bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the velocity field on scalar transport in gaseous transverse jets
Authors: Gevorkyan L. , Shoji T. , Peng W. Y. , Karagozian A. R.
Published: November 2017

The present experiments explored the dynamical character of the gaseous jet injected flush into cross-flow for variable jet-to-cross-flow momentum flux ratios$J$(5, 12 and 41) and density ratios$S$(0.35 and 1.0). Contoured nozzle and straight pipe injectors were studied here, with the jet Reynolds number fixed at 1900 as other flow parameters were varied. Simultaneous acetone planar laser-induced fluorescence (PLIF) imaging and stereo particle image velocimetry (PIV) were used to study the relationships between scalar and velocity/vorticity fields, with a special focus on comparing PLIF-based extraction of scalar dissipation rates and local strain rates with PIV-based local strain rates in the upstream and downstream shear layers of the jet. There was remarkable similarity between the scalar and vorticity fields for the jet in cross-flow, spanning conditions for absolutely unstable upstream jet shear layers at low$J$or$S$values to conditions for convectively unstable shear layers for larger$J$, equidensity conditions (Megerianet al.,J. Fluid Mech., vol. 593, 2007, pp. 93–129; Getsingeret al.,Exp. Fluids, vol. 53, 2012, pp. 783–801). Proper orthogonal decomposition applied to both scalar and velocity fields revealed strengthening instabilities in both the upstream shear layer and in the jet’s wake as$J$was reduced. The simultaneous measurements allowed PLIF-extracted scalar dissipation rates and strain rates to be determined via a flamelet-like model and compared with PIV-extracted strain rates, each in the diffusion layer-normal direction. There was generally very good qualitative and quantitative agreement for these metrics in both the jet upstream and downstream shear layers for most flow conditions, with excellent correspondence to locations of shear layer vorticity roll up, although downstream shear layer strain rates in some cases showed lesser correspondence between PLIF- and PIV-based data. Such differences are shown to potentially result from diffusion and resolution effects as well as the influence of three-dimensional and transient effects which can be more significant in the lee side of the jet. Nevertheless, the present results reveal interesting dynamics and demonstrate the importance of strain fields in enhanced diffusion and transport phenomena.
Poleward propagation of near-inertial waves induced by fluctuating winds over a baroclinically unstable zonal jet
Authors: Tort Marine , Winters Kraig B.
Published: November 2017

We investigate the excitation and radiation of near-inertial internal gravity waves continuously excited by a latitudinally confined temporally fluctuating wind in a numerical model of a stratified ocean on a $\unicode[STIX]{x1D6FD}$-plane at mid-latitude. The surface wind forcing contains both high- and low-frequency components which excite propagating waves and a baroclinically unstable zonal jet respectively. Wentzel–Kramers–Brillouin (WKB) ray theory implies that near-inertial waves propagate strictly towards the equator. We seek to refine this view here by (i) adding the non-traditional Coriolis force (accounting for the horizontal component of the Earth’s rotation) into the equations of motion, in order to allow poleward sub-inertial propagation to occur, and (ii) relaxing the conceptual constraint of no zonal variability, to allow the zonal jet to undergo instability, to meander and to sustain an active field of mesoscale eddies, potentially impacting the excitation of near-inertial waves. The key results are that, while (i) permits weakly stratified waveguides with sub-inertial poleward wave propagation to develop in accord with theory, the sub-inertial energy flux observed is very small compared with the equatorward flux. Thus, in terms of energy radiated from the storm track, non-traditional effects are small for wind-driven near-inertial waves. The consequences of (ii) are much more pronounced. Refinement (ii) produces a radiating wave field that is bidirectional, i.e. with both poleward and equatorward components. We show that the presence of regions of significant background vorticity with horizontal scales significantly smaller than the width of the storm track provides the scale selection mechanism to excite waves with sufficiently super-inertial frequencies to propagate poleward distances of the order of 1000 km.
The nonlinear states of viscous capillary jets confined in the axial direction
Authors: Martínez-Calvo A. , Rubio-Rubio M. , Sevilla A.
Published: November 2017

We report an experimental and theoretical study of the global stability and nonlinear dynamics of vertical jets of viscous liquid confined in the axial direction due to their impact on a bath of the same liquid. Previous works demonstrated that in the absence of axial confinement the steady liquid thread becomes unstable due to an axisymmetric global mode for values of the flow rate, $Q$, below a certain critical value, $Q_{c}$, giving rise to oscillations of increasing amplitude that finally lead to a dripping regime (Sauter & Buggisch, J. Fluid Mech., vol. 533, 2005, pp. 237–257; Rubio-Rubio et al., J. Fluid Mech., vol. 729, 2013, pp. 471–483). Here we focus on the effect of the jet length, $L$, on the transitions that take place for decreasing values of $Q$. The linear stability analysis shows good agreement with our experiments, revealing that $Q_{c}$ increases monotonically with $L$, reaching the semi-infinite jet asymptote for sufficiently large values of $L$. Moreover, as $L$ decreases a quasi-static limit is reached, whereby $Q_{c}\rightarrow 0$ and the neutral conditions are given by a critical length determined by hydrostatics. Our experiments have also revealed the existence of a new regime intermediate between steady jetting and dripping, in which the thread reaches a limit-cycle state without breakup. We thus show that there exist three possible states depending on the values of the control parameters, namely steady jetting, oscillatory jetting and dripping. For two different combinations of liquid viscosity, $\unicode[STIX]{x1D708}$, and injector radius, $R$, the boundaries separating these regimes have been determined in the $(Q,L)$ parameter plane, showing that steady jetting exists for small enough values of $L$ or large enough values of $Q$, dripping prevails for small enough values of $Q$ or sufficiently large values of $L$, and oscillatory jetting takes place in an intermediate region whose size increases with $\unicode[STIX]{x1D708}$ and decreases with $R$.
Heat transfer in laminar Couette flow laden with rigid spherical particles
Authors: Niazi Ardekani M. , Abouali O. , Picano F. , Brandt L.
Published: November 2017

We study heat transfer in plane Couette flow laden with rigid spherical particles by means of direct numerical simulations. In the simulations we use a direct-forcing immersed boundary method to account for the dispersed phase together with a volume-of-fluid approach to solve the temperature field inside and outside the particles. We focus on the variation of the heat transfer with the particle Reynolds number, total volume fraction (number of particles) and the ratio between the particle and fluid thermal diffusivity, quantified in terms of an effective suspension diffusivity. We show that, when inertia at the particle scale is negligible, the heat transfer increases with respect to the unladen case following an empirical correlation recently proposed in the literature. In addition, an average composite diffusivity can be used to approximate the effective diffusivity of the suspension in the inertialess regime when varying the molecular diffusion in the two phases. At finite particle inertia, however, the heat transfer increase is significantly larger, smoothly saturating at higher volume fractions. By phase-ensemble-averaging we identify the different mechanisms contributing to the total heat transfer and show that the increase of the effective conductivity observed at finite inertia is due to the increase of the transport associated with fluid and particle velocity. We also show that the contribution of the heat conduction in the solid phase to the total wall-normal heat flux reduces when increasing the particle Reynolds number, so that particles of low thermal diffusivity weakly alter the total heat flux in the suspension at finite particle Reynolds numbers. On the other hand, a higher particle thermal diffusivity significantly increases the total heat transfer.
A generalized action-angle representation of wave interaction in stratified shear flows
Authors: Heifetz Eyal , Guha Anirban
Published: November 2017

In this paper we express the linearized dynamics of interacting interfacial waves in stratified shear flows in the compact form of action-angle Hamilton’s equations. The pseudo-energy serves as the Hamiltonian of the system, the action coordinates are the contribution of the interfacial waves to the wave action and the angles are the phases of the interfacial waves. The term ‘generalized action angle’ aims to emphasize that the action of each wave is generally time dependent and this allows for instability. An attempt is made to relate this formalism to the action at a distance resonance instability mechanism between counter-propagating vorticity waves via the global conservations of pseudo-energy and pseudo-momentum.
Turbulence kinetic energy exchanges in flows with highly variable fluid properties
Authors: Dupuy Dorian , Toutant Adrien , Bataille Françoise
Published: November 2017

This paper investigates the energy exchanges associated with the half-trace of the velocity fluctuation correlation tensor in a strongly anisothermal low Mach fully developed turbulent channel flow. The study is based on direct numerical simulations of the channel within the low Mach number hypothesis and without gravity. The overall flow behaviour is governed by the variable fluid properties. The temperature of the two channel walls are imposed at 293 K and 586 K to generate the temperature gradient. The mean friction Reynolds number of the simulation is 180. The analysis is carried out in the spatial and spectral domains. The spatial and spectral studies use the same decomposition of the terms of the evolution equation of the half-trace of the velocity fluctuation correlation tensor. The importance of each term of the decomposition in the energy exchanges is assessed. This lets us identify the terms associated with variations or fluctuations of the fluid properties that are not negligible. Then, the behaviour of the terms is investigated. The spectral energy exchanges are first discussed in the incompressible case since the analysis is not present in the literature with the decomposition used in this study. The modification of the energy exchanges by the temperature gradient is then investigated in the spatial and spectral domains. The temperature gradient generates an asymmetry between the two sides of the channel. The asymmetry can in a large part be explained by the combined effect of the mean local variations of the fluid properties, combined with a Reynolds number effect.
Modelling of noise reduction in complex multistream jets
Authors: Papamoschou Dimitri
Published: November 2017

The paper presents a low-order prediction scheme for the noise change in multistream jets when the nozzle geometry is altered from a known baseline. The essence of the model is to predict the changes in acoustics due to the redistribution of the mean flow as computed by a Reynolds-averaged Navier–Stokes (RANS) solver. A RANS-based acoustic analogy framework is developed that addresses the noise in the polar direction of peak emission and uses the Reynolds stress as a time-averaged representation of the action of the coherent turbulent structures. The framework preserves the simplicity of the Lighthill acoustic analogy, using the free-space Green’s function, while accounting for azimuthal effects via special forms for the space–time correlation combined with source–observer relations based on the Reynolds stress distribution in the jet plume. Results are presented for three-stream jets with offset secondary and tertiary flows that reduce noise in specific azimuthal directions. The model reproduces well the experimental noise reduction trends. Principal mechanisms of noise reduction are elucidated.
From Vance Palmer's 'The Passage' to Susan Johnson's 'The Landing'
Authors: Lever Susan
Published: November 2017

This article compares Vance Palmer’s classic novel, The Passage (1930), set in Caloundra, with Susan Johnson’s The Landing (2015), a comic novel of manners set at the northern end of the contemporary Sunshine Coast. It considers the novels’ different perspectives on Australian society and changing values, including attitudes to nature, arguing that Palmer’s novel now seems more idealistic than realist while Johnson’s cynicism about Australian life shows some disturbing elements beneath the comedy.
Ironbark and stone
Authors: Frank Jane
Published: November 2017

This article discusses Sunshine Coast writer Inga Simpson’s nature writing in three recent novels, Mr Wigg (2013), Nest (2014b) and Where the Trees Were (2016c). It addresses Simpson’s self-categorisation as a nature writer, and shows how the recurrent motif of sacred trees allows three introspective protagonists to reach new understandings of universal themes: loss of love and innocence, ageing, inheritance, childlessness, sexuality, death, ancient cultures, cultural integrity and preservation of the environment. The article considers Simpson’s ‘anti-Gothic’ approach to landscape in her novels, yet also shows how her ‘realist’ depictions of place evoke unease surrounding the issue of white belonging in Australia. Simpson’s metaphoric self-identification with trees, particularly theAustralian ironbark, is pivotal to the quiet power of her fiction’s exploration of belonging in the Australian landscape.
Ray Whitrod, 'Before I Sleep: My Life Fighting Crime and Corruption', Brisbane: University of Queensland Press, 2015, 240 pp., IBSN 9 7807 0225 3409, A$32.94
Authors: Dukova Anastasia
Published: November 2017

Ray Whitrod, Before I Sleep: My Life Fighting Crime and Corruption, Brisbane: University of Queensland Press, 2015, 240 pp., IBSN 9 7807 0225 3409, A$32.94
Brain activation during emotion regulation in women with premenstrual dysphoric disorder
Authors: Petersen Nicole , Ghahremani Dara G. , Rapkin Andrea J. , Berman Steven M. , Liang Letty , London Edythe D.
Published: November 2017

Background

Difficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD.

Methods

On the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle.

Results

Women with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants.

Conclusions

During the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.
Poverty, rural population distribution and climate change
Authors: Barbier Edward B. , Hochard Jacob P.
Published: November 2017

Our spatial analysis indicates that in 2000 over one third of the rural population in developing countries was located on less favored agricultural land and areas, which are constrained by biophysical conditions or poor market access. We examine whether these spatial distributions of rural population in 2000 influence subsequent changes in the rate of poverty from 2000 to 2012 in 83 developing countries. We find no evidence of a direct impact on changes in poverty, but there is a significant indirect impact via the elasticity of poverty reduction with respect to growth. If climate change leads to more people concentrated in these areas, or an increase in unfavorable agricultural regions, then the poverty-reducing impact of overall per capita income growth could be further weakened. Reducing poverty will require targeting rural populations in less favored lands and remote areas and encouraging out-migration.
Ageing prisoners: An introduction to geriatric health-care challenges in correctional facilities
Authors: Bedard Rachael , Metzger Lia , Williams Brie
Published: November 2017

The rise in the number of older prisoners in many nations has been described as a correctional “ageing crisis” which poses an urgent financial, medical and programmatic challenge for correctional health-care systems. In 2016, the International Committee of the Red Cross hosted a conference entitled “Ageing and Imprisonment: Identifying the Needs of Older Prisoners” to discuss the institutional, legal and health-care needs of incarcerated older adults, and the approaches some correctional facilities have taken to meeting these needs. This article describes some of the challenges facing correctional systems tasked with providing health care to older adults, highlights some strategies to improve their medical care, and identifies areas in need of reform. It draws principally on research and examples from the United States to offer insights and recommendations that may be considered in other systems as well.
Spray Penetration into a Strawberry Canopy as Affected by Canopy Structure, Nozzle Type, and Application Volume
Authors: Sharpe Shaun M. , Boyd Nathan S. , Dittmar Peter J. , MacDonald Greg E. , Darnell Rebecca L. , Ferrell Jason A.
Published: November 2017

Strawberries, an important Florida crop, are grown on raised beds covered with plastic mulch. The plastic mulch provides good control of many weeds, but some problem species can emerge from the transplant hole during crop establishment. POST herbicide options for broadleaf weed control within the strawberry bed is limited to clopyralid, which only provides suppression. Strawberry canopy shielding may be responsible for the observed incomplete control with clopyralid application for problematic broadleaf weed species such as black medic and Carolina geranium. Two field experiments were established on mature strawberries to evaluate spray penetration through the canopy. The first examined spray penetration through the canopy of multiple strawberry cultivars at various distances from the crown. The second examined the effects of application volumes and nozzle selection on spray penetration. Cultivar selection had no effect on spray penetration through the canopy. In the first study, when applying at 281 L ha−1, the area around the planting hole (0 to 5 cm from the crown) had 8% coverage below the canopy while the area below the canopy edge (10 to 15 cm from the crown) had 27% coverage. In the second study, increasing the application volume from 187 to 375 L ha−1increased coverage by 81%. Increasing the application volume from 375 to 740 L ha−1increased coverage 33% with maximal coverage of 53% at 740 L ha−1. Nozzle type (standard even flat spray tip, Drift Guard, or TwinJet nozzles) did not affect coverage or deposition volume below the canopy. Overall, mature strawberry canopies demonstrated similar spray droplet penetration across cultivars with increased penetration with increased distance from the crown. Penetration increased with increasing application volume, but the nozzle types used in this experiment did not affect penetration. Additional research is needed to better define the effect of application volume on herbicide efficacy.
Glyphosate-Induced Antagonism in Rapid Response Giant Ragweed (Ambrosia trifida)
Authors: Harre Nick T. , Young Julie M. , Young Bryan G.
Published: November 2017

Glyphosate application to the rapid-response (RR) biotype of glyphosate-resistant (GR) giant ragweed ensues in loss of foliage via rapid tissue death, thereby reducing glyphosate translocation. Experiments were performed to determine if this GR response, in contrast to a non-rapid response (NRR) GR biotype, results in antagonism of the selective herbicides atrazine, cloransulam, dicamba, lactofen, and topramezone. Application of glyphosate at 1,680 g ae ha–1in the greenhouse resulted in antagonism between all five selective herbicides for the RR biotype, whereas glyphosate applied at 420 g ha–1was antagonistic only for cloransulam. Application of selective herbicides 2 d prior to glyphosate treatment avoided the antagonism observed in the RR biotype. In the field, glyphosate mixtures with dicamba and topramezone were antagonistic on the RR biotype across both 2015 and 2016 field seasons. Thus, the RR effectively reduces glyphosate efficacy but also has potential to diminish the activity of glyphosate mixtures with selective herbicides, and the degree of antagonism between these mixtures escalates at increasing glyphosate rates.
Cover Crops Suppression of Palmer Amaranth (Amaranthus palmeri) in Cotton
Authors: Palhano Matheus G. , Norsworthy Jason K. , Barber Tom
Published: November 2017

With the recent confirmation of protoporphyrinogen oxidase (PPO)-resistant Palmer amaranth in the US South, concern is increasing about the sustainability of weed management in cotton production systems. Cover crops can help to alleviate this problem, as they can suppress weed emergence via allelochemicals and/or a physical residue barrier. Field experiments were conducted in 2014 and 2015 at the Arkansas Agricultural Research and Extension Center to evaluate various cover crops for suppressing weed emergence and protecting cotton yield. In both years, cereal rye and wheat had the highest biomass production, whereas the amount of biomass present in spring did not differ among the remaining cover crops. All cover crops initially diminished Palmer amaranth emergence. However, cereal rye provided the greatest suppression, with 83% less emergence than in no cover crop plots. Physical suppression of Palmer amaranth and other weeds with cereal residues is probably the greatest contributor to reducing weed emergence. Seed cotton yield in the legume and rapeseed cover crop plots were similar when compared with the no cover crop treatment. The seed cotton yield collected from cereal cover crop plots was lower than from other treatments due to decreased cotton stand.
Gender Differences in Political Knowledge: Bringing Situation Back In
Authors: Ihme Toni Alexander , Tausendpfund Markus
Published: November 2017

One of the best-known empirical findings in the political sciences is the gender difference in political knowledge: women show less political knowledge than men. Conventional research argues that this difference is mainly a product of socialization, structural factors, and biology. Our paper brings a new perspective to the explanation of the gender gap in political knowledge. Based on an online survey and an experiment1, we emphasize the relevance of gender stereotypes as a situational pressure that reduces the performance of women in a political knowledge test. Two conclusions emerge from the analysis: First, our results indicate the existence of a negative stereotype related to the political knowledge of women. Second, the activation of gender stereotypes affects performance on a political knowledge test. Consistent with previous research on stereotype threat, our results indicate that the performance of men on a political knowledge test is affected by gender stereotypes.
Offen oder heimlich?
Authors: Osterfeld Margret
Published: November 2017

Zusammenfassung. In der Öffentlichkeit findet dieses Thema kaum Beachtung, doch als Experte Betroffener zu werden bedeutet die völlige Umkehr bestehender und selbstverständlicher Arbeits- und Lebensverhältnisse. Doch es entsteht ein Wissen der „doppelten Experten“, das zur überfälligen Weiterentwicklung der Psychiatrie genutzt werden sollte. Ein Erfahrungsbericht.
Über die Diagnose hinweg auf meine Individualität eingehen
Authors: Hahn Sabine
Published: November 2017

Zusammenfassung. Sabine Rühle Andersson, lic. phil. in Kunstwissenschaft und Germanistik, ist Betroffene mit Krankheitserfahrung, Wissenschaftliche Assistentin in angewandter Forschung und Entwicklung/Dienstleistung (aF&E/D) an der Berner Fachhochschule (BFH). Sven Andersson ist Bildungsverantwortlicher, Diplomierter Psychiatrie-Pflegefachmann, Diplomierter Erwachsenenbildner HF AEB, MAS Mental Health, Universitäre Psychiatrische Dienste Bern. Sabine ist seit Februar 2008 erkrankt, Sven seit 1993 beruflich in der Psychiatrie tätig.
Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations
Authors: Williams Wilton B. , Zhang Jinsong , Jiang Chuancang , Nicely Nathan I. , Fera Daniela , Luo Kan , Moody M. Anthony , Liao Hua-Xin , Alam S. Munir , Kepler Thomas B. , Ramesh Akshaya , Wiehe Kevin , Holland James A. , Bradley Todd , Vandergrift Nathan , Saunders Kevin O. , Parks Robert , Foulger Andrew , Xia Shi-Mao , Bonsignori Mattia , Montefiori David C. , Louder Mark , Eaton Amanda , Santra Sampa , Scearce Richard , Sutherland Laura , Newman Amanda , Bouton-Verville Hilary , Bowman Cindy , Bomze Howard , Gao Feng , Marshall Dawn J. , Whitesides John F. , Nie Xiaoyan , Kelsoe Garnett , Reed Steven G. , Fox Christopher B. , Clary Kim , Koutsoukos Marguerite , Franco David , Mascola John R. , Harrison Stephen C. , Haynes Barton F. , Verkoczy Laurent
Published: November 2017

A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env+B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env−upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env+(non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools.
Simulating quantum light propagation through atomic ensembles using matrix product states
Authors: Manzoni Marco T. , Chang Darrick E. , Douglas James S.
Published: November 2017

A powerful method to interface quantum light with matter is to propagate the light through an ensemble of atoms. Recently, a number of such interfaces have emerged, most prominently Rydberg ensembles, that enable strong nonlinear interactions between propagating photons. A largely open problem is whether these systems produce exotic many-body states of light and developing new tools to study propagation in the large photon number limit is highly desirable. Here we provide a method based on a “spin model” that maps quasi one-dimensional (1D) light propagation to the dynamics of an open 1D interacting spin system, where all photon correlations are obtained from those of the spins. The spin dynamics in turn are numerically solved using the toolbox of matrix product states. We apply this formalism to investigate vacuum induced transparency, wherein the different photon number components of a pulse propagate with number-dependent group velocity and separate at output.
Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types
Authors: van Unen Vincent , Höllt Thomas , Pezzotti Nicola , Li Na , Reinders Marcel J. T. , Eisemann Elmar , Koning Frits , Vilanova Anna , Lelieveldt Boudewijn P. F.
Published: November 2017

Mass cytometry allows high-resolution dissection of the cellular composition of the immune system. However, the high-dimensionality, large size, and non-linear structure of the data poses considerable challenges for the data analysis. In particular, dimensionality reduction-based techniques like t-SNE offer single-cell resolution but are limited in the number of cells that can be analyzed. Here we introduce Hierarchical Stochastic Neighbor Embedding (HSNE) for the analysis of mass cytometry data sets. HSNE constructs a hierarchy of non-linear similarities that can be interactively explored with a stepwise increase in detail up to the single-cell level. We apply HSNE to a study on gastrointestinal disorders and three other available mass cytometry data sets. We find that HSNE efficiently replicates previous observations and identifies rare cell populations that were previously missed due to downsampling. Thus, HSNE removes the scalability limit of conventional t-SNE analysis, a feature that makes it highly suitable for the analysis of massive high-dimensional data sets.
Whole blood stabilization for the microfluidic isolation and molecular characterization of circulating tumor cells
Authors: Wong Keith H. K. , Tessier Shannon N. , Miyamoto David T. , Miller Kathleen L. , Bookstaver Lauren D. , Carey Thomas R. , Stannard Cleo J. , Thapar Vishal , Tai Eric C. , Vo Kevin D. , Emmons Erin S. , Pleskow Haley M. , Sandlin Rebecca D. , Sequist Lecia V. , Ting David T. , Haber Daniel A. , Maheswaran Shyamala , Stott Shannon L. , Toner Mehmet
Published: November 2017

Precise rare-cell technologies require the blood to be processed immediately or be stabilized with fixatives. Such restrictions limit the translation of circulating tumor cell (CTC)-based liquid biopsy assays that provide accurate molecular data in guiding clinical decisions. Here we describe a method to preserve whole blood in its minimally altered state by combining hypothermic preservation with targeted strategies that counter cooling-induced platelet activation. Using this method, whole blood preserved for up to 72 h can be readily processed for microfluidic sorting without compromising CTC yield and viability. The tumor cells retain high-quality intact RNA suitable for single-cell RT-qPCR as well as RNA-Seq, enabling the reliable detection of cancer-specific transcripts including the androgen-receptor splice variant 7 in a cohort of prostate cancer patients with an overall concordance of 92% between fresh and preserved blood. This work will serve as a springboard for the dissemination of diverse blood-based diagnostics.
Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function
Authors: Balsevich Georgia , Häusl Alexander S. , Meyer Carola W. , Karamihalev Stoyo , Feng Xixi , Pöhlmann Max L. , Dournes Carine , Uribe-Marino Andres , Santarelli Sara , Labermaier Christiana , Hafner Kathrin , Mao Tianqi , Breitsamer Michaela , Theodoropoulou Marily , Namendorf Christian , Uhr Manfred , Paez-Pereda Marcelo , Winter Gerhard , Hausch Felix , Chen Alon , Tschöp Matthias H. , Rein Theo , Gassen Nils C. , Schmidt Mathias V.
Published: November 2017

The co-chaperone FKBP5 is a stress-responsive protein-regulating stress reactivity, and its genetic variants are associated with T2D related traits and other stress-related disorders. Here we show that FKBP51 plays a role in energy and glucose homeostasis. Fkbp5 knockout (51KO) mice are protected from high-fat diet-induced weight gain, show improved glucose tolerance and increased insulin signaling in skeletal muscle. Chronic treatment with a novel FKBP51 antagonist, SAFit2, recapitulates the effects of FKBP51 deletion on both body weight regulation and glucose tolerance. Using shorter SAFit2 treatment, we show that glucose tolerance improvement precedes the reduction in body weight. Mechanistically, we identify a novel association between FKBP51 and AS160, a substrate of AKT2 that is involved in glucose uptake. FKBP51 antagonism increases the phosphorylation of AS160, increases glucose transporter 4 expression at the plasma membrane, and ultimately enhances glucose uptake in skeletal myotubes. We propose FKBP51 as a mediator between stress and T2D development, and potential target for therapeutic approaches.
Chinese CO2 emission flows have reversed since the global financial crisis
Authors: Mi Zhifu , Meng Jing , Guan Dabo , Shan Yuli , Song Malin , Wei Yi-Ming , Liu Zhu , Hubacek Klaus
Published: November 2017

This study seeks to estimate the carbon implications of recent changes in China’s economic development patterns and role in global trade in the post-financial-crisis era. We utilised the latest socioeconomic datasets to compile China’s 2012 multiregional input-output (MRIO) table. Environmentally extended input-output analysis and structural decomposition analysis (SDA) were applied to investigate the driving forces behind changes in CO2 emissions embodied in China’s domestic and foreign trade from 2007 to 2012. Here we show that emission flow patterns have changed greatly in both domestic and foreign trade since the financial crisis. Some economically less developed regions, such as Southwest China, have shifted from being a net emission exporter to being a net emission importer. In terms of foreign trade, emissions embodied in China’s exports declined from 2007 to 2012 mainly due to changes in production structure and efficiency gains, while developing countries became the major destination of China’s export emissions.
T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity
Authors: Schmid Daniela , Park Chun Gwon , Hartl Christina A. , Subedi Nikita , Cartwright Adam N. , Puerto Regina Bou , Zheng Yiran , Maiarana James , Freeman Gordon J. , Wucherpfennig Kai W. , Irvine Darrell J. , Goldberg Michael S.
Published: November 2017

Targeted delivery of compounds to particular cell subsets can enhance therapeutic index by concentrating their action on the cells of interest. Because attempts to target tumors directly have yielded limited benefit, we instead target endogenous immune cell subsets in the circulation that can migrate actively into tumors. We describe antibody-targeted nanoparticles that bind to CD8+ T cells in the blood, lymphoid tissues, and tumors of mice. PD-1+ T cells are successfully targeted in the circulation and tumor. The delivery of an inhibitor of TGFβ signaling to PD-1-expressing cells extends the survival of tumor-bearing mice, whereas free drugs have no effect at such doses. This modular platform also enables PD-1-targeted delivery of a TLR7/8 agonist to the tumor microenvironment, increasing the proportion of tumor-infiltrating CD8+ T cells and sensitizing tumors to subsequent anti-PD-1. Targeted delivery of immunotherapy to defined subsets of endogenous leukocytes may be superior to administration of free drugs.
Switchable photovoltaic windows enabled by reversible photothermal complex dissociation from methylammonium lead iodide
Authors: Wheeler Lance M. , Moore David T. , Ihly Rachelle , Stanton Noah J. , Miller Elisa M. , Tenent Robert C. , Blackburn Jeffrey L. , Neale Nathan R.
Published: November 2017

Materials with switchable absorption properties have been widely used for smart window applications to reduce energy consumption and enhance occupant comfort in buildings. In this work, we combine the benefits of smart windows with energy conversion by producing a photovoltaic device with a switchable absorber layer that dynamically responds to sunlight. Upon illumination, photothermal heating switches the absorber layer—composed of a metal halide perovskite-methylamine complex—from a transparent state (68% visible transmittance) to an absorbing, photovoltaic colored state (less than 3% visible transmittance) due to dissociation of methylamine. After cooling, the methylamine complex is re-formed, returning the absorber layer to the transparent state in which the device acts as a window to visible light. The thermodynamics of switching and performance of the device are described. This work validates a photovoltaic window technology that circumvents the fundamental tradeoff between efficient solar conversion and high visible light transmittance that limits conventional semitransparent PV window designs.
Divergent synthesis of N-heterocycles via controllable cyclization of azido-diynes catalyzed by copper and gold
Authors: Shen Wen-Bo , Sun Qing , Li Long , Liu Xin , Zhou Bo , Yan Juan-Zhu , Lu Xin , Ye Long-Wu
Published: November 2017

Gold-catalyzed intermolecular alkyne oxidation by an N–O bond oxidant has proven to be a powerful method in organic synthesis during the past decade, because this approach would enable readily available alkynes as precursors in generating α-oxo gold carbenes. Among those, gold-catalyzed oxidative cyclization of dialkynes has received particular attention as this chemistry offers great potential to build structurally complex cyclic molecules. However, these alkyne oxidations have been mostly limited to noble metal catalysts, and, to our knowledge, non-noble metal-catalyzed reactions such as diyne oxidations have not been reported. Herein, we disclose a copper-catalyzed oxidative diyne cyclization, allowing the facile synthesis of a wide range of valuable pyrrolo[3,4-c]quinolin-1-ones. Interestingly, by employing the same starting materials, the gold-catalyzed cascade cyclization leads to the divergent formation of synthetically useful pyrrolo[2,3-b]indoles. Furthermore, the proposed mechanistic rationale for these cascade reactions is strongly supported by both control experiments and theoretical calculations.
Quantifying protein densities on cell membranes using super-resolution optical fluctuation imaging
Authors: Lukeš Tomáš , Glatzová Daniela , Kvíčalová Zuzana , Levet Florian , Benda Aleš , Letschert Sebastian , Sauer Markus , Brdička Tomáš , Lasser Theo , Cebecauer Marek
Published: November 2017

Quantitative approaches for characterizing molecular organization of cell membrane molecules under physiological and pathological conditions profit from recently developed super-resolution imaging techniques. Current tools employ statistical algorithms to determine clusters of molecules based on single-molecule localization microscopy (SMLM) data. These approaches are limited by the ability of SMLM techniques to identify and localize molecules in densely populated areas and experimental conditions of sample preparation and image acquisition. We have developed a robust, model-free, quantitative clustering analysis to determine the distribution of membrane molecules that excels in densely labeled areas and is tolerant to various experimental conditions, i.e. multiple-blinking or high blinking rates. The method is based on a TIRF microscope followed by a super-resolution optical fluctuation imaging (SOFI) analysis. The effectiveness and robustness of the method is validated using simulated and experimental data investigating nanoscale distribution of CD4 glycoprotein mutants in the plasma membrane of T cells.
R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature
Authors: Li Fangfei , Sawada Junko , Komatsu Masanobu
Published: November 2017

The formation of endothelial lumen is fundamental to angiogenesis and essential to the oxygenation of hypoxic tissues. The molecular mechanism underlying this important process remains obscure. Here, we show that Akt activation by a Ras homolog, R-Ras, stabilizes the microtubule cytoskeleton in endothelial cells leading to endothelial lumenogenesis. The activation of Akt by the potent angiogenic factor VEGF-A does not strongly stabilize microtubules or sufficiently promote lumen formation, hence demonstrating a distinct role for the R-Ras-Akt axis. We show in mice that this pathway is important for the lumenization of new capillaries and microvessels developing in ischemic muscles to allow sufficient tissue reperfusion after ischemic injury. Our work identifies a role for Akt in lumenogenesis and the significance of the R-Ras-Akt signaling for the patency of regenerating blood vessels.
Assembly of CRISPR ribonucleoproteins with biotinylated oligonucleotides via an RNA aptamer for precise gene editing
Authors: Carlson-Stevermer Jared , Abdeen Amr A. , Kohlenberg Lucille , Goedland Madelyn , Molugu Kaivalya , Lou Meng , Saha Krishanu
Published: November 2017

Writing specific DNA sequences into the human genome is challenging with non-viral gene-editing reagents, since most of the edited sequences contain various imprecise insertions or deletions. We developed a modular RNA aptamer-streptavidin strategy, termed S1mplex, to complex CRISPR-Cas9 ribonucleoproteins with a nucleic acid donor template, as well as other biotinylated molecules such as quantum dots. In human cells, tailored S1mplexes increase the ratio of precisely edited to imprecisely edited alleles up to 18-fold higher than standard gene-editing methods, and enrich cell populations containing multiplexed precise edits up to 42-fold. These advances with versatile, preassembled reagents could greatly reduce the time and cost of in vitro or ex vivo gene-editing applications in precision medicine and drug discovery and aid in the development of increased and serial dosing regimens for somatic gene editing in vivo.
Josephson emission with frequency span 1–11 THz from small Bi2Sr2CaCu2O8+δ
mesa structures
Authors: Borodianskyi E. A. , Krasnov V. M.
Published: November 2017

Mesa structures made of Bi2Sr2CaCu2O8+δ
high-temperature superconductor represent stacks of atomic scale intrinsic Josephson junctions. They can be used for generation of high-frequency electromagnetic waves. Here we analyze Josephson emission from small-but-high mesas (with a small area, but containing many stacked junctions). We have found strong evidence for tunable terahertz emission with a good efficacy in a record high-frequency span 1–11 THz, approaching the theoretical upper limit for this superconductor. Emission maxima correspond to in-phase cavity modes in the mesas, indicating coherent superradiant nature of the emission. We conclude that terahertz emission requires a threshold number of junctions N ~ 100. The threshold behavior is not present in the classical description of stacked Josephson junctions and suggests importance of laser-like cascade amplification of the photon number in the cavity.
Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening
Authors: Hou Panpan , Eldstrom Jodene , Shi Jingyi , Zhong Ling , McFarland Kelli , Gao Yuan , Fedida David , Cui Jianmin
Published: November 2017

In voltage-activated ion channels, voltage sensor (VSD) activation induces pore opening via VSD-pore coupling. Previous studies show that the pore in KCNQ1 channels opens when the VSD activates to both intermediate and fully activated states, resulting in the intermediate open (IO) and activated open (AO) states, respectively. It is also well known that accompanying KCNQ1 channel opening, the ionic current is suppressed by a rapid process called inactivation. Here we show that inactivation of KCNQ1 channels derives from the different mechanisms of the VSD-pore coupling that lead to the IO and AO states, respectively. When the VSD activates from the intermediate state to the activated state, the VSD-pore coupling has less efficacy in opening the pore, producing inactivation. These results indicate that different mechanisms, other than the canonical VSD-pore coupling, are at work in voltage-dependent ion channel activation.
Complex three-dimensional self-assembly in proxies for atmospheric aerosols
Authors: Pfrang C. , Rastogi K. , Cabrera-Martinez E. R. , Seddon A. M. , Dicko C. , Labrador A. , Plivelic T. S. , Cowieson N. , Squires A. M.
Published: November 2017

Aerosols are significant to the Earth’s climate, with nearly all atmospheric aerosols containing organic compounds that often contain both hydrophilic and hydrophobic parts. However, the nature of how these compounds are arranged within an aerosol droplet remains unknown. Here we demonstrate that fatty acids in proxies for atmospheric aerosols self-assemble into highly ordered three-dimensional nanostructures that may have implications for environmentally important processes. Acoustically trapped droplets of oleic acid/sodium oleate mixtures in sodium chloride solution are analysed by simultaneous synchrotron small-angle X-ray scattering and Raman spectroscopy in a controlled gas-phase environment. We demonstrate that the droplets contained crystal-like lyotropic phases including hexagonal and cubic close-packed arrangements of spherical and cylindrical micelles, and stacks of bilayers, whose structures responded to atmospherically relevant humidity changes and chemical reactions. Further experiments show that self-assembly reduces the rate of the reaction of the fatty acid with ozone, and that lyotropic-phase formation also occurs in more complex mixtures more closely resembling compositions of atmospheric aerosols. We suggest that lyotropic-phase formation likely occurs in the atmosphere, with potential implications for radiative forcing, residence times and other aerosol characteristics.
Repeated storage of respired carbon in the equatorial Pacific Ocean over the last three glacial cycles
Authors: Jacobel A. W. , McManus J. F. , Anderson R. F. , Winckler G.
Published: November 2017

As the largest reservoir of carbon exchanging with the atmosphere on glacial–interglacial timescales, the deep ocean has been implicated as the likely location of carbon sequestration during Pleistocene glaciations. Despite strong theoretical underpinning for this expectation, radiocarbon data on watermass ventilation ages conflict, and proxy interpretations disagree about the depth, origin and even existence of the respired carbon pool. Because any change in the storage of respiratory carbon is accompanied by corresponding changes in dissolved oxygen concentrations, proxy data reflecting oxygenation are valuable in addressing these apparent inconsistencies. Here, we present a record of redox-sensitive uranium from the central equatorial Pacific Ocean to identify intervals associated with respiratory carbon storage over the past 350 kyr, providing evidence for repeated carbon storage over the last three glacial cycles. We also synthesise our data with previous work and propose an internally consistent picture of glacial carbon storage and equatorial Pacific Ocean watermass structure.