Towards a quantum representation of the ampere using single electron pumps

Electron pumps generate a macroscopic electric current by controlled manipulation of single electrons. Despite intensive research towards a quantum current standard over the last 25 years, making a fast and accurate quantised electron pump has proved extremely difficult. Here we demonstrate that the accuracy of a semiconductor quantum dot pump can be dramatically improved by using specially designed gate drive waveforms. Our pump can generate a current of up to 150 pA, corresponding to almost a billion electrons per second, with an experimentally demonstrated current accuracy better than 1.2 parts per million (ppm) and strong evidence, based on fitting data to a model, that the true accuracy is approaching 0.01 ppm. This type of pump is a promising candidate for further development as a realisation of the SI base unit ampere, following a re-definition of the ampere in terms of a fixed value of the elementary charge.Comment: 8 pages, 7 figure

Kinetics of Biodiesel Production from Microalgae Using Microbubble Interfacial Technology

As an alternative to fossil fuels, biodiesel can be a source of clean and environmentally friendly energy source. However, its commercial application is limited by expensive feedstock and the slow nature of the pretreatment step-acid catalysis. The conventional approach to carry out this reaction uses stirred tank reactors. Recently, the lab-scale experiments using microbubble mediated mass transfer technology have demonstrated its potential use at commercial scale. However, all the studies conducted so far have been at a lab scale~100 mL of feedstock. To analyze the feasibility of microbubble technology, a larger pilot scale study is required. In this context, a kinetic study of microbubble technology at an intermediate scale is conducted (3 L of oil). Owing to the target for industrial application of the process, a commercial feedstock (Spirulina), microalgae oil (MO) and a commercial catalyst para-toluene sulfonic acid (PTSA) are used. Experiments to characterize the kinetics space (response surface, RSM) required for up-scaling are designed to develop a robust model. The model is compared with that developed by the gated recurrent unit (GRU) method. The maximum biodiesel conversion of 99.45 ± 1.3% is achieved by using these conditions: the molar ratio of MO to MeOH of 1:23.73 ratio, time of 60 min, and a catalyst loading of 3.3 wt% MO with an MO volume of 3 L. Furthermore, predicted models of RSM and GRU show proper fits to the experimental result. It was found that GRU produced a more accurate and robust model with correlation coefficient R2 = 0.9999 and root-mean-squared error (RSME) = 0.0515 in comparison with RSM model with R2 = 0.9844 and RMSE = 3.0832, respectively. Although RSM and GRU are fully empirical representations, they can be used for reactor up-scaling horizontally with microbubbles if the liquid layer height is held constant while the microbubble injection replicates along the floor of the reactor vessel—maintaining the tessellation pattern of the smaller vessel. This scaling approach maintains the local mixing profile, which is the major uncontrolled variable in conventional stirred tank reactor up-scaling

MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation.

Roughly half of all high-risk neuroblastoma patients present with MYCN amplification. The molecular consequences of MYCN overexpression in this aggressive pediatric tumor have been studied for decades, but thus far, our understanding of the early initiating steps of MYCN-driven tumor formation is still enigmatic. We performed a detailed transcriptome landscaping during murine TH-MYCN-driven neuroblastoma tumor formation at different time points. The neuroblastoma dependency factor MEIS2, together with ASCL1, was identified as a candidate tumor-initiating factor and shown to be a novel core regulatory circuit member in adrenergic neuroblastomas. Of further interest, we found a KEOPS complex member (gm6890), implicated in homologous double-strand break repair and telomere maintenance, to be strongly upregulated during tumor formation, as well as the checkpoint adaptor Claspin (CLSPN) and three chromosome 17q loci CBX2, GJC1 and LIMD2. Finally, cross-species master regulator analysis identified FOXM1, together with additional hubs controlling transcriptome profiles of MYCN-driven neuroblastoma. In conclusion, time-resolved transcriptome analysis of early hyperplastic lesions and full-blown MYCN-driven neuroblastomas yielded novel components implicated in both tumor initiation and maintenance, providing putative novel drug targets for MYCN-driven neuroblastoma

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and >18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (>21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

Propensity score matching in estimating the effect of managerial education on academic planning behavior. Study design: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>In many academic settings teaching a particular topic is applied to every student enrolled in the same academic year, it is a difficult task for researchers to design a randomized control group study. This research aimed to estimate the effect of teaching management and planning on increasing academic planning behavior (APB), using propensity score matching (PSM).</p> <p>Methods</p> <p>In a cross-sectional survey utilizing a self-reported structured questionnaire on a systematic random sample of 421 students in Hanoi Medical University, one of the eight medical schools in Vietnam, this evaluation study adopted regression procedures to assess model fit, then PSM to create a matched control group in order to allow for evaluating the effect of management education.</p> <p>Results</p> <p>The study showed both direct and indirect effects of the education on behavior. After PSM to adjust for the possible confounders to balance statistically two groups - with and without management education, there is statistically a significant difference in APB between these two groups, making a net difference of 18.60% (p < .05). The estimated 18.6 percentage point increase can be translated into the practice of APB by 670 students in the population. This number of academic planners can be attributed to a high recall of important management and planning education.</p> <p>Conclusions</p> <p>The study provided theoretical as well as practical implications to guide the design of the education and evaluation of teaching.</p