Neural crest migration is driven by a few trailblazer cells with a unique molecular signature narrowly confined to the invasive front

Neural crest (NC) cell migration is crucial to the formation of peripheral tissues during vertebrate development. However, how NC cells respond to different microenvironments to maintain persistence of direction and cohesion in multicellular streams remains unclear. To address this, we profiled eight subregions of a typical cranial NC cell migratory stream. Hierarchical clustering showed significant differences in the expression profiles of the lead three subregions compared with newly emerged cells. Multiplexed imaging of mRNA expression using fluorescent hybridization chain reaction (HCR) quantitatively confirmed the expression profiles of lead cells. Computational modeling predicted that a small fraction of lead cells that detect directional information is optimal for successful stream migration. Single-cell profiling then revealed a unique molecular signature that is consistent and stable over time in a subset of lead cells within the most advanced portion of the migratory front, which we term trailblazers. Model simulations that forced a lead cell behavior in the trailing subpopulation predicted cell bunching near the migratory domain entrance. Misexpression of the trailblazer molecular signature by perturbation of two upstream transcription factors agreed with the in silico prediction and showed alterations to NC cell migration distance and stream shape. These data are the first to characterize the molecular diversity within an NC cell migratory stream and offer insights into how molecular patterns are transduced into cell behaviors

Maximizing the optical performance of planar CH3NH3PbI3 hybrid perovskite heterojunction stacks

A vapour-phase reaction process has been used to deposit smooth and uniform CH3NH3PbI3 perovskite material to enable the measurement of its optical dispersion relations, n and k, by ellipsometry. Fitting was achieved with a combination of Tauc-Lorenz, critical point parabolic band (CPPB) and harmonic oscillators. We have used the dispersion relations in an all-optical model of new planar device architectures in order to establish design rules for future materials choices to maximize the short-circuit current (Jsc) performance. For 500nm of MAPI with no window layer, the maximum performance expected from the model is Jsc=21.63mAcm-2. The ability of thin layers (in the range 20-60nm) of a range of window layer materials (TiO2, WO3, ZnO, Nb2O5, CdS, and Cd0.4 Zn0.6S) to enhance the short-circuit current of the devices was investigated. The performance of the oxides showed interference behaviour, with the first maxima in their J sc curves exceeding the value achievable without a window layer. However, after the first maximum, the performance generally fell off with increasing thickness. The only material to stay greater than the no-window condition for the entire investigated range is WO3. The highest performance (J sc of 22.47mAcm-2) was obtained with 59nm of WO3, with that of TiO2, ZnO, and Nb2O5 being marginally lower. Parasitic absorption in CdS window layers caused the J sc to decrease for all non-zero thicknesses - it gives no interference enhancement and its use cannot be recommended on optical grounds. Use of the wider gap alloy Cd0.4Zn0.6S gave higher currents than did CdS but its performance was not so high as for the oxides. Observations are made on the practicalities of fabricating the target structures in the fabrication of practical PV devices

Perturbative Construction of Models of Algebraic Quantum Field Theory

We review the construction of models of algebraic quantum field theory by renormalized perturbation theory.Comment: 38 page

Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996

Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region

Neither fair nor unchangeable but part of the natural order: orientations towards inequality in the face of criticism of the economic system

The magnitude of climate change threats to life on the planet is not matched by the level of current mitigation strategies. To contribute to our understanding of inaction in the face of climate change, the reported study draws upon the pro status quo motivations encapsulated within System Justification Theory. In an online questionnaire study, participants (N = 136) initially completed a measure of General System Justification. Participants in a “System-critical” condition were then exposed to information linking environmental problems to the current economic system; participants in a Control condition were exposed to information unrelated to either environmental problems or the economic system. A measure of Economic System Justification was subsequently administered. Regressions of Economic System Justification revealed interactions between General System Justification and Information Type: higher general system justifiers in the System-critical condition rated the economic system as less fair than did their counterparts in the Control condition. However, they also indicated inequality as more natural than did their counterparts in the Control condition. The groups did not differ in terms of beliefs about the economic system being open to change. The results are discussed in terms of how reassurance about the maintenance of the status quo may be bolstered by recourse to beliefs in a natural order

Interocular Symmetry of Foveal Cone Topography in Congenital Achromatopsia

PURPOSE: To determine interocular symmetry of foveal cone topography in achromatopsia (ACHM) using non-confocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). METHODS: Split-detector AOSLO images of the foveal cone mosaic were acquired from both eyes of 26 subjects (mean age 24.3 years; range 8 - 44 years, 14 females) with genetically confirmed CNGA3- or CNGB3-associated ACHM. Cones were identified within a manually delineated rod-free zone. Peak cone density (PCD) was determined using an 80 × 80 μm sampling window within the rod-free zone. The mean and standard deviation (SD) of intercell distance (ICD) were calculated to derive the coefficient of variation (CV). Cone density difference maps were generated to compare cone topography between eyes. RESULTS: PCD (mean ± SD) was 17,530 ± 9,614 cones/mm2 and 17,638 ± 9,753 cones/mm2 for right and left eyes, respectively (p = 0.677, Wilcoxon test). The mean (± SD) for ICD was 9.05 ± 2.55 µm and 9.24 ± 2.55 µm for right and left eyes, respectively (p = 0.410, paired t test). The mean (± SD) for CV of ICD was 0.16 ± 0.03 µm and 0.16 ± 0.04 µm for right and left eyes, respectively (p = 0.562, paired t test). Cone density maps demonstrated that cone topography of the ACHM fovea is non-uniform with local variations in cone density between eyes. CONCLUSIONS: These results demonstrate interocular symmetry of the foveal cone mosaic (both density and packing) in ACHM. As cone topography can differ between eyes of a subject, PCD does not completely describe the foveal cone mosaic in ACHM. Nonetheless, these findings are of value in longitudinal monitoring of patients during treatment trials and further suggest that both eyes of a given subject may have similar therapeutic potential and non-study eye can be used as a control

The Social and Political Dimensions of the Ebola Response: Global Inequality, Climate Change, and Infectious Disease

The 2014 Ebola crisis has highlighted public-health vulnerabilities in Liberia, Sierra Leone, and Guinea – countries ravaged by extreme poverty, deforestation and mining-related disruption of livelihoods and ecosystems, and bloody civil wars in the cases of Liberia and Sierra Leone. Ebola’s emergence and impact are grounded in the legacy of colonialism and its creation of enduring inequalities within African nations and globally, via neoliberalism and the Washington Consensus. Recent experiences with new and emerging diseases such as SARS and various strains of HN influenzas have demonstrated the effectiveness of a coordinated local and global public health and education-oriented response to contain epidemics. To what extent is international assistance to fight Ebola strengthening local public health and medical capacity in a sustainable way, so that other emerging disease threats, which are accelerating with climate change, may be met successfully? This chapter considers the wide-ranging socio-political, medical, legal and environmental factors that have contributed to the rapid spread of Ebola, with particular emphasis on the politics of the global and public health response and the role of gender, social inequality, colonialism and racism as they relate to the mobilization and establishment of the public health infrastructure required to combat Ebola and other emerging diseases in times of climate change

Quantum control of hybrid nuclear-electronic qubits

Pulsed magnetic resonance is a wide-reaching technology allowing the quantum state of electronic and nuclear spins to be controlled on the timescale of nanoseconds and microseconds respectively. The time required to flip either dilute electronic or nuclear spins is orders of magnitude shorter than their decoherence times, leading to several schemes for quantum information processing with spin qubits. We investigate instead the novel regime where the eigenstates approximate 50:50 superpositions of the electronic and nuclear spin states forming "hybrid nuclear-electronic" qubits. Here we demonstrate quantum control of these states for the first time, using bismuth-doped silicon, in just 32 ns: this is orders of magnitude faster than previous experiments where pure nuclear states were used. The coherence times of our states are five orders of magnitude longer, reaching 4 ms, and are limited by the naturally-occurring 29Si nuclear spin impurities. There is quantitative agreement between our experiments and no-free-parameter analytical theory for the resonance positions, as well as their relative intensities and relative Rabi oscillation frequencies. In experiments where the slow manipulation of some of the qubits is the rate limiting step, quantum computations would benefit from faster operation in the hybrid regime.Comment: 20 pages, 8 figures, new data and simulation

In vivo imaging and quantitative analysis of leukocyte directional migration and polarization in inflamed tissue

Directional migration of transmigrated leukocytes to the site of injury is a central event in the inflammatory response. Here, we present an in vivo chemotaxis assay enabling the visualization and quantitative analysis of subtype-specific directional motility and polarization of leukocytes in their natural 3D microenvironment. Our technique comprises the combination of i) semi-automated in situ microinjection of chemoattractants or bacteria as local chemotactic stimulus, ii) in vivo near-infrared reflected-light oblique transillumination (RLOT) microscopy for the visualization of leukocyte motility and morphology, and iii) in vivo fluorescence microscopy for the visualization of different leukocyte subpopulations or fluorescence-labeled bacteria. Leukocyte motility parameters are quantified off-line in digitized video sequences using computer-assisted single cell tracking. Here, we show that perivenular microinjection of chemoattractants [macrophage inflammatory protein-1alpha (MIP-1alpha/Ccl3), platelet-activating factor (PAF)] or E. coli into the murine cremaster muscle induces target-oriented intravascular adhesion and transmigration as well as polarization and directional interstitial migration of leukocytes towards the locally administered stimuli. Moreover, we describe a crucial role of Rho kinase for the regulation of directional motility and polarization of transmigrated leukocytes in vivo. Finally, combining in vivo RLOT and fluorescence microscopy in Cx3CR1(gfp/gfp) mice (mice exhibiting green fluorescent protein-labeled monocytes), we are able to demonstrate differences in the migratory behavior of monocytes and neutrophils.Taken together, we propose a novel approach for investigating the mechanisms and spatiotemporal dynamics of subtype-specific motility and polarization of leukocytes during their directional interstitial migration in vivo

Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb

The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb -- the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells -- are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures