Large-scale surveys of single-cell gene expression have the potential to reveal rare cell populations and lineage relationships but require efficient methods for cell capture and mRNA sequencing. ...Although cellular barcoding strategies allow parallel sequencing of single cells at ultra-low depths, the limitations of shallow sequencing have not been investigated directly. By capturing 301 single cells from 11 populations using microfluidics and analyzing single-cell transcriptomes across downsampled sequencing depths, we demonstrate that shallow single-cell mRNA sequencing (~50,000 reads per cell) is sufficient for unbiased cell-type classification and biomarker identification. In the developing cortex, we identify diverse cell types, including multiple progenitor and neuronal subtypes, and we identify EGR1 and FOS as previously unreported candidate targets of Notch signaling in human but not mouse radial glia. Our strategy establishes an efficient method for unbiased analysis and comparison of cell populations from heterogeneous tissue by microfluidic single-cell capture and low-coverage sequencing of many cells.
We present a fully relativistic energy-conserving binary collision model for particle simulations with large density scale plasmas. Our model deals with collisions between weighted particles of ...arbitrary species, conserving energy perfectly in each collision while momentum is conserved on the average. We also discuss a new method to model extremely high densities, applicable to a wide range of plasmas from the cold, non-relativistic to the ultra-relativistic regime in the high energy density physics.
Photo-ID is widely used in security settings, despite research showing that viewers find it very difficult to match unfamiliar faces. Here we test participants with specialist experience and training ...in the task: passport-issuing officers. First, we ask officers to compare photos to live ID-card bearers, and observe high error rates, including 14% false acceptance of 'fraudulent' photos. Second, we compare passport officers with a set of student participants, and find equally poor levels of accuracy in both groups. Finally, we observe that passport officers show no performance advantage over the general population on a standardised face-matching task. Across all tasks, we observe very large individual differences: while average performance of passport staff was poor, some officers performed very accurately--though this was not related to length of experience or training. We propose that improvements in security could be made by emphasising personnel selection.
Granitic plutonism is the principal agent of crustal differentiation, but linking granite emplacement to crust formation requires knowledge of the magmatic evolution, which is notoriously difficult ...to reconstruct from bulk rock compositions. We unlocked the plutonic archive through hafnium (Hf) and oxygen (O) isotope analysis of zoned zircon crystals from the classic hornblende-bearing (I-type) granites of eastern Australia. This granite type forms by the reworking of sedimentary materials by mantle-like magmas instead of by remelting ancient metamorphosed igneous rocks as widely believed. I-type magmatism thus drives the coupled growth and differentiation of continental crust.
The continental crust is the archive of the geological history of the Earth. Only 7% of the crust is older than 2.5 Ga, and yet significantly more crust was generated before 2.5 Ga than subsequently. ...Zircons offer robust records of the magmatic and crust-forming events preserved in the continental crust. They yield marked peaks of ages of crystallization and of crust formation. The latter might reflect periods of high rates of crust generation, and as such be due to magmatism associated with deep-seated mantle plumes. Alternatively the peaks are artefacts of preservation, they mark the times of supercontinent formation, and magmas generated in some tectonic settings may be preferentially preserved. There is increasing evidence that depletion of the upper mantle was in response to early planetary differentiation events. Arguments in favour of large volumes of continental crust before the end of the Archaean, and the thickness of felsic and mafic crust, therefore rely on thermal models for the progressively cooling Earth. They are consistent with recent estimates that the rates of crust generation and destruction along modern subduction zones are strikingly similar. The implication is that the present volume of continental crust was established 2-3 Ga ago.
Patients requiring surgery for locally advanced rectal cancer often additionally undergo neoadjuvant chemoradiotherapy (NACRT), of which the effects on physical fitness are unknown. The aim of this ...feasibility and pilot study was to investigate the effects of NACRT and a 6 week structured responsive exercise training programme (SRETP) on oxygen uptake (V˙O2) at lactate threshold ( θˆL) in such patients.
We prospectively studied 39 consecutive subjects (27 males) with T3–4/N+ resection margin threatened rectal cancer who completed standardized NACRT. Subjects underwent cardiopulmonary exercise testing at baseline (pre-NACRT), at week 0 (post-NACRT), and week 6 (post-SRETP). Twenty-two subjects undertook a 6 week SRETP on a training bike (three sessions per week) between week 0 and week 6 (exercise group). These were compared with 17 contemporaneous non-randomized subjects (control group). Changes in V˙O2 at θˆL over time and between the groups were compared using a compound symmetry covariance linear mixed model.
Of 39 recruited subjects, 22 out of 22 (exercise) and 13 out of 17 (control) completed the study. There were differences between the exercise and control groups at baseline age, ASA score physical status, World Health Organisation performance status, and Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) predicted mortality. In all subjects, V˙O2 at θˆL significantly reduced between baseline and week 0 −1.9 ml kg−1 min−1; 95% confidence interval (CI) −1.3, −2.6; P<0.0001. In the exercise group, V˙O2 at θˆL significantly improved between week 0 and week 6 (+2.1 ml kg−1 min−1; 95% CI +1.3, +2.9; P<0.0001), whereas the control group values were unchanged (−0.7 ml kg−1 min−1; 95% CI −1.66, +0.37; P=0.204).
NACRT before rectal cancer surgery reduces physical fitness. A structured exercise intervention is feasible post-NACRT and returns fitness to baseline levels within 6 weeks.
NCT: 01325909.
The continental crust covers nearly a third of the Earth's surface. It is buoyant--being less dense than the crust under the surrounding oceans--and is compositionally evolved, dominating the Earth's ...budget for those elements that preferentially partition into silicate liquid during mantle melting. Models for the differentiation of the continental crust can provide insights into how and when it was formed, and can be used to show that the composition of the basaltic protolith to the continental crust is similar to that of the average lower crust. From the late Archaean to late Proterozoic eras (some 3-1 billion years ago), much of the continental crust appears to have been generated in pulses of relatively rapid growth. Reconciling the sedimentary and igneous records for crustal evolution indicates that it may take up to one billion years for new crust to dominate the sedimentary record. Combining models for the differentiation of the crust and the residence time of elements in the upper crust indicates that the average rate of crust formation is some 2-3 times higher than most previous estimates.
Most studies of logistics outsourcing have focused on cost reduction, while few studies have reported on service benefits. This study empirically examines if outsourcing different logistics ...activities results in differences in logistics service performance. We identify and analyze the outsourcing of four levels of logistics activities: transportation (level 1), packaging (level 2), transportation management (level 3), and distribution network management (level 4). A research framework was formulated to discuss the effect of the outsourcing decision of different levels on perceived logistics service performance and includes the moderating role that supply chain complexity may play in the proposed relationships. Our findings show that outsourcing has no direct impact on service performance (delivery reliability, flexibility and lead-time) in any of the four levels. However, the performance when outsourcing level 4 activities increases with an increasing degree of demand complexity. Furthermore, chilled foods have higher service performance than non-chilled foods. These findings show the complex relationships between levels of outsourcing, performance and supply chain characteristics.
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