Sub-second Range Research Articles

Direct Fourier Inversion Reconstruction Algorithm for Computed Laminography.

Synchrotron radiation computed laminography (CL) was developed to complement the conventional computed tomography as a non-destructive 3D imaging method for the inspection of flat thin objects. Recent progress in hardware at synchrotron sources allows one to record internal evolution of specimens at the micrometer scale and sub-second range but also requires increased reconstruction speed to follow structural changes online. A 3D image of the sample interior is usually reconstructed by the well-established filtered backprojection (FBP) approach. Despite of a great success in the reduction of reconstruction time via parallel computations, the FBP algorithm still remains a time-consuming procedure. A promising way to significantly shorten computation time is to directly perform backprojection in frequency domain (a direct Fourier inversion approach). The corresponding algorithms are rarely considered in the literature because of a poor performance or inferior reconstruction quality resulted from inaccurate interpolation in Fourier domain. In this paper, we derive a Fourier-based reconstruction equation designed for the CL scanning geometry. Furthermore, we outline the translation of the continuous solution to a discrete version, which utilizes 3D sinc interpolation. A projection resampling technique allowing for the reduction of the expensive interpolation to its 1D version is proposed. A series of numerical experiments confirms that the resulting image quality is well comparable with the FBP approach while reconstruction time is drastically reduced.

Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis.

Spontaneous fluctuations of neuronal activity in large-scale distributed networks are a hallmark of the resting brain. In relapsing-remitting multiple sclerosis (RRMS) several fMRI studies have suggested altered resting-state connectivity patterns. Topographical EEG analysis reveals much faster temporal fluctuations in the tens of milliseconds time range (termed “microstates”), which showed altered properties in a number of neuropsychiatric conditions.We investigated whether these microstates were altered in patients with RRMS, and if the microstates' temporal properties reflected a link to the patients' clinical features.We acquired 256-channel EEG in 53 patients (mean age 37.6 years, 45 females, mean disease duration 9.99 years, Expanded Disability Status Scale ≤ 4, mean 2.2) and 49 healthy controls (mean age 36.4 years, 33 females). We analyzed segments of a total of 5 min of EEG during resting wakefulness and determined for both groups the four predominant microstates using established clustering methods.We found significant differences in the temporal dynamics of two of the four microstates between healthy controls and patients with RRMS in terms of increased appearance and prolonged duration. Using stepwise multiple linear regression models with 8-fold cross-validation, we found evidence that these electrophysiological measures predicted a patient's total disease duration, annual relapse rate, disability score, as well as depression score, and cognitive fatigue measure.In RRMS patients, microstate analysis captured altered fluctuations of EEG topographies in the sub-second range. This measure of high temporal resolution provided potentially powerful markers of disease activity and neuropsychiatric co-morbidities in RRMS.

Analysis of Genetic and Non-Genetic Factors Influencing Timing and Time Perception.

Performance on different psychophysical tasks measuring the sense of time indicates a large amount of individual variation in the accuracy and precision of timing in the hundredths of milliseconds-to-minutes range. Quantifying factors with an influence on timing is essential to isolating a biological (genetic) contribution to the perception and estimation of time. In the largest timing study to date, 647 participants completed a duration-discrimination task in the sub-second range and a time-production task in the supra-second range. We confirm the stability of a participant’s time sense across multiple sessions and substantiate a modest sex difference on time production. Moreover, we demonstrate a strong correlation between performance on a standardized cognitive battery and performance in both duration-discrimination and time-production tasks; we further show that performance is uncorrelated with age after controlling for general intelligence. Additionally, we find an effect of ethnicity on time sense, with African Americans and possibly Hispanics in our cohort differing in accuracy and precision from other ethnic groups. Finally, a preliminary genome-wide association and exome chip study was performed on 148 of the participants, ruling out the possibility for a single common variant or groups of low-frequency coding variants within a single gene to explain more than ~18% of the variation in the sense of time.

Visual-auditory differences in duration discrimination of intervals in the subsecond and second range.

A common finding in time psychophysics is that temporal acuity is much better for auditory than for visual stimuli. The present study aimed to examine modality-specific differences in duration discrimination within the conceptual framework of the Distinct Timing Hypothesis. This theoretical account proposes that durations in the lower milliseconds range are processed automatically while longer durations are processed by a cognitive mechanism. A sample of 46 participants performed two auditory and visual duration discrimination tasks with extremely brief (50-ms standard duration) and longer (1000-ms standard duration) intervals. Better discrimination performance for auditory compared to visual intervals could be established for extremely brief and longer intervals. However, when performance on duration discrimination of longer intervals in the 1-s range was controlled for modality-specific input from the sensory-automatic timing mechanism, the visual-auditory difference disappeared completely as indicated by virtually identical Weber fractions for both sensory modalities. These findings support the idea of a sensory-automatic mechanism underlying the observed visual-auditory differences in duration discrimination of extremely brief intervals in the millisecond range and longer intervals in the 1-s range. Our data are consistent with the notion of a gradual transition from a purely modality-specific, sensory-automatic to a more cognitive, amodal timing mechanism. Within this transition zone, both mechanisms appear to operate simultaneously but the influence of the sensory-automatic timing mechanism is expected to continuously decrease with increasing interval duration.

Situational context is important: perceptual grouping modulates temporal perception.

Subjective time of an event in the sub-second range is often compressed or dilated by the situational context created by preceding and succeeding stimuli. How such context distorts psychological time is still an open question. Here, we pursued this issue by examining whether the perceptual grouping among successive visual stimuli modulates the perceived duration. Using a duration comparison task, we asked observers to judge the relative duration of a target and a comparison item, and estimated the apparent duration of the target from the corresponding psychometric function. The target was temporally flanked by a preceding item and a succeeding item. In different conditions, the target was more similar to either the preceding or the succeeding item. Results showed that perceptual grouping based on similarity modulated perceived duration. Specifically, when the target was grouped with the preceding item, its subjective duration was shorter than when it was grouped with the succeeding item. Interestingly, this pattern was observed when the preceding and target items were kept constant while the succeeding item was manipulated, suggesting that the effect depends, to some degree, on the holistic perceptual grouping rather than on fragmented processes. These results demonstrate that the situational context is an important factor in shaping temporal codes, thus bridging the seemingly independent perceptual feature processes and temporal representation.

Structural Dynamics of Ribosome Subunit Association Studied by Mixing-Spraying Time-Resolved Cryogenic Electron Microscopy

Ribosomal subunit association is a key checkpoint in translation initiation but its structural dynamics are poorly understood. Here, we used a recently developed mixing-spraying, time-resolved, cryogenic electron microscopy (cryo-EM) method to study ribosomal subunit association in the sub-second time range. We have improved this method and increased the cryo-EM data yield by tenfold. Pre-equilibrium states of the association reaction were captured by reacting the mixture of ribosomal subunits for 60ms and 140ms. We also identified three distinct ribosome conformations in the associated ribosomes. The observed proportions of these conformations are the same in these two time points, suggesting that ribosomes equilibrate among the three conformations within less than 60ms upon formation. Our results demonstrate that the mixing-spraying method can capture multiple states of macromolecules during a sub-second reaction. Other fast processes, such as translation initiation, decoding, and ribosome recycling, are amenable to study with this method.

Temporal perception in visual processing as a research tool.

Accumulated evidence has shown that the subjective time in the sub-second range can be altered by different factors; some are related to stimulus features such as luminance contrast and spatial frequency, others are processes like perceptual grouping and contextual modulation. These findings indicate that temporal perception uses neural signals involved in non-temporal feature processes and that perceptual organization plays an important role in shaping the experience of elapsed time. We suggest that the temporal representation of objects can be treated as a feature of objects. This new concept implies that psychological time can serve as a tool to study the principles of neural codes in the perception of objects like “reaction time (RT).” Whereas “RT” usually reflects the state of transient signals crossing decision thresholds, “apparent time” in addition reveals the dynamics of sustained signals, thus providing complementary information of what has been obtained from “RT” studies.

Time-Resolved cryo-EM Study of Ribosome Subunit Association by Mixing-Spraying

Time-resolved cryogenic electron microscopy (cryo-EM) is a technique for visualizing transient structures in a biological specimen in a pre-equilibrium system. Capturing reactions in the sub-second range has been a practical challenge, due to the requirement of depositing the specimen rapidly on the grid without blotting. To capture faster reactions in the sub-second range, Lu and coworkers [1] developed a mixing-spraying method, which allows a reaction involving two macromolecular components to proceed for tens to hundreds of milliseconds. The first study of ribosome subunit association using time-resolved cryo-EM, by Shaikh et al. [2], were performed at 9.4 ms and 43 ms. In present work, we improved the mixing-spraying method, by designing an environmental chamber and optimizing the EM data yield, and applied the method to the study of ribosome subunit association. We captured the subunit association reaction in a pre-equilibrium state, by mixing the subunits and reacting for 60 ms and 140 ms. Our results showed that at 60 ms and 140 ms time points, 33% and 42% of the large subunits have associated into 70S ribosomes, respectively, compared with 85% in a 15-min incubation control experiment. Three distinct conformations of the 70S ribosome were found: non-rotated, non-rotated with 30S head swiveled and rotated. Our results demonstrate the capability of the mixing-spraying method of time-resolve cryo-EM to visualize multiple states of macromolecules in a reaction within a sub-second time frame. In the future, the mixing-spraying method will be applied to study translation initiation, to gain insights on the role of mRNA, initiator tRNA and initiation factors. Supported by HHMI and NIH R01 GM29169 and GM55440 (to J.F.) [1] Lu, Z., et al. (2009). J. Struct. Biol. 168, 388-395. [2] Shaikh, T.R., et al. (2014). Proc. Natl. Acad. Sci. USA 111, 9822-9827.

High-frequency variations of hydrogen spectral lines in the B3V star η UMa

We reported the detection of high-frequency variations in the hydrogen Balmer lines in the hot star η UMa of spectral class B3V. Spectral observations of η UMa were carried out with slitless spectrograph (R∼100) installed on the 60 cm Carl Zeiss telescope in the Andrushivka Observatory. Spectra were obtained with a time resolution in the sub-second range. It has been found that the η UMa shows rapid variations in the hydrogen lines Hα, Hβ, Hγ, as well as variations in the atmospheric oxygen lines. The intensity variations in the hydrogen lines varies from 0.2% to 0.5%, and that of the oxygen lines is approximately 2%.

On-chip lysis of mammalian cells through a handheld corona device.

On-chip lysis is required in many lab-on-chip applications involving cell studies. In these applications, the complete disruption of the cellular membrane and a high lysis yield is essential. Here, we present a novel approach to lyse cells on-chip through the application of electric discharges from a corona handheld device. The method only requires a microfluidic chip and a low-cost corona device. We demonstrate the effective lysis of BHK and eGFP HCT 116 cells in the sub-second time range using an embedded microelectrode. We also show cell lysis of non-adherent K562 leukemia cells without the use of an electrode in the chip. Cell lysis has been assessed through the use of bright-field microscopy, high-speed imaging and cell-viability fluorescence probes. The experimental results show effective cell lysis without any bubble formation or significant heating. Due to the simplicity of both the components involved and the lysis procedure, this technique offers an inexpensive lysis option with the potential for integration into lab-on-a-chip devices.

Elite athletes refine their internal clocks.

Evaluating time properly is crucial for everyday activities from fundamental behaviors to refined coordinative movements such as in sport playing. Lately the concept of the existence of a unique internal clock for evaluating time in different scales has been challenged by recent neurophysiology studies. Here we provide evidence that individuals evaluate time durations below and above a second based on two different internal clocks for sub- and suprasecond time ranges: a faster clock for the subsecond range and a slower one for suprasecond time. Interestingly, the level of precision presented by these two clocks can be finely tuned through long-term sport training: Elite athletes, independently from their sport domains, generate better time estimates than nonathletes by showing higher accuracy and lower variability, particularly for subsecond time. We interpret this better time estimation in the short durations as being due to their extraordinary perceptual and motor ability in fast actions.

Increased Timing Variability in Schizophrenia and Bipolar Disorder

Theoretical and empirical evidence suggests that impaired time perception and the neural circuitry underlying internal timing mechanisms may contribute to severe psychiatric disorders, including psychotic and mood disorders. The degree to which alterations in temporal perceptions reflect deficits that exist across psychosis-related phenotypes and the extent to which mood symptoms contribute to these deficits is currently unknown. In addition, compared to schizophrenia, where timing deficits have been more extensively investigated, sub-second timing has been studied relatively infrequently in bipolar disorder. The present study compared sub-second duration estimates of schizophrenia (SZ), schizoaffective disorder (SA), non-psychotic bipolar disorder (BDNP), bipolar disorder with psychotic features (BDP), and healthy non-psychiatric controls (HC) on a well-established time perception task using sub-second durations. Participants included 66 SZ, 37 BDNP, 34 BDP, 31 SA, and 73 HC who participated in a temporal bisection task that required temporal judgements about auditory durations ranging from 300 to 600 milliseconds. Timing variability was significantly higher in SZ, BDP, and BDNP groups compared to healthy controls. The bisection point did not differ across groups. These findings suggest that both psychotic and mood symptoms may be associated with disruptions in internal timing mechanisms. Yet unexpected findings emerged. Specifically, the BDNP group had significantly increased variability compared to controls, but the SA group did not. In addition, these deficits appeared to exist independent of current symptom status. The absence of between group differences in bisection point suggests that increased variability in the SZ and bipolar disorder groups are due to alterations in perceptual timing in the sub-second range, possibly mediated by the cerebellum, rather than cognitive deficits.

Timing as an intrinsic property of neural networks: evidence from in vivo and in vitro experiments

The discrimination and production of temporal patterns on the scale of hundreds of milliseconds are critical to sensory and motor processing. Indeed, most complex behaviours, such as speech comprehension and production, would be impossible in the absence of sophisticated timing mechanisms. Despite the importance of timing to human learning and cognition, little is known about the underlying mechanisms, in particular whether timing relies on specialized dedicated circuits and mechanisms or on general and intrinsic properties of neurons and neural circuits. Here, we review experimental data describing timing and interval-selective neurons in vivo and in vitro. We also review theoretical models of timing, focusing primarily on the state-dependent network model, which proposes that timing in the subsecond range relies on the inherent time-dependent properties of neurons and the active neural dynamics within recurrent circuits. Within this framework, time is naturally encoded in populations of neurons whose pattern of activity is dynamically changing in time. Together, we argue that current experimental and theoretical studies provide sufficient evidence to conclude that at least some forms of temporal processing reflect intrinsic computations based on local neural network dynamics.

Moisture effect on the combustion of a single copper concentrate particle in a flash smelting furnace

A mathematical model has been presented to study the combustion of a single copper concentrate particle with high moisture content. By using the presented model, the effect of particle moisture content on particle temperature, sulfur oxidation, and combustion heat generation has been evaluated. The mineralogical composition of the commonly used concentrate at Khatoonabad flash smelting furnace has been used in this study. It was found that the particle moisture content is removed in the sub-second time range and thus the moisture has marginal impact on the variation of particle temperature and on the reaction rate when the gas temperature is assumed to be constant in the reaction shaft. When a concentrate with high moisture content is charged, the particle size enlargement due to the agglomeration of concentrate particles causes an abrupt fall in the particle reaction rate.

Ordinal judgments in the rat: An understanding of longer and shorter for suprasecond, but not subsecond, durations.

An emerging corpus of clinical and neuroimaging data suggests that subsecond and suprasecond durations are represented via 2 distinct mechanisms in humans; however, surprisingly, behavioral data to this effect are lacking. In our first experiment, we perform the first systematic exploration of subsecond and suprasecond timing within the same session in nonhuman subjects. Rats were trained to judge the relative duration of 2 sequential stimuli, responding on one lever if the first stimulus was longer or on a second lever if the converse was true. Our data provide strong evidence of an abstract understanding of longer and shorter for durations in the suprasecond range, whereas responding was at chance levels for durations in the subsecond range. Data from a second experiment reveal that this pattern is not due to an inability to time subsecond signals, as rats respond systematically in subsecond and suprasecond bisection tasks. Together, our results provide the first clear behavioral evidence of a discontinuity in the mental time line. These data from rats are discussed in light of similar findings of a discontinuity in the mental number line in human infants.

Single Part Influence on Assemblies for a Cycle Time Able Quality Control as well as a Suitable Toleration

The complex interrelations of force and stiffness during the clamping process of freeform shaped parts in car body fixtures cannot be described in a universal valid way by membrane theory. So calculations with FEM are used for this. However due to the long calculating time FEM is not suitable for fast quality decisions during the process. The paper presents a new method that is able to calculate adjustments and combination possibilities of different part failure classes within sub-second range. In addition the new method, that is based on a systematic analyze of the single part influences to the assembly, gives an understanding of the interrelations of all components of an assembly. So a suitable toleration is possible. The method is shown by means of an assembly example.

A Time-Resolved CRYO-EM Study of Ribosome Subunit Association by Mixing-Spraying

The emergence of a high-throughput data processing pipeline and efficient classification algorithms has revived the idea of time-resolved cryogenic electron microscopy (cryo-EM), i.e., capturing time-dependent structures in a biological specimen using cryo-EM. The blotting method now routinely used to prepare cryo-EM specimen is sufficient only to study a reaction in the second to minute range. Capturing faster reactions, in the sub-second range, has been a practical challenge, due to the required step of depositing the specimen on the grid. To address this challenge, Lu et al. (2009) have developed a novel method to prepare time-resolved cryo-EM specimens, by using a nano-fabricated mixing-spraying chip. The mixing-spraying chip allows a two-component reaction to proceed inside the chip for tens to hundreds of milliseconds (ms), which is then stopped by fast freezing. Here we used the improved mixing-spraying method to study ribosome subunit association, and particularly to capture the conformational changes of the ribosome in this reaction. Ribosome subunit association is a pivotal step in translation initiation. Previous ensemble kinetic studies suggested that the ribosome subunit association is a multi-step process, with the ribosomal inter-subunit bridges sequentially formed. Using time-resolved cryo-EM, we were able to capture the association reaction in a pre-equilibrium state by mixing the two ribosomal subunits and reacting for 140ms. However, the fraction population of the associated ribosomes in each conformation was stable from 140ms to 75min, indicating that the ribosome undergoes conformational changes faster than the 140ms time frame upon association of the subunits. Thus, we have demonstrated that the mixing-spraying method of time-resolved cryo-EM is able to visualize the states of macromolecules in a reaction within a sub-second time frame.

Temporal Perceptual Learning

Our interaction with the environment and each other is inherently time-varying in nature. It is thus not surprising that the nervous systems of animals have evolved sophisticated mechanisms to not only tell time, but to learn to discriminate and produce temporal patterns. Indeed some of the most sophisticated human behaviors, such as speech and music, would not exist if the human brain was unable to learn to discriminate and produce temporal patterns. Compared to the study of other forms of learning, such as visual perceptual learning, the study of the learning of interval and temporal pattern discrimination in the subsecond range is relatively recent. A growing number of studies over the past 15 years, however, have established that perceptual and motor timing undergo robust learning. One of the principles to have emerged from these studies is that temporal learning is generally specific to the trained interval, an observation that has important implications to the neural mechanisms underlying our ability to tell time.

Time flies when we view a sport action

Humans' time evaluation within the range of hundreds of milliseconds is often distorted, and time is judged as much longer than actually is. This consistent overestimation has been interpreted as an indicator of the threshold level for the sensitivity of the perceptuomotor system. The purpose of this study was to investigate how the perception of time, both in sub- and supra-second timescales, changes for elite athletes that are considered as individuals with highly developed motor perceptual capabilities and with great sense of time particularly for the extremely short timescales. For this purpose, we asked elite pole-vaulters to reproduce the exposure times of a familiar image showing a pole-vault jump and non-familiar images as a fencing lunge and scrambled pixels and compared their estimates with controls. While the time distortion in the supra-second range was similar for athletes and controls independently from the image presented, in the sub-second range of time, athletes were more accurate and less variable than controls, while for all the participants, the images were perceived differently. Time was perceived as shorter when viewing the pole-vault jump image followed by the fencing lunge and last the scrambled pixels, providing the evidence that action observation distorts individuals' time perception by compressing the perceived passage of time. Remarkably though pole-vaulters' higher precision and lower variability than controls indicate their ability to compensate for this distortion due to a well-refined internal clock developed through sport training.

Temporally Specific Sensory Signals for the Detection of Stimulus Omission in the Primate Deep Cerebellar Nuclei

The cerebellum is implicated in sensory prediction in the subsecond range. To explore how neurons in the cerebellum encode temporal information for the prediction of sensory events, we trained monkeys to make a saccade in response to either a single omission or deviation of isochronous repetitive stimuli. We found that neurons in the cerebellar dentate nucleus exhibited a gradual elevation of the baseline firing rate as the repetition progressed. Most neurons showed a transient suppression for each stimulus, and this firing modulation also increased gradually, opposed to the sensory adaptation. The magnitude of the enhanced sensory response positively correlated with interstimulus interval. Furthermore, when stimuli appeared unexpectedly earlier than the regular timing, the neuronal modulation became smaller, suggesting that the sensory response depended on the time elapsed since the previous stimulus. The enhancement of neuronal modulation was context dependent and was reduced or even absent when monkeys were unmotivated to detect stimulus omission. A significant negative correlation between neuronal activity at stimulus omission and saccade latency suggested that the timing of each stimulus was predicted by the amount of recovery from the transient response. Because inactivation of the recording sites delayed the detection of stimulus omission but only slightly altered the detection of stimulus deviation, these signals might be necessary for the prediction of stimulus timing but may not be involved only in the generation of saccades. Our results demonstrate a novel mechanism for temporal prediction of upcoming stimuli that accompanies the time-dependent modification of sensory gain in the cerebellum.