Experimental investigation of planar ion traps

Chiaverini et al. [Quant. Inf. Comput. 5, 419 (2005)] recently suggested a linear Paul trap geometry for ion trap quantum computation that places all of the electrodes in a plane. Such planar ion traps are compatible with modern semiconductor fabrication techniques and can be scaled to make compact, many zone traps. In this paper we present an experimental realization of planar ion traps using electrodes on a printed circuit board to trap linear chains of tens of 0.44 micron diameter charged particles in a vacuum of 15 Pa (0.1 torr). With these traps we address concerns about the low trap depth of planar ion traps and develop control electrode layouts for moving ions between trap zones without facing some of the technical difficulties involved in an atomic ion trap experiment. Specifically, we use a trap with 36 zones (77 electrodes) arranged in a cross to demonstrate loading from a traditional four rod linear Paul trap, linear ion movement, splitting and joining of ion chains, and movement of ions through intersections. We further propose an additional DC biased electrode above the trap which increases the trap depth dramatically, and a novel planar ion trap geometry that generates a two dimensional lattice of point Paul traps.Comment: 11 pages, 20 figure

Spontaneous Transition of Turbulent Flames to Detonations in Unconfined Media

Deflagration-to-detonation transition (DDT) can occur in environments ranging from experimental and industrial systems to astrophysical thermonuclear (type Ia) supernovae explosions. Substantial progress has been made in explaining the nature of DDT in confined systems with walls, internal obstacles, or pre-existing shocks. It remains unclear, however, whether DDT can occur in unconfined media. Here we use direct numerical simulations (DNS) to show that for high enough turbulent intensities unconfined, subsonic, premixed, turbulent flames are inherently unstable to DDT. The associated mechanism, based on the nonsteady evolution of flames faster than the Chapman-Jouguet deflagrations, is qualitatively different from the traditionally suggested spontaneous reaction wave model, and thus does not require the formation of distributed flames. Critical turbulent flame speeds, predicted by this mechanism for the onset of DDT, are in agreement with DNS results.Comment: 4 pages, 3 figures; accepted to Physical Review Letter

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

The potential effects of climate change on air quality across the conterminous US at 2030 under three Representative Concentration Pathways

The potential impacts of climate change on regional ozone (O3) and fine particulate (PM2.5) air quality in the United States (US) are investigated by linking global climate simulations with regional-scale meteorological and chemical transport models. Regional climate at 2000 and at 2030 under three Representative Concentration Pathways (RCPs) is simulated by using the Weather Research and Forecasting (WRF) model to downscale 11-year time slices from the Community Earth System Model (CESM). The downscaled meteorology is then used with the Community Multiscale Air Quality (CMAQ) model to simulate air quality during each of these 11-year periods. The analysis isolates the future air quality differences arising from climate-driven changes in meteorological parameters and specific natural emissions sources that are strongly influenced by meteorology. Other factors that will affect future air quality, such as anthropogenic air pollutant emissions and chemical boundary conditions, are unchanged across the simulations. The regional climate fields represent historical daily maximum and daily minimum temperatures well, with mean biases of less than 2&thinsp;K for most regions of the US and most seasons of the year and good representation of variability. Precipitation in the central and eastern US is well simulated for the historical period, with seasonal and annual biases generally less than 25&thinsp;%, with positive biases exceeding 25&thinsp;% in the western US throughout the year and in part of the eastern US during summer. Maximum daily 8&thinsp;h ozone (MDA8 O3) is projected to increase during summer and autumn in the central and eastern US. The increase in summer mean MDA8 O3 is largest under RCP8.5, exceeding 4&thinsp;ppb in some locations, with smaller seasonal mean increases of up to 2&thinsp;ppb simulated during autumn and changes during spring generally less than 1&thinsp;ppb. Increases are magnified at the upper end of the O3 distribution, particularly where projected increases in temperature are greater. Annual average PM2.5 concentration changes range from −1.0 to 1.0&thinsp;µg&thinsp;m−3. Organic PM2.5 concentrations increase during summer and autumn due to increased biogenic emissions. Aerosol nitrate decreases during winter, accompanied by lesser decreases in ammonium and sulfate, due to warmer temperatures causing increased partitioning to the gas phase. Among meteorological factors examined to account for modeled changes in pollution, temperature and isoprene emissions are found to have the largest changes and the greatest impact on O3 concentrations.</p

Common variants in signaling transcription-factor-binding sites drive phenotypic variability in red blood cell traits

Genome-wide association studies identify genomic variants associated with human traits and diseases. Most trait-associated variants are located within cell-type-specific enhancers, but the molecular mechanisms governing phenotypic variation are less well understood. Here, we show that many enhancer variants associated with red blood cell (RBC) traits map to enhancers that are co-bound by lineage-specific master transcription factors (MTFs) and signaling transcription factors (STFs) responsive to extracellular signals. The majority of enhancer variants reside on STF and not MTF motifs, perturbing DNA binding by various STFs (BMP/TGF-β-directed SMADs or WNT-induced TCFs) and affecting target gene expression. Analyses of engineered human blood cells and expression quantitative trait loci verify that disrupted STF binding leads to altered gene expression. Our results propose that the majority of the RBC-trait-associated variants that reside on transcription-factor-binding sequences fall in STF target sequences, suggesting that the phenotypic variation of RBC traits could stem from altered responsiveness to extracellular stimuli

The genetics of cortical organisation and development: A study of 2,347 neuroimaging phenotypes

Our understanding of the genetic architecture of the human cerebral cortex is limited both in terms of the diversity of brain structural phenotypes and the anatomical granularity of their associations with genetic variants. Here, we conducted genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,843 individuals from the UK Biobank and the ABCD cohorts. These phenotypes include cortical thickness, surface area, grey matter volume, and measures of folding, neurite density, and water diffusion. We identified 4,349 experiment-wide significant loci associated with global and regional phenotypes. Multiple lines of analyses identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with surface area and volume specifically are associated with cephalic disorders. Finally, we identified complex inter-phenotype and inter-regional genetic relationships among the 13 phenotypes which reflect developmental differences among them. These analyses help refine the role of common genetic variants in human cortical development and organisation

Flexural isostatic response of continental-scale deltas to climatically driven sea level changes

The interplay between climate-forced sea level change, erosional and depositional processes, and flexural isostasy in deep time on passive margin deltas remains poorly understood. We performed a series of conceptual simulations to investigate flexural isostatic responses to high-frequency fluctuations in water and sediment load associated with climatically driven sea level changes. We model a large drainage basin that discharges to a continental margin and produces a large deltaic depocenter, then prescribe synthetic and climatic-driven sea level curves of different frequencies to assess flexural response. Results show that flexural isostatic responses are bidirectional over 100–1000 kyr timescales and are in sync with the magnitude, frequency, and direction of sea level fluctuations and that isostatic adjustments play an important role in driving along-strike and cross-shelf river mouth migration and sediment accumulation. Our findings demonstrate that climate-forced sea level changes produce a feedback mechanism that results in self-sustaining creation of accommodation into which sediment is deposited and plays a major role in delta morphology and stratigraphic architecture.</p

A distant trophoblast-specific enhancer controls HLA-G expression at the maternal–fetal interface

HLA-G, a nonclassical HLA molecule uniquely expressed in the placenta, is a central component of fetus-induced immune tolerance during pregnancy. The tissue-specific expression of HLA-G, however, remains poorly understood. Here, systematic interrogation of the HLA-G locus using massively parallel reporter assay (MPRA) uncovered a previously unidentified cis-regulatory element 12 kb upstream of HLA-G with enhancer activity, Enhancer L. Strikingly, clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of this enhancer resulted in ablation of HLA-G expression in JEG3 cells and in primary human trophoblasts isolated from placenta. RNA-seq analysis demonstrated that Enhancer L specifically controls HLA-G expression. Moreover, DNase-seq and chromatin conformation capture (3C) defined Enhancer L as a cell type-specific enhancer that loops into the HLA-G promoter. Interestingly, MPRA-based saturation mutagenesis of Enhancer L identified motifs for transcription factors of the CEBP and GATA families essential for placentation. These factors associate with Enhancer L and regulate HLA-G expression. Our findings identify long-range chromatin looping mediated by core trophoblast transcription factors as the mechanism controlling tissue-specific HLA-G expression at the maternal–fetal interface. More broadly, these results establish the combination of MPRA and CRISPR/Cas9 deletion as a powerful strategy to investigate human immune gene regulation

Systemic Stimulation of TLR2 Impairs Neonatal Mouse Brain Development

Background: Inflammation is associated with perinatal brain injury but the underlying mechanisms are not completely characterized. Stimulation of Toll-like receptors (TLRs) through specific agonists induces inflammatory responses that trigger both innate and adaptive immune responses. The impact of engagement of TLR2 signaling pathways on the neonatal brain is still unclear. The aim of this study was to investigate the potential effect of a TLR2 agonist on neonatal brain development. Methodology/Principal Findings: Mice were injected intraperitoneally (i.p.) once a day from postnatal day (PND) 3 to PND11 with endotoxin-free saline, a TLR2 agonist Pam$_{3}$CSK$_{4}$ (5 mg/kg) or Lipopolysaccharide (LPS, 0.3 mg/kg). Pups were sacrificed at PND12 or PND53 and brain, spleen and liver were collected and weighed. Brain sections were stained for brain injury markers. Long-term effects on memory function were assessed using the Trace Fear Conditioning test at PND50. After 9 days of Pam$_{3}$CSK$_{4}$ administration, we found a decreased volume of cerebral gray matter, white matter in the forebrain and cerebellar molecular layer that was accompanied by an increase in spleen and liver weight at PND12. Such effects were not observed in Pam$_{3}$CSK$_{4}$-treated TLR 2-deficient mice. Pam$_{3}$CSK$_{4}$-treated mice also displayed decreased hippocampus neuronal density, and increased cerebral microglia density, while there was no effect on caspase-3 or general cell proliferation at PND12. Significantly elevated levels of IL-1β, IL-6, KC, and MCP-1 were detected after the first Pam$_{3}$CSK$_{4}$ injection in brain homogenates of PND3 mice. Pam$_{3}$CSK$_{4}$administration did not affect long-term memory function nor the volume of gray or white matter. Conclusions/Significance: Repeated systemic exposure to the TLR2 agonist Pam$_{3}$CSK$_{4}$ can have a short-term negative impact on the neonatal mouse brain