Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype

BACKGROUND: Pulmonary fibrosis is a debilitating and lethal disease with no effective treatment options. Understanding the pathological processes at play will direct the application of novel therapeutic avenues. Hypoxia has been implicated in the pathogenesis of pulmonary fibrosis yet the precise mechanism by which it contributes to disease progression remains to be fully elucidated. It has been shown that chronic hypoxia can alter DNA methylation patterns in tumour-derived cell lines. This epigenetic alteration can induce changes in cellular phenotype with promoter methylation being associated with gene silencing. Of particular relevance to idiopathic pulmonary fibrosis (IPF) is the observation that Thy-1 promoter methylation is associated with a myofibroblast phenotype where loss of Thy-1 occurs alongside increased alpha smooth muscle actin (α-SMA) expression. The initial aim of this study was to determine whether hypoxia regulates DNA methylation in normal human lung fibroblasts (CCD19Lu). As it has been reported that hypoxia suppresses Thy-1 expression during lung development we also studied the effect of hypoxia on Thy-1 promoter methylation and gene expression.

METHODS: CCD19Lu were grown for up to 8 days in hypoxia and assessed for global changes in DNA methylation using flow cytometry. Real-time PCR was used to quantify expression of Thy-1, α-SMA, collagen I and III. Genomic DNA was bisulphite treated and methylation specific PCR (MSPCR) was used to examine the methylation status of the Thy-1 promoter.

RESULTS: Significant global hypermethylation was detected in hypoxic fibroblasts relative to normoxic controls and was accompanied by increased expression of myofibroblast markers. Thy-1 mRNA expression was suppressed in hypoxic cells, which was restored with the demethylating agent 5-aza-2'-deoxycytidine. MSPCR revealed that Thy-1 became methylated following fibroblast exposure to 1% O2.

CONCLUSION: These data suggest that global and gene-specific changes in DNA methylation may play an important role in fibroblast function in hypoxia.

Driver response time of queuing vehicles at urban signalized intersections

Driver response (reaction) time (tr) of the second queuing vehicle is generally longer than other vehicles at signalized intersections. Though this phenomenon was revealed in 1972, the above factor is still ignored in conventional departure models. This paper highlights the need for quantitative measurements and analysis of queuing vehicle performance in spontaneous discharge pattern because it can improve microsimulation. Video recording from major cities in Australia plus twenty two sets of vehicle trajectories extracted from the Next Generation Simulation (NGSIM) Peachtree Street Dataset have been analyzed to better understand queuing vehicle performance in the discharge process. Findings from this research will alleviate driver response time and also can be used for the calibration of the microscopic traffic simulation model.

Residence time investigation in a co-axial dielectric barrier discharge reactor

The residence time distribution (RTD) is a crucial parameter when treating engine exhaust emissions with a Dielectric Barrier Discharge (DBD) reactor. In this paper, the residence time of such a reactor is investigated using a finite element based software: COMSOL Multiphysics 4.3. Non-thermal plasma (NTP) discharge is being introduced as a promising method for pollutant emission reduction. DBD is one of the most advantageous of NTP technologies. In a two cylinder co-axial DBD reactor, tubes are placed between two electrodes and flow passes through the annuals between these barrier tubes. If the mean residence time increases in a DBD reactor, there will be a corresponding increase in reaction time and consequently, the pollutant removal efficiency can increase. However, pollutant formation can occur during increased mean residence time and so the proportion of fluid that may remain for periods significantly longer than the mean residence time is of great importance. In this study, first, the residence time distribution is calculated based on the standard reactor used by the authors for ultrafine particle (10-500 nm) removal. Then, different geometrics and various inlet velocities are considered. Finally, for selected cases, some roughness elements added inside the reactor and the residence time is calculated. These results will form the basis for a COMSOL plasma and CFD module investigation.

Do drinking and riding mix? Effects of legal doses of alcohol on balance ability in experienced motorcyclists

The appropriateness of applying drink driving legislation to motorcycle riding has been questioned as there may be fundamental differences in the effects of alcohol on these two activities. For example, while the distribution of blood alcohol content (BAC) levels among fatally injured male drivers compared to riders is similar, a greater proportion of motorcycle fatalities involve levels in the lower (0 to .10% BAC) range. Several psychomotor and higher-order cognitive skills underpinning riding performance appear to be significantly influenced by low levels of alcohol. For example, at low levels (.02 to .046% BAC), riders show significant increases in reaction time to hazardous stimuli, inattention to the riding task, performance errors such as leaving the roadway and a reduced ability to complete a timed course. It has been suggested that alcohol may redirect riders’ focus from higher-order cognitive skills to more physical skills such as maintaining balance. As part of a research program to investigate the potential benefits of introducing a zero, or reduced, BAC for all riders in Queensland regardless of their licence status, the effects of low doses of alcohol on balance ability were investigated in a laboratory setting. The static balance of ten experienced riders was measured while they performed either no secondary task, a visual search task, or a cognitive (arithmetic) task following the administration of alcohol (0; 0.02, and 0.05% BAC). Subjective ratings of intoxication and balance impairment increased in a dose-dependent manner; however, objective measures of static balance were negatively affected only at the .05% BAC dose. Performance on a concurrent secondary visual search task, but not a purely cognitive (arithmetic) task, improved postural stability across all BAC levels. Finally, the .05% BAC dose was associated with impaired performance on the cognitive (arithmetic) task, but not the visual search task, when participants were balancing, but neither task was impaired by alcohol when participants were standing on the floor. Implications for road safety and future ‘drink riding’ policy considerations are discussed.

A parametric duration model of the reaction times of drivers distracted by mobile phone conversations

The use of mobile phones while driving is more prevalent among young drivers—a less experienced cohort with elevated crash risk. The objective of this study was to examine and better understand the reaction times of young drivers to a traffic event originating in their peripheral vision whilst engaged in a mobile phone conversation. The CARRS-Q Advanced Driving Simulator was used to test a sample of young drivers on various simulated driving tasks, including an event that originated within the driver’s peripheral vision, whereby a pedestrian enters a zebra crossing from a sidewalk. Thirty-two licensed drivers drove the simulator in three phone conditions: baseline (no phone conversation), hands-free and handheld. In addition to driving the simulator each participant completed questionnaires related to driver demographics, driving history, usage of mobile phones while driving, and general mobile phone usage history. The participants were 21 to 26 years old and split evenly by gender. Drivers’ reaction times to a pedestrian in the zebra crossing were modelled using a parametric accelerated failure time (AFT) duration model with a Weibull distribution. Also tested where two different model specifications to account for the structured heterogeneity arising from the repeated measures experimental design. The Weibull AFT model with gamma heterogeneity was found to be the best fitting model and identified four significant variables influencing the reaction times, including phone condition, driver’s age, license type (Provisional license holder or not), and self-reported frequency of usage of handheld phones while driving. The reaction times of drivers were more than 40% longer in the distracted condition compared to baseline (not distracted). Moreover, the impairment of reaction times due to mobile phone conversations was almost double for provisional compared to open license holders. A reduction in the ability to detect traffic events in the periphery whilst distracted presents a significant and measurable safety concern that will undoubtedly persist unless mitigated.

Mussel-inspired bioceramics with self-assembled Ca-P/polydopamine composite nanolayer : preparation, formation mechanism, improved cellular bioactivity and osteogenic differentiation of bone marrow stromal cells

The nanostructured surface of biomaterials plays an important role in improving their in vitro cellular bioactivity as well as stimulating in vivo tissue regeneration. Inspired by the mussel’s adhesive versatility, which is thought to be due to the plaque–substrate interface being rich in 3,4-dihydroxy-L-phenylalamine (DOPA) and lysine amino acids, in this study we developed a self-assembly method to prepare a uniform calcium phosphate (Ca-P)/polydopamine composite nanolayer on the surface of b-tricalcium phosphate (b-TCP) bioceramics by soaking b-TCP bioceramics in Tris–dopamine solution. It was found that the addition of dopamine, reaction temperature and reaction time are three key factors inducing the formation of a uniform Ca-P/polydopamine composite nanolayer. The formation mechanism of a Ca-P/polydopamine composite nanolayer involved two important steps: (i) the addition of dopamine to Tris–HCl solution decreases the pH value and accelerates Ca and P ionic dissolution from the crystal boundaries of b-TCP ceramics; (ii) dopamine is polymerized to form self-assembled polydopamine film and, at the same time, nanosized Ca-P particles are mineralized with the assistance of polydopamine, in which the formation of polydopamine occurs simultaneously with Ca-P mineralization (formation of nanosized microparticles composed of calcium phosphate-based materials), and finally a self-assembled Ca-P/polydopamine composite nanolayer forms on the surface of the b-TCP ceramics. Furthermore, the formed self-assembled Ca-P/polydopamine composite nanolayer significantly enhances the surface roughness and hydrophilicity of b-TCP ceramics, and stimulates the attachment, proliferation, alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, COL1 and Runx2) of human bone marrow stromal cells. Our results suggest that the preparation of self-assembled Ca-P/polydopamine composite nanolayers is a viable method to modify the surface of biomaterials by significantly improving their surface physicochemical properties and cellular bioactivity for bone regeneration application.

Cortical organization of environmental sounds by attribute

Semantic knowledge is supported by a widely distributed neuronal network, with differential patterns of activation depending upon experimental stimulus or task demands. Despite a wide body of knowledge on semantic object processing from the visual modality, the response of this semantic network to environmental sounds remains relatively unknown. Here, we used fMRI to investigate how access to different conceptual attributes from environmental sound input modulates this semantic network. Using a range of living and manmade sounds, we scanned participants whilst they carried out an object attribute verification task. Specifically, we tested visual perceptual, encyclopedic, and categorical attributes about living and manmade objects relative to a high-level auditory perceptual baseline to investigate the differential patterns of response to these contrasting types of object-related attributes, whilst keeping stimulus input constant across conditions. Within the bilateral distributed network engaged for processing environmental sounds across all conditions, we report here a highly significant dissociation within the left hemisphere between the processing of visual perceptual and encyclopedic attributes of objects.

The effect of prior visual information on recognition of speech and sounds

To identify and categorize complex stimuli such as familiar objects or speech, the human brain integrates information that is abstracted at multiple levels from its sensory inputs. Using cross-modal priming for spoken words and sounds, this functional magnetic resonance imaging study identified 3 distinct classes of visuoauditory incongruency effects: visuoauditory incongruency effects were selective for 1) spoken words in the left superior temporal sulcus (STS), 2) environmental sounds in the left angular gyrus (AG), and 3) both words and sounds in the lateral and medial prefrontal cortices (IFS/mPFC). From a cognitive perspective, these incongruency effects suggest that prior visual information influences the neural processes underlying speech and sound recognition at multiple levels, with the STS being involved in phonological, AG in semantic, and mPFC/IFS in higher conceptual processing. In terms of neural mechanisms, effective connectivity analyses (dynamic causal modeling) suggest that these incongruency effects may emerge via greater bottom-up effects from early auditory regions to intermediate multisensory integration areas (i.e., STS and AG). This is consistent with a predictive coding perspective on hierarchical Bayesian inference in the cortex where the domain of the prediction error (phonological vs. semantic) determines its regional expression (middle temporal gyrus/STS vs. AG/intraparietal sulcus).

Emotion as a boost to metacognition : how worry enhances the quality of confidence

Emotion and cognition are known to interact during human decision processes. In this study we focus on a specific kind of cognition, namely metacognition. Our experiment induces a negative emotion, worry, during a perceptual task. In a numerosity task subjects have to make a two alternative forced choice and then reveal their confidence in this decision. We measure metacognition in terms of discrimination and calibration abilities. Our results show that metacognition, but not choice, is affected by the level of worry anticipatedbefore the decision. Under worry individuals tend to have better metacognition in terms of the two measures. Furthermore understanding the formation of confidence is better explained with taking into account the level of worry in the model. This study shows the importance of an emotional component in the formation and the quality of the subjective probabilities.

The semantic interference effect in the picture-word paradigm: An event-related fMRI study employing overt responses

We used event-related functional magnetic resonance imaging (fMRI) to investigate neural responses associated with the semantic interference (SI) effect in the picture-word task. Independent stage models of word production assume that the locus of the SI effect is at the conceptual processing level (Levelt et al. [1999]: Behav Brain Sci 22:1-75), whereas interactive models postulate that it occurs at phonological retrieval (Starreveld and La Heij [1996]: J Exp Psychol Learn Mem Cogn 22:896-918). In both types of model resolution of the SI effect occurs as a result of competitive, spreading activation without the involvement of inhibitory links. These assumptions were tested by randomly presenting participants with trials from semantically-related and lexical control distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt vocalization of picture names occurred in the absence of scanner noise, allowing reaction time (RT) data to be collected. Analysis of the RT data confirmed the SI effect. Regions showing differential hemodynamic responses during the SI effect included the left mid section of the middle temporal gyrus, left posterior superior temporal gyrus, left anterior cingulate cortex, and bilateral orbitomedial prefrontal cortex. Additional responses were observed in the frontal eye fields, left inferior parietal lobule, and right anterior temporal and occipital cortex. The results are interpreted as indirectly supporting interactive models that allow spreading activation between both conceptual processing and phonological retrieval levels of word production. In addition, the data confirm that selective attention/response suppression has a role in resolving the SI effect similar to the way in which Stroop interference is resolved. We conclude that neuroimaging studies can provide information about the neuroanatomical organization of the lexical system that may prove useful for constraining theoretical models of word production.

Evaluation of residence time on nitrogen oxides removal in non-thermal plasma reactor

Non-thermal plasma (NTP) has been introduced over the last few years as a promising after- treatment system for nitrogen oxides and particulate matter removal from diesel exhaust. NTP technology has not been commercialised as yet, due to its high rate of energy consumption. Therefore, it is important to seek out new methods to improve NTP performance. Residence time is a crucial parameter in engine exhaust emissions treatment. In this paper, different electrode shapes are analysed and the corresponding residence time and NOx removal efficiency are studied. An axisymmetric laminar model is used for obtaining residence time distribution numerically using FLUENT software. If the mean residence time in a NTP plasma reactor increases, there will be a corresponding increase in the reaction time and consequently the pollutant removal efficiency increases. Three different screw thread electrodes and a rod electrode are examined. The results show the advantage of screw thread electrodes in comparison with the rod electrode. Furthermore, between the screw thread electrodes, the electrode with the thread width of 1 mm has the highest NOx removal due to higher residence time and a greater number of micro-discharges. The results show that the residence time of the screw thread electrode with a thread width of 1 mm is 21% more than for the rod electrode.

Turning visual search time on its head

Our everyday visual experience frequently involves searching for objects in clutter. Why are some searches easy and others hard? It is generally believed that the time taken to find a target increases as it becomes similar to its surrounding distractors. Here, I show that while this is qualitatively true, the exact relationship is in fact not linear. In a simple search experiment, when subjects searched for a bar differing in orientation from its distractors, search time was inversely proportional to the angular difference in orientation. Thus, rather than taking search reaction time (RT) to be a measure of target-distractor similarity, we can literally turn search time on its head (i.e. take its reciprocal 1/RT) to obtain a measure of search dissimilarity that varies linearly over a large range of target-distractor differences. I show that this dissimilarity measure has the properties of a distance metric, and report two interesting insights come from this measure: First, for a large number of searches, search asymmetries are relatively rare and when they do occur, differ by a fixed distance. Second, search distances can be used to elucidate object representations that underlie search - for example, these representations are roughly invariant to three-dimensional view. Finally, search distance has a straightforward interpretation in the context of accumulator models of search, where it is proportional to the discriminative signal that is integrated to produce a response. This is consistent with recent studies that have linked this distance to neuronal discriminability in visual cortex. Thus, while search time remains the more direct measure of visual search, its reciprocal also has the potential for interesting and novel insights. (C) 2012 Elsevier Ltd. All rights reserved.

Dynamics of the reaction between the free end of a tethered self-avoiding polymer and a flat penetrable surface: A renormalization group study

The average time tau(r) for one end of a long, self-avoiding polymer to interact for the first time with a flat penetrable surface to which it is attached at the other end is shown here to scale essentially as the square of the chain's contour length N. This result is obtained within the framework of the Wilemski-Fixman approximation to diffusion-limited reactions, in which the reaction time is expressed as a time correlation function of a ``sink'' term. In the present work, this sink-sink correlation function is calculated using perturbation expansions in the excluded volume and the polymer-surface interactions, with renormalization group methods being used to resum the expansion into a power law form. The quadratic dependence of tau(r) on N mirrors the behavior of the average time tau(c) of a free random walk to cyclize, but contrasts with the cyclization time of a free self-avoiding walk (SAW), for which tau(r) similar to N-2.2. A simulation study by Cheng and Makarov J. Phys. Chem. B 114, 3321 (2010)] of the chain-end reaction time of an SAW on a flat impenetrable surface leads to the same N-2.2 behavior, which is surprising given the reduced conformational space a tethered polymer has to explore in order to react. (C) 2014 AIP Publishing LLC.

运动距离效应的认知编码机制

Among the cognitive studies of action, an important behavioral method is used to observe Reaction Time (RT) and Movement Time (MT) as the functions of motor parameters. RT is measured from the beginning of target presentation to the initiation of a movement, which is regarded as the programming of the ongoing movement. MT is measured from the initiation to the end of the movement, which is regarded as the execution of the movement. However, the relationship between RT and motor parameters remains uncertain till now. Under the uncertainty many related issues cannot be settled for long period, especially the issues as whether the amplitude effect appears during RT, or what should the amplitude effect be during RT. The present study aimed to find out the amplitude effect and the related cognitive process under different experimental conditions. First, we discussed the potential composition of RT and suggested that RT that normally measured in previous experiments might not reflect motor programming very well. Then we designed a series experiments to observe the relationship between RT and motor programming by using different Index of Difficulty (ID), different instructions in which speed and accuracy were emphasized respectively, different vision condition during movement execution and Go/NoGo paradigm. Meanwhile, we compared the amplitude effect under the respective RT to make the specific conclusion about the amplitude effect, and the relationship between RT and MT as well. The main findings are showed as following. 1) Because of the existing of “preview”, “visual feedback control” and “speed-accuracy tradeoff”, RT reflects motor programming differently under different experimental conditions. 2) Under different experimental conditions, the amplitude effect on RT varies. RT could be too short to exhibit the amplitude effect. Or the amplitude effect could be that more RT is needed for shorter movement when RT is prolonged. Or the amplitude effect could be that more RT is needed for longer movement when RT is further prolonged. 3) Under the present experimental conditions, the amplitude effect on MT showed consistently that longer movement needs longer MT. 4) Under the present experimental conditions, the relationship between RT and MT is a kind of compensation. The present study has important theoretic significance. The cognitive process of action is an important part of human cognitive behavior. The related studies could be very helpful for human people to know about themselves and the relation between themselves and the surroundings as well. Keywords motor programming; amplitude effect; Reaction Time (RT); Movement Time (MT)

应急疏散语音告警信号设计参数的研究

Voice alarm plays an important role in emergency evacuation of public place, because it can provide information and instruct evacuation. This paper studied the optimization of acoustic and semantic parameters of voice alarms in emergency evacuation, so that alarm design can improve the evacuation performance. Both method of magnitude estimation and scale were implemented to investigate participants' perceived urgency of the alarms with different parameters. The results indicated that, participants evaluated the alarms with faster speech rate, with greater signal to noise ratio (SNR) and under louder noises more urgent. There was an interaction between noise level and content of voice alarm. Signals with speech rate below 4 characters / second were evaluated as non urgent at all. Intelligibility of the voice alarm was investigated by evaluating the key pointed recognition performance. The results showed that, speech rate’s effect was a marginal significance, and 7 characters / second has the highest intelligibility. It might because that the faster the signal spoken, the more attention was paid. Gender of speaker and SNR did not have a significant effect on the signals’ intelligibility. This paper also investigated impact of voice alarms' content on human behavior in emergency evacuation in a 3-D virtual reality environment. In condition of "telling the occupants what had happened and what to do", the number of participants who succeeded in evacuation was the largest. Further study, in which similar numbers of participants evacuate successfully in three conditions, indicated that the reaction time and evacuation time was the shortest in the aforesaid condition. Although one-way ANOVA shows that the difference was not significant, the results still provided some reference to the alarm design. In sum, parameters of voice alarm in emergency evacuation should be chosen to meet needs from both perceived urgency and intelligibility. Contents of the alarms should include "what had happened and what to do", and should vary according to noise levels in different public places.