bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial Instrument Evaluation And Performance Monitoring For SEMs
Authors: Chapman Steve
Published: March 2018

Microscopes in an electron microscope laboratory are built to be within specific tolerances in relation to resolution and magnification. The final specification from the manufacturer should include detail of magnification accuracy, drift rate, contamination rate and resolution, On delivery, the onus is on the installation engineer to confirm that the microscope meets specification. However, the final responsibility for microscope acceptance to specifications is the responsibility of the lab management.. Energy dispersive instrumentation is also specified as to specific resolution; and should also be confirmed on installation.

In some cases, those with final responsibility for equipment performance might not resolve with the manufacturer's representee, at installation, that the instrumentation meets all specifications.
Introduction to Automated Particle Analysis
Authors: Vander Wood TB
Published: March 2018

A microscopist is presented with a special problem when asked to characterize a population of particles. In order to adequately describe the sample, it may be necessary to examine hundreds or even thousands of individual particles, recording the size, shape, identity or other parameters of interest. To manually characterize a statistically significant fraction of the sample could require many hours of tedious work at the scope, followed by still more tedious hours of data reduction. What is needed is a technique to automate the repetitive parts of this process: the recognition and characterization of particles in the sample and the reduction of data and presentation of results. This technique is automated particle analysis.
FLASH in Cells
Authors: Carmichael Stephen W
Published: March 2018

The ability to attach fluorescent molecules onto proteins has allowed specific localization of these proteins within living cells. The traditional approach has been to purify the protein of interest then attach a fluorescent (or another useful tag) molecule in vitro, then somehow introduce the labeled protein into the cell. Whereas this and related techniques have been very useful, there are limitations because each of these three steps is often difficult. Wouldn't it be great if we had a “lock and key” system whereby a protein of interest could be modified to be a specific “lock” and a small tsggable molecule (the “key“) could diffuse into the cell and plug specifically into the lock? Albert Griffin, Stephen Adams, and Roger Tsien have developed such a system
Semiconductor X-Ray Detectors
Authors: Sareen Rob
Published: March 2018

Detection of characteristic x-rays is a fascinating and challenging subject. From its early beginnings with gas proportional counters it has evolved, like many branches of technology, into the use of a variety of semiconductors.

The lithium compensated silicon detector [Si(Li)] has been the predominant measuring tool over the last two decades, in the last five years, increasing numbers of high purity germanium detectors (HPG) have appeared and more recently a plethora of new materials and concepts are seeing a successful introduction. Among these newer materials are compound semiconductors like mercuric iodide, cadmium telluride, cadmium zinc telluride, gallium arsenide, lead iodide, indium phosphide and diamond. Among the new concepts are Bolometers, Transition Edge Detectors, Drift Detectors, PIN Diodes, CCD arrays and PN CCD arrays.
Down With Magnification: The Micron Marker Rules!
Authors: Geller Joe
Published: March 2018

With today's current wave of quality consciousness, our quality control people tell us we MUST calibrate our instruments using standards that are traceable to the national laboratories (NIST - National Institute of Standards and Technology in the U.S.,. NPL - National Physical Laboratory in the UK, and others). But, is it really magnification that should be calibrated?

While recently walking around the exhibit floor at the Microscopy & Micrcanalysis ‘98 Conference, I noticed the large SEM image display screens that now present our highly magnified specimens. Almost all vividly show a micron (using SI units this should be a “micrometer”) marker as well as the magnification. No doubt the accuracy is within the ± 3% that is commonly quoted by the manufacturers.
What is Project Micro?
Authors: Schooley Caroline
Published: March 2018

Project MICRO (Microscopy in Curriculum - Research Outreach) is the Microscopy Society of America's educational outreach program for middle schools. The idea began in 1993, but has taken a lot of time and effort to implement. MSA's early decision to collaborate with experienced science educators at the Lawrence Hall of Science (LHS) of the University of California at Berkeley was a wise one as their educational materials have a well-earned national reputation for excellence. The first phase of MICRO has just been completed, with the publication of a LHS teacher's manual that will support the MSA/MICRO effort to get microscopist-volunteers into classrooms nationwide.
A Simplified Method For Modifying TEM Copper Grids For Use With The Small Angle Cleavage Technique
Authors: Walck Scott D
Published: March 2018

The Small Angle Cleavage Technique (SACT) developed by John McCaffrey is an extremely easy and cost-effective technique for producing superior cross sectional TEM samples from semiconductor and other single crystal materials. In the original technique, a special jig is required to be made in order to make too cuts in a 2 x 0.5 mm slotted capper TEM grid to create vertical tabs to mount the cleaved samples. This jig is not commercially available and the actual cutting and bending of the grids require a significant amount of manual dexterity. (Fat fingered fellows, like myself, need not apply.) Early on, John proposed a design for a commercial grid that could easily be bent into the required shape with no cutting, but the electron microscopy supply houses passed on the idea. Until now, microscopists wanting to experiment with the technique had to invest in the cost of having one of these jigs made.
Imaging Based on Elasticity
Authors: Carmichael Stephen W
Published: March 2018

There are scores of microscopes that detect different properties of a specimen. Typically we image ‘visible” properties, but, for example, even the commonly-used atomic force microscope detects physical interactions rather than “visible” characteristics, Mostafa Fatemi and James Greenleaf have introduced the principle of imaging the elastic features of a specimen. This is done with sound waves, but we are not talking about just another acoustic microscope.

The method demonstrated by Fatemi and Greenleaf uses radiation force to image the acoustic response of a specimen to mechanical excitation. The mechanical excitation results from focusing two coaxial and confocal ultrasound beams of slightly different frequencies onto a selected region of the specimen.
Liquid Nitrogen Safety
Authors: Butterick Charles J
Published: March 2018

Recent Internet postings on the Microscopy listserver indicate paradoxical views on the personal protective equipment (PPE) necessary to handle liquid nitrogen (LN2) safely. Those views range from full protective gear to, somewhat facetiously, complete nudity. The crux of the paradox is that both extremes have points of validity.

The gist of preventing frostbite or cold injury to the skin is to prevent continuous contact with LN2. The physics of the Leidenfrost effect (LE) protects the skin from momentary contact or splashes of LN2. A layer of gas between the LN2 and the skin prevents significant heat transfer from the skin, stopping damage. The LE does not apply to inadvertent splashes of LN2 to the cornea. Alternatively, using protective equipment insulates the skin and prevents trapping of the cryogen by allowing the LN2 to run off.
An Inexpensive Frame Grabber for the Microscopist
Authors: Brown Richard S
Published: March 2018

Having shopped for an inexpensive but powerful digital imaging system for the last four years, I have finally found a device that will satisfy even the most frugal budget. The Snappy Video Snapshot by Play, Incl, is a 24-bit true color frame grabber that plugs into your PC printer port. After plugging the Snappy device into your printer port (Figure 1) and spending approximately six minutes loading the Snappy software provided, you can connect a color or black and white camera, VCR, or television set and capture your first digital image. Because the device plugs into a printer port, it is completely portable. A switch box is needed if you will be changing between digital image acquisition and printing tasks frequently.
Why Pressure Scales Cause So Much Confusion
Authors: Buonaquisti Anthony D
Published: March 2018

Pressure scales can be extremely confusing to new operators. This is not surprising. To my mind, there are three primary areas of confusion.

Firstly, the pressure of gas inside an instrument changes over many orders of magnitude during pumpdown. The change is about 9 orders of magnitude for a traditional Scanning Electron Microscope and about 13 orders of magnitude for an ultra-high vacuum instrument such as a Scanning Auger Microprobe.

To give an idea about the scale of change involved in vacuum, consider that the change in going from ambient pressure to that inside a typical ultra high vacuum system is like comparing one meter with the mean radius of the planet Pluto's orbit. The fact is that we don't often get to play with things on that scale. As a consequence, many of us have to keep reminding ourselves that 1 X 10-3 is one thousand times the value of 1 X 10-6 - not twice the value.
Breaking Old Rules
Authors: Carmichael Stephen W
Published: March 2018

It has been dogma for more than a hundred years that the light microscope cannot resolve structures that are much closer together than the length of the wavelength of light. This limit is on the order of a few hundred nanometers. This rule was “broken” by using the electron beam as the illumination source. The shorter wavelength of the electron beam gave correspondingly better resolution, down in the nanometer range. The rule was “broken” again when non-optical scanning probe microscopes (such as the scanning tunneling and atomic force microscopes) were developed. This technology gave us resolution in the sub-nanometer range, imaging individual atoms and molecules. However, scanning probe microscopes scan the surface of the specimen, excluding what's underneath from our view.
Exploring the Detection Limits of Chemical Microscopy
Authors: Milne C , Morris C , MacDonald HS
Published: March 2018

Chemical microscopy techniques were once a major source of information for scientists who wanted to detect the presence of metals in samples. Many microscopists used such techniques, which, when properly applied and appropriate checks for interferences made, could conclusively prove the presence of small quantities of specific metals.

The fact that the identification could be conclusive for trace amounts following relatively simple and cheap processes, and that visual evidence resulted, made these techniques quite robust, Chamot and Mason's lest “Handbook of Chemical Microscopy” is held to be a definitive resource for these techniques1. With the development of absorpilon and emission based spectral analytical techniques, the application of chemical microscopy techniques dwindled, perhaps because the skills needed by analysts using spectral techniques were to be more rapidly acquired than those involving microscopy,
Some Reflections On How Much Information la There On A Piece Of Film, On How Film Compares With CCD Cameras And What Features A Scanner Would Meed To Digitize TEM Negatives
Authors: Eades Alwyn
Published: March 2018

The world of electron microscopy is in a period of transition from acquiring images on film to acquiring images digitally, using CCD cameras, for example. It would be useful to knew how much information there is on a piece of film, in order to know how film compares with digital methods and to be able to make good judgements on the optimum moment to change from one technology to the other.

This is an attempt to use simple arguments to estimate just how much information there is in an image exposed on film in the transmission electron microscope, the main reason for addressing this issue Is that, while many people are affected by it there seems to be little agreement on the answer.
Uranium Is The Issue
Authors: Soeldner Al
Published: March 2018

Uranium compounds, especially uranyl acetate, have been widely and routinely used as transmission electron microscopy centrist stains for biological materials since 1958. Those of us who do TEM of biologicals use small quantities of uranyl acetate, nitrate, formate, sulfate and perhaps other uranium compounds almost daily and therefore keep inventories of these salts and their solutions.

In the 1980's growing concerns about medical and research wastes entering regional dump sites prompted state radiation officials in Oregon to begin tightening the regulations for monitoring and controlling all radioactive substances including the uranium compounds commonly used in processing biological specimens for TEM.
The Champagne Artifact in Negative Staining TEM
Authors: Bozzola John J
Published: March 2018

Negative staining is a simple yet extremely useful procedure for examining nanometer-sized specimens such as intact microorganisms (viruses and some bacteria), subcellular components, and even nonbidogical particulates. It is a well established procedure, with extensive literature in many disciplines (Hayat and Miller, 1990). Although numerous variations exist, the basic procedure involves placing the specimen and stain onto a grid containing a substrate - usually plastic with or without a carbon backing. The stains consist of salts of heavy metals such as tungsten, uranium, or molybdenum which surround and often penetrate the specimen. Afier drying into an amorphous, glass-like background, the stains provide contrast based upon differential thickness.
The Nematode Caenorhabditis elegans A Model Animal “Made for Microscopy”
Authors: Hall David H
Published: March 2018

The small unassuming nematode, Caenorhabditis elegans is only one millimeter long and lives in the soil munching on bacteria. While many nematode (roundworm) species are parasites with medical or agricultural importance, C. elegans seems to harm no one. Yet, this animal has attained a status in medical science that compares to more complex organisms such as the mouse or fruit fly in its utility for scientific discovery. It has been the subject of thousands of studies dealing with topics as diverse as nutrition, aging, and nervous system development. About 5000 scientists are now pursuing this single species in hundreds of laboratories worldwide. In 2002, the Nobel Prize in Medicine was awarded to three of the pioneers in establishing C. elegans as a “model organism“: Sydney Brenner, John Sulston, and H. Robert Horvitz. Why study worms?

Sydney Brenner first turned his attention to C. elegans in the 1960's. Working at the Medical Research Council in England, he was looking for a small animal with inexpensive tastes that could be easily cultured in the laboratory.
Lightning and the Electron Microscope
Authors: Rivaud Lydia
Published: March 2018

The chain of events that led to the invention of the electron microscope is an interesting story by itself. This chain has a common theme, namely electrons, and its first link is a natural phenomenon: lightning.

A flash of lightning generates a stream of electrons with a potential energy difference of 100 to 200 megavolts between clouds acting as electrodes, Benjamin Franklin envisioned this as a source of energy and tried to snatch electricity from the skies, but this proved to be too dangerous.

At the beginning of the century, lightning was a problem for electrical utilities because it produced surges that disrupted the steady flow of electricity along high tension lines. For this reason, in 1929 a high tension laboratory was founded in Germany with the sole aim of finding a way to test electrical transmission lines so as to make them capable of withstanding the lightning surges.
Modern Microscopy on The Light Side: An Instrumental Approach to Small Particle Identification
Authors: Gavrilovic John
Published: March 2018

Developments in space exploration, microelectronics, and other high-tech industries have promoted cleanroom technology and increased the need to identify particles sometimes too small to handle with the polarizing light microscope. Light microscopy has traditionally been the most commonly used technique for small particle identification and many microscopists are very proficient in identifying particles using a polarizing light microscope as the principal investigative tool. The polarizing light microscope, in the hands of a good microscopist, is an extremely efficient instrument for particles down to a few micrometers in size. However, in the size range below 5 pm, an instrumental approach to small particle identification is essential. The development of electron microbeam instruments in the early '60s and 70s introduced a new dimension to small particle identification. In these instruments, particles of 1 urn and smaller can be chemically identified when chemical characterization of particles is combined with cathodoluminesence and a relatively simple optical characterization in the instrument itself.
Photon Tunneling Microscopy
Authors: Guerra John M
Published: March 2018

The Photon Tunneling Microscope is used to provide high resolution (subnanometer vertical), quantifiable, real-time, 3-D (with continuously variable viewpoint) imaging and profilometry of homogenous dielectric samples, whether transparent or absorbing. A partial list of these includes: thin films (micraroughness. damage evaluation, step height) optical storage media (pit depth and shape measurement), magnetic media (microroughness, wear tracks), polymers (surface characterization), optical surfaces (microroughness, damage, polishing evaluation), diamond-turned optical surfaces (tool and machine characteristics from surface topography), binary optic surfaces, porous silicon structure, photographic grain analysis, replicas of metal surfaces, microlithography evaluation, and manufacturing web evaluation (film base, magnetic media base).
Theory of Mind and Humanoid Robots From a Lifespan Perspective
Authors: Marchetti Antonella , Manzi Federico , Itakura Shoji , Massaro Davide
Published: March 2018

Abstract. This review focuses on some relevant issues concerning the relationship between theory of mind (ToM) and humanoid robots. Humanoid robots are employed in different everyday-life contexts, so it seems relevant to question whether the relationships between human beings and humanoids can be characterized by a mode of interaction typical of the relationships between human beings, that is, the attribution of mental states. Because ToM development continuously undergoes changes from early childhood to late adulthood, we adopted a lifespan perspective. We analyzed contributions from the literature by organizing them around the partition between “mental states and actions” and “human-like features.” Finally, we considered how studying human–robot interaction, within a ToM context, can contribute to our understanding of the intersubjective nature of this interaction.
U.S. Scientists Safely Retrieved from Ice-Bound Antarctic Island
Authors: Showstack Randy
Published: March 2018

Argentineans came to the aid of stranded scientists.
Prebiotic attenuation of olanzapine-induced weight gain in rats: analysis of central and peripheral biomarkers and gut microbiota
Authors: Kao Amy Chia-Ching , Spitzer Sonia , Anthony Daniel C. , Lennox Belinda , Burnet Philip W. J.
Published: March 2018

Olanzapine is an effective antipsychotic drug but since it causes significant weight gain, it is not well tolerated by psychosis patients. The prebiotic, B-GOS®, attenuates metabolic dysfunction in obese subjects, and in rodents, alters central NMDA receptors and may affect serotonin receptors that are relevant in psychosis. We have determined whether B-GOS®influenced olanzapine-associated weight gain and central NMDA and serotonin receptors. Circulating acetate, IL-1β, IL-8 and TNFα, liver acetyl-CoA carboxylase (ACC), white adipose tissue (WAT) acetate receptor GPR43, and specific faecal bacteria genera were also measured to provide mechanistic information. Adult female Sprague-Dawley rats were administered a B-GOS®(0.5 g/kg/day) solution or water for 21 days, and received a single, daily, intraperitoneal injection of olanzapine or saline on days 8–21. The intake of B-GOS®significantly attenuated olanzapine-induced weight gain without altering frontal cortex 5-HT2AR blockade. Cortical GluN1 levels were elevated by olanzapine in the presence of B-GOS®. Plasma acetate concentrations increased following B-GOS®or olanzapine administration alone, but reduced when prebiotic and drug were administered in combination. This pattern was paralleled by hepatic ACC mRNA expression. The abundance of WAT GPR43 mRNA was reduced by olanzapine, only in the absence of B-GOS®. Co-administration of B-GOS®and olanzapine also elevated plasma TNFα, which is reported to influence lipid metabolism. Finally, B-GOS®elevated faecalBifidobacteriumspp. and reduced some bacteria in the Firmicutes phylum, whilst olanzapine treatment either alone or with B-GOS®, was without effect. These data suggest that inclusion of B-GOS®as an adjunct to olanzapine treatment in schizophrenia may prevent weight gain and have benefits on cognitive function in psychosis. The role of acetate in these effects requires further investigation.
Understanding and tailoring ligand interactions in the self-assembly of branched colloidal nanocrystals into planar superlattices
Authors: Castelli Andrea , de Graaf Joost , Marras Sergio , Brescia Rosaria , Goldoni Luca , Manna Liberato , Arciniegas Milena P.
Published: March 2018

Colloidal nanocrystals can self-assemble into highly ordered superlattices. Recent studies have focused on changing their morphology by tuning the nanocrystal interactions via ligand-based surface modification for simple particle shapes. Here we demonstrate that this principle is transferable to and even enriched in the case of a class of branched nanocrystals made of a CdSe core and eight CdS pods, so-called octapods. Through careful experimental analysis, we show that the octapods have a heterogeneous ligand distribution, resembling a cone wrapping the individual pods. This induces location-specific interactions that, combined with variation of the pod aspect ratio and ligands, lead to a wide range of planar superlattices assembled at an air–liquid interface. We capture these findings using a simple simulation model, which reveals the necessity of including ligand-based interactions to achieve these superlattices. Our work evidences the sensitivity that ligands offer for the self-assembly of branched nanocrystals, thus opening new routes for metamaterial creation.
Suppression of low-frequency charge noise in superconducting resonators by surface spin desorption
Authors: de Graaf S. E. , Faoro L. , Burnett J. , Adamyan A. A. , Tzalenchuk A. Ya. , Kubatkin S. E. , Lindström T. , Danilov A. V.
Published: March 2018

Noise and decoherence due to spurious two-level systems located at material interfaces are long-standing issues for solid-state quantum devices. Efforts to mitigate the effects of two-level systems have been hampered by a lack of knowledge about their chemical and physical nature. Here, by combining dielectric loss, frequency noise and on-chip electron spin resonance measurements in superconducting resonators, we demonstrate that desorption of surface spins is accompanied by an almost tenfold reduction in the charge-induced frequency noise in the resonators. These measurements provide experimental evidence that simultaneously reveals the chemical signatures of adsorbed magnetic moments and highlights their role in generating charge noise in solid-state quantum devices.
Inhibitory gain modulation of defense behaviors by zona incerta
Authors: Chou Xiao-lin , Wang Xiyue , Zhang Zheng-gang , Shen Li , Zingg Brian , Huang Junxiang , Zhong Wen , Mesik Lukas , Zhang Li I. , Tao Huizhong Whit
Published: March 2018

Zona incerta (ZI) is a functionally mysterious subthalamic nucleus containing mostly inhibitory neurons. Here, we discover that GABAergic neurons in the rostral sector of ZI (ZIr) directly innervate excitatory but not inhibitory neurons in the dorsolateral and ventrolateral compartments of periaqueductal gray (PAG), which can drive flight and freezing behaviors respectively. Optogenetic activation of ZIr neurons or their projections to PAG reduces both sound-induced innate flight response and conditioned freezing response, while optogenetic suppression of these neurons enhances these defensive behaviors, likely through a mechanism of gain modulation. ZIr activity progressively increases during extinction of conditioned freezing response, and suppressing ZIr activity impairs the expression of fear extinction. Furthermore, ZIr is innervated by the medial prefrontal cortex (mPFC), and silencing mPFC prevents the increase of ZIr activity during extinction and the expression of fear extinction. Together, our results suggest that ZIr is engaged in modulating defense behaviors.
The prevalence of chaotic dynamics in games with many players
Authors: Sanders James B. T. , Farmer J. Doyne , Galla Tobias
Published: March 2018

We study adaptive learning in a typical p-player game. The payoffs of the games are randomly generated and then held fixed. The strategies of the players evolve through time as the players learn. The trajectories in the strategy space display a range of qualitatively different behaviours, with attractors that include unique fixed points, multiple fixed points, limit cycles and chaos. In the limit where the game is complicated, in the sense that the players can take many possible actions, we use a generating-functional approach to establish the parameter range in which learning dynamics converge to a stable fixed point. The size of this region goes to zero as the number of players goes to infinity, suggesting that complex non-equilibrium behaviour, exemplified by chaos, is the norm for complicated games with many players.
Solutions for maximum coupling in multiferroic magnetoelectric composites by material design
Authors: Jayachandran K. P. , Guedes J. M. , Rodrigues H. C.
Published: March 2018

Electrical control of magnetization offers an extra degree of freedom in materials possessing both electric and magnetic dipole moments. A stochastic optimization combined with homogenization is applied for the solution for maximum magnetoelectric (ME) coupling coefficient α of a laminar ME composite with the thickness and orientation of ferroelectric phase as design variables. Simulated annealing with a generalized Monte Carlo scheme is used for optimization problem. Optimal microstructure with single and poly-crystalline configurations that enhances the overall α is identified. It is found that juxtaposing a preferentially oriented ferroelectric material with a ferromagnetic ferrite into a composite would result in manifold increase in magnetoelectric coupling. The interface shear strains are found to be richly contributing to the ME coupling. The preferential orientation of the ferroelectric phase in the optimal ME composite laminate is demonstrated using the optimal pole figure analyses.
Modeling Environmentally-Induced Motor Neuron Degeneration in Zebrafish
Authors: Morrice Jessica R. , Gregory-Evans Cheryl Y. , Shaw Christopher A.
Published: March 2018

Zebrafish have been used to investigate motor neuron degeneration, including as a model system to examine the pathogenesis of amyotrophic lateral sclerosis (ALS). The use of zebrafish for this purpose has some advantages over otherin vivomodel systems. In the current paper, we show that bisphenol A (BPA) exposure in zebrafish embryos results in motor neuron degeneration with affected motor function, reduced motor axon length and branching, reduced neuromuscular junction integrity, motor neuron cell death and the presence of activated microglia. In zebrafish, motor axon length is the conventional method for estimating motor neuron degeneration, yet this measurement has not been confirmed as a valid surrogate marker. We also show that reduced motor axon length as measured from the sagittal plane is correlated with increased motor neuron cell death. Our preliminary timeline studies suggest that axonopathy precedes motor cell death. This outcome may have implications for early phase treatments of motor neuron degeneration.
Effect of CCL5 expression in the recruitment of immune cells in triple negative breast cancer
Authors: Araujo Jhajaira M. , Gomez Andrea C. , Aguilar Alfredo , Salgado Roberto , Balko Justin M. , Bravo Leny , Doimi Franco , Bretel Denisse , Morante Zaida , Flores Claudio , Gomez Henry L. , Pinto Joseph A.
Published: March 2018

Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine’s expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells. With this aim we evaluated a retrospective cohort of 72 TNBC patients as well as publicly available datasets. TILs were correlated with residual tumor size after neoadjuvant chemotherapy (NAC) and CCL5 expression. In univariate analysis, TILs and CCL5 were both associated to the distant recurrence free survival; however, in a multivariate analysis, TILs was the only significant marker (HR = 0.336; 95%IC: 0.150–0.753; P = 0.008). CIBERSORT analysis suggested that a high CCL5 expression was associated with recruitment of CD8 T cells, CD4 activated T cells, NK activated cells and macrophages M1. The CD8A gene (encoding for CD8) was associated with an improved outcome in several public breast cancer datasets.
Climate change effect on wheat phenology depends on cultivar change
Authors: Rezaei Ehsan Eyshi , Siebert Stefan , Hüging Hubert , Ewert Frank
Published: March 2018

Changing crop phenology is considered an important bio-indicator of climate change, with the recent warming trend causing an advancement in crop phenology. Little is known about the contributions of changes in sowing dates and cultivars to long-term trends in crop phenology, particularly for winter crops such as winter wheat. Here, we analyze a long-term (1952–2013) dataset of phenological observations across western Germany and observations from a two-year field experiment to directly compare the phenologies of winter wheat cultivars released between 1950 and 2006. We found a 14–18% decline in the temperature sum required from emergence to flowering for the modern cultivars of winter wheat compared with the cultivars grown in the 1950s and 1960s. The trends in the flowering day obtained from a phenology model parameterized with the field observations showed that changes in the mean temperature and cultivar properties contributed similarly to the trends in the flowering day, whereas the effects of changes in the sowing day were negligible. We conclude that the single-cultivar concept commonly used in climate change impact assessments results in an overestimation of winter wheat sensitivity to increasing temperature, which suggests that studies on climate change effects should consider changes in cultivars.
Author Correction: CRISPR/Cas9-mediated genome editing efficiently creates specific mutations at multiple loci using one sgRNA in Brassica napus
Authors: Yang Hong , Wu Jia-Jing , Tang Ting , Liu Ke-De , Dai Cheng
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Expression of Carbonic Anhydrase III, a Nucleus Pulposus Phenotypic Marker, is Hypoxia-responsive and Confers Protection from Oxidative Stress-induced Cell Death
Authors: Silagi Elizabeth S. , Batista Philip , Shapiro Irving M. , Risbud Makarand V.
Published: March 2018

The integrity of the avascular nucleus pulposus (NP) phenotype plays a crucial role in the maintenance of intervertebral disc health. While advances have been made to define the molecular phenotype of healthy NP cells, the functional relevance of several of these markers remains unknown. In this study, we test the hypothesis that expression of Carbonic Anhydrase III (CAIII), a marker of the notochordal NP, is hypoxia-responsive and functions as a potent antioxidant without a significant contribution to pH homeostasis. NP, but not annulus fibrosus or end-plate cells, robustly expressed CAIII protein in skeletally mature animals. Although CAIII expression was hypoxia-inducible, we did not observe binding of HIF-1α to select hypoxia-responsive-elements on Car3 promoter using genomic chromatin-immunoprecipitation. Similarly, analysis of discs from NP-specific HIF-1α null mice suggested that CAIII expression was independent of HIF-1α. Noteworthy, silencing CAIII in NP cells had no effect on extracellular acidification rate, CO2 oxidation rate, or intracellular pH, but rather sensitized cells to oxidative stress-induced death mediated through caspase-3. Our data clearly suggests that CAIII serves as an important antioxidant critical in protecting NP cells against oxidative stress-induced injury.
Dual Role of CREB in The Regulation of VSMC Proliferation: Mode of Activation Determines Pro- or Anti-Mitogenic Function
Authors: Hudson Claire , Kimura Tomomi E. , Duggirala Aparna , Sala-Newby Graciela B. , Newby Andrew C. , Bond Mark
Published: March 2018

Vascular smooth muscle cell (VSMC) proliferation has been implicated in the development of restenosis after angioplasty, vein graft intimal thickening and atherogenesis. We investigated the mechanisms underlying positive and negative regulation of VSMC proliferation by the transcription factor cyclic AMP response element binding protein (CREB). Incubation with the cAMP elevating stimuli, adenosine, prostacyclin mimetics or low levels of forksolin activated CREB without changing CREB phosphorylation on serine-133 but induced nuclear translocation of the CREB co-factors CRTC-2 and CRTC-3. Overexpression of CRTC-2 or -3 significantly increased CREB activity and inhibited VSMC proliferation, whereas CRTC-2/3 silencing inhibited CREB activity and reversed the anti-mitogenic effects of adenosine A2B receptor agonists. By contrast, stimulation with serum or PDGFBB significantly increased CREB activity, dependent on increased CREB phosphorylation at serine-133 but not on CRTC-2/3 activation. CREB silencing significantly inhibited basal and PDGF induced proliferation. These data demonstrate that cAMP activation of CREB, which is CRTC2/3 dependent and serine-133 independent, is anti-mitogenic. Growth factor activation of CREB, which is serine-133-dependent and CRTC2/3 independent, is pro-mitogenic. Hence, CREB plays a dual role in the regulation of VSMC proliferation with the mode of activation determining its pro- or anti-mitogenic function.
Slow Electron Making More Efficient Radiation Emission
Authors: Wuu Dong-Sing , Ou Sin-Liang , Tien Ching-Ho
Published: March 2018

In conventional emitting devices, the mobility of electron is much higher than that of hole, which increases the non-recombination rate. To generate slow electrons, we demonstrate an electron retarding n-electrode (ERN) on the n-GaN layer of InGaN blue light emitting diode (LED), making more efficient radiation emission. Transparent conductive oxides are estimated to be more suitable for ERN materials. However, for ERN materials used in InGaN LEDs, three requirements should be satisfied, i.e., Ohmic contact to n-GaN, dilute magnetic doping, and good electrical conductivity. The pulsed-laser deposited cobalt-doped ZnO film prepared at 400 °C was chosen as the ERN. The electron retarding of 120-nm-thick ERN/n-GaN reached 19.9% compared to the n-GaN. The output powers (@350 mA) of LEDs with and without the ERN were 246.7 and 212.9 mW, while their wall-plug efficiencies were 18.2% and 15.1%, respectively. Moreover, owing to the efficient filling of electrons in the quantum wells by inserting the ERN, the bandgap of quantum wells was enlarged, inducing the blue-shift in the emission wavelength of LED. The slow electron generated from the ERN technique paves the way to solve the problem of large difference between electron and hole velocities and improve the optoelectronic performance of emitting devices.
Impact of Different Visual Field Testing Paradigms on Sample Size Requirements for Glaucoma Clinical Trials
Authors: Wu Zhichao , Medeiros Felipe A.
Published: March 2018

Visual field testing is an important endpoint in glaucoma clinical trials, and the testing paradigm used can have a significant impact on the sample size requirements. To investigate this, this study included 353 eyes of 247 glaucoma patients seen over a 3-year period to extract real-world visual field rates of change and variability estimates to provide sample size estimates from computer simulations. The clinical trial scenario assumed that a new treatment was added to one of two groups that were both under routine clinical care, with various treatment effects examined. Three different visual field testing paradigms were evaluated: a) evenly spaced testing, b) United Kingdom Glaucoma Treatment Study (UKGTS) follow-up scheme, which adds clustered tests at the beginning and end of follow-up in addition to evenly spaced testing, and c) clustered testing paradigm, with clusters of tests at the beginning and end of the trial period and two intermediary visits. The sample size requirements were reduced by 17–19% and 39–40% using the UKGTS and clustered testing paradigms, respectively, when compared to the evenly spaced approach. These findings highlight how the clustered testing paradigm can substantially reduce sample size requirements and improve the feasibility of future glaucoma clinical trials.
Two-phase flow visualization under reservoir conditions for highly heterogeneous conglomerate rock: A core-scale study for geologic carbon storage
Authors: Kim Kue-Young , Oh Junho , Han Weon Shik , Park Kwon Gyu , Shinn Young Jae , Park Eungyu
Published: March 2018

Geologic storage of carbon dioxide (CO2) is considered a viable strategy for significantly reducing anthropogenic CO2 emissions into the atmosphere; however, understanding the flow mechanisms in various geological formations is essential for safe storage using this technique. This study presents, for the first time, a two-phase (CO2 and brine) flow visualization under reservoir conditions (10 MPa, 50 °C) for a highly heterogeneous conglomerate core obtained from a real CO2 storage site. Rock heterogeneity and the porosity variation characteristics were evaluated using X-ray computed tomography (CT). Multiphase flow tests with an in-situ imaging technology revealed three distinct CO2 saturation distributions (from homogeneous to non-uniform) dependent on compositional complexity. Dense discontinuity networks within clasts provided well-connected pathways for CO2 flow, potentially helping to reduce overpressure. Two flow tests, one under capillary-dominated conditions and the other in a transition regime between the capillary and viscous limits, indicated that greater injection rates (potential causes of reservoir overpressure) could be significantly reduced without substantially altering the total stored CO2 mass. Finally, the capillary storage capacity of the reservoir was calculated. Capacity ranged between 0.5 and 4.5%, depending on the initial CO2 saturation.
Identification and Characterization of Fusarium proliferatum, a New Species of Fungi that Cause Fungal Keratitis
Authors: Sun Shengtao , Lui Qixue , Han Lei , Ma Qiufei , He Siyu , Li Xiaohua , Zhang Hongmin , Zhang Junjie , Liu Xiaohui , Wang Liya
Published: March 2018

Fusarium proliferatum (F. proliferatum) is known as a pathogen of corn and other crops, but its role in fungal keratitis has not been well investigated. Among 877 Fusarium isolates, we identified 155 (17.7%) stains as F. proliferatum according to their morphological features and partial DNA sequencing of translation elongation factor-$$1\alpha $$
1

α

(EF-$$1\alpha $$
1

α

) in this study. In vitro antifungal susceptibility tests showed that the F. proliferatum strains were sensitive to natamycin and vorionazole but resistant to amphotericin B, fluconazol, ketoconazole and itaconazole. Most of the F. proliferatum-positive keratitis patients (44/155,28.4%) were aged 51–60 years old. The main cause of infection was injury by a plant (51/155, 32.9%). A combination of 1% amphotericin B and 3% ketoconazole cured 45.2% (14/31) and a combination of 0.5% natamycin and 0.5% voriconazole cured 59.1% (13/22) of F. proliferatum-positive patients. The date suggests that F. proliferatum identified through EF-1ɑ DNA sequencing is an important new species that causes fungal keratitis. Based on antifungal susceptibility, treatment with a combination of 0.5% natamycin and 0.5% voriconazole improves the therapeutic efficacy in F. prolifertum-positive patients.
Physical characterization and in vivo organ distribution of coated iron oxide nanoparticles
Authors: Sharma Anirudh , Cornejo Christine , Mihalic Jana , Geyh Alison , Bordelon David E. , Korangath Preethi , Westphal Fritz , Gruettner Cordula , Ivkov Robert
Published: March 2018

Citrate-stabilized iron oxide magnetic nanoparticles (MNPs) were coated with one of carboxymethyl dextran (CM-dextran), polyethylene glycol-polyethylene imine (PEG-PEI), methoxy-PEG-phosphate+rutin, or dextran. They were characterized for size, zeta potential, hysteresis heating in an alternating magnetic field, dynamic magnetic susceptibility, and examined for their distribution in mouse organs following intravenous delivery. Except for PEG-PEI-coated nanoparticles, all coated nanoparticles had a negative zeta potential at physiological pH. Nanoparticle sizing by dynamic light scattering revealed an increased nanoparticle hydrodynamic diameter upon coating. Magnetic hysteresis heating changed little with coating; however, the larger particles demonstrated significant shifts of the peak of complex magnetic susceptibility to lower frequency. 48 hours following intravenous injection of nanoparticles, mice were sacrificed and tissues were collected to measure iron concentration. Iron deposition from nanoparticles possessing a negative surface potential was observed to have highest accumulation in livers and spleens. In contrast, iron deposition from positively charged PEG-PEI-coated nanoparticles was observed to have highest concentration in lungs. These preliminary results suggest a complex interplay between nanoparticle size and charge determines organ distribution of systemically-delivered iron oxide magnetic nanoparticles.
SDH-deficient renal cell carcinoma associated with biallelic mutation in succinate dehydrogenase A: comprehensive genetic profiling and its relation to therapy response
Authors: McEvoy Christopher R. , Koe Lisa , Choong David Y. , Leong Huei San , Xu Huiling , Karikios Deme , Plew Jeffrey D. , Prall Owen W. , Fellowes Andrew P. , Fox Stephen B.
Published: March 2018

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare RCC subtype that is caused by biallelic mutation of one of the four subunits of the SDH complex (SDHA, B, C, and D) and results in inactivation of the SDH enzyme. Here we describe a case of genetically characterized SDH-deficient RCC caused by biallelic (germline plus somatic) SDHA mutations. SDHA pathogenic variants were detected using comprehensive genomic profiling and SDH absence was subsequently confirmed by immunohistochemistry. Very little is known regarding the genomic context of SDH-deficient RCC. Interestingly we found genomic amplifications commonly observed in RCC but there was an absence of additional variants in common cancer driver genes. Prior to genetic testing a PD-1 inhibitor treatment was administered. However, following the genetic results a succession of tyrosine kinase inhibitors were administered as targeted treatment options and we highlight how the genetic results provide a rationale for their effectiveness. We also describe how the genetic results benefited the patient by empowering him to adopt dietary and lifestyle changes in accordance with knowledge of the mechanisms of SDH-related tumorigenesis.
Prescribable mHealth apps identified from an overview of systematic reviews
Authors: Byambasuren Oyungerel , Sanders Sharon , Beller Elaine , Glasziou Paul
Published: March 2018

Mobile health apps aimed towards patients are an emerging field of mHealth. Their potential for improving self-management of chronic conditions is significant. Here, we propose a concept of “prescribable” mHealth apps, defined as apps that are currently available, proven effective, and preferably stand-alone, i.e., that do not require dedicated central servers and continuous monitoring by medical professionals. Our objectives were to conduct an overview of systematic reviews to identify such apps, assess the evidence of their effectiveness, and to determine the gaps and limitations in mHealth app research. We searched four databases from 2008 onwards and the Journal of Medical Internet Research for systematic reviews of randomized controlled trials (RCTs) of stand-alone health apps. We identified 6 systematic reviews including 23 RCTs evaluating 22 available apps that mostly addressed diabetes, mental health and obesity. Most trials were pilots with small sample size and of short duration. Risk of bias of the included reviews and trials was high. Eleven of the 23 trials showed a meaningful effect on health or surrogate outcomes attributable to apps. In conclusion, we identified only a small number of currently available stand-alone apps that have been evaluated in RCTs. The overall low quality of the evidence of effectiveness greatly limits the prescribability of health apps. mHealth apps need to be evaluated by more robust RCTs that report between-group differences before becoming prescribable. Systematic reviews should incorporate sensitivity analysis of trials with high risk of bias to better summarize the evidence, and should adhere to the relevant reporting guideline.
Improved formation of electrically-deposited enzyme-embedded chitosan coatings onto carbon fiber microelectrodes
Authors: Donahue Caitlin E. T. , Miller David R. , Beger Tyler W. , Johann Timothy W. , Keithley Richard B.
Published: March 2018

The addition of CAM into coating solutions provides for more robust enzyme modified carbon fiber microelectrodes.
Electrokinetic desalination of brackish water and associated challenges in the water and energy nexus
Authors: Pan Shu-Yuan , Snyder Seth W. , Lin Yupo J. , Chiang Pen-Chi
Published: March 2018

This article presents the challenges and opportunities of electrokinetic desalination for brackish water and its recent development and prospective.
Degradation of major allergens and allergenicity reduction of soybean meal through solid-state fermentation with microorganisms
Authors: Yang Anshu , Zuo LingLing , Cheng Youfei , Wu Zhihua , Li Xin , Tong Ping , Chen Hongbing
Published: March 2018

The effect of fermentation on allergenicity of soybean meal was assessed both in vitro and in vivo.
para-Aminosalicylic acid in the treatment of manganese toxicity. Complexation of Mn2+ with 4-amino-2-hydroxybenzoic acid and its N-acetylated metabolite
Authors: Lachowicz Joanna Izabela , Nurchi Valeria Marina , Crisponi Guido , Cappai Ilaria , Cappai Rosita , Busato Matteo , Melchior Andrea , Tolazzi Marilena , Peana Massimiliano , Garribba Eugenio , Zoroddu Maria Antonietta , Coni Pierpaolo , Pichiri Giuseppina , Aaseth Jan
Published: March 2018

Manganese excess can induce in humans neurological disorders known as manganism.