bluuebunny/crossref_metadata_2025 huggingface dataset:
A computational model of amoeboid cell swimming
Authors: Campbell Eric J. , Bagchi Prosenjit
Published: October 2017

Amoeboid cells propel by generating pseudopods that are finger-like protrusions of the cell body that continually grow, bifurcate, and retract. Pseudopod-driven motility of amoeboid cells represents a complex and multiscale process that involves bio-molecular reactions, cell deformation, and cytoplasmic and extracellular fluid motion. Here we present a 3D model of pseudopod-driven swimming of an amoeba suspended in a fluid without any adhesion and in the absence of any chemoattractant. Our model is based on front-tracking/immersed-boundary methods, and it combines large deformation of the cell, a coarse-grain model for molecular reactions, and cytoplasmic and extracellular fluid flow. The predicted shapes of the swimming cell from our model show similarity with experimental observations. We predict that the swimming behavior changes from random-like to persistent unidirectional motion, and that the swimming speed increases, with increasing cell deformability and protein diffusivity. The unidirectionality in cell swimming is observed without any external cues and as a direct result of a change in pseudopod dynamics. We find that pseudopods become preferentially focused near the front of the cell and appear in greater numbers with increasing cell deformability and protein diffusivity, thereby increasing the swimming speed and making the cell shape more elongated. We find that the swimming speed is minimum when the cytoplasm viscosity is close to the extracellular fluid viscosity. We further find that the speed increases significantly as the cytoplasm becomes less viscous compared with the extracellular fluid, resembling the viscous fingering phenomenon observed in interfacial flows. While these results support the notion that softer cells migrate more aggressively, they also suggest a strong coupling between membrane elasticity, membrane protein diffusivity, and fluid viscosity.
Phase diagrams of magnetic state transformations in multiferroic composites controlled by size, shape and interfacial coupling strain
Authors: Sheng Qiang , Liu X. L. , Chen W. J. , Xiong W. M. , Jiang G. L. , Zheng Yue
Published: October 2017

This work aims to give a comprehensive view of magnetic state stability and transformations in PZT-film/FeGa-dot multiferroic composite systems due to the combining effects of size, shape and interfacial coupling strain. It is found that the stable magnetic state of the FeGa nanodots is not only a function of the size and shape of the nanodot but also strongly sensitive to the interfacial coupling strain modified by the polarization state of PZT film. In particular, due to the large magnetostriction of FeGa, the phase boundaries between different magnetic states (i.e., in-plane/out-of-plane polar states, and single-/multi-vortex states) of FeGa nanodots can be effectively tuned by the polarization-mediated strain. Fruitful strain-mediated transformation paths of magnetic states including those between states with different orderings (i.e., one is polar and the other is vortex), as well as those between states with the same ordering (i.e., both are polar or both are vortex) have been revealed in a comprehensive view. Our result sheds light on the potential of utilizing electric field to induce fruitful magnetic state transformation paths in multiferroic film-dot systems towards a development of novel magnetic random access memories.
A microfluidic needle for sampling and delivery of chemical signals by segmented flows
Authors: Feng Shilun , Liu Guozhen , Jiang Lianmei , Zhu Yonggang , Goldys Ewa M. , Inglis David W.
Published: October 2017

We have developed a microfluidic needle-like device that can extract and deliver nanoliter samples. The device consists of a T-junction to form segmented flows, parallel channels to and from the needle tip, and seven hydrophilic capillaries at the tip that form a phase-extraction region. The main microchannel is hydrophobic and carries segmented flows of water-in-oil. The hydrophilic capillaries transport the aqueous phase with a nearly zero pressure gradient but require a pressure gradient of 19 kPa for mineral oil to invade and flow through. Using this device, we demonstrate the delivery of nanoliter droplets and demonstrate sampling through the formation of droplets at the tip of our device. During sampling, we recorded the fluorescence intensities of the droplets formed at the tip while varying the concentration of dye outside the tip. We measured a chemical signal response time of approximately 3 s. The linear relationship between the recorded fluorescence intensity of samples and the external dye concentration (10–40 μg/ml) indicates that this device is capable of performing quantitative, real-time measurements of rapidly varying chemical signals.
Shock-induced compaction of nanoparticle layers into nanostructured coating
Authors: Mayer Alexander E. , Ebel Andrei A.
Published: October 2017

A new process of shock wave consolidation of nanoparticles into a nanocrystalline coating is theoretically considered. In the proposed scheme, the nanoparticle layers, which are attached to the substrate surface by adhesion, are compacted by plane ultra-short shock waves coming from the substrate. The initial adhesion is self-arisen at any contact between the nanoparticles without a pre-compression. The absence of the nanoparticle ejections due to the shock wave action is connected with the strong adhesive forces, which allow nanoparticles to be attached to each other and to substrate while they are being compacted; this should be valid for small enough nanoparticles. Severe plastic deformation of the nanoparticles and the increased temperature due to collapse of voids between them facilitate their compaction into the monolithic nanocrystalline layer. We consider the examples of Cu and Ni nanoparticles on Al substrate using molecular dynamic simulations. We show the efficiency of the action of multiple shock waves with the duration in the range 2–20 ps and the amplitude in the range 4–12 GPa for sequential layerwise compaction of nanoparticles. A series of shock waves can be created by a repetitive powerful pulsed laser irradiation of the opposite surface of the substrate. The method offers the challenge for the formation of nanostructured coatings of various compositions. The thickness of the compacted nanocrystalline coating can be locally varied and controlled by the number of acting pulses.
Note: A simple system for low-temperature experiments in a large-volume multi-anvil press
Authors: Yong W. , Secco R. A.
Published: October 2017

A simple cooling system for a 3000-ton multi-anvil press was developed for temperatures below room temperature at high pressures. It is much simpler in design, easier to make and use, and has the same cooling capability as the previous design. The new system uses a steel ring surrounding the module wedges, which contains liquid nitrogen (LN2) that flows freely through a port to flood the interior of the pressure module. O-rings on the steel ring seal in LN2 while permitting compression. Two different cooling systems reach ∼220 K which suggests that thermal equilibrium for this press is reached between the removal and influx of heat.
Enhancement of the thermo-optical response of silver nanoparticles due to surface plasmon resonance
Authors: Hashemi Zadeh Sakineh , Rashidi-Huyeh Majid , Palpant Bruno
Published: October 2017

Owing to their remarkable optical properties, noble metals' nanoparticles are proposed for many applications. Controlling the temperature dependence of these properties may then appear to be of great relevance. In this paper, we investigate the thermo-optical properties of silver nanoparticles. Different silver nanocolloids were prepared with different surface plasmon resonance modes. The thermo-extinction spectra of the colloidal solutions were then evaluated by measuring the extinction spectra at different temperatures. This reveals a typical peak-valley profile around each surface plasmon resonance mode. Mie theory was used to study theoretically the impact of nanoparticle size on the thermo-optical properties. The results allow us to interpret properly the experimental findings.
Relationship between streamwise and azimuthal length scales in a turbulent pipe flow
Authors: Ahn Junsun , Sung Hyung Jin
Published: October 2017

The statistical relationships among the turbulence structures of the streamwise velocity fluctuations along the streamwise and azimuthal directions in a turbulent pipe flow were examined using direct numerical simulation data at Reτ = 3008. Two-point correlations of the streamwise velocity fluctuations showed a linear relationship between the streamwise and azimuthal length scales (lx and lθ), where lθ/lx = 0.07 along the wall-normal distance, indicating the long coherent structures called very-large-scale motions (VLSMs). The one-dimensional pre-multiplied energy spectra of the streamwise velocity fluctuations showed that the streamwise and the azimuthal wavelengths (λx and λθ) grew linearly along the wall-normal distance, λx/y = 20 and λθ/y = 7, respectively. The ratio between the two linear relationships was determined to be λθ/λx = 0.35, indicative of large-scale motions (LSMs). The energetic modes obtained from a proper orthogonal decomposition (POD) analysis using the translational invariance method showed that the averaged helical angles of the wall mode (ix < iθ; β < 0.1 rad, where ix and iθ are the streamwise and azimuthal mode numbers and β is the helical angle) and lift mode (ix ≥ iθ; β ≥ 0.1 rad) were related to lθ/lx = 0.07 (VLSMs) and λθ/λx ≈ 0.35 (LSMs), respectively. The superposition of the energetic POD modes showed the superimposed X-shaped patterns. The helical angle of the wall mode in the near-wall region was similar to that in the outer region, implying the existence of the VLSMs in the entire wall-normal distance. The LSMs showed more inclined X-shaped patterns. The LSMs were concatenated with the azimuthal offsets to form meandering VLSMs. Most of the VLSMs and LSMs in the near-wall region inclined smaller and larger than 10° (0.17 rad), respectively. In the core region, VLSMs were distributed more helically along the azimuthal direction due to the space limitations of the pipe geometry.
Two states or not two states: Single-molecule folding studies of protein L
Authors: Aviram Haim Yuval , Pirchi Menahem , Barak Yoav , Riven Inbal , Haran Gilad
Published: October 2017

Experimental tools of increasing sophistication have been employed in recent years to study protein folding and misfolding. Folding is considered a complex process, and one way to address it is by studying small proteins, which seemingly possess a simple energy landscape with essentially only two stable states, either folded or unfolded. The B1-IgG binding domain of protein L (PL) is considered a model two-state folder, based on measurements using a wide range of experimental techniques. We applied single-molecule fluorescence resonance energy transfer (FRET) spectroscopy in conjunction with a hidden Markov model analysis to fully characterize the energy landscape of PL and to extract the kinetic properties of individual molecules of the protein. Surprisingly, our studies revealed the existence of a third state, hidden under the two-state behavior of PL due to its small population, ∼7%. We propose that this minority intermediate involves partial unfolding of the two C-terminal β strands of PL. Our work demonstrates that single-molecule FRET spectroscopy can be a powerful tool for a comprehensive description of the folding dynamics of proteins, capable of detecting and characterizing relatively rare metastable states that are difficult to observe in ensemble studies.
Gaussian and plane-wave mixed density fitting for periodic systems
Authors: Sun Qiming , Berkelbach Timothy C. , McClain James D. , Chan Garnet Kin-Lic
Published: October 2017

We introduce a mixed density fitting scheme that uses both a Gaussian and a plane-wave fitting basis to accurately evaluate electron repulsion integrals in crystalline systems. We use this scheme to enable efficient all-electron Gaussian based periodic density functional and Hartree-Fock calculations.
Experimental study of mitigation of a spiral vortex breakdown at high Reynolds number under an adverse pressure gradient
Authors: Goyal Rahul , Gandhi Bhupendra K. , Cervantes Michel J.
Published: October 2017

The flow in the off-design operation of a Francis turbine may lead to the formation of spiral vortex breakdowns in the draft tube, a diffuser installed after the runner. The spiral vortex breakdown, also named a vortex rope, may induce several low-frequency fluctuations leading to structural vibrations and a reduction in the overall efficiency of the turbine. In the present study, synchronized particle image velocimetry, pressure, and turbine flow parameter (Q, H, α, and T) measurements have been carried out in the draft tube cone of a high head model Francis turbine. The transient operating condition from the part load to the best efficiency point was selected to investigate the mitigation of the vortex rope in the draft tube cone. The experiments were performed 20 times to assess the significance of the results. A precession frequency of 1.61 Hz [i.e., 0.29 times the runner rotational frequency (Rheingans frequency)] is observed in the draft tube cone. The frequency is captured in both pressure and velocity data with its harmonics. The accelerating flow condition at the center of the cone with a guide vane opening is observed to diminish the spiral form of the vortex breakdown in the quasi-stagnant region. This further mitigates the stagnant part of the cone with a highly dominated axial flow condition of the turbine at the best efficiency point. The disappearance of the stagnant region is the most important state in the present case, which mitigates the spiral vortex breakdown of the cone at high Reynolds numbers. In contrast to a typical transition, a new type of transition from wake to jet is observed during the mitigation of the breakdown. The obtained 2D instantaneous velocity fields demonstrate the disappearance region of shear layers and stagnation in the cone. The results also demonstrate the existence of high axial velocity gradients in an elbow draft tube cone.
Enhancement of thermoelectric power factor of Sr2CoMoO6 double perovskite by annealing in reducing atmosphere
Authors: Tanwar Khagesh , Saxena Mandvi , Maiti Tanmoy
Published: October 2017

In general, n-type thermoelectric materials are rather difficult to design. This study particularly pivoted on designing potential environmentally benign oxides based n-type thermoelectric material. We synthesized Sr2CoMoO6 (SCMO) polycrystalline ceramics via the solid-state synthesis route. XRD, SEM, and thermoelectric measurements were carried out for phase constitution, microstructure analysis, and to determine its potential for thermoelectric applications. As-sintered SCMO sample showed an insulator like behavior till 640 °C after which it exhibited an n-type non-degenerate semiconductor behavior followed by a p-n type conduction switching. To stabilize a high temperature n-type behavior, annealing of SCMO in reducing atmosphere (H2) at 1000 °C was carried out. After annealing, the SCMO demonstrated an n-type semiconductor behavior throughout the temperature range of measurement. The electrical conductivity (σ) and the power factor (S2σ) were found to be increased manifold in the annealed SCMO double perovskite.
Advanced thermo-mechanical analysis in the magnetic hyperthermia
Authors: Iordana Astefanoaei , Alexandru Stancu
Published: October 2017

In magnetic hyperthermia, the spatial distribution of the magnetic nanoparticles (MNPs) inside a malignant tissue, after ferrofluid injection influences significantly the therapeutic temperature field. The inclusion of any intra-tumoral pressure as a result of ferrofluid injection modifies considerably the MNP distribution within the tumor volume. We show that this effect has crucial importance in the magnetic hyperthermia analysis. The temperature field can be controlled by the infusion parameters such as: (i) the ferrofluid infusion rate and (ii) the needle gauge size of the syringe. This paper describes the temperature field within a malignant tissue as a function of the infusion parameters. The local displacements of the tissue during the ferrofluid infusion process were considered. The therapeutic temperature field developed by the magnetite particles when an external magnetic field was applied depends strongly on the elastic parameters of the malignant tissue. The analytical model developed in this paper provides the optimum dosage of the magnetite which has to be injected within a soft malignant tissue with a large size, to achieve the hyperthermic temperature. An analysis of the spatial MNP distributions and their heating in the linear relaxation theory was done for different ferrofluid infusion parameters.
Improved resistive switching reliability by using dual-layer nanoporous carbon structure
Authors: Tao Ye , Li Xuhong , Wang Zhongqiang , Xu Haiyang , Ding Wentao , Ma Jiangang , Liu Yichun
Published: October 2017

We optimized the diameter and microgeometry of preformed conductive filaments (CFs) to improve the switching reliability of copper/nanoporous amorphous carbon (a-C)/platinum memory devices. Forming-free devices were obtained because of the introduction of preformed CFs into the nanoporous layer during the copper electrode evaporation process. The switching fluctuation decreased with the increasing preformed CF size in a certain range; however, the device with stronger preformed CFs suffered from high current in the first RESET process. Furthermore, to achieve both high switching uniformity and low power consumption, a dual-layer structure was proposed to regulate the microgeometry of preformed CFs. Compared with those of a pristine device and single-layer nanoporous device, the fluctuation of high/low resistance values was further suppressed to 26% and 21%, respectively. In addition, Resistive random access memory (RRAM) devices exhibited a fast switching speed (<50 ns), excellent endurance (>105 cycles), and long retention time (>105 s at 85 °C). These results reveal the key role of preformed CF optimization in resistive switching performance improvement, providing an effective approach to develop high-performance RRAM devices.
Internal sub-sonic burning during an explosion viewed via dynamic X-ray radiography
Authors: Smilowitz L. , Henson B. F. , Oschwald D. , Suvorova N. , Remelius D.
Published: October 2017

We observe internal convective and conductive burn front propagation and solid consumption subsequent to thermal ignition for plastic bonded formulations of the solid organic secondary explosives octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine and 1,3,5-triamino-2,4,6-trinitrobenzene. This work describes x-ray radiographic diagnostics enabling the study of solid density in a fully encased explosive during internal burning subsequent to ignition. The result of this study is the ability to directly observe and measure rates of energy release during a thermal explosion.
Design and operating characteristic of a vacuum furnace for time-of-flight inelastic neutron scattering measurements
Authors: Niedziela J. L. , Mills R. , Loguillo M. J. , Skorpenske H. D. , Armitage D. , Smith H. L. , Lin J. Y. Y. , Lucas M. S. , Stone M. B. , Abernathy D. L.
Published: October 2017

We present the design and operating characteristics of a vacuum furnace used for inelastic neutron scattering experiments on a time-of-flight chopper spectrometer. The device is an actively water cooled radiant heating furnace capable of performing experiments up to 1873 K. Inelastic neutron scattering studies performed with this furnace include studies of phonon dynamics and metallic liquids. We describe the design, control, characterization, and limitations of the equipment. Further, we provide comparisons of the neutron performance of our device with commercially available options. Finally we consider upgrade paths to improve performance and reliability.
Vortex dynamics and flow-induced vibrations arising from a vortex ring passing tangentially over a flexible plate
Authors: Pirnia Alireza , Hu JiaCheng , Peterson Sean D. , Erath Byron D.
Published: October 2017

The extraction of energy from vortical structures advecting through an ambient environment is a topic of interest due to the potential to power miniature in situ sensors and monitors. This work investigates the vortex dynamics and flow-induced vibrations of a flexible plate arising from a vortex ring passing tangentially over it. Experimental measurements of the flow field and plate dynamics are performed in tandem with a coupled potential flow/Kirchhoff-Love plate model in order to (i) elucidate the physics of the vortex-plate interactions in the specified orientation and relate the energy exchange between the ring and the plate to the attendant vortex dynamics; (ii) validate the potential flow model and provide any needed corrections to account for the simplifying assumptions; and (iii) provide empirical data for estimating energy harvesting capabilities in the specified orientation. The plate loading arises as a result of an initial down-wash, followed quickly by a region of reduced pressure as the vortex core passes over the plate. The fundamental physics of the interaction is discussed, identifying three regimes. When the centerline of the vortex ring is positioned greater than approximately 2 vortex ring radii away from the plate it can be considered to be in the far-field, and the resulting vibrations are well predicted through potential flow, once the plate dynamics are corrected for edge effects arising from a finite plate width. As the offset distance of the vortex ring is decreased, diffusion of induced vorticity on the plate into the flow field significantly alters the fluid dynamics, pressure loading, and the resultant plate dynamics, and dramatically increases the strain energy in comparison with the potential flow model predictions. A first-order correction to the potential flow model is proposed to account for the finite plate width, while empirical correlations are presented for the plate strain energy in cases where ring/induced vorticity interactions are significant.
Quantitative angle-insensitive flow measurement using relative standard deviation OCT
Authors: Zhu Jiang , Zhang Buyun , Qi Li , Wang Ling , Yang Qiang , Zhu Zhuqing , Huo Tiancheng , Chen Zhongping
Published: October 2017

Incorporating different data processing methods, optical coherence tomography (OCT) has the ability for high-resolution angiography and quantitative flow velocity measurements. However, OCT angiography cannot provide quantitative information of flow velocities, and the velocity measurement based on Doppler OCT requires the determination of Doppler angles, which is a challenge in a complex vascular network. In this study, we report on a relative standard deviation OCT (RSD-OCT) method which provides both vascular network mapping and quantitative information for flow velocities within a wide range of Doppler angles. The RSD values are angle-insensitive within a wide range of angles, and a nearly linear relationship was found between the RSD values and the flow velocities. The RSD-OCT measurement in a rat cortex shows that it can quantify the blood flow velocities as well as map the vascular network in vivo.
Detailed images of hydropower turbine reveals a region vital to a destructive phenomenon
Authors: Bello Mark
Published: October 2017

A detailed study of Francis turbines reveals that the disappearance of a stagnation region that develops at part-load operation mitigates vortex breakdown, a destructive effect.
Thermal explosions imaged with table-top X-ray radiography
Authors: Woo Marcus
Published: October 2017

Researchers adapt a table-top medical X-ray imaging device to better study secondary high explosions as they undergo ignition.
Acoustic levitation widens the study of droplet jetting
Authors: Wilson R. Mark
Published: October 2017

To investigate the fission of charged droplets, a pair of chemists holds one stationary in electrified midair.
Refracturing may not be all it’s cracked up to be
Authors: Kramer David
Published: October 2017

Restimulating oil and gas wells that have been fracked will be worthwhile in some cases, but not all.
The relentless pursuit of hypersonic flight
Authors: Leyva Ivett A.
Published: October 2017

How much new science will it take to design a vehicle that can routinely fly at many times the speed of sound?
Preparing physics students for 21st-century careers
Authors: McNeil Laurie , Heron Paula
Published: October 2017

Whether they end up in industrial, governmental, business, or academic settings, college graduates need plenty of skills beyond an ability to solve problem sets.
In celebration of Ilya Lifshitz
Authors: Grosberg Alexander Y. , Halperin Bertrand , Singleton John
Published: October 2017

This year marks the centenary of the birth of Ilya Mikhailovich Lifshitz, who helped found the field of fermiology and made important contributions to condensed-matter physics and biophysics.
Cyanothioacetamide: a polyfunctional reagent with broad synthetic utility
Authors: Dyachenko Vladimir D. , Dyachenko Ivan V. , Nenajdenko Valentine G.
Published: October 2017

The review integrates and analyzes the published data on the chemical reactivity of α-cyanothioacetamide, a convenient starting compound for the preparation of activated alkenes, functionally substituted pyrans, thiopyrans, pyridines, thiophenes, pyrroles, quinolines, isoquinolines, pyrimidines, thienopyrroles, pyrazolopyridines, pyridothienopyrimidines and pyrimidothienodiazines. The relatively small α-cyanothioacetamide molecule has several reaction centres. Nucleophilic reactions of the methylene group are covered most extensively, including the Thorpe reaction; reactions with diazonium salts, azides, iso(thio)cyanates and nitroso compounds; nucleopilic substitution; Knoevenagel condensation; Michael reaction; and multicomponent syntheses. Separate parts of the review are devoted to nucleophilic reactions involving the thiocarbonyl and amino groups and electrophilic reactions involving thiocarbonyl and nitrile groups. The focus is on the publications of the last 15 years.

The bibliography includes 350 references.
Metal-inorganic frameworks with pnictogen linkers
Authors: Shestimerova Tatiana A. , Shevelkov Andrei V.
Published: October 2017

Metal-inorganic frameworks are all-inorganic counterparts of well-known and extensively investigated metal-organic frameworks. Metal atoms connected by linkers form structures of different dimensionality with channels filled with atoms, ions or molecules. The review is devoted to metal-inorganic frameworks assembled from transition metal atoms, mainly mercury and silver, linked to phosphorus, arsenic or antimony atoms or groups of atoms of different shapes (dumbbells, rings, clusters, chains or helices). This assembly gives rise to frameworks of different geometry and with different topology. In all cases, the positively charged framework is composed of transition metal cations and pnictogen atoms as linkers. The positive charge of the framework is compensated by guest anions. Depending on the charge of the framework and the nature of the anion, compounds with different structures and properties can be produced. Specific features of metal-inorganic frameworks, the influence of weak interactions on the framework architecture and possibilities of designing new frameworks are discussed.

The bibliography includes 82 references.
A spectacular new genus of Staphylinini rove beetle from the tropical Andes and its phylogenetic assessment (Coleoptera : Staphylinidae)
Authors: Jenkins Shaw Josh , Żyła Dagmara , Solodovnikov Alexey
Published: October 2017

Devilleferus brunkei Jenkins Shaw & Solodovnikov, gen. et sp. nov., a distinctive new genus and species of Staphylinini rove beetle with an unusual set of morphological characters is described from the tropical Andes (Ecuador and possibly Colombia and Bolivia) in South America. To resolve systematic placement of the new genus within Staphylinini we assembled a dataset of 68 morphological characters scored for 34 taxa representing a broad sample of the respective rove beetle tribe, and performed Bayesian inference and maximum parsimony phylogenetic analyses. Both analytical methods unambiguously placed Devilleferus as sister to the subtribe Amblyopinina, and overall they corroborated recently established subtribal systematics for Staphylinini inferred mainly from molecular markers. Based on the shared synapomorphies, Devilleferus is assigned to the subtribe Amblyopinina. The internal relationships within Amblyopinina remain to be clarified in a broader study of that very poorly explored austral lineage.
Impact of whole genome sequencing in Public Health reference laboratories
Authors: Jennison Amy V
Published: October 2017

Public Health Microbiology reference laboratories fulfil a critical role in providing overarching testing and surveillance for notifiable, emerging and important pathogens. These duties require the laboratory to possess an extensive repertoire of validated assays and the ability to rapidly respond to novel threats and outbreaks. For these, among other reasons, the ‘one stop shop' approach of whole genome sequencing (WGS) has been embraced by microbiology reference laboratories. The ability to replace multiple labour-intensive assays with a single technique of superior typeability and discrimination at an often competitive price, although not without its challenges, has already begun to change the workflow of Public Health reference laboratories.
High-throughput characterization of protein–protein interactions by reprogramming yeast mating
Authors: Younger David , Berger Stephanie , Baker David , Klavins Eric
Published: October 2017

Significance

De novo design of protein binders often requires experimental screening to select functional variants from a design library. We have achieved high-throughput, quantitative characterization of protein–protein binding interactions without requiring purified recombinant proteins, by linking interaction strength with yeast mating. Using a next-generation sequencing output, we have characterized protein networks consisting of thousands of pairwise interactions in a single tube and have demonstrated the effect of changing the binding environment. This approach addresses an existing bottleneck in protein binder design by enabling the high-throughput and quantitative characterization of binding strength between designed protein libraries and multiple target proteins in a fully defined environment.
Efficient gene knockin in axolotl and its use to test the role of satellite cells in limb regeneration
Authors: Fei Ji-Feng , Schuez Maritta , Knapp Dunja , Taniguchi Yuka , Drechsel David N. , Tanaka Elly M.
Published: October 2017

Significance

Salamanders have great potential to regenerate damaged organs upon injury, and thus provide an important model for understanding the mechanisms of tissue regeneration; however, genetic studies have been limited due to a lack of gene knockin strategies. In this study, we have established efficient CRISPR/Cas9 mediated gene knockin approaches in the axolotl (
Ambystoma mexicanum
), which has allowed us to genetically mark two critical stem cell pools for limb and spinal cord regeneration. Our genetic fate mapping establishes the role of PAX7
+
satellite cells for limb muscle regeneration. This method opens up the possibility of marking and perturbing gene function inducibly in any definable cell populations in the axolotl, a key functionality required for the precise, rigorous understanding of processes such as regeneration.
Methyl-compound use and slow growth characterize microbial life in 2-km-deep subseafloor coal and shale beds
Authors: Trembath-Reichert Elizabeth , Morono Yuki , Ijiri Akira , Hoshino Tatsuhiko , Dawson Katherine S. , Inagaki Fumio , Orphan Victoria J.
Published: October 2017

Significance

Microbial cells are widespread in diverse deep subseafloor environments; however, the viability, growth, and ecophysiology of these low-abundance organisms are poorly understood. Using single-cell–targeted stable isotope probing incubations combined with nanometer-scale secondary ion mass spectrometry, we measured the metabolic activity and generation times of thermally adapted microorganisms within Miocene-aged coal and shale bed samples collected from 2 km below the seafloor during Integrated Ocean Drilling Program Expedition 337. Microorganisms from the shale and coal were capable of metabolizing methylated substrates, including methylamine and methanol, when incubated at their in situ temperature of 45 °C, but had exceedingly slow growth, with biomass generation times ranging from less than a year to hundreds of years as measured by the passive tracer deuterated water.
Natural climate solutions
Authors: Griscom Bronson W. , Adams Justin , Ellis Peter W. , Houghton Richard A. , Lomax Guy , Miteva Daniela A. , Schlesinger William H. , Shoch David , Siikamäki Juha V. , Smith Pete , Woodbury Peter , Zganjar Chris , Blackman Allen , Campari João , Conant Richard T. , Delgado Christopher , Elias Patricia , Gopalakrishna Trisha , Hamsik Marisa R. , Herrero Mario , Kiesecker Joseph , Landis Emily , Laestadius Lars , Leavitt Sara M. , Minnemeyer Susan , Polasky Stephen , Potapov Peter , Putz Francis E. , Sanderman Jonathan , Silvius Marcel , Wollenberg Eva , Fargione Joseph
Published: October 2017

Significance

Most nations recently agreed to hold global average temperature rise to well below 2 °C. We examine how much climate mitigation nature can contribute to this goal with a comprehensive analysis of “natural climate solutions” (NCS): 20 conservation, restoration, and/or improved land management actions that increase carbon storage and/or avoid greenhouse gas emissions across global forests, wetlands, grasslands, and agricultural lands. We show that NCS can provide over one-third of the cost-effective climate mitigation needed between now and 2030 to stabilize warming to below 2 °C. Alongside aggressive fossil fuel emissions reductions, NCS offer a powerful set of options for nations to deliver on the Paris Climate Agreement while improving soil productivity, cleaning our air and water, and maintaining biodiversity.
The human visual cortex response to melanopsin-directed stimulation is accompanied by a distinct perceptual experience
Authors: Spitschan Manuel , Bock Andrew S. , Ryan Jack , Frazzetta Giulia , Brainard David H. , Aguirre Geoffrey K.
Published: October 2017

Significance

Melanopsin-containing retinal cells detect bright light and contribute to reflex visual responses such as pupil constriction. Their role in conscious, cortical vision is less understood. Using functional MRI to measure brain activity, we find that melanopsin-directed stimulation reaches the visual cortex in people. Such stimulation also produces a distinct perceptual experience. Our results have clinical importance as melanopsin function may contribute to the discomfort that some people experience from bright light.
Electrical synapses mediate synergism between pheromone and food odors in
Drosophila melanogaster
Authors: Das Sudeshna , Trona Federica , Khallaf Mohammed A. , Schuh Elisa , Knaden Markus , Hansson Bill S. , Sachse Silke
Published: October 2017

Significance

We elucidated the neuronal mechanism underlying the interaction of two ecologically relevant odors in the fly brain. Our study demonstrates that exposure to the male-produced sex pheromone
cis
-vaccenyl acetate, in combination with the complex food odor vinegar, evokes an enhanced and synergistic functional response in the primary olfactory center of virgin female flies. This effect arises within the neuronal network of the antennal lobe and is mediated by electrical synapses. The synergistic response in virgin females leads to an increased sensitivity to the pheromone, and therefore an enhanced female receptivity during courtship. This mechanism is highly useful, since it promotes mating in females when food is present: that is, when the nutritional supply of the female and its offspring is guaranteed.
Chasing the open-state structure of pentameric ligand-gated ion channels
Authors: Gonzalez-Gutierrez Giovanni , Wang Yuhang , Cymes Gisela D. , Tajkhorshid Emad , Grosman Claudio
Published: October 2017

Remarkable advances have been made toward the structural characterization of ion channels in the last two decades. However, the unambiguous assignment of well-defined functional states to the obtained structural models has proved challenging. In the case of the superfamily of nicotinic-receptor channels (also referred to as pentameric ligand-gated ion channels [pLGICs]), for example, two different types of model of the open-channel conformation have been proposed on the basis of structures solved to resolutions better than 4.0 Å. At the level of the transmembrane pore, the open-state models of the proton-gated pLGIC from Gloeobacter violaceus (GLIC) and the invertebrate glutamate-gated Cl– channel (GluCl) are very similar to each other, but that of the glycine receptor (GlyR) is considerably wider. Indeed, the mean distances between the axis of ion permeation and the Cα atoms at the narrowest constriction of the pore (position −2′) differ by ∼2 Å in these two classes of model, a large difference when it comes to understanding the physicochemical bases of ion conduction and charge selectivity. Here, we take advantage of the extreme open-channel stabilizing effect of mutations at pore-facing position 9′. We find that the I9′A mutation slows down entry into desensitization of GLIC to the extent that macroscopic currents decay only slightly by the end of pH 4.5 solution applications to the extracellular side for several minutes. We crystallize (at pH 4.5) two variants of GLIC carrying this mutation and solve their structures to resolutions of 3.12 Å and 3.36 Å. Furthermore, we perform all-atom molecular dynamics simulations of ion permeation and picrotoxinin block, using the different open-channel structural models. On the basis of these results, we favor the notion that the open-channel structure of pLGICs from animals is much closer to that of the narrow models (of GLIC and GluCl) than it is to that of the GlyR.
Analysis of the quality of crystallographic data and the limitations of structural models
Authors: Arkhipova Valentina , Guskov Albert , Slotboom Dirk-Jan
Published: October 2017

Crystal structures provide visual models of biological macromolecules, which are widely used to interpret data from functional studies and generate new mechanistic hypotheses. Because the quality of the collected x-ray diffraction data directly affects the reliability of the structural model, it is essential that the limitations of the models are carefully taken into account when making interpretations. Here we use the available crystal structures of members of the glutamate transporter family to illustrate the importance of inspecting the data that underlie the structural models. Crystal structures of glutamate transporters in multiple different conformations have been solved, but most structures were determined at relatively low resolution, with deposited models based on crystallographic data of moderate quality. We use these examples to demonstrate the extent to which mechanistic interpretations can be made safely.
Dissociating the physiological components of unconscious emotional responses
Authors: Tooley Michael D , Carmel David , Chapman Angus , Grimshaw Gina M
Published: October 2017

Conscious emotional processing is characterized by a coordinated set of responses across multiple physiological systems. Although emotional stimuli can evoke certain physiological responses even when they are suppressed from awareness, it is not known whether unconscious emotional responses comprise a similar constellation or are confined to specific systems. To compare physiological responses to emotional stimuli with and without awareness, we measured a range of responses while participants viewed positive, negative and neutral images that were accompanied by noise bursts to elicit startle reflexes. We measured four responses simultaneously – skin conductance and heart rate changes in response to the images themselves; and startle eye-blink and post-auricular reflexes in response to the noise bursts that occurred during image presentation. For half of the participants, the images were masked from awareness using continuous flash suppression. The aware group showed the expected pattern of response across physiological systems: emotional images (regardless of valence) evoked larger skin conductance responses (SCRs) and greater heart rate deceleration than neutral images, negative images enhanced eye-blink reflexes and positive images enhanced post-auricular reflexes. In contrast, we found a striking dissociation between measures for the unaware group: typical modulation of SCRs and post-auricular reflexes, but no modulation of heart rate deceleration or eye-blink reflexes. Our findings suggest that although some physiological systems respond to emotional stimuli presented outside of awareness, conscious emotional processing may be characterized by a broad and coordinated set of responses across systems.
Informed Consent Documents Used in Critical Care Trials Often Do Not Implement Recommendations*
Authors: Atwere Pearl , McIntyre Lauralyn , Carroll Kelly , Hayes Tavis , Brehaut Jamie C.
Published: October 2017

Objective:

Informed consent documents are often poorly understood by research participants. In critical care, issues such as time pressure, patient capacity, and surrogate decision making complicate the consent process further. Recommendations exist for addressing critical care–specific consent issues; we examined how well existing practice implements these recommendations.

Design:

We conducted a systematic search of the literature for recommendations specific to critical care informed consent and rated existing informed consent documents on their implementation of 1) 18 of these critical care recommendations and 2) 36 previously developed general informed consent recommendations. Four hundred twelve registered critical care trials were identified and a request sent to the principal investigators for an example of the informed consent document associated with the trial. Each consent document was rated on both set of recommendations.

Setting:

We evaluated informed consent documents for trials conducted in English or French registered with clinicaltrials.gov.

Patients:

Not applicable.

Interventions:

Not applicable.

Measurements and Main Results:

Independent coders rated implementation of each recommendation on a four-point scale. Of 412 requests, 137 informed consent documents were returned, for a response rate of 34.1%. Of these, 86 met inclusion criteria and were assessed. Overall agreement between raters was 90.6% (weighted κ = 0.79; 0.77–0.81). Implementation of the 18 critical care recommendations was highly variable, ranging between 2% and 96.5%.

Conclusions:

Critical care studies often do not provide the information recommended for those providing consent for research. These clear recommendations provide testable hypotheses about how to improve the consent process for patients and family members considering trial participation in the critical care setting.
MINIMAL OPTICAL COHERENCE TOMOGRAPHY B-SCAN DENSITY FOR RELIABLE DETECTION OF INTRARETINAL AND SUBRETINAL FLUID IN MACULAR DISEASES
Authors: Fang Petra P. , Domdei Niklas , Herrmann Philipp , Schmitz-Valckenberg Steffen , Holz Frank G. , Harmening Wolf M. , Krohne Tim U.
Published: October 2017

Purpose:

To determine the minimal optical coherence tomography B-scan density for reliable detection of intraretinal and subretinal fluid.

Methods:

Spectral domain optical coherence tomography raster scanning (Spectralis; Heidelberg Engineering, Heidelberg, Germany) using a scan field of 20° × 20° of 97 B-scans with an interscan distance (ISD) of 60 μm was performed in 150 eyes of 150 consecutive patients at monitoring visits for intravitreal anti–vascular endothelial growth factor therapy. Using custom software, every other B-scan was repeatedly deleted to generate additional data sets with an ISD of 120 μm (49 B-scans), 240 μm (25 B-scans), and 480 μm (13 B-scans). Two independent reviewers evaluated the data sets for the presence of cystoid spaces of intraretinal fluid and subretinal fluid.

Results:

Treatment diagnoses were neovascular age-related macular degeneration (68.0%), macular edema secondary to retinal vein occlusion (20.7%), diabetic macular edema (10.7%), and other retinal diseases (4.0%). Using the source data sets with an ISD of 60 μm, intraretinal fluid was detected in 56.0%, subretinal fluid in 19.3%, and either/both in 68.7%. Compared with these results, the sensitivity of detection of intraretinal fluid and/or subretinal fluid using an ISD of 120 μm, 240 μm, and 480 μm was 99.0% (95% confidence interval, 94.7–100.0; P = 0.5), 97.1% (91.7–99.4; P = 0.1), and 87.4% (79.4–93.1; P = 0.0001), respectively.

Conclusion:

An increase of ISD up to 240 μm does not significantly impair the detection of treatment-relevant exudative retinal changes in monitoring during intravitreal therapy of macular diseases. These findings are relevant for the choice of optical coherence tomography B-scan density in both routine clinical care and interventional clinical studies.
Improvements in Antimicrobial Prescribing and Outcomes in Pediatric Complicated Appendicitis
Authors: Willis Zachary I. , Duggan Eileen M. , Gillon Jessica , Blakely Martin L. , Di Pentima M. Cecilia
Published: October 2017

Background:

Complicated appendicitis, characterized by perforation and/or peritonitis, is common in children, and late infectious complications are frequent. The best antibiotic treatment approach is unknown, resulting in substantial variation in care. We evaluated the effects of 2 successive interventions, an antimicrobial stewardship program (ASP) and a condition-specific clinical practice guideline (CPG), on antimicrobial utilization and patient outcomes in these patients.

Methods:

The ASP at our institution was begun in March 2012. The CPG, a standardized antibiotic treatment, was implemented in July 2013. We reviewed every case of complicated appendicitis managed with early appendectomy between January 2011 and October 2014. Patients were thus divided into 3 eras based on their exposure to the following: (1) neither intervention, (2) ASP only or (3) both ASP and CPG. We compared measures of antibiotic utilization and clinical outcomes among the 3 eras.

Results:

A total of 313 patients were included in the study: 91 exposed to neither intervention; 100 exposed to only the ASP; and 122 exposed to both interventions. With ASP implementation, there were declines in the use of unnecessarily broad or toxic antibiotic regimens. With CPG implementation, there was a decrease in total antibiotic utilization and discharges with intravenous antibiotics. Compliance with CPG-recommended antibiotics exceeded 90%. There was no significant change in overall adverse events; there was a decline in the incidence of surgical-site infections in patients exposed to both interventions.

Conclusions:

Complicated appendicitis is an important target for antimicrobial stewardship and quality improvement efforts. A condition-specific CPG can improve both antimicrobial utilization and clinical outcomes.