Comparing the Differences in Brain Activities and Neural Comodulations Associated With Motion Sickness Between Drivers and Passengers.

It is common to believe that passengers are more adversely affected by motion sickness than drivers. However, no study has compared passengers and drivers' neural activities and drivers experiencing motion sickness (MS). Therefore, this study attempts to explore brain dynamics in motion sickness among passengers and drivers. Eighteen volunteers participated in simulating the driving winding road experiment while their subjective motion sickness levels and electroencephalogram (EEG) signals were simultaneously recorded. Independent Component Analysis (ICA) was employed to isolate MS-related independent components (ICs) from EEG. Furthermore, comodulation analysis was applied to decompose spectra of interest ICs, related to MS, to find the specific spectra-related temporally independent modulators (IMs). The results showed that passengers' alpha band (8-12 Hz) power increased in correlation with the MS level in the parietal, occipital midline and left and right motor areas, and drivers' alpha band (8-12 Hz) power showed relatively smaller increases than those in the passenger. Further, the results also indicate that the enhanced activation of alpha IMs in the passenger than the driver is due to a higher degree of motion sickness. In conclusion, compared to the driver, the passenger experience more conflicts among multimodal sensory systems and demand neuro-physiological regulation.

New Flexible Silicone-Based EEG Dry Sensor Material Compositions Exhibiting Improvements in Lifespan, Conductivity, and Reliability.

This study investigates alternative material compositions for flexible silicone-based dry electroencephalography (EEG) electrodes to improve the performance lifespan while maintaining high-fidelity transmission of EEG signals. Electrode materials were fabricated with varying concentrations of silver-coated silica and silver flakes to evaluate their electrical, mechanical, and EEG transmission performance. Scanning electron microscope (SEM) analysis of the initial electrode development identified some weak points in the sensors' construction, including particle pull-out and ablation of the silver coating on the silica filler. The newly-developed sensor materials achieved significant improvement in EEG measurements while maintaining the advantages of previous silicone-based electrodes, including flexibility and non-toxicity. The experimental results indicated that the proposed electrodes maintained suitable performance even after exposure to temperature fluctuations, 85% relative humidity, and enhanced corrosion conditions demonstrating improvements in the environmental stability. Fabricated flat (forehead) and acicular (hairy sites) electrodes composed of the optimum identified formulation exhibited low impedance and reliable EEG measurement; some initial human experiments demonstrate the feasibility of using these silicone-based electrodes for typical lab data collection applications.

An Inflatable and Wearable Wireless System for Making 32-Channel Electroencephalogram Measurements.

Potable electroencephalography (EEG) devices have become critical for important research. They have various applications, such as in brain-computer interfaces (BCI). Numerous recent investigations have focused on the development of dry sensors, but few concern the simultaneous attachment of high-density dry sensors to different regions of the scalp to receive qualified EEG signals from hairy sites. An inflatable and wearable wireless 32-channel EEG device was designed, prototyped, and experimentally validated for making EEG signal measurements; it incorporates spring-loaded dry sensors and a novel gasbag design to solve the problem of interference by hair. The cap is ventilated and incorporates a circuit board and battery with a high-tolerance wireless (Bluetooth) protocol and low power consumption characteristics. The proposed system provides a 500/250 Hz sampling rate, and 24 bit EEG data to meet the BCI system data requirement. Experimental results prove that the proposed EEG system is effective in measuring audio event-related potential, measuring visual event-related potential, and rapid serial visual presentation. Results of this work demonstrate that the proposed EEG cap system performs well in making EEG measurements and is feasible for practical applications.

EEG Alpha and Gamma Modulators Mediate Motion Sickness-Related Spectral Responses.

Motion sickness (MS) is a common experience of travelers. To provide insights into brain dynamics associated with MS, this study recruited 19 subjects to participate in an electroencephalogram (EEG) experiment in a virtual-reality driving environment. When riding on consecutive winding roads, subjects experienced postural instability and sensory conflict between visual and vestibular stimuli. Meanwhile, subjects rated their level of MS on a six-point scale. Independent component analysis (ICA) was used to separate the filtered EEG signals into maximally temporally independent components (ICs). Then, reduced logarithmic spectra of ICs of interest, using principal component analysis, were decomposed by ICA again to find spectrally fixed and temporally independent modulators (IMs). Results demonstrated that a higher degree of MS accompanied increased activation of alpha (r = 0.421) and gamma (r =0.478) IMs across remote-independent brain processes, covering motor, parietal and occipital areas. This co-modulatory spectral change in alpha and gamma bands revealed the neurophysiological demand to regulate conflicts among multi-modal sensory systems during MS.

Extracting patterns of single-trial EEG using an adaptive learning algorithm.

The improvement of brain imaging technique brings about an opportunity for developing and investigating brain-computer interface (BCI) which is a way to interact with computer and environment. The measured brain activities usually constitute the signals of interest and noises. Applying the portable device and removing noise are the benefits to real-world BCI. In this study, one portable electroencephalogram (EEG) system non-invasively acquired brain dynamics through wireless transmission while six subjects participated in the rapid serial visual presentation (RSVP) paradigm. The event-related potential (ERP) was traditionally estimated by ensemble averaging (EA) to increase the signal-to-noise ratio. One adaptive filter of data-reusing radial basis function network (DR-RBFN) was also utilized as the estimator. The results showed that this portable EEG system stably acquired brain activities. Furthermore, the task-related potentials could be clearly explored from the limited samples of EEG data through DR-RBFN. According to the artifact-free data from the portable device, this study demonstrated the potential to move the BCI from laboratory research to real-life application in the near future.

Design, Fabrication, and Experimental Validation of Novel Flexible Silicon-Based Dry Sensors for Electroencephalography Signal Measurements.

Many commercially available electroencephalography (EEG) sensors, including conventional wet and dry sensors, can cause skin irritation and user discomfort owing to the foreign material. The EEG products, especially sensors, highly prioritize the comfort level during devices wear. To overcome these drawbacks for EEG sensors, this paper designs Societe Generale de Surveillance S [Formula: see text] A [Formula: see text] (SGS)-certified, silicon-based dry-contact EEG sensors (SBDSs) for EEG signal measurements. According to the SGS testing report, SBDSs extract does not irritate skin or induce noncytotoxic effects on L929 cells according to ISO10993-5. The SBDS is also lightweight, flexible, and nonirritating to the skin, as well as capable of easily fitting to scalps without any skin preparation or use of a conductive gel. For forehead and hairy sites, EEG signals can be measured reliably with the designed SBDSs. In particular, for EEG signal measurements at hairy sites, the acicular and flexible design of SBDS can push the hair aside to achieve satisfactory scalp contact, as well as maintain low skin-electrode interface impedance. Results of this paper demonstrate that the proposed sensors perform well in the EEG measurements and are feasible for practical applications.

The effects of stem length and core placement on shRNA activity.

BACKGROUND: Expressed short hairpin RNAs (shRNA) used in mammalian RNA interference (RNAi) are often designed around a specific short interfering RNA (siRNA) core. Whilst there are algorithms to aid siRNA design, hairpin-specific characteristics such as stem-length and siRNA core placement within the stem are not well defined. RESULTS: Using more than 91 hairpins designed against HIV-1 Tat and Vpu, we investigated the influence of both of these factors on suppressive activity, and found that stem length does not correspond with predictable changes in suppressive activity. We also detected multiple processed products for all stem lengths tested. However, the entire length of the hairpin stem was not equally processed into active products. As such, the placement of the siRNA core at the base terminus was critical for activity. CONCLUSION: We conclude that there is no fixed correlation between stem length and suppressive activity. Instead, core selection and placement likely have a greater influence on the effectiveness of shRNA-based silencing.

Multiple shRNA combinations for near-complete coverage of all HIV-1 strains.

BACKGROUND: Combinatorial RNA interference (co-RNAi) approaches are needed to account for viral variability in treating HIV-1 with RNAi, as single short hairpin RNAs (shRNA) are rapidly rendered ineffective by resistant strains. Current work suggests that 4 simultaneously expressed shRNAs may prevent the emergence of resistant strains. RESULTS: In this study we assembled combinations of highly-conserved shRNAs to target as many HIV-1 strains as possible. We analyzed intersecting conservations of 10 shRNAs to find combinations with 4+ matching the maximum number of strains using 1220+ HIV-1 sequences from the Los Alamos National Laboratory (LANL). We built 26 combinations of 2 to 7 shRNAs with up to 87% coverage for all known strains and 100% coverage of clade B subtypes, and characterized their intrinsic suppressive activities in transient expression assays. We found that all combinations had high combined suppressive activities, though there were also large changes in the individual activities of the component shRNAs in our multiple expression cassette configurations. CONCLUSION: By considering the intersecting conservations of shRNA combinations we have shown that it is possible to assemble combinations of 6 and 7 highly active, highly conserved shRNAs such that there is always at least 4 shRNAs within each combination covering all currently known variants of entire HIV-1 subtypes. By extension, it may be possible to combine several combinations for complete global coverage of HIV-1 variants.

Cassette deletion in multiple shRNA lentiviral vectors for HIV-1 and its impact on treatment success.

BACKGROUND: Multiple short hairpin RNA (shRNA) gene therapy strategies are currently being investigated for treating viral diseases such as HIV-1. It is important to use several different shRNAs to prevent the emergence of treatment-resistant strains. However, there is evidence that repeated expression cassettes delivered via lentiviral vectors may be subject to recombination-mediated repeat deletion of 1 or more cassettes. RESULTS: The aim of this study was to determine the frequency of deletion for 2 to 6 repeated shRNA cassettes and mathematically model the outcomes of different frequencies of deletion in gene therapy scenarios. We created 500+ clonal cell lines and found deletion frequencies ranging from 2 to 36% for most combinations. While the central positions were the most frequently deleted, there was no obvious correlation between the frequency or extent of deletion and the number of cassettes per combination. We modeled the progression of infection using combinations of 6 shRNAs with varying degrees of deletion. Our in silico modeling indicated that if at least half of the transduced cells retained 4 or more shRNAs, the percentage of cells harboring multiple-shRNA resistant viral strains could be suppressed to < 0.1% after 13 years. This scenario afforded a similar protection to all transduced cells containing the full complement of 6 shRNAs. CONCLUSION: Deletion of repeated expression cassettes within lentiviral vectors of up to 6 shRNAs can be significant. However, our modeling showed that the deletion frequencies observed here for 6x shRNA combinations was low enough that the in vivo suppression of replication and escape mutants will likely still be effective.

96 shRNAs designed for maximal coverage of HIV-1 variants.

BACKGROUND: The RNA interference (RNAi) pathway is a mechanism of gene-suppression with potential gene therapy applications for treating viral disease such as HIV-1. The most suitable inducer of RNAi for this application is short hairpin RNA (shRNA) although it is limited to suppressing a single target. A successful anti-HIV-1 therapy will require combinations of multiple highly active, highly conserved shRNAs to adequately counter the emergence of resistant strains. RESULTS: We calculated the percentage conservations of 8, 846 unique 19 nucleotide HIV-1 targets amongst 37, 949 HIV-1 gene sequence fragments containing 24.8 million 19 mers. We developed a novel method of determining conservation in 'profile' sets of 5 overlapping 19 mer sequences (covering 23 nucleotides in total) to ensure that the intended conservation of each shRNA would be unaffected by possible variations in shRNA processing. Ninety six of the top ranking targets from 22 regions were selected based on conservation profiles, predicted activities, targets and specific nucleotide inclusion/exclusion criteria. We constructed 53 shRNAs with 20 bp stems and 43 shRNAs with 21 bp stems which we tested and ranked using fluorescent reporter and HIV-1 expression assays. Average suppressive activities ranged from 71 - 75%, with 65 hairpins classed as highly active (> 75% activity). Overall we found little difference in activities from minor changes in stem length (20 cf. 21), or between neighboring targets differing by a single nucleotide in start position. However, there were several exceptions which suggest that all sequences, irrespective of similarities in target site or design, may be useful candidates. We encountered technical limitations with GFP reporter assays when the target domain was long and or when the distance between the target site and fusion junction was large. Assay performance was improved by dividing large targets into several shorter domains. CONCLUSION: In summary, our novel selection process resulted in a large panel of highly active shRNAs spanning the HIV-1 genome, representing excellent candidates for use in multiple shRNA gene therapies. Our core selection method ensuring maximal conservation in the processed product(s) is also widely applicable to other shRNA applications.