With remarkable precision and reproducibility, cells orchestrate the cooperative action of thousands of nanometre-sized molecular motors to carry out mechanical tasks at much larger length scales, ...such as cell motility, division and replication. Besides their biological importance, such inherently non-equilibrium processes suggest approaches for developing biomimetic active materials from microscopic components that consume energy to generate continuous motion. Being actively driven, these materials are not constrained by the laws of equilibrium statistical mechanics and can thus exhibit sought-after properties such as autonomous motility, internally generated flows and self-organized beating. Here, starting from extensile microtubule bundles, we hierarchically assemble far-from-equilibrium analogues of conventional polymer gels, liquid crystals and emulsions. At high enough concentration, the microtubules form a percolating active network characterized by internally driven chaotic flows, hydrodynamic instabilities, enhanced transport and fluid mixing. When confined to emulsion droplets, three-dimensional networks spontaneously adsorb onto the droplet surfaces to produce highly active two-dimensional nematic liquid crystals whose streaming flows are controlled by internally generated fractures and self-healing, as well as unbinding and annihilation of oppositely charged disclination defects. The resulting active emulsions exhibit unexpected properties, such as autonomous motility, which are not observed in their passive analogues. Taken together, these observations exemplify how assemblages of animate microscopic objects exhibit collective biomimetic properties that are very different from those found in materials assembled from inanimate building blocks, challenging us to develop a theoretical framework that would allow for a systematic engineering of their far-from-equilibrium material properties.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transport of fluid through a pipe is essential for the operation of macroscale machines and microfluidic devices. Conventional fluids only flow in response to external pressure. We demonstrate that ...an active isotropic fluid, composed of microtubules and molecular motors, autonomously flows through meter-long three-dimensional channels. We establish control over the magnitude, velocity profile, and direction of the self-organized flows and correlate these to the structure of the extensile microtubule bundles. The inherently three-dimensional transition from bulk-turbulent to confined-coherent flows occurs concomitantly with a transition in the bundle orientational order near the surface and is controlled by a scale-invariant criterion related to the channel profile. The nonequilibrium transition of confined isotropic active fluids can be used to engineer self-organized soft machines.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions ...in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
We report a one-pot chemical approach for the synthesis of highly monodisperse colloidal nanophosphors displaying bright upconversion luminescence under 980 nm excitation. This general method ...optimizes the synthesis with initial heating rates up to 100°C/minute generating a rich family of nanoscale building blocks with distinct morphologies (spheres, rods, hexagonal prisms, and plates) and upconversion emission tunable through the choice of rare earth dopants. Furthermore, we employ an interfacial assembly strategy to organize these nanocrystals (NCs) into superlattices over multiple length scales facilitating the NC characterization and enabling systematic studies of shape-directed assembly. The global and local ordering of these superstructures is programmed by the precise engineering of individual NC's size and shape. This dramatically improved nanophosphor synthesis together with insights from shape-directed assembly will advance the investigation of an array of emerging biological and energy-related nanophosphor applications.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Summary
Background
TCS (topical corticosteroids) are the first‐line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, ...pimecrolimus and ciclosporin for OLP is still controversial.
Objectives
To compare the efficacy and safety of TCI vs. TCS for OLP.
Methods
The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events.
Results
Twenty‐one trials involving 965 patients were included in the analysis. For the treatment of OLP (3–8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus–TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short‐term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious.
Conclusions
The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short‐term treatment in recalcitrant OLP. Further well‐designed trials are warranted to evaluate the long‐term efficacy and safety of TCI.
What's already known about this topic?
The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS).
Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs.
Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune‐mediated diseases.
What does this study add?
TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short‐term treatment of OLP.
The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious.
The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short‐term and long‐term efficacy and safety of TCI compared with TCS.
Linked Comment: Thongprasom. Br J Dermatol 2019; 181:1120.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
X-ray fluorescence (XRF) scanning of unlithified, untreated sediment cores is becoming an increasingly common method used to obtain paleoproxy data from lake records. XRF-scanning is fast and ...delivers high-resolution records of relative variations in the elemental composition of the sediment. However, lake sediments display extreme variations in their organic matter content, which can vary from just a few percent to well over 50%. As XRF scanners are largely insensitive to organic material in the sediment, increasing levels of organic material effectively dilute those components that can be measured, such as the lithogenic material (the closed-sum effect). Consequently, in sediments with large variations in organic material, the measured variations in an element will to a large extent mirror the changes in organic material. It is therefore necessary to normalize the elements in the lithogenic component of the sediment against a conservative element to allow changes in the input of the elements to be addressed. In this study we show that Al, which is the lightest element that can be measured using the Itrax XRF-scanner, can be used to effectively normalize the elements of the lithogenic fraction of the sediment against variations in organic content. We also show that care must be taken when choosing resolution and exposure time to ensure optimal output from the measurements.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aerosol mixtures composed of coarse mode desert dust combined with fine mode combustion generated aerosols (from fossil fuel and biomass burning sources) were investigated at three locations that are ...in and/or downwind of major global aerosol emission source regions. Multiyear monitoring data at Aerosol Robotic Network sites in Beijing (central eastern China), Kanpur (Indo-Gangetic Plain, northern India), and Ilorin (Nigeria, Sudanian zone of West Africa) were utilized to study the climatological characteristics of aerosol optical properties. Multiyear climatological averages of spectral single scattering albedo (SSA) versus fine mode fraction (FMF) of aerosol optical depth at 675 nm at all three sites exhibited relatively linear trends up to 50% FMF. This suggests the possibility that external linear mixing of both fine and coarse mode components (weighted by FMF) dominates the SSA variation, where the SSA of each component remains relatively constant for this range of FMF only. However, it is likely that a combination of other factors is also involved in determining the dynamics of SSA as a function of FMF, such as fine mode particles adhering to coarse mode dust. The spectral variation of the climatological averaged aerosol absorption optical depth (AAOD) was nearly linear in logarithmic coordinates over the wavelength range of 440-870 nm for both the Kanpur and Ilorin sites. However, at two sites in China (Beijing and Xianghe), a distinct nonlinearity in spectral AAOD in logarithmic space was observed, suggesting the possibility of anomalously strong absorption in coarse mode aerosols increasing the 870 nm AAOD.
The motility of cilia and flagella is driven by thousands of dynein motors that hydrolyze adenosine triphosphate (ATP). Despite decades of genetic, biochemical, structural, and biophysical studies, ...some aspects of ciliary motility remain elusive, such as the regulation of beating patterns and the energetic efficiency of these nanomachines. In this study, we introduce an experimental method to measure ATP consumption of actively beating axonemes on a single-cell level. We encapsulated individual sea urchin sperm with demembranated flagellum inside water-in-oil emulsion droplets and measured the axoneme’s ATP consumption by monitoring fluorescence intensity of a fluorophore-coupled reporter system for ATP turnover in the droplet. Concomitant phase contrast imaging allowed us to extract a linear dependence between the ATP consumption rate and the flagellar beating frequency, with ∼2.3 × 105 ATP molecules consumed per beat of a demembranated flagellum. Increasing the viscosity of the aqueous medium led to modified beating waveforms of the axonemes and to higher energy consumption per beat cycle. Our single-cell experimental platform provides both new insights, to our knowledge, into the beating mechanism of flagella and a powerful tool for future studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT To date, the Burst Alert Telescope (BAT) onboard Swift has detected ∼1000 gamma-ray bursts (GRBs), of which ∼360 GRBs have redshift measurements, ranging from z = 0.03 to z = 9.38. We ...present the analyses of the BAT-detected GRBs for the past ∼11 years up through GRB 151027B. We report summaries of both the temporal and spectral analyses of the GRB characteristics using event data (i.e., data for each photon within approximately 250 s before and 950 s after the BAT trigger time), and discuss the instrumental sensitivity and selection effects of GRB detections. We also explore the GRB properties with redshift when possible. The result summaries and data products are available at http://swift.gsfc.nasa.gov/results/batgrbcat/index.html. In addition, we perform searches for GRB emissions before or after the event data using the BAT survey data. We estimate the false detection rate to be only one false detection in this sample. There are 15 ultra-long GRBs (∼2% of the BAT GRBs) in this search with confirmed emission beyond ∼1000 s of event data, and only two GRBs (GRB 100316D and GRB 101024A) with detections in the survey data prior to the starting of event data.
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