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As the increase of train speed and the adoption of lightweight technology, the vibration induced by wheel-rail interaction transmitted to the passengers via suspensions, bogies, carbody and seat becomes intensified, which worsens ride comfort. The human-seat system is always ignored in the study of ride comfort. And the existing studies of the biodynamics of human body and the dynamic characteristics of human-seat system are mainly focused on single-axis vibrations, which shows their limitations when applied to typical multi-axis vibration environment of rail vehicles. Further comprehensive research needs to be carried out to advance the understanding under typical multiaxis vibrations and apply to the study of ride comfort of rail vehicles. Firstly, a vertical train model incorporated with calibrated human-seat systems was developed for studying ride comfort. The relationship between the ride comfort and geometry filter effect of vehicle was analyzed, and the influencing factors of ride comfort were revealed and discussed. In addition, the contribution of different modes of carbody to ride comfort was defined and analyzed. A field measurement was carried out on a high-speed train for the vibration transmission of the seat, and the data were analyzed with a proposed new multi-input and single-output (MISO) system. The new method has the advantage of evaluating the contribution of inputs and their coherent part to the output independently of the sequences of inputs compared with the original method. It was found three inputs (vertical, lateral and roll accelerations) from the carbody floor could well account for the vertical, lateral or roll vibrations at the seat pan or backrest. An experimental study of the biodynamics of seated human body exposed to vertical, lateral and roll vibration was carried out. The principal resonance frequencies of the apparent masses generally had a negative correlation with the weighted root-sum-square (r.s.s.) value of the lateral, ver

Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.

Genome editing using programmable nucleases has revolutionized biomedical research. CRISPR-Cas9 mediated zygote genome editing enables high efficient production of knockout animals suitable for studying development and relevant human diseases. Here we report efficient disabling pancreatogenesis in pig embryos via zygotic co-delivery of Cas9 mRNA and dual sgRNAs targeting the PDX1 gene, which when combined with chimeric-competent human pluriopotent stem cells may serve as a suitable platform for the xeno-generation of human tissues and organs in pigs.

The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency. Amt-87 works by activating the human transcriptional elongation factor P-TEFb, a CDK9-cyclin T1 heterodimer that is part of the super elongation complex (SEC) used by the viral encoded Tat protein to activate HIV transcription. Amt-87 does so by promoting the phosphorylation of CDK9 at the T-loop, liberating P-TEFb from the inactive 7SK snRNP, and inducing the formation of the Tat-SEC complex at the viral promoter. Together, our data reveal chalcones as a promising category of compounds that should be further explored to identify effective LRAs for targeted reversal of HIV latency.

Maternal exposures to traffic-related air pollution have been associated with adverse pregnancy outcomes. Exposures to traffic-related air pollutants are strongly influenced by time spent near traffic. However, little is known about women's travel activities during pregnancy and whether questionnaire-based data can provide reliable information on travel patterns during pregnancy.Examine women's in-vehicle travel behavior during pregnancy and examine the difference in travel data collected by questionnaire and global positioning system (GPS) and their potential for exposure error.We measured work-related travel patterns in 56 pregnant women using a questionnaire and one-week GPS tracking three times during pregnancy (<20 weeks, 20-30 weeks, and >30 weeks of gestation). We compared self-reported activities with GPS-derived trip distance and duration, and examined potentially influential factors that may contribute to differences. We also described in-vehicle travel behavior by pregnancy periods and influences of demographic and personal factors on daily travel times. Finally, we estimated personal exposure to particle-bound polycyclic aromatic hydrocarbon (PB-PAH) and examined the magnitude of exposure misclassification using self-reported vs. GPS travel data.Subjects overestimated both trip duration and trip distance compared to the GPS data. We observed moderately high correlations between self-reported and GPS-recorded travel distance (home to work trips: r = 0.88; work to home trips: r = 0.80). Better agreement was observed between the GPS and the self-reported travel time for home to work trips (r = 0.77) than work to home trips (r = 0.64). The subjects on average spent 69 and 93 minutes traveling in vehicles daily based on the GPS and self-reported data, respectively. Longer daily travel time was observed among participants in early pregnancy, and during certain pregnancy periods in women with higher education attainment, higher income

BackgroundExposure to polycyclic aromatic hydrocarbon (PAH) has been linked to various adverse health outcomes. Personal PAH exposures are usually measured by personal monitoring or biomarkers, which are costly and impractical for a large population. Modeling is a cost-effective alternative to characterize personal PAH exposure although challenges exist because the PAH exposure can be highly variable between locations and individuals in non-occupational settings. In this study we developed models to estimate personal inhalation exposures to particle-bound PAH (PB-PAH) using data from global positioning system (GPS) time-activity tracking data, traffic activity, and questionnaire information.MethodsWe conducted real-time (1-min interval) personal PB-PAH exposure sampling coupled with GPS tracking in 28 non-smoking women for one to three sessions and one to nine days each session from August 2009 to November 2010 in Los Angeles and Orange Counties, California. Each subject filled out a baseline questionnaire and environmental and behavior questionnaires on their typical activities in the previous three months. A validated model was used to classify major time-activity patterns (indoor, in-vehicle, and other) based on the raw GPS data. Multiple-linear regression and mixed effect models were developed to estimate averaged daily and subject-level PB-PAH exposures. The covariates we examined included day of week and time of day, GPS-based time-activity and GPS speed, traffic- and roadway-related parameters, meteorological variables (i.e. temperature, wind speed, relative humidity), and socio-demographic variables and occupational exposures from the questionnaire.ResultsWe measured personal PB-PAH exposures for 180 days with more than 6 h of valid data on each day. The adjusted R2 of the model was 0.58 for personal daily exposures, 0.61 for subject-level personal exposures, and 0.75 for subject-level micro-environmental exposures. The amount of time in vehicle (ave

BackgroundPeople's time-location patterns are important in air pollution exposure assessment because pollution levels may vary considerably by location. A growing number of studies are using global positioning systems (GPS) to track people's time-location patterns. Many portable GPS units that archive location are commercially available at a cost that makes their use feasible for epidemiological studies.MethodsWe evaluated the performance of five portable GPS data loggers and two GPS cell phones by examining positional accuracy in typical locations (indoor, outdoor, in-vehicle) and factors that influence satellite reception (building material, building type), acquisition time (cold and warm start), battery life, and adequacy of memory for data storage. We examined stationary locations (eg, indoor, outdoor) and mobile environments (eg, walking, traveling by vehicle or bus) and compared GPS locations to highly-resolved US Geological Survey (USGS) and Digital Orthophoto Quarter Quadrangle (DOQQ) maps.ResultsThe battery life of our tested instruments ranged from <9 hours to 48 hours. The acquisition of location time after startup ranged from a few seconds to >20 minutes and varied significantly by building structure type and by cold or warm start. No GPS device was found to have consistently superior performance with regard to spatial accuracy and signal loss. At fixed outdoor locations, 65%-95% of GPS points fell within 20-m of the corresponding DOQQ locations for all the devices. At fixed indoor locations, 50%-80% of GPS points fell within 20-m of the corresponding DOQQ locations for all the devices except one. Most of the GPS devices performed well during commuting on a freeway, with >80% of points within 10-m of the DOQQ route, but the performance was significantly impacted by surrounding structures on surface streets in highly urbanized areas.ConclusionsAll the tested GPS devices had limitations, but we identified several devices which showed promising per