bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of carbamates from amines and N-tosylhydrazones under atmospheric pressure of carbon dioxide without an external base
Authors: Hong Ji Young , Seo Ue Ryung , Chung Young Keun
Published: April 2016

A synthetic method to carbamates from amines and N-tosylhydrazones in the presence of 1 atm of carbon dioxide was developed.
Alginate–marine collagen–agarose composite hydrogels as matrices for biomimetic 3D cell spheroid formation
Authors: Shin Suil , Ikram Muhammad , Subhan Fazli , Kang Hae Yeong , Lim Yeseon , Lee Rira , Jin Songwan , Jeong Young Hun , Kwak Jong-Young , Na Yong-Jin , Yoon Sik
Published: April 2016

We report a novel, customizable, transparent, biocompatible, functional, easy-to-produce, efficient and cost-effective AmCA scaffold for 3D cell culture.
Mechanical activation of volcanic ash for geopolymer synthesis: effect on reaction kinetics, gel characteristics, physical and mechanical properties
Authors: Yankwa Djobo Jean Noël , Elimbi Antoine , Tchakouté Hervé Kouamo , Kumar Sanjay
Published: April 2016

Mechanical activation is a suitable route to enhance the reactivity of volcanic ash and the final properties of the resulting geopolymers.
Cu-doped mesoporous graphitic carbon nitride for enhanced visible-light driven photocatalysis
Authors: Le Shukun , Jiang Tingshun , Zhao Qian , Liu XiuFang , Li Yingying , Fang Bingwei , Gong Ming
Published: April 2016

A series of Cu-doped mesoporous graphitic carbon nitride (Cu/mpg-C3N4) photocatalysts with Cu introduced from 0.1 to 5 wt% were prepared using cupric chloride and melamine as precursors.
Adsorption of heterocyclic sulfur and nitrogen compounds in liquid hydrocarbons on activated carbons modified by oxidation: capacity, selectivity and mechanism
Authors: Qu Dong , Feng Xiao , Li Na , Ma Xiaoliang , Shang Chao , Chen Xiao Dong
Published: April 2016

Careful design and modification of carbon adsorbents was performed to selectively remove undesired compounds from liquid hydrocarbons.
Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury
Authors: Roy Sanchari , Benz Fabian , Alder Jan , Bantel Heike , Janssen Joern , Vucur Mihael , Gautheron Jeremie , Schneider Anne , Schüller Florian , Loosen Sven , Luedde Mark , Koch Alexander , Tacke Frank , Luedde Tom , Trautwein Christian , Roderburg Christoph
Published: April 2016

miR-192-5p has gained increasing relevance in various diseases, however, its function in acute liver injury is currently unknown. We analysed miR-192-5p serum levels and hepatic miR-192-5p expression in mice after hepatic ischaemia and reperfusion (I/R) as well as in toxic liver injury. On a functional level, miRNA levels were analysed in the different hepatic cell-compartments and in the context of tumour necrosis factor (TNF)-dependent liver cell death. We detected increased serum levels of miR-192-5p after hepatic I/R- and carbon tetrachloride (CCl4)-induced liver injury. miR-192-5p levels correlated with the degree of liver damage and the presence of hepatic cell death detected by TUNEL stainings (terminal deoxynucleotidyltransferase-mediated dUTP biotin nick-end labelling stainings). Moreover, expression of miR-192-5p was increased in a hypoxia/reoxygenation (H/R) model of in vitro hepatocyte injury, supporting that the passive release of miR-192-5p represents a surrogate for hepatocyte death in liver injury. In critically ill patients, miR-192-5p levels were elevated selectively in patients with liver injury and closely correlated with the presence of hepatic injury. In contrast with up-regulated miR-192-5p in the serum, we detected a down-regulation of miR-192-5p in both injured mouse and human livers. Deregulation of miR-192-5p in livers was dependent on stimulation with TNF. Functional experiments confirmed a protective effect of down-regulation of miR-192-5p in hepatocytes, suggesting a role of miR-192-5p in limiting liver injury. Finally, we identified Zeb2, an important regulator of cell death, as a potential target gene mediating the function of miR-192-5p. Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury.
Two basic leader connection scenarios observed in negative lightning attachment process
Authors: Lu Weitao , Qi Qi , Ma Ying , Chen Luwen , Yan Xu , Rakov Vladimir A. , Wang Daohong , Zhang Yijun
Published: April 2016

High‐speed video images of 24 downward negative lightning flashes terminating on tall structures in Guangzhou are selected to analyse the connecting behaviour of the downward and upward leaders during the attachment process preceding the first return stroke. Three types of leader connecting behaviour have been observed: Type I, the tip of downward leader (DL) to the tip of upward connecting leader (UCL), which accounts for 42% of all the events (10/24); Type II, the DL's tip to the lateral surface of UCL, which accounts for 50% (12/24); and Type III, the combination of Types I and II, which accounts for 8% (2/24). For the two cases of Type III behaviour, each case had two junction points (one with Type I and the other with Type II behaviour) between the downward and upward leaders. Therefore, Types I and II can be viewed as the two basic types of the leader connecting behaviour during the attachment process in negative lightning. No attachment process exhibited the connection of the UCL's tip to the lateral surface of DL. The presence of multiple DL branches and their integrated effect on the development of positive UCL/UCLs are likely to be the main reasons for the Type II behaviour.
Fabrication of petal-shaped masks for suppression of the on-axis Poisson spot in telescope systems
Authors: Shiri Ron , Stein Ryan , Murphy Kaitlin , Hagopian Kimberly , Salari Shirin , Sankar Shannon , Hagopian John , Showalter Matthew , Stevenson Thomas , Quijada Manuel , Threat Felix , Friedlander Jay , Dillon Thomas , Livas Jeffrey
Published: April 2016

The presence of a bright (Poisson) spot in the geometrical shadow of circular/spherical shapes has been known for the past two centuries. A broad class of telescopes that involve simultaneous transmit and receive require suppression of the reflected light from the secondary mirror on the detector. For instance, the on-axis design of optical telescope for the evolved Laser Interferometric Space Antenna (eLISA), a re-scoped version of the baseline LISA mission concept, requires suppression of reflected laser light from the secondary mirror on the detector. In the past few years, the hypergaussian functions with petal-shaped realization have been shown to significantly suppress intensity along the optical axis. This work reports on fabrication of a series of petal-shaped masks using a variety of techniques such as 3D printing, photolithography, and wire Electro Discharge Machining. These masks are designed and fabricated to operate in the range of Fresnel numbers between 4 and 120. This paper discusses the challenges, successes, and failures of each fabrication technique and the optical performance of typical masks with suggestions for potential follow up work.
Experimental characterization of nonlinear processes of whistler branch waves
Authors: Tejero E. M. , Crabtree C. , Blackwell D. D. , Amatucci W. E. , Ganguli G. , Rudakov L.
Published: April 2016

Experiments in the Space Physics Simulation Chamber at the Naval Research Laboratory isolated and characterized important nonlinear wave-wave and wave-particle interactions that can occur in the Earth's Van Allen radiation belts by launching predominantly electrostatic waves in the intermediate frequency range with wave normal angle greater than 85° and measuring the nonlinearly generated electromagnetic scattered waves. The scattered waves have a perpendicular wavelength that is nearly an order of magnitude larger than that of the pump wave. Calculations of scattering efficiency from experimental measurements demonstrate that the scattering efficiency is inversely proportional to the damping rate and trends towards unity as the damping rate approaches zero. Signatures of both wave-wave and wave-particle scatterings are also observed in the triggered emission process in which a launched wave resonant with a counter-propagating electron beam generates a large amplitude chirped whistler wave. The possibility of nonlinear scattering or three wave decay as a saturation mechanism for the triggered emission is suggested. The laboratory experiment has inspired the search for scattering signatures in the in situ data of chorus emission in the radiation belts.
Direct drive: Simulations and results from the National Ignition Facility
Authors: Radha P. B. , Hohenberger M. , Edgell D. H. , Marozas J. A. , Marshall F. J. , Michel D. T. , Rosenberg M. J. , Seka W. , Shvydky A. , Boehly T. R. , Collins T. J. B. , Campbell E. M. , Craxton R. S. , Delettrez J. A. , Dixit S. N. , Frenje J. A. , Froula D. H. , Goncharov V. N. , Hu S. X. , Knauer J. P. , McCrory R. L. , McKenty P. W. , Meyerhofer D. D. , Moody J. , Myatt J. F. , Petrasso R. D. , Regan S. P. , Sangster T. C. , Sio H. , Skupsky S. , Zylstra A.
Published: April 2016

Direct-drive implosion physics is being investigated at the National Ignition Facility. The primary goal of the experiments is twofold: to validate modeling related to implosion velocity and to estimate the magnitude of hot-electron preheat. Implosion experiments indicate that the energetics is well-modeled when cross-beam energy transfer (CBET) is included in the simulation and an overall multiplier to the CBET gain factor is employed; time-resolved scattered light and scattered-light spectra display the correct trends. Trajectories from backlit images are well modeled, although those from measured self-emission images indicate increased shell thickness and reduced shell density relative to simulations. Sensitivity analyses indicate that the most likely cause for the density reduction is nonuniformity growth seeded by laser imprint and not laser-energy coupling. Hot-electron preheat is at tolerable levels in the ongoing experiments, although it is expected to increase after the mitigation of CBET. Future work will include continued model validation, imprint measurements, and mitigation of CBET and hot-electron preheat.
Influence of nanoparticle-ion and nanoparticle-polymer interactions on ion transport and viscoelastic properties of polymer electrolytes
Authors: Mogurampelly Santosh , Sethuraman Vaidyanathan , Pryamitsyn Victor , Ganesan Venkat
Published: April 2016

We use atomistic simulations to probe the ion conductivities and mechanical properties of polyethylene oxide electrolytes containing Al2O3 nanoparticles. We specifically study the influence of repulsive polymer-nanoparticle and ion-nanoparticle interactions and compare the results with those reported for electrolytes containing the polymorph β-Al2O3 nanoparticles. We observe that incorporating repulsive nanoparticle interactions generally results in increased ionic mobilities and decreased elastic moduli for the electrolyte. Our results indicate that both ion transport and mechanical properties are influenced by the polymer segmental dynamics in the interfacial zones of the nanoparticle in the ion-doped systems. Such effects were seen to be determined by an interplay between the nanoparticle-polymer, nanoparticle-ion, and ion-polymer interactions. In addition, such interactions were also observed to influence the number of dissociated ions and the resulting conductivities. Within the perspective of the influence of nanoparticles on the polymer relaxation times in ion-doped systems, our results in the context of viscoelastic properties were consistent with the ionic mobilities. Overall, our results serve to highlight some issues that confront the efforts to use nanoparticle dispersions to simultaneously enhance the conductivity and the mechanical strength of polymer electrolyte.
Density functional theory based simulations of silicon nanowire field effect transistors
Authors: Shin Mincheol , Jeong Woo Jin , Lee Jaehyun
Published: April 2016

First-principles density functional theory (DFT) based, atomistic, self-consistent device simulations are performed for realistically sized Si nanowire field effect transistors (NW FETs) having tens of thousands of atoms. Through mode space transformation, DFT Hamiltonian and overlap matrices are reduced in size from a few thousands to around one hundred. Ultra-efficient quantum-mechanical transport calculations in the non-equilibrium Green's function formalism in a non-orthogonal basis are therefore made possible. The n-type and p-type Si NW FETs are simulated and found to exhibit similar device performance in the nanoscale regime.
Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states
Authors: Qiao Qin , Zhang Hou-Dao , Huang Xuhui
Published: April 2016

Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.
Role of (Bi1/2K1/2)TiO3 in the dielectric relaxations of BiFeO3-(Bi1/2K1/2)TiO3 ceramics
Authors: Cheon Chae Il , Choi Jin Hong , Kim Jeong Seog , Zang Jiadong , Frömling Till , Rödel Jürgen , Jo Wook
Published: April 2016

Temperature-dependent dielectric relaxations of (1 − x)BiFeO3-x(Bi1/2K1/2)TiO3 (BF-BKT) lead-free piezoceramics (0.4 ≤ x ≤ 0.8) were investigated via impedance spectroscopic techniques. Regardless of the compositions, the dielectric maximum temperatures exhibit a frequency-dependent dispersion, originating from a Debye relaxation due to the presence of oxygen vacancies. It was also observed that there exist local dielectric maxima due to the relaxation of polar nanoregions as a shoulder on the lower temperature side. The onset temperature for the Debye-type relaxation decreased with decreasing BKT content, gradually overlapping with the low-temperature dielectric dispersion from the relaxation of polar nanoregions. It is proposed that the role of BKT in the BF-BKT system is to enhance the random fields that favor a relaxor state and to suppress the Debye-type relaxation of oxygen vacancy related dipoles.
Revisiting the plasma sheath—dust in plasma sheath
Authors: Das G. C. , Deka R. , Bora M. P.
Published: April 2016

In this work, we have considered the formation of warm plasma sheath in the vicinity of a wall in a plasma with considerable presence of dust particles. As an example, we have used the parameters relevant in case of plasma sheath formed around surfaces of various solid bodies in space, though the results obtained in this work can be applied to any other physical situation such as laboratory plasma. In the ion-acoustic time scale, we neglect the dust dynamics. The dust particles affect the sheath dynamics by affecting the Poisson equation which determines the plasma potential in the sheath region. It is important to note that our calculations are valid only when the amount of dust particles is not sufficient so as to affect the plasma dynamics in the dust-acoustic time scale, but enough to affect the plasma sheath. We have assumed the current to a dust particle to be balanced throughout the analysis. This makes the grain potential dependent on plasma potential, which is then incorporated into the Poisson equation. The resultant numerical model becomes an initial value problem, which is described by a 1-D integro-differential equation, which is then solved self-consistently by incorporating the change in plasma potential caused by inclusion of the dust potential in the Poisson equation.
The nature of the CO2− radical anion in water
Authors: Janik Ireneusz , Tripathi G. N. R.
Published: April 2016

The reductive conversion of CO2 into industrial products (e.g., oxalic acid, formic acid, methanol) can occur via aqueous CO2− as a transient intermediate. While the formation, structure, and reaction pathways of this radical anion have been modelled for decades using various spectroscopic and theoretical approaches, we present here, for the first time, a vibrational spectroscopic investigation in liquid water, using pulse radiolysis time-resolved resonance Raman spectroscopy for its preparation and observation. Excitation of the radical in resonance with its 235 nm absorption displays a transient Raman band at 1298 cm−1, attributed to the symmetric CO stretch, which is at ∼45 cm−1 higher frequency than in inert matrices. Isotopic substitution at C (13CO2−) shifts the frequency downwards by 22 cm−1, which confirms its origin and the assignment. A Raman band of moderate intensity compared to the stronger 1298 cm−1 band also appears at 742 cm−1 and is assignable to the OCO bending mode. A reasonable resonance enhancement of this mode is possible only in a bent CO2−(C2v/Cs) geometry. These resonance Raman features suggest a strong solute-solvent interaction, the water molecules acting as constituents of the radical structure, rather than exerting a minor solvent perturbation. However, there is no evidence of the non-equivalence (Cs) of the two CO bonds. A surprising resonance Raman feature is the lack of overtones of the symmetric CO stretch, which we interpret due to the detachment of the electron from the CO2− moiety towards the solvation shell. Electron detachment occurs at the energies of 0.28 ± 0.03 eV or higher with respect to the zero point energy of the ground electronic state. The issue of acid-base equilibrium of the radical, which has been in contention for decades, as reflected in a wide variation in the reported pKa (−0.2 to 3.9), has been resolved. A value of 3.4 ± 0.2 measured in this work is consistent with the vibrational properties, bond structure, and charge distribution in aqueous CO2−.
Communication: Charge-population based dispersion interactions for molecules and materials
Authors: Stöhr Martin , Michelitsch Georg S. , Tully John C. , Reuter Karsten , Maurer Reinhard J.
Published: April 2016

We introduce a system-independent method to derive effective atomic C6 coefficients and polarizabilities in molecules and materials purely from charge population analysis. This enables the use of dispersion-correction schemes in electronic structure calculations without recourse to electron-density partitioning schemes and expands their applicability to semi-empirical methods and tight-binding Hamiltonians. We show that the accuracy of our method is en par with established electron-density partitioning based approaches in describing intermolecular C6 coefficients as well as dispersion energies of weakly bound molecular dimers, organic crystals, and supramolecular complexes. We showcase the utility of our approach by incorporation of the recently developed many-body dispersion method [Tkatchenko et al., Phys. Rev. Lett. 108, 236402 (2012)] into the semi-empirical density functional tight-binding method and propose the latter as a viable technique to study hybrid organic-inorganic interfaces.
Sex differences in the circadian regulation of sleep and waking cognition in humans
Authors: Santhi Nayantara , Lazar Alpar S. , McCabe Patrick J. , Lo June C. , Groeger John A. , Dijk Derk-Jan
Published: April 2016

Significance

Circadian rhythms affect our physiology and psychology, in health and disease. Most of our knowledge about the human circadian timing system is based on research in men. Some circadian characteristics, such as the intrinsic frequency of the circadian clock and the amplitude of the melatonin rhythm, have been shown to differ between men and women. Whether the circadian regulation of mental functions differs between men and women is unknown. Here we show that circadian rhythmicity in mental functions exhibits sex differences so that the night-time impairment in cognitive performance is greater in women than in men. These findings are significant in view of shift-work–related cognitive deficits and disturbances of mood, which are more prevalent in women.
Gelada vocal sequences follow Menzerath’s linguistic law
Authors: Gustison Morgan L. , Semple Stuart , Ferrer-i-Cancho Ramon , Bergman Thore J.
Published: April 2016

Significance

Human language follows a variety of structural principles, known as linguistic laws. One of these, Menzerath’s law, states that, the larger the size of the construct (e.g., the size of a word in terms of syllable number), the smaller the size of the individual constituent parts (e.g., syllables). We show for the first time (to our knowledge) that Menzerath’s law also holds in the vocal communication of a nonhuman species. In the gelada (Theropithecus gelada), a primate living in the highlands of Ethiopia, longer vocal sequences produced by adult males were associated with shorter individual calls. This result suggests that general—perhaps universal—principles underpin the structure of vocal communication in our own species and others.
Phosphorylation of synaptotagmin-1 controls a post-priming step in PKC-dependent presynaptic plasticity
Authors: de Jong Arthur P. H. , Meijer Marieke , Saarloos Ingrid , Cornelisse Lennart Niels , Toonen Ruud F. G. , Sørensen Jakob B. , Verhage Matthijs
Published: April 2016

Significance

Synapses can be temporarily strengthened by bursts of action potentials, which are thought to be a central aspect of information processing in the brain. This study provides evidence that protein kinase C (PKC)-dependent phosphorylation of synaptotagmin-1 is an essential step in this strengthening. A mutation that prevents synaptotagmin-1 phosphorylation abolishes this strengthening, both after action potential bursts and upon direct PKC activation by a synthetic analog of diacylglycerol, whereas basal synaptic transmission is unaffected. This suggests that synaptotagmin-1 acts in a cooperative fashion with Munc18-1 and Munc13-1, which were previously identified as essential diacylglycerol/PKC substrates. Together these data identify a central pathway linking bursts of action potentials to enhanced synaptic strength.
Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3
Authors: Liang Wenguang G. , Triandafillou Catherine G. , Huang Teng-Yi , Zulueta Medel Manuel L. , Banerjee Shiladitya , Dinner Aaron R. , Hung Shang-Cheng , Tang Wei-Jen
Published: April 2016

Significance

Oligomerization and glycosaminoglycan (GAG) binding are key regulatory steps for many extracellular ligands. Our analyses provide a structural basis of CC chemokine ligand 5 (CCL5) and CCL3 oligomerization and explain how oligomerization affects the interaction of these chemokines with GAG and their functions. Our GAG-bound chemokine structures reveal how CCL5 and CCL3 oligomerization creates distinctive GAG-binding grooves to enhance GAG binding via avidity for regulating chemokine functions. Furthermore, our CCL5 structure may explain how CXCL4, a CXC chemokine, heterooligomerizes with CCL5 to modulate chemokine-mediated activities. Together, these data provide new structural insights into how oligomerization and GAG binding are coupled to regulate functions of CC chemokines and offer novel pharmacophores for the design of therapeutics for treating chemokine-mediated human diseases.
Effects of serotonin 2A/1A receptor stimulation on social exclusion processing
Authors: Preller Katrin H. , Pokorny Thomas , Hock Andreas , Kraehenmann Rainer , Stämpfli Philipp , Seifritz Erich , Scheidegger Milan , Vollenweider Franz X.
Published: April 2016

Significance

Social cognition critically impacts the development, progression, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. By applying a multimodal brain imaging strategy, the present study demonstrated the importance of the serotonin 2A/1A receptor system in the modulation of social exclusion processing. Understanding the biochemical underpinnings of the social rejection experience is important for increasing our knowledge about social/emotional processing and the related neural responses. The identification of relevant neural responses is in turn crucial for the efficacious management of disorders influenced by social factors. Our findings may help to diminish a knowledge gap that currently restrains the development of pharmacotherapies for sociocognitive deficits in psychiatric disorders.
Fluctuating survival selection explains variation in avian group size
Authors: Brown Charles R. , Brown Mary Bomberger , Roche Erin A. , O’Brien Valerie A. , Page Catherine E.
Published: April 2016

Significance

A characteristic feature of animal groups is extensive variation in size. Biologists have recognized that group size can often have profound effects on the fitness of individuals, and often certain group sizes afford greater short-term benefits than others. When individuals in some group sizes are less successful, what maintains pervasive variation in group sizes in nature remains a fundamental problem in behavioral biology. In colonial cliff swallows, survival advantages regularly fluctuate among group sizes over time. This study shows that changes in the direction and form of natural selection on colony size serve to maintain a wide range of group sizes and represents the first case, to our knowledge, in which the advantages and disadvantages of different group sizes regularly fluctuate in a natural vertebrate population.
Antibiotic treatment enhances the genome-wide mutation rate of target cells
Authors: Long Hongan , Miller Samuel F. , Strauss Chloe , Zhao Chaoxian , Cheng Lei , Ye Zhiqiang , Griffin Katherine , Te Ronald , Lee Heewook , Chen Chi-Chun , Lynch Michael
Published: April 2016

Significance

The evolution of antibiotic resistance by pathogenic bacteria poses a major challenge for human health. Whereas it is clear that natural selection promotes resistance-conferring mutations, our understanding of the response of the mutation rate to antibiotics is limited. With hundreds of
Escherichia coli
cell lines evolving in a near-neutral scenario under exposure to the fluoroquinolone norfloxacin, this study reveals a significant linear relationship between the mutation rate and antibiotic concentration, while also demonstrating that antibiotic treatment compromises the efficiency of DNA oxidative-damage repair and postreplicative mismatch repair. Thus, antibiotics not only impose a selective challenge to target and off-target bacteria but also accelerate the rate of adaptation by magnifying the rate at which advantageous mutations arise.
Real-time single-molecule electronic DNA sequencing by synthesis using polymer-tagged nucleotides on a nanopore array
Authors: Fuller Carl W. , Kumar Shiv , Porel Mintu , Chien Minchen , Bibillo Arek , Stranges P. Benjamin , Dorwart Michael , Tao Chuanjuan , Li Zengmin , Guo Wenjing , Shi Shundi , Korenblum Daniel , Trans Andrew , Aguirre Anne , Liu Edward , Harada Eric T. , Pollard James , Bhat Ashwini , Cech Cynthia , Yang Alexander , Arnold Cleoma , Palla Mirkó , Hovis Jennifer , Chen Roger , Morozova Irina , Kalachikov Sergey , Russo James J. , Kasianowicz John J. , Davis Randy , Roever Stefan , Church George M. , Ju Jingyue
Published: April 2016

Significance

Efficient cost-effective single-molecule sequencing platforms will facilitate deciphering complete genome sequences, determining haplotypes, and identifying alternatively spliced mRNAs. We demonstrate a single-molecule nanopore-based sequencing by synthesis approach that accurately distinguishes four DNA bases by electronically detecting and differentiating four different polymer tags attached to the terminal phosphate of the nucleotides during their incorporation into a growing DNA strand in the polymerase reaction. With nanopore detection, the distinct polymer tags are much easier to differentiate than natural nucleotides. After tag release, growing DNA chains consist of natural nucleotides allowing long reads. Sequencing is realized on an electronic chip containing an array of independently addressable electrodes, each with a single polymerase–nanopore complex, potentially offering the high throughput required for precision medicine.
Ontogenetic Development of Otoliths in Alligator Gar
Authors: Long James M. , Snow Richard A.
Published: April 2016

The Alligator Gar Atractosteus spatula is a species of conservation concern throughout its range, and better definition of otoliths during early development would aid understanding its life history and ecology. We conducted X‐ray computed tomography scans, scanning electron microscopy, and light microscopy to examine the three pairs of otoliths and how they developed over time in relation to fish size and age. The sagittae are the largest, possessing distinct dorsal and ventral lobes covered with small otoconia concentrated in the sulcul region. The sagittae exhibited allometric growth, increasing more rapidly in the ventral lobe than in the dorsal. The asterisci were smaller and also exhibited small otoconia on their surface, but much less than the sagittae. The lapilli were oriented laterally, in contrast to the sagittae and asterisci, which were oriented vertically, with a hump on the dorsum and very large otoconia on the lateral surface that appeared to fuse into the main otolith as the fish grew. Based on size measurements and ring counts in all three pairs of otoliths from 101 known‐age Alligator Gar sampled weekly through 91 d after hatch, we developed regression models to examine otolith growth and predict age. All relationships were significant and highly explanatory, but the strongest relationships were between otolith and fish size (for measurements from sagittae) and for age predictions from the lapillus. Age prediction models all resulted in a slope near unity, indicating that ring deposition occurred approximately daily. The first ring in sagittae and lapilli corresponded to swim‐up, whereas the first ring formed in asterisci approximately 8 d after swim‐up. These results fill a gap in knowledge and can aid understanding of evolutionary processes as well as provide useful information for management and conservation.

Received September 2, 2015; accepted December 15, 2015 Published online April 19, 2016
Objective vs. Online Ratings: Are Low Correlations Unexpected and Does It Matter? A Commentary on de Langhe, Fernbach, and Lichtenstein
Authors: Winer Russell S. , Fader Peter S.
Published: April 2016

The major point of the article by de Langhe, Fernbach, and Lichtenstein (2016, in this issue) is that objective ratings produced by Consumer Reports and online consumer ratings have a low correlation. We argue in this comment that this result is unsurprising due to some unresolved statistical issues, heterogeneity in terms of consumers’ use of ratings and of the underlying consumer population and contexts, dynamics in the ratings system, and the complexity of modeling the generation of the consumer ratings. We also question why this low correlation matters given the fact that consumers use multiple sources of information, and more uncorrelated sources lead to more efficient decision making.
A 1966 Anesthetic Administered by Robert D. Dripps, M.D., Demonstrated His Experimental Style of Clinical Care
Authors: Johnstone Robert E. , Fleisher Lee A.
Published: April 2016

AbstractAbstract

Robert D. Dripps, M.D. (1911 to 1973), helped found academic anesthesiology. Newly reviewed teaching slides from the University of Pennsylvania (Philadelphia, Pennsylvania) contain six anesthesia records from 1965 to 1967 that involved Dripps. They illustrate the clinical philosophy he taught—to consider administration of each anesthetic a research study. Intense public criticism in 1967 for improper experimentation on patients during anesthesia changed his clinical and research philosophies and teaching.

An anesthesia record of Robert Dripps, M.D., from 1966 illustrates his philosophy that clinical anesthetics are research studies. This philosophy led in 1967 to criticisms over patient consents, which changed his teaching.
The Effect of Microphone Placement on Interaural Level Differences and Sound Localization Across the Horizontal Plane in Bilateral Cochlear Implant Users
Authors: Jones Heath G. , Kan Alan , Litovsky Ruth Y.
Published: April 2016

Objective:

This study examined the effect of microphone placement on the interaural level differences (ILDs) available to bilateral cochlear implant (BiCI) users, and the subsequent effects on horizontal-plane sound localization.

Design:

Virtual acoustic stimuli for sound localization testing were created individually for eight BiCI users by making acoustic transfer function measurements for microphones placed in the ear (ITE), behind the ear (BTE), and on the shoulders (SHD). The ILDs across source locations were calculated for each placement to analyze their effect on sound localization performance. Sound localization was tested using a repeated-measures, within-participant design for the three microphone placements.

Results:

The ITE microphone placement provided significantly larger ILDs compared to BTE and SHD placements, which correlated with overall localization errors. However, differences in localization errors across the microphone conditions were small.

Conclusions:

The BTE microphones worn by many BiCI users in everyday life do not capture the full range of acoustic ILDs available, and also reduce the change in cue magnitudes for sound sources across the horizontal plane. Acute testing with an ITE placement reduced sound localization errors along the horizontal plane compared to the other placements in some patients. Larger improvements may be observed if patients had more experience with the new ILD cues provided by an ITE placement.
Distal Femoral Replacement for Acute Distal Femoral Fractures in Elderly Patients
Authors: Bettin Clayton C. , Weinlein John C. , Toy Patrick C. , Heck Robert K.
Published: April 2016

Objectives:

To evaluate outcomes and complications using cemented modular distal femoral replacement in elderly patients with distal femoral fractures.

Design:

Retrospective chart review, case series.

Setting:

A Level 1 and Level 2 trauma center, both tertiary referral hospitals.

Patients/Participants:

Eighteen patients older than 60 years (average age 77 years) who had cemented distal femoral replacement for distal femoral fractures (comminuted, intraarticular, osteoporotic, arthritic) between 2005 and 2013. Patients with previous knee surgery were excluded.

Intervention:

Cemented modular distal femoral replacement.

Main Outcome Measures:

Implant status, complications, Knee Society Score, Musculoskeletal Tumor Society score, and Western Ontario and McMaster Osteoarthritis Index.

Results:

All patients were extremely or very satisfied with their outcomes. For patients with functional outcome data, Knee Society Score averaged 85.7 with a functional score of 35, Musculoskeletal Tumor Society score averaged 19.2, and Western Ontario and McMaster Osteoarthritis Index score averaged 23.1 at an average follow-up of 2.3 years. Range of motion was 1–99 degrees. Implant-related complications occurred in 2 patients (11%); one required revision to total femoral replacement because of periprosthetic fracture and the other had a deep infection that required exchange of the components. No patient had aseptic loosening or patellar maltracking. There were no perioperative deaths or late amputations.

Conclusions:

Cemented modular distal femoral replacement is a viable treatment option in elderly patients that permits immediate full weight-bearing, with most patients returning to preoperative functional status.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Treatment of Comminuted Talar Neck Fractures With Use of Minifragment Plating
Authors: Maceroli Michael A. , Wong Christopher , Sanders Roy W. , Ketz John P.
Published: April 2016

Objectives:

To assess the healing and radiographic outcomes of displaced and comminuted talar neck fractures treated with medial position screws augmented with lateral minifragment plate fixation.

Design:

Retrospective case series.

Setting:

Two level I trauma centers.

Patients:

The records of 26 patients with displaced and comminuted talar neck fractures who underwent open reduction and internal fixation with medial-sided position screws augmented with lateral minifragment plates.

Intervention:

Surgery consisted of medial and lateral approaches to the talus, fixation with a laterally placed minifragment plate, and screw construct augmenting sagittal-plane-oriented, medial-sided position screws.

Main Outcome Measurements:

The incidences of nonunion, malunion, avascular necrosis, post-traumatic arthritis, and symptomatic implants.

Results:

Nonunion occurred in 3/26 (11.5%) displaced and comminuted talar neck fractures. There were no instances of malunion. Avascular necrosis developed in 7/26 (27%) cases. Post-traumatic arthritis was the most common complication affecting 10/26 (38%) tali. The subtalar joint was most commonly affected. There were no instances of hardware removal due to symptomatic medial impingement.

Conclusions:

Lateral minifragment plate fixation augmenting medially placed sagittal plane position screws provides a length stable construct that prevents talar neck shortening and malunion. Medial position screws can help avoid secondary surgeries for removal of symptomatic implants due to medial impingement as is common with medially based minifragment plates. This fixation strategy should be considered in the setting of displaced and comminuted talar neck fractures.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Delayed Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Inhibition by Trametinib Attenuates Systemic Inflammatory Responses and Multiple Organ Injury in Murine Sepsis*
Authors: Smith Joshua A. , Mayeux Philip R. , Schnellmann Rick G.
Published: April 2016

Objective:

The mitogen-activated protein kinase/extracellular signal–regulated kinase signaling pathway is an essential component of innate immunity necessary for mediating proinflammatory responses in the setting of sepsis. We previously demonstrated that the mitogen-activated protein kinase 1/2 inhibitor trametinib prevents endotoxin-induced renal injury in mice. We therefore assessed efficacy of trametinib in a more clinically relevant experimental model of sepsis.

Design:

Controlled in vivo laboratory study.

Setting:

University animal research laboratory.

Subjects:

Male C57BL/6 mice.

Interventions:

Mice were subjected to cecal ligation and puncture to induce sepsis or underwent sham operation as controls. Six hours after cecal ligation and puncture, mice were randomized to four experimental groups as follows: 1) sham control; 2) sham control + trametinib (1 mg/kg, IP); 3) cecal ligation and puncture; and 4) cecal ligation and puncture + trametinib. All animals received buprenorphine (0.05 mg/kg, SC) and imipenem/cilastatin (14 mg/kg, SC) in 1.5 mL of warm saline (40 mL/kg) at the 6-hour time point. Mice were euthanized at 18 hours after induction of cecal ligation and puncture.

Measurements and Main Results:

Trametinib inhibition of mitogen-activated protein kinase/extracellular signal–regulated kinase signaling 6 hours after cecal ligation and puncture attenuated increases in circulating proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6, and granulocyte macrophage colony-stimulating factor) and hypothermia at 18 hours. Trametinib also attenuated multiple organ injury as determined by serum creatinine, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. At the organ level, trametinib completely restored peritubular capillary perfusion in the kidney. Restoration of microvascular perfusion was associated with reduced messenger RNA expression of well-characterized markers of proximal tubule injury. mitogen-activated protein kinase/extracellular signal–regulated kinase blockade attenuated cecal ligation and puncture-mediated up-regulation of cytokines (tumor necrosis factor-α, interleukin-1β) and restored interleukin-6 to control levels in the renal cortex, indicating the protective effects on the proximal tubule occur primarily through modulation of the proinflammatory response in sepsis.

Conclusions:

These data reveal that the mitogen-activated protein kinase/extracellular signal–regulated kinase inhibitor trametinib attenuates systemic inflammation and multiple organ damage in a clinically relevant model of sepsis. Because trametinib has been safely used in humans, we propose that this drug might represent a translatable approach to limit organ injury in septic patients.
Metabolite Profiles in Sepsis: Developing Prognostic Tools Based on the Type of Infection*
Authors: Neugebauer Sophie , Giamarellos-Bourboulis Evangelos J. , Pelekanou Aimilia , Marioli Androniki , Baziaka Fotini , Tsangaris Iraklis , Bauer Michael , Kiehntopf Michael
Published: April 2016

Objectives:

Currently used biomarkers insufficiently discriminate between patients with systemic inflammatory response syndrome of non-infectious origin and sepsis. The aim of this study was to identify surrogate markers that distinguish between systemic inflammatory response syndrome and sepsis as well as the underlying type of infection by targeted metabolomics.

Design:

Retrospective analysis.

Settings:

Six sites of the Hellenic Sepsis Study Group and at Jena University Hospital.

Patients:

A total of 406 patients were analyzed: 66 fulfilling criteria for diagnosis of systemic inflammatory response syndrome, 100 for community-acquired pneumonia, 112 for urinary tract infection, 83 for intra-abdominal infection and 45 for bloodstream infection. Patients were divided into test cohort (n = 268) and confirmation cohort (n = 138).

Interventions:

A total of 186 metabolites were determined by liquid chromatography tandem mass spectrometry.

Measurements and Main Results:

Serum concentrations of most acylcarnitines, glycerophospholipids and sphingolipids were altered in sepsis compared to systemic inflammatory response syndrome. A regression model combining the sphingolipid SM C22:3 and the glycerophospholipid lysoPCaC24:0 was discovered for sepsis diagnosis with a sensitivity of 84.1% and specificity of 85.7%. Furthermore, specific metabolites could be used for the discrimination of different types of infection. The glycerophospholipid lysoPCaC26:1 identified patients with community-acquired pneumonia in sepsis or severe sepsis/septic shock. Within severe sepsis/septic shock, patients with bloodstream infection could be discriminated by a decrease of acetylornithine. Changes of metabolites between sepsis and severe sepsis/septic shock also varied according to the underlying type of infection, showing that putrescine, lysoPCaC18:0 and SM C16:1 are associated with unfavorable outcome in community-acquired pneumonia, intra-abdominal infections and bloodstream infections, respectively.

Conclusions:

Using a metabolomics approach, single metabolites are identified that allow a good, albeit at about 14% false positive rate of sepsis diagnosis. Additionally, metabolites might be also useful for differentiation and prognosis according to the type of underlying infection. However, confirmation of the findings in ongoing studies is mandatory before they can be applied in the development of novel diagnostic tools for the management of sepsis.
Teaching Electronic Health Record Communication Skills
Authors: Palumbo Mary Val , Sandoval Marie , Hart Vicki , Drill Clarissa
Published: April 2016

This pilot study investigated nurse practitioner students' communication skills when utilizing the electronic health record during history taking. The nurse practitioner students (n = 16) were videotaped utilizing the electronic health record while taking health histories with standardized patients. The students were videotaped during two separate sessions during one semester. Two observers recorded the time spent (1) typing and talking, (2) typing only, and (3) looking at the computer without talking. Total history taking time, computer placement, and communication skills were also recorded. During the formative session, mean history taking time was 11.4 minutes, with 3.5 minutes engaged with the computer (30.6% of visit). During the evaluative session, mean history taking time was 12.4 minutes, with 2.95 minutes engaged with the computer (24% of visit). The percentage of time individuals spent changed over the two visits: typing and talking, −3.1% (P = .3); typing only, +12.8% (P = .038); and looking at the computer, −9.6% (P = .039). This study demonstrated that time spent engaged with the computer during a patient encounter does decrease with student practice and education. Therefore, students benefit from instruction on electronic health record-specific communication skills, and use of a simple mnemonic to reinforce this is suggested.
Assessment of the Need to Integrate Academic Electronic Medical Records Into the Undergraduate Clinical Practicum
Authors: Choi Mona , Park Joon Ho , Lee Hyeong Suk
Published: April 2016

As healthcare systems demand that nurses be competent in using electronic medical records for patient care, the integration of electronic medical records into nursing curricula has become necessary. The purpose of this study was to explore how students, new nurses, clinical instructors, and faculty perceive the integration of academic electronic medical records into the undergraduate clinical practicum. From January to February 2014, four focus group interviews with 18 participants were conducted based on purposive sampling. Content analysis was used on the unabridged transcripts to extract themes and develop meaningful categories. Three major themes and eight subthemes were revealed from the focus group interviews. The major themes were “electronic medical record as a learning tool for clinical practicum,” “essential functions of academic electronic medical records,” and “expected outcomes of academic electronic medical record.” Participants expected academic electronic medical records to enhance students’ nursing informatics competencies. The findings of this study can inform the process of developing academic electronic medical records for clinical practicum, which will then augment students’ informatics competencies.