was acquired with a free-breathing three-dimensional inversion recovery Turbo fast low-angle shot (3D IR Turbo FLASH). Neither stenosis nor delayed enhancement of arterial wall was shown in the control group. In patients with stable TA, arterial stenosis was observed on MRA. On DCE-MR, delayed enhancement of arterial walls could be observed in the active TA group but not in the stable TA group or the control group. Stenotic arteries on MRA were comparable in the active TA and stable TA (χ = 2.70, P = .259); however, delayed enhancement of arterial walls in the active-TA group were more than those in the stable group (χ = 27.00, P < .001). Our results suggest that DCE-MRI with the free-breathing 3D IR Turbo FLASH sequence could assess TA and delayed enhancement on DCE-MRI is one characteristics of the active TA. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Periodicity and global exponential stability of generalized Cohen-Grossberg neural networks with discontinuous activations and mixed delays.

PubMed

Wang, Dongshu; Huang, Lihong

2014-03-01

In this paper, we investigate the periodic dynamical behaviors for a class of general Cohen-Grossberg neural networks with discontinuous right-hand sides, time-varying and distributed delays. By means of retarded differential inclusions theory and the fixed point theorem of multi-valued maps, the existence of periodic solutions for the neural networks is obtained. After that, we derive some sufficient conditions for the global exponential stability and convergence of the neural networks, in terms of nonsmooth analysis theory with generalized Lyapunov approach. Without assuming the boundedness (or the growth condition) and monotonicity of the discontinuous neuron activation functions, our results will also be valid. Moreover, our results extend previous works not only on discrete time-varying and distributed delayed neural networks with continuous or even Lipschitz continuous activations, but also on discrete time-varying and distributed delayed neural networks with discontinuous activations. We give some numerical examples to show the applicability and effectiveness of our main results. Copyright © 2013 Elsevier Ltd. All rights reserved.

Delayed ignition and propulsion of catalytic microrockets based on fuel-induced chemical dealloying of the inner alloy layer.

PubMed

Jodra, Adrián; Soto, Fernando; Lopez-Ramirez, Miguel Angel; Escarpa, Alberto; Wang, Joseph

2016-09-27

The delayed ignition and propulsion of catalytic tubular microrockets based on fuel-induced chemical dealloying of an inner alloy layer is demonstrated. Such timed delay motor activation process relies on the preferential gradual corrosion of Cu from the inner Pt-Cu alloy layer by the peroxide fuel. The dealloying process exposes the catalytically active Pt surface to the chemical fuel, thus igniting the microrockets propulsion autonomously without external stimuli. The delayed motor activation relies solely on the intrinsic material properties of the micromotor and the surrounding solution. The motor activation time can thus be tailored by controlling the composition of the Cu-Pt alloy layer and the surrounding media, including the fuel and NaCl concentrations and local pH. Speed acceleration in a given fuel solution is also demonstrated and reflects the continuous exposure of the Pt surface. The versatile "blastoff" control of these chemical microrockets holds considerable promise for designing self-regulated chemically-powered nanomachines with a "built-in" activation mechanism for diverse tasks.

YneA, an SOS-Induced Inhibitor of Cell Division in Bacillus subtilis, Is Regulated Posttranslationally and Requires the Transmembrane Region for Activity▿ †

PubMed Central

Mo, Allison H.; Burkholder, William F.

2010-01-01

Cell viability depends on the stable transmission of genetic information to each successive generation. Therefore, in the event of intrinsic or extrinsic DNA damage, it is important that cell division be delayed until DNA repair has been completed. In Bacillus subtilis, this is accomplished in part by YneA, an inhibitor of division that is induced as part of the SOS response. We sought to gain insight into the mechanism by which YneA blocks cell division and the processes involved in shutting off YneA activity. Our data suggest that YneA is able to inhibit daughter cell separation as well as septum formation. YneA contains a LysM peptidoglycan binding domain and is predicted to be exported. We established that the YneA signal peptide is rapidly cleaved, resulting in secretion of YneA into the medium. Mutations within YneA affect both the rate of signal sequence cleavage and the activity of YneA. YneA does not stably associate with the cell wall and is rapidly degraded by extracellular proteases. Based on these results, we hypothesize that exported YneA is active prior to signal peptide cleavage and that proteolysis contributes to the inactivation of YneA. Finally, we identified mutations in the transmembrane segment of YneA that abolish the ability of YneA to inhibit cell division, while having little or no effect on YneA export or stability. These data suggest that protein-protein interactions mediated by the transmembrane region may be required for YneA activity. PMID:20400548

Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting--a report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society.

PubMed

Gorcsan, John; Abraham, Theodore; Agler, Deborah A; Bax, Jeroen J; Derumeaux, Genevieve; Grimm, Richard A; Martin, Randy; Steinberg, Jonathan S; Sutton, Martin St John; Yu, Cheuk-Man

2008-03-01

Echocardiography plays an evolving and important role in the care of heart failure patients treated with biventricular pacing, or cardiac resynchronization therapy (CRT). Numerous recent published reports have utilized echocardiographic techniques to potentially aide in patient selection for CRT prior to implantation and to optimized device settings afterwards. However, no ideal approach has yet been found. This consensus report evaluates the contemporary applications of echocardiography for CRT including relative strengths and technical limitations of several techniques and proposes guidelines regarding current and possible future clinical applications. Principal methods advised to qualify abnormalities in regional ventricular activation, known as dyssynchrony, include longitudinal velocities by color-coded tissue Doppler and the difference in left ventricular to right ventricular ejection using routine pulsed Doppler, or interventricular mechanical delay. Supplemental measures of radial dynamics which may be of additive value include septal-to-posterior wall delay using M-mode in patients with non-ischemic disease with technically high quality data, or using speckle tracking radial strain. A simplified post-CRT screening for atrioventricular optimization using Doppler mitral inflow velocities is also proposed. Since this is rapidly changing field with new information being added frequently, future modification and refinements in approach are anticipated to continue.

Europe's other debt crisis caused by the long legacy of future extinctions.

PubMed

Dullinger, Stefan; Essl, Franz; Rabitsch, Wolfgang; Erb, Karl-Heinz; Gingrich, Simone; Haberl, Helmut; Hülber, Karl; Jarosík, Vojtech; Krausmann, Fridolin; Kühn, Ingolf; Pergl, Jan; Pysek, Petr; Hulme, Philip E

2013-04-30

Rapid economic development in the past century has translated into severe pressures on species survival as a result of increasing land-use change, environmental pollution, and the spread of invasive alien species. However, though the impact of these pressures on biodiversity is substantial, it could be seriously underestimated if population declines of plants and animals lag behind contemporary environmental degradation. Here, we test for such a delay in impact by relating numbers of threatened species appearing on national red lists to historical and contemporary levels of socioeconomic pressures. Across 22 European countries, the proportions of vascular plants, bryophytes, mammals, reptiles, dragonflies, and grasshoppers facing medium-to-high extinction risks are more closely matched to indicators of socioeconomic pressures (i.e., human population density, per capita gross domestic product, and a measure of land use intensity) from the early or mid-, rather than the late, 20th century. We conclude that, irrespective of recent conservation actions, large-scale risks to biodiversity lag considerably behind contemporary levels of socioeconomic pressures. The negative impact of human activities on current biodiversity will not become fully realized until several decades into the future. Mitigating extinction risks might be an even greater challenge if temporal delays mean many threatened species might already be destined toward extinction.

Europe’s other debt crisis caused by the long legacy of future extinctions

PubMed Central

Dullinger, Stefan; Essl, Franz; Rabitsch, Wolfgang; Erb, Karl-Heinz; Gingrich, Simone; Haberl, Helmut; Hülber, Karl; Jarošík, Vojtech; Krausmann, Fridolin; Kühn, Ingolf; Pergl, Jan; Pyšek, Petr; Hulme, Philip E.

2013-01-01

Rapid economic development in the past century has translated into severe pressures on species survival as a result of increasing land-use change, environmental pollution, and the spread of invasive alien species. However, though the impact of these pressures on biodiversity is substantial, it could be seriously underestimated if population declines of plants and animals lag behind contemporary environmental degradation. Here, we test for such a delay in impact by relating numbers of threatened species appearing on national red lists to historical and contemporary levels of socioeconomic pressures. Across 22 European countries, the proportions of vascular plants, bryophytes, mammals, reptiles, dragonflies, and grasshoppers facing medium-to-high extinction risks are more closely matched to indicators of socioeconomic pressures (i.e., human population density, per capita gross domestic product, and a measure of land use intensity) from the early or mid-, rather than the late, 20th century. We conclude that, irrespective of recent conservation actions, large-scale risks to biodiversity lag considerably behind contemporary levels of socioeconomic pressures. The negative impact of human activities on current biodiversity will not become fully realized until several decades into the future. Mitigating extinction risks might be an even greater challenge if temporal delays mean many threatened species might already be destined toward extinction. PMID:23589873

Descending necrotizing mediastinitis: report of a case following steroid neck injection.

PubMed

Harar, R P S; Cranston, C; Warwick-Brown, N

2002-10-01

Cervical necrotizing fasciitis is a rare, rapidly progressive, severe bacterial infection of the soft tissues of the neck. Uncommonly, it may descend into the mediastinum. We describe a case of descending necrotizing mediastinitis in a young man, where there was diagnostic confusion and delay, with an eventual fatal outcome. A steroid injection for neck pain is thought to be the source of infection. In this case, the signs of mediastinitis were initially masked, and the diagnosis delayed until cardiopulmonary arrest occurred. Early recognition with a low threshold for computed tomography (CT) scanning is essential. Aggressive multidisciplinary therapy with mediastinal drainage is mandatory.

Methods of and apparatus for recording images occurring just prior to a rapid, random event

DOEpatents

Kelley, Edward F.

1994-01-01

An apparatus and a method are disclosed for recording images of events in a medium wherein the images that are recorded are of conditions existing just prior to and during the occurrence of an event that triggers recording of these images. The apparatus and method use an optical delay path that employs a spherical focusing mirror facing a circular array of flat return mirrors around a central flat mirror. The image is reflected in a symmetric pattern which balances astigmatism which is created by the spherical mirror. Delays on the order of hundreds of nanoseconds are possible.

Polyphenol content in white table grape (Vitis Vinifera) berries of cultivar Italia: interactive effect of irrigation, delayed harvest and storage.

PubMed

Capriotti, Anna Laura; Caruso, Giuseppe; Cavaliere, Chiara; Foglia, Patrizia; Laganà, Aldo; Samperi, Roberto

2012-01-01

Polyphenol concentrations were quantified by rapid resolution liquid chromatography/mass spectrometry in white table grape. The experimental vineyard was subjected to different kinds of water supply and supply rates. Samples from the same vineyards were also analysed after 6 weeks of storage in a refrigerator and after 6 weeks of delayed harvesting. Berry skins and seeds were analysed separately. A statistical treatment of the screening kind, namely the 2(k) full factorial design, was used for the interpretation of results. Storage, delayed harvesting and the different kinds of water supply appeared to be the variables most affecting grape polyphenol content. In some cases, results showed that polyphenol content diminished by more than 50% after 6 weeks if the grapes were stored in a refrigerator, or if a sprinkler was used for irrigation.

Delayed-onset Reversible Cortical Blindness after Resuscitation from Cardiac Arrest

PubMed Central

de Souza, Aaron; de Souza, Rainha J.; Pai Kakode, Varun R.

2017-01-01

We present a patient who presented with cortical blindness (CB) 1 week after repeated cardiac arrest while undergoing treatment for an acute myocardial infarction. He had been revived within 5 min in each instance and was apparently neurologically normal until presentation. Magnetic resonance imaging showed subtle hyperintensities on fluid-attenuated inversion recovery and diffusion-weighted imaging in both temporooccipital cortices. A rapid recovery over the next 2 weeks was remarkable for the appearance of metamorphopsia. CB may present even days to weeks after hypoxic-ischemic encephalopathy following cardiac arrest, even in patients apparently without immediate neurological sequelae. The pathogenesis of this phenomenon remains to be fully elucidated, but is likely to be due to delayed effects of anoxia on the occipital cortex and may be analogous to the previously described syndrome of delayed posthypoxic leukoencephalopathy. Prognosis for visual recovery appears to be good. PMID:28936091

Reconstructive challenges in war wounds

PubMed Central

Bhandari, Prem Singh; Maurya, Sanjay; Mukherjee, Mrinal Kanti

2012-01-01

War wounds are devastating with extensive soft tissue and osseous destruction and heavy contamination. War casualties generally reach the reconstructive surgery centre after a delayed period due to additional injuries to the vital organs. This delay in their transfer to a tertiary care centre is responsible for progressive deterioration in wound conditions. In the prevailing circumstances, a majority of war wounds undergo delayed reconstruction, after a series of debridements. In the recent military conflicts, hydrosurgery jet debridement and negative pressure wound therapy have been successfully used in the preparation of war wounds. In war injuries, due to a heavy casualty load, a faster and reliable method of reconstruction is aimed at. Pedicle flaps in extremities provide rapid and reliable cover in extremity wounds. Large complex defects can be reconstructed using microvascular free flaps in a single stage. This article highlights the peculiarities and the challenges encountered in the reconstruction of these ghastly wounds. PMID:23162233

On delay adjustment for dynamic load balancing in distributed virtual environments.

PubMed

Deng, Yunhua; Lau, Rynson W H

2012-04-01

Distributed virtual environments (DVEs) are becoming very popular in recent years, due to the rapid growing of applications, such as massive multiplayer online games (MMOGs). As the number of concurrent users increases, scalability becomes one of the major challenges in designing an interactive DVE system. One solution to address this scalability problem is to adopt a multi-server architecture. While some methods focus on the quality of partitioning the load among the servers, others focus on the efficiency of the partitioning process itself. However, all these methods neglect the effect of network delay among the servers on the accuracy of the load balancing solutions. As we show in this paper, the change in the load of the servers due to network delay would affect the performance of the load balancing algorithm. In this work, we conduct a formal analysis of this problem and discuss two efficient delay adjustment schemes to address the problem. Our experimental results show that our proposed schemes can significantly improve the performance of the load balancing algorithm with neglectable computation overhead.

Delayed-onset and recurrent limb weakness associated with West Nile virus infection.

PubMed

Sejvar, James J; Davis, Larry E; Szabados, Erica; Jackson, Alan C

2010-02-01

Human neurologic illness following infection with West Nile virus (WNV) may include meningitis, encephalitis, and acute flaccid paralysis (AFP). Most WNV-associated AFP is due to involvement of the spinal motor neurons producing an anterior (polio)myelitis. WNV poliomyelitis is typically characterized by acute and rapidly progressing limb weakness occurring early in the course of illness, which is followed by death or clinical plateauing with subsequent improvement to varying degrees. We describe four cases of WNV poliomyelitis in which the limb weakness was characterized by an atypical temporal pattern, including one case with onset several weeks after illness onset, and three cases developing relapsing or recurrent limb weakness following a period of clinical plateauing or improvement. Delayed onset or recurrent features may be due to persistence of viral infection or delayed neuroinvasion with delayed injury by excitotoxic or other mechanisms, by immune-mediated mechanisms, or a combination thereof. Further clinical and pathogenesis studies are needed to better understand the mechanisms for these phenomena. Clinicians should be aware of these clinical patterns in patients with WNV poliomyelitis.

Teaching Students to Request the Continuation of Routine Activities by Using Time Delay and Decreasing Physical Assistance in the Context of Chain Interruption.

ERIC Educational Resources Information Center

Gee, Kathleen; And Others

1991-01-01

Three students (ages 5-10) with profound intellectual, sensory, and physical disabilities were taught to activate a communication device to request the continuation of activities in which they were involved. The intervention consisted of a consistent response interval and increasing time delay paired with decreasing physical assistance in…

The Effect of Delayed Auditory Feedback on Activity in the Temporal Lobe while Speaking: A Positron Emission Tomography Study

ERIC Educational Resources Information Center

Takaso, Hideki; Eisner, Frank; Wise, Richard J. S.; Scott, Sophie K.

2010-01-01

Purpose: Delayed auditory feedback is a technique that can improve fluency in stutterers, while disrupting fluency in many nonstuttering individuals. The aim of this study was to determine the neural basis for the detection of and compensation for such a delay, and the effects of increases in the delay duration. Method: Positron emission…

The role of early visual cortex in visual short-term memory and visual attention.

PubMed

Offen, Shani; Schluppeck, Denis; Heeger, David J

2009-06-01

We measured cortical activity with functional magnetic resonance imaging to probe the involvement of early visual cortex in visual short-term memory and visual attention. In four experimental tasks, human subjects viewed two visual stimuli separated by a variable delay period. The tasks placed differential demands on short-term memory and attention, but the stimuli were visually identical until after the delay period. Early visual cortex exhibited sustained responses throughout the delay when subjects performed attention-demanding tasks, but delay-period activity was not distinguishable from zero when subjects performed a task that required short-term memory. This dissociation reveals different computational mechanisms underlying the two processes.

Rapid Access Real-Time device and Rapid Access software: new tools in the armamentarium of capsule endoscopy.

PubMed

Spada, Cristiano; Riccioni, Maria Elena; Costamagna, Guido

2007-07-01

Small bowel capsule endoscopy represents a significant advance in the investigation of the small bowel, allowing direct visualization of this section of the gastrointestinal system. More recently, new video capsules have been released, specifically designed to investigate the esophagus and the colon. In June 2006, Given Imaging Ltd received marketing clearance from the US FDA for the Rapid Access Real-Time (RT) and Rapid Access software. The Rapid Access RT is a handheld device that enables real-time viewing during capsule endoscopy procedures. To date, the clinical benefits of this device are unknown as studies on the Rapid Access RT system have not yet been published. However, it appears that the Rapid Access RT system may reduce the examination and reading time, and may impact significantly in cases where it is important to know the precise localization of the capsule (during PillCam ESO ingestion procedures, PillCam Colon examinations or when delayed gastric transit is suspected) or in case of severe gastrointestinal bleeding (when a therapeutic procedure is required urgently).

76 FR 25240 - Clothianidin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... neurotoxicity were exhibited in both rats (decreased arousal, motor activity and locomotor activity) and mice... (decreased body weight gains and absolute thymus weights in pups, delayed sexual maturation and an increase.../day FQPA SF = 1x day.. based on decreased body weight gains and delayed sexual maturation, decreased...

Typology of nonlinear activity waves in a layered neural continuum.

PubMed

Koch, Paul; Leisman, Gerry

2006-04-01

Neural tissue, a medium containing electro-chemical energy, can amplify small increments in cellular activity. The growing disturbance, measured as the fraction of active cells, manifests as propagating waves. In a layered geometry with a time delay in synaptic signals between the layers, the delay is instrumental in determining the amplified wavelengths. The growth of the waves is limited by the finite number of neural cells in a given region of the continuum. As wave growth saturates, the resulting activity patterns in space and time show a variety of forms, ranging from regular monochromatic waves to highly irregular mixtures of different spatial frequencies. The type of wave configuration is determined by a number of parameters, including alertness and synaptic conditioning as well as delay. For all cases studied, using numerical solution of the nonlinear Wilson-Cowan (1973) equations, there is an interval in delay in which the wave mixing occurs. As delay increases through this interval, during a series of consecutive waves propagating through a continuum region, the activity within that region changes from a single-frequency to a multiple-frequency pattern and back again. The diverse spatio-temporal patterns give a more concrete form to several metaphors advanced over the years to attempt an explanation of cognitive phenomena: Activity waves embody the "holographic memory" (Pribram, 1991); wave mixing provides a plausible cause of the competition called "neural Darwinism" (Edelman, 1988); finally the consecutive generation of growing neural waves can explain the discontinuousness of "psychological time" (Stroud, 1955).

Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model

PubMed Central

Pissadaki, Eleftheria Kyriaki; Sidiropoulou, Kyriaki; Reczko, Martin; Poirazi, Panayiota

2010-01-01

The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting, but how these changes affect information processing remains unclear. Using a detailed CA1 pyramidal neuron model, we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and proximal dendritic layers influence the information content of model responses. We find that the temporal delay between activation of the two layers acts as a switch between excitability modes: short delays induce bursting while long delays decrease firing. For long delays, the average firing frequency of the model response discriminates spatially clustered from diffused inputs to the distal dendritic tree. For short delays, the onset latency and inter-spike-interval succession of model responses can accurately classify input signals as temporally close or distant and spatially clustered or diffused across different stimulation protocols. These findings suggest that a CA1 pyramidal neuron may be capable of encoding and transmitting presynaptic spatiotemporal information about the activity of the entorhinal cortex-hippocampal network to higher brain regions via the selective use of either a temporal or a rate code. PMID:21187899

Recent advances in pacemaker and implantable defibrillator therapy for young patients.

PubMed

Walsh, Edward P; Cecchin, Frank

2004-03-01

This review is intended to highlight major clinical advances over the past year related to (1). biventricular pacing as a treatment for dilated myopathy, (2). growing clinical experience with implantable cardioverter defibrillators in pediatrics, (3). technical advances in standard antibradycardia pacing, and (4). an appraisal of the newly updated ACC/AHA/NASPE guidelines for device implant in children and adolescents. Complex rhythm devices are being used more frequently in children. Biventricular pacing to improve ventricular contractility is a rapidly evolving technology that has now been applied to children and young adults with intraventricular conduction delay, such as bundle branch block after cardiac surgery. Implantable defibrillators are also being used for an expanding list of conditions, although lead dysfunction is seen as a fairly common complication in active young patients. Guidelines for device implantation have been developed, but the weight of evidence remains somewhat limited by the paucity of pediatric data in this field. Thanks to refinements in lead design and generator technology, coupled with rapidly expanding clinical indications, pacemakers and implantable defibrillators have become increasingly important components of cardiac therapy for young patients. Expanded multicenter clinical studies will be needed to develop more objective guidelines for use of this advanced technology.

Information needs for the rapid response team electronic clinical tool.

PubMed

Barwise, Amelia; Caples, Sean; Jensen, Jeffrey; Pickering, Brian; Herasevich, Vitaly

2017-10-02

Information overload in healthcare is dangerous. It can lead to critical errors and delays. During Rapid Response Team (RRT) activations providers must make decisions quickly to rescue patients from physiological deterioration. In order to understand the clinical data required and how best to present that information in electronic systems we aimed to better assess the data needs of providers on the RRT when they respond to an event. A web based survey to evaluate clinical data requirements was created and distributed to all RRT providers at our institution. Participants were asked to rate the importance of each data item in guiding clinical decisions during a RRT event response. There were 96 surveys completed (24.5% response rate) with fairly even distribution throughout all clinical roles on the RRT. Physiological data including heart rate, respiratory rate, and blood pressure were ranked by more than 80% of responders as being critical information. Resuscitation status was also considered critically useful by more than 85% of providers. There is a limited dataset that is considered important during an RRT. The data is widely available in EMR. The findings from this study could be used to improve user-centered EMR interfaces.

Revisiting the rise and fall of false recall: presentation rate effects depend on retention interval.

PubMed

Smith, Troy A; Kimball, Daniel R

2012-01-01

Leading theories of false memory predict that veridical and false recall of lists of semantically associated words can be dissociated by varying the presentation speed during study. Specifically, as presentation rate increases from milliseconds to seconds, veridical recall is predicted to increase monotonically while false recall is predicted to show a rapid rise and then a slow decrease--a pattern shown by McDermott and Watson (2001) in a study using immediate recall tests. In three experiments we tested the generality of the effects of rapid presentation rates on veridical and false memory. In Experiments 1 and 2 participants exhibited high levels of false recall on a delayed recall test, even for very fast stimulus onset asynchronies (SOA)--contrary to predictions from leading theories of false memory. When we switched to an immediate recall test in Experiment 3 we replicated the pattern predicted by the theories and observed by McDermott and Watson. Follow-up analyses further showed that the relative output position of false recalls is not affected by presentation rate, contrary to predictions from fuzzy trace theory. Implications for theories of false memory, including activation monitoring theory and fuzzy trace theory, are discussed.

Narrow infrasound pulses from lightning; are they of electrostatic or thermal origin?

NASA Astrophysics Data System (ADS)

CHUM, Jaroslav; Diendorfer, Gerhard; Šindelářová, Tereza; Baše, Jiří; Hruška, František

2014-05-01

Narrow (~1-2 s) infrasound pulses that followed, with ~11 to ~50 s delays, rapid changes of electrostatic field were observed by a microbarometer array in the Czech Republic during thunderstorm activity. The angles of arrival (azimuth and elevation) were analyzed for selected distinct events. Comparisons of distances and azimuths of infrasound sources from the center of microbarometer array with lightning locations determined by EUCLID lightning detection network show that most of the selected events are most likely associated with intra-cloud (IC) discharges. Preceding rapid changes of electrostatic field, potential association of infrasound pulses with IC discharges, and high elevation angles of arrival for near infrasound sources indicate that an electrostatic mechanism is probably responsible for their generation. It is discussed that distinguishing of the relative role of thermal and electrostatic mechanism is difficult, and that none of published models of electrostatic production of infrasound thunder can explain the presented observations precisely. A modification of the current models, based on consideration of at least two charged layers is suggested. Further theoretical and experimental investigations are however needed to get a better description of the generation mechanism of those infrasound pulses.

Methylphenidate does not improve interference control during a working memory task in young patients with attention-deficit hyperactivity disorder.

PubMed

Prehn-Kristensen, Alexander; Krauel, Kerstin; Hinrichs, Hermann; Fischer, Jochen; Malecki, Ulrike; Schuetze, Hartmut; Wolff, Stephan; Jansen, Olav; Duezel, Emrah; Baving, Lioba

2011-05-04

Patients with attention-deficit/hyperactivity disorder (ADHD) show deficits in working memory (WM) which may be related to prefrontal dysfunction. Methylphenidate (MPH) can restore WM deficits in ADHD by enhancing prefrontal activity. At the same time, changes in striatal activation could cause ADHD patients to be more interference-sensitive during working memory tasks. However, it is unclear whether MPH reduces WM distractibility in ADHD. In this fMRI study, 12 ADHD patients and 12 healthy controls participated on two separate days in a delayed-match-to-sample test. During the delay interval, a distractor stimulus was presented in half of the trials. Children and adolescents with ADHD received MPH only on one of the two sessions. Behavioral data analyses revealed that MPH normalized WM in ADHD. However, MPH did not improve WM performance when a distractor was presented during the delay interval. Functional images showed that MPH enhanced prefrontal activity during the delay in ADHD patients when no distractor was present. If the delay was interrupted by a distractor, only healthy controls showed activation of the caudate. In patients with ADHD, however, in line with behavioral data, MPH did not enhance caudate activity. In healthy youth, caudate activity is involved in interference control allowing the successful maintenance of information in working memory even in the presence of distraction. Our findings suggest that interference control, linked to caudate activity, is not adequately enhanced by MPH in ADHD. Copyright © 2011 Elsevier B.V. All rights reserved.

Computer laboratory notification system via short message service to reduce health care delays in management of tuberculosis in Taiwan.

PubMed

Chen, Tun-Chieh; Lin, Wei-Ru; Lu, Po-Liang; Lin, Chun-Yu; Lin, Shu-Hui; Lin, Chuen-Ju; Feng, Ming-Chu; Chiang, Horn-Che; Chen, Yen-Hsu; Huang, Ming-Shyan

2011-06-01

We investigated the impacts of introducing an expedited acid-fast bacilli (AFB) smear laboratory procedure and an automatic, real-time laboratory notification system by short message with mobile phones on delays in prompt isolation of patients with pulmonary tuberculosis (TB). We analyzed the data for all patients with active pulmonary tuberculosis at a hospital in Kaohsiung, Taiwan, a 1,600-bed medical center, during baseline (January 2004 to February 2005) and intervention (July 2005 to August 2006) phases. A total of 96 and 127 patients with AFB-positive TB was reported during the baseline and intervention phases, respectively. There were significant decreases in health care system delays (ie, laboratory delays: reception of sputum to reporting, P < .001; response delays: reporting to patient isolation, P = .045; and interval from admission to patient isolation, P < .001) during the intervention phase. Significantly fewer nurses were exposed to each patient with active pulmonary TB during the intervention phase (P = .039). Implementation of expedited AFB smear laboratory procedures and an automatic, real-time laboratory mobile notification system significantly decreased delays in the diagnosis and isolation of patients with active TB. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Age-dependent effects of topiramate on the acquisition and the retention of rapid kindling.

PubMed

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2007-04-01

To examine antiepileptogenic, disease modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Afterdischarge threshold (ADT) and duration (ADD) were examined in 2-, 3-, and 5-week-old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10-s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 h after the protocol were compared between topiramate and vehicle-treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. In 2-week-old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In 3-week-old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of 5-week-old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty-four h after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle-treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages.

Age-Dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling

PubMed Central

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2008-01-01

Summary Purpose To examine antiepileptogenic, disease-modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Methods Afterdischarge threshold (ADT) and duration (ADD) were examined in two-, three-, and five-week old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10 second trains, bipolar 20 Hz square wave pulses delivered every five minutes). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 hours after the protocol were compared between topiramate and vehicle treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. Results In two-week old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In three-week old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of five-week old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty four hours after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Conclusions Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages. PMID:17319916

Feasibility of rapid discharge after transoral robotic surgery of the oropharynx.

PubMed

Richmon, Jeremy D; Feng, Allen L; Yang, Wuyang; Starmer, Heather; Quon, Harry; Gourin, Christine G

2014-11-01

To investigate the use of an algorithm for rapid discharge after transoral robotic surgery (TORS) and its effect on postoperative complications. Retrospective cohort study. A retrospective analysis of TORS cases from September 2009 to February 2013 was conducted. The effect of patient and tumor characteristics on postoperative length of stay (LOS) and complications were analyzed. A total of 91 patients were included; 79 underwent TORS for malignancy and 12 for a benign process. The mean LOS was 1.51 days (range, 1-5 days) with a median of 1 day. The mean time to initiation of oral diet was 1.26 days (range, 1-7 days) with a median of 1 day. Eleven (12%) patients experienced one or more complications during their postoperative course. Multivariate analysis demonstrated a significant association between patient and procedure variables and postoperative complications. TORS base of tongue reduction for obstructive sleep apnea (OSA) was associated with a significantly greater mean incremental time to initiation of oral diet (1.0 days, 95% confidence interval [CI]: 0.4 to 1.7, P < .001). A significantly greater mean incremental LOS was observed for patients with advanced comorbidity and a delay in initiation of oral diet beyond 24 hours. Rapid initiation of oral diet and rapid discharge home is feasible and not associated with postoperative complications. Similarly, the performance of a concurrent neck dissection does not contribute to LOS or the development of postoperative complications. Patients undergoing TORS for OSA are at greater risk of delay in initiation of oral diet and increased LOS. 4 © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control.

PubMed

Luo, C; Yao, X; Li, J; He, B; Liu, Q; Ren, H; Liang, F; Li, M; Lin, H; Peng, J; Yuan, T F; Pei, Z; Su, H

2016-03-31

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4(-/-) mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.

A non-metastatic remote effect of lung carcinoma.

PubMed

van der Pol, B A; Planten, J T

1987-01-01

A 37-year-old man, who had an oat cell carcinoma of the left lung, lost in a few months a substantial part of both visual fields, on account of a destructive retinal process. This syndrome is known in the literature as a visual paraneoplastic syndrome, which clinically shows the very rapid development of a pseudoretinitis pigmentosa sine pigmento. For most of the patients described the visual problem was the presenting symptom. In contrast with most other described cases, our patient responded very well to systemic tumor treatment and his ocular process also came to a standstill after some delay. The nature of the relationship between the primary tumor and the photoreceptor destruction is not yet clear in detail. An auto-immune process probably forms the basis of the syndrome, but hormonal activity of the tumor could not be excluded in all cases.

Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys

PubMed Central

Maguire, David R; Gerak, Lisa R; France, Charles P

2015-01-01

Opioid abusers discount delayed reinforcers more rapidly than non-users; however, it is unclear whether chronic drug administration or its discontinuation impact discounting. This study examined daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered 1 food pellet immediately; responding on another lever delivered 2 food pellets either immediately or after a delay (30–120 sec) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032–5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e., rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g., decrease in the number of trials completed as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest factors other than, or in addition to, changes in discounting might play a role. PMID:26397762

Heart Rate Recovery, Physical Activity Level, and Functional Status in Subjects With COPD.

PubMed

Morita, Andrea A; Silva, Laís K O; Bisca, Gianna W; Oliveira, Joice M; Hernandes, Nidia A; Pitta, Fabio; Furlanetto, Karina C

2018-05-15

A normal heart rate reflects the balance between the sympathetic and parasympathetic autonomic nervous system. When the difference between heart rate at the end of an exercise test and after 1 min of recovery, known as the 1-min heart rate recovery, is ≤ 12 beats/min, this may indicate an abnormal delay. We sought to compare physical activity patterns and subjects' functional status with COPD with or without delayed 1-min heart rate recovery after the 6-min walk test (6MWT). 145 subjects with COPD (78 men, median [interquartile range (IQR)] age 65 [60-73] y, body mass index 25 [21-30] kg/m 2 , FEV 1 45 ± 15% predicted) were underwent the following assessments: spirometry, 6MWT, functional status, and physical activity in daily life (PADL). A delayed heart rate recovery of 1 min was defined as ≤ 12 beats/min. Subjects with delayed 1-min heart rate recovery walked a shorter distance in the 6MWT compared to subjects without delayed heart rate recovery (median [IQR] 435 [390-507] m vs 477 [425-515] m, P = .01; 81 [71-87] vs 87 [79-98]% predicted, P = .002). Regarding PADL, subjects with delayed heart rate recovery spent less time in the standing position (mean ± SD 185 ± 89 min vs 250 ± 107 min, P = .002) and more time in sedentary positions (472 ± 110 min vs 394 ± 129 min, P = .002). Scores based on the self-care domain of the London Chest Activity of Daily Living questionnaire and the activity domain of the Pulmonary Functional Status and Dyspnea questionnaire were also worse in the group with delayed heart rate recovery (6 ± 2 points vs 5 ± 2 points; P = .039 and 29 ± 24 points vs 19 ± 17 points; P = .037, respectively). Individuals with COPD who exhibit delayed 1-min heart rate recovery after the 6MWT exhibited worse exercise capacity as well as a more pronounced sedentary lifestyle and worse functional status than those without delayed heart rate recovery. Despite its assessment simplicity, heart rate recovery after the 6MWT can be further explored as a promising outcome in COPD. Copyright © 2018 by Daedalus Enterprises.

Willing to wait: Elevated reward-processing EEG activity associated with a greater preference for larger-but-delayed rewards.

PubMed

Pornpattananangkul, Narun; Nusslock, Robin

2016-10-01

While almost everyone discounts the value of future rewards over immediate rewards, people differ in their so-called delay-discounting. One of the several factors that may explain individual differences in delay-discounting is reward-processing. To study individual-differences in reward-processing, however, one needs to consider the heterogeneity of neural-activity at each reward-processing stage. Here using EEG, we separated reward-related neural activity into distinct reward-anticipation and reward-outcome stages using time-frequency characteristics. Thirty-seven individuals first completed a behavioral delay-discounting task. Then reward-processing EEG activity was assessed using a separate reward-learning task, called a reward time-estimation task. During this EEG task, participants were instructed to estimate time duration and were provided performance feedback on a trial-by-trial basis. Participants received monetary-reward for accurate-performance on Reward trials, but not on No-Reward trials. Reward trials, relative to No-Reward trials, enhanced EEG activity during both reward-anticipation (including, cued-locked delta power during cue-evaluation and pre-feedback alpha suppression during feedback-anticipation) and reward-outcome (including, feedback-locked delta, theta and beta power) stages. Moreover, all of these EEG indices correlated with behavioral performance in the time-estimation task, suggesting their essential roles in learning and adjusting performance to maximize winnings in a reward-learning situation. Importantly, enhanced EEG power during Reward trials, as reflected by stronger 1) pre-feedback alpha suppression, 2) feedback-locked theta and 3) feedback-locked beta, was associated with a greater preference for larger-but-delayed rewards in a separate, behavioral delay-discounting task. Results highlight the association between a stronger preference toward larger-but-delayed rewards and enhanced reward-processing. Moreover, our reward-processing EEG indices detail the specific stages of reward-processing where these associations occur. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2011-09-07

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

Polar Cooperative Navigation Algorithm for Multi-Unmanned Underwater Vehicles Considering Communication Delays.

PubMed

Yan, Zheping; Wang, Lu; Wang, Tongda; Yang, Zewen; Chen, Tao; Xu, Jian

2018-03-30

To solve the navigation accuracy problems of multi-Unmanned Underwater Vehicles (multi-UUVs) in the polar region, a polar cooperative navigation algorithm for multi-UUVs considering communication delays is proposed in this paper. UUVs are important pieces of equipment in ocean engineering for marine development. For UUVs to complete missions, precise navigation is necessary. It is difficult for UUVs to establish true headings because of the rapid convergence of Earth meridians and the severe polar environment. Based on the polar grid navigation algorithm, UUV navigation in the polar region can be accomplished with the Strapdown Inertial Navigation System (SINS) in the grid frame. To save costs, a leader-follower type of system is introduced in this paper. The leader UUV helps the follower UUVs to achieve high navigation accuracy. Follower UUVs correct their own states based on the information sent by the leader UUV and the relative position measured by ultra-short baseline (USBL) acoustic positioning. The underwater acoustic communication delay is quantized by the model. In this paper, considering underwater acoustic communication delay, the conventional adaptive Kalman filter (AKF) is modified to adapt to polar cooperative navigation. The results demonstrate that the polar cooperative navigation algorithm for multi-UUVs that considers communication delays can effectively navigate the sailing of multi-UUVs in the polar region.

Polar Cooperative Navigation Algorithm for Multi-Unmanned Underwater Vehicles Considering Communication Delays

PubMed Central

Yan, Zheping; Wang, Lu; Wang, Tongda; Yang, Zewen; Chen, Tao; Xu, Jian

2018-01-01

To solve the navigation accuracy problems of multi-Unmanned Underwater Vehicles (multi-UUVs) in the polar region, a polar cooperative navigation algorithm for multi-UUVs considering communication delays is proposed in this paper. UUVs are important pieces of equipment in ocean engineering for marine development. For UUVs to complete missions, precise navigation is necessary. It is difficult for UUVs to establish true headings because of the rapid convergence of Earth meridians and the severe polar environment. Based on the polar grid navigation algorithm, UUV navigation in the polar region can be accomplished with the Strapdown Inertial Navigation System (SINS) in the grid frame. To save costs, a leader-follower type of system is introduced in this paper. The leader UUV helps the follower UUVs to achieve high navigation accuracy. Follower UUVs correct their own states based on the information sent by the leader UUV and the relative position measured by ultra-short baseline (USBL) acoustic positioning. The underwater acoustic communication delay is quantized by the model. In this paper, considering underwater acoustic communication delay, the conventional adaptive Kalman filter (AKF) is modified to adapt to polar cooperative navigation. The results demonstrate that the polar cooperative navigation algorithm for multi-UUVs that considers communication delays can effectively navigate the sailing of multi-UUVs in the polar region. PMID:29601537