bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral Simulation With Nist-Nih Desktop Spectrum Analyzer (Dtsa): A Critical Tool for Estimating Limits of Detection
Authors: Newbury Dale E
Published: July 2020

X-ray microanalysis often must estimate limits of detection for specific specimen compositions to optimize analytical strategy and to adequately describe results. Several approaches are available which make use of experimentally measured spectra to obtain peak and local background intensities. One of the oldest and simplest involves the use of pure element spectra. However, such an estimate procedure does not take into account the matrix effects, particularly absorption, which can be quite important in defining limits of detection in a particular multi-element composition. If a microhomogeneous standard is available with the appropriate matrix that also contains the other constituent(s) of interest at a known level, ideally at a minor constituent level (0.01 to 0.1 mass fraction), then the limit of detection, CDL, can be estimated through the use of the expression:
Mouse Sperm Association During Epididymal Transit
Authors: Monclus M , Burgos M H , Fornés MW
Published: July 2020

Head-to-head sperm association was described in some species as a normal phenomenon during epididyma transit (Phillips and Bedford, 1987). Recently, a new sperm head association (SHA) was characterized in the rat (Fornés & Burgos 1990; 1994).

At this moment, the study of SHA was extended to mouse sperm. SHA is a type of cell-cell interaction clearly observed when an a drop of epididymal fluid, obtained by a puncture of epididymal duct, is placed in a culture medium (HMB media: Modified Ringers medium).

This preparation can be observed under contrast phase microscope (optiphot-2, Nikkon) with or without fixative (2% paraformaldehyde and 2% glutaraldehyde in 0.01 M PBS buffer, pH 7,2). The mass of spermatozoa begin to move but not as a single sperm. They move as a clump of sperm and without fixative the sperm motility alone disaggregate the SHA.
Development of Ion Channel Analysor Employing Pores of Subunit C of ATP Synthase
Authors: McGeoch J E M
Published: July 2020

Many pathological states are related to aberrant functioning of ion channels. Cures for these conditions involve the design of chemicals that will interact with the ion channels or a channel regulator to return their function to the normal level. A notable example of a pathological state associated with ion channel malfunction is the abnormal conductance of inward rectifying potassium channels associated with irregular heart beat. The development of drugs targeting ion channels requires efficient screening of thousands of potential channel ligands. Classically the function of ion channels are assayed by patch clamping which is a fairly elaborate technique and not efficient from the point of screening thousands of ligands. Here is described the development of a compact sensor device where an ion channel is made to function in a lipid bilayer in 50nm holes in silicon or polymer hardware.
Key Elements of Biomedical Polymer-based Opto Electro Mechanical Systems for a New Generation of Microscope and Microanalysis Biochips
Authors: Lee Luke P
Published: July 2020

In this talk, the development of key elements for BioPOEMS (Biomedical Polymer-based Opto Electro Mechanical Systems) will be discussed as a new generation of microscopic and microanalysis biochips. Current BioMEMS (Biomedical Microelectromechanical Systems) technology is in its infancy stage. Just as silicon-based microelectronics technology went through many stages since the late ‘60's, BioMEMS technology will have to overcome many obstacles before becoming a mature industry. The IC industry was made possible by the development of fabrication processes, integration technologies, and design tools. Similarly, the field of BioMEMS must prepare new components with biomaterials and tools for the development of new microsystems, enabling the combination of biological sensors and actuators with the rapidly growing capabilities of bioinformatics.

Polymers are not only used in macroscopic systems, but are now increasingly finding use in the microscopic realm such as microfluidic devices. Among the many different classes of polymers, it is the fluoropolymers that provide the most unique material characteristics.
Bioactive Ceramic And Model Surfaces Adsorb Ligands and Factors That Stimulate Cellular Function
Authors: Composto Russell J , Ducheyne Paul , Effah Kaufman Elsie
Published: July 2020

Microscopy and microanalysis techniques have played an important role in our understanding of how biomaterials interact with their environment. In first part of this study, we will focus on the behavior of bioactive glass, whereas in the second a model surface will be investigated. Upon implantation bioactive glass undergoes a series of reactions that leads to the formation of a calcium phosphate-rich layer. Most in vitro studies of the changes that occur on the surface of bioactive glass have employed the use of buffer solutions with compositions reflecting the ionic composition of interstitial fluid. Although these studies have documented the physical and chemical changes associated with bioactive glass immersed in aqueous media, they do not reveal the effect of serum proteins and cells which are present at the implantation site. In the present study, we document, using atomic force microscopy (AFM) and Rutherford backscattering spectrometry (RBS), significant differences in reaction layer composition, thickness, morphology and kinetics of formation arising from the presence of serum proteins.
Protein Characterization by Low-Angle, Rotary-Replication Electron Microscopy
Authors: Samuelsson S
Published: July 2020

There are several established strategies for visualizing proteins by transmission electron microscopy (TEM). These include negative staining, cryo-TEM, glycerol-spray/rotary-replication, mica-flake/freeze-fracture. Of these, low-angle, rotary-replication of proteins dried out of glycerol has proven to be a reliable and accurate method for studying surface topologies of macromolecular assemblies and particles. We have characterized many proteins, both chimeras and wild type; methods, caveats and the surface structure of a couple examples are described here.

The technique of using heavy metals to cast replicas of proteins and particles has been around for decades (metal replication of proteins was first described in 1956) and continues to provide an excellent method for evaluating protein topology. The success of this method is based on the physical properties of protein in contact with freshly cleaved mica, glycerol and atomic platinum. Mica is easily split and atomically flat making it an excellent substrate.
High-Resolution Three-Dimensional Microscopy System
Authors: Kerschmann Russell
Published: July 2020

The demand for new methods of three-dimensional imaging of biological systems grown significantly over the past decades. Systems for volumetric analysis of macroscopic structures have been addressed through the introduction of modem CT/MRI systems; and on the cellular level, confocal microscopy has evolved into a powerful research tool for the examination of both biological tissues and manufactured goods. However, there persists a need for the visualization and analysis of types of material in the cubic millimeter size range, a class of materials which has not been adequately addressed by either radiological or optical sectioning techniques. These materials include research and clinical biological tissue samples, as well as many types of manufactured materials such as textiles and paper.

The main method currently in use for the examination of such materials is standard histopathology. Whether one is concerned with the diagnosis of a human tumor or the arrangement of cells in the leaf of a plant,
Ultrasound Biomicroscopy of Cancer Therapy Effects: Correlation between Light and Electron Microscopy, and a New Non-Invasive Ultrasound Imaging Method for Detecting Apoptosis
Authors: Czarnota GJ , Kolios MC , Heng YM , Devaraj K , Tam C , Tan L , Ottensmeyer FP , Hunt JW , Sherar MD
Published: July 2020

We have discovered that high-frequency ultrasound imaging, or ultrasound biomicroscopy, can be used to detect apoptosis in a number of experimental systems. We have shown that such detection with 30-40 MHz ultrasound is possible using cells in an in vitro system (AML-3 leukemia cells) made to undergo apoptosis in response to treatment with a variety of cancer killing chemotherapeutic drugs. We have shown that ultrasound biomicroscopy can also detect programmed cell death in tissues made to undergo apoptosis in response to photodynamic therapy, currently an experimental cancer treating regimen. Lastly, we have shown that this ultrasound imaging approach works in vivo, using living animals where apoptosis has been induced similarly using photodynamic therapy. Specifically, apoptotic cells and regions of apoptosis in tissues exhibit up to a 36-fold increase in ultrasound backscatter intensity permitting this type of cell death to be readily discriminated from surrounding viable tissue.
The Optimum CS Condition for High-Resolution Transmission Electron Microscopy
Authors: O'Keefe Michael A
Published: July 2020

High-resolution electron microscopists are familiar with the concept of an “optimum defocus” for obtaining highresolution transmission electron microscope images. Scherzer recognized that it is possible to balance the phase changes imposed by the spherical aberration of the TEM objective lens by adjustments to lens defocus. Selection of this focus condition maximizes the same-phase transfer of structural information carried by electrons scattered from the specimen. The upper limit of spatial frequencies transferred with the same phase change determines the resolution of the microscope. The resolution and “optimum defocus” depend only on the electron wavelength of the microscope and the spherical aberration coefficient, CS, of its objective lens. Reduction of Cs is the major route to improved resolution.

With the advent of electron-optical systems able to generate negative spherical aberration (usually called “Cs correctors“), it has now become feasible to zero-out objective lens Cs in the high-resolution transmission electron microscope.
Creep Mechanism Determination on Dispersed Phase Amalgams using High Resolution Electron Microscopy (HRTEM) Observation
Authors: Amado Quintero H , Ramon A Caballero A , G. O Hilders
Published: July 2020

Creep mechanism determination on dental amalgams has been a subject of interest in recent research works. Most of these studies conclude that the creep behavior can be explained by the well-known expression: ɛ = A σnexp (-Q/RT). Reported values for n (potential coefficient of stress) are in the order of 3 for phase dispersed dental amalgams and 2 for conventional amalgams. It suggests a grain sliding creep mechanism for conventional amalgams and a climb dislocation mechanism for creep in phase dispersed amalgams due to interactions with the dispersed CuxSny particles typical of this kind of amalgam(l). For both cases, the creep process occurs inside the γ (Ag2Hg3) phase matrix of low melting point (310 °K) which is slightly higher than typical mouth temperatures of about 400 °K (37 °C). In this work some microestructural evidences are obtained to support the behavior described above by using High Resolution Transmission Electron Microscopy (HRTEM).
HREM Analysis of ∑3 ﹛112﹜ Tilt Grain Boundaries in Au Bicrystals Observed in < 111 > Projection
Authors: Hetherington CJD , Dahmen U
Published: July 2020

Grain boundaries in fee metals with low stacking fault energy are known to undergo extended relaxations that can at times lead to a thin layer of a different structure. In Cu, for example, it has been found that ∑3﹛ 112﹜ boundaries relax into a 9R phase [1]. In this work, we have used high resolution electron microscopy to investigate the atomic structure of ∑3 grain boundaries in mazed bicrystal films of Au. Using ﹛111﹜ Ge surfaces as a template, Au bicrystals can be grown in two orientation variants, related to each other by a 60° rotation about the surface normal. As described previously, such films have a strong tendency to facet onto the coherent twin plane parallel to the substrate [2], also known as “double positioning” [3]. If films are made very thin, the likelihood for such in-plane boundaries to lie in the foil decreases, and it becomes possible to observe the atomic structure of edge-on interfaces along <111>.
A TEM Study of Cr Based Contacts to (0001) 6H-SiC
Authors: Liu R-J , Kim M J , Carpenter R W , Porter L M , Scheunemann L P , Davis R F
Published: July 2020

6H-SiC is a wide band-gap semiconductor. In recent years, a variety of high-power, -temperature, -speed and optoelectronic devices have been produced in SiC films. The search for metals which can form thermally stable, uniform ohmic contacts with SiC with low resistivity is still ongoing. In this study, Cr and CrBx (1<x<2) films were deposited by electron beam evaporation onto p-type, vicinal Si-terminated (0001) 6H-SiC surface. Both contacts exhibited rectifying behavior in the as-deposited condition. Ohmic-like behavior was observed for Cr/SiC system after annealing at 1000 °C for 240 seconds in a rapid thermal anneal furnace in an Ar atmosphere. It was also reported that ohmic behavior was observed for CrB2 /SiC system after annealing at 1100 °C for 2 minutes at a pressure of 5x10“7 Torr.2 The microstructure and chemistry of these two contact systems in both as-deposited and annealed conditions were investigated by transmission electron microscopy (TEM).
Lateral Epitaxial Overgrowth of GaSb on GaAs and GaSb Substrates
Authors: Inoki C K , Harris D L , Kuan T S , Yi S S , Hansen D M , Kuech T F
Published: July 2020

Lateral epitaxial overgrowth (LEO) technique has recently been used to improve the quality of semiconductor layers grown on a substrate. Previous studies with GaN grown on sapphire showed a significant reduction in dislocation density in LEO layers. The LEO technique uses a thin mask layer to achieve selective epitaxy, allowing vertical and lateral growth through patterned windows. Reduced defect density is expected in laterally grown materials, since no lattice mismatch is involved. In practice, however, the thermal and mismatch stresses often cause dislocations to propagate laterally during LEO, and excessive dislocation activities induced by the stresses also tilt the LEO regions. GaSb-based semiconductors, which are of interest for infrared optoelectronic device applications, have much larger (∼8%) lattice constants than the commonly used GaAs substrate. The LEO technique is therefore of particular interest for its potential to significantly reduce the defect density in GaSb films grown on GaAs substrates.
A Copper Leadframe Oxidation Investigation by Electron Energy-Loss Spectroscopy
Authors: Rucki A , Lee C
Published: July 2020

Copper alloys are widely used as a leadframe (chip carrier) material in plastic packaged semiconductor devices. The oxidation of Cu leadframes during the assembly process can result in poor adhesion between the moulding compound and the die-pad. This often leads to interfacial delamination and contributes to popcorn cracking during the component-board attachment process. The main cause of poor adhesion has been attributed to the weak Cu oxide(s) layer on the leadframe surface. Studies have shown that the moulding compound/leadframe adhesion decreases with increasing oxide thickness.

The aim of this investigation is to give a detailed analysis of the phase formation of a CuNiSi alloy during oxidation and to identify the locus of failure for the interfacial delamination. The Cu leadframes were oxidized in an air oven at 240° C for up to 200 min exposures before encapsulation. A scanning acoustic microscope was used to locate delamination regions along the moulding compound/leadframe interface.
Interfacial Structure and Defects in GaN/AlGaN Heterojunction Epitaxially Grown on LiGa02 Substrate by Molecular Beam Epitaxy
Authors: Dai Z R , Kang Sangbeom , Doolittle W Alan , Wang Z L , Brown April S
Published: July 2020

The performance of III-Nitride based Light Emitting Diodes (LEDs), LASERs, GaN/AlGaN MODFETs (Modulation-doped Field Effect Transistors) and HEMTs (High Electron Mobility Transistors) have been improved dramatically over the past few years [1,2], despite the relatively poor material quality of GaN, as compared to GaAs, for example. The intrinsic properties of the materials system make it extremely well suited to both optoelectronic and microwave power transistor applications. Typically, GaN is grown on substrates such as GaAs, Al2O3 (sapphire) or SiC with large lattice mismatch. This has usually resulted in an extremely high defect density in the GaN layer. The growth of GaN on lithium gallate LiGaO2 (LGO) affords many advantages compared to all other available substrates. LGO offers the smallest average lattice mismatch of any available substrate for the Ill-nitrides. This facilitates the growth of high quality GaN directly on Lithium Gallate without the need for a defective buffer to decouple the strain associated with the large lattice mismatch of other substrates [3].
SIO2-Supported Metallocene Catalysts for Propene Polymerization: Electron Microscopic Studies and Tomographical Reconstructions of Polymer Growth
Authors: Steinmetz B , Weimann B , Fink G , Tesche B
Published: July 2020

Summary:

The polypropylene growth process on silica supported metallocene catalysts was examined by electron microscopy and kinetic investigations. It was possible to identify different polymerization stages with different characteristic kinetic data in the slurry phase which led to the development of a refined polymer growth model [1-2]. Tomographical reconstruction of shortly polymerized catalyst particles obtained by electron micrographs of serial microtome sections turned out to be a useful tool to achieve a better understanding of the heterogeneous polymerization process and the influence of the support structure on polymer growth.

1. Introduction

Single-site metallocene catalysts produce extremely uniform polymers with molecular weight distributions (MWD) of 2 or less and very narrow compositional distributions in comparison to conventional Ziegler-catalysts. For industrial gas phase or bulk polymerization in existing plants (drop-in-technology) it is necessary to fix the catalytically active components on a heterogeneous support.
Investigation of Polymerized Phospholipid Monolayer Thin Film Structures by Energy- Filtered Transmission Electron Diffraction
Authors: Stevens M , Longo ML , Spence J
Published: July 2020

The photopolymerizable, conductive, and chromatic behavior of diacetylene containing films has lead to a number of investigations into possible applications. For example, when diacetylene films were investigated as photoresists it was demonstrated that 50 nm resolution could be achieved by electron lithography. Polymerized diacetylene layers display enviromentally dependent chromatic transitions and thus have been studied for sensor applications. Single crystals of polymerized diacetylene films belong to a class of one-dimensional semiconductors. Thus, conductive materials have been constructed using extended multilayers and monolayer of such polymers. For example, the conductive and self-supportive nature of films containing polymerized diacetylene makes them ideal for imaging large embedded molecules. The purpose of this article is to report the details of preparation of ultrathin Langmuir-Blodgett deposited phospholipid films containing polymerized diacetylene groups and analysis of the energy filtered electron diffraction spot intensities. This work shows promise that useful structural information of such systems can be obtained by TEM where owing to their finite grain size and radiation sensitivity,
Experimental Method to Measure the Detective Quantum Efficiency of a Charge-Coupled Device Camera for Electron Microscopy.
Authors: Favia P , Cooper S , Mooney P E
Published: July 2020

The Detective Quantum Efficiency (DQE) is one of the best parameters to characterize the performance of a charge-coupled device (CCD) camera when electron dose is an issue. This can be when there are beam source brightness limitations as in high-resolution applications or when specimen dose must be limited. For single parameter detectors such as a backscatter detector in a SEM, the DQE is defined as the square of the signal-to noise ratio (SNR) at the output divided by the square of the signal-to-noise ratio at the input:

where S, N, and n are respectively the signal, the noise and the electron dose. This definition is not valid to describe the performance of a multi-component device as an imaging detector. In fact a CCD camera is composed of many elements or pixels.
Image Management for a Multi-Instrument, Multi-Platform Teaching Facility and Implications for Outreach Programs
Authors: Murphy Judy A
Published: July 2020

In the digital age, the management of images can be very time consuming when there are several digital image acquisition systems involved. For simplicity in this article, databases have been categorized as active or passive. Active databases are those where the categorization of the image is done during the image acquisition. Passive databases by this definition use saved images that are then categorized after image acquisition. The databases can be further separated based on whether they are multi-platform where they usually use a browser of some sort or Java script, or are specific to a certain platform such that no browser is involved. Some databases allow user defined fields, and some do not. Many of the image database software packages were made for categorizing images after they were collected i.e. passive, and developed for photography, catalogues, newspapers, etc. which do not necessarily cater to the needs in microscopy.
“Microscopic Explorations“: One Kit Many uses.
Authors: McKernan Stuart
Published: July 2020

Since 1996 the Minnesota Microscopy Society (MMS) has had several different opportunities to use the “Microscopic Explorations” [1] handbook that has been developed by MSA in collaboration with the Lawrence Hall of Science [2] as part of their Great Explorations in Math and Science (GEMS) series. Initially we used a beta-test version of the manual and worked with several different schools in the St. Paul's school district. Since then we have broadened the range of our outreach, and have interacted with different school districts, as well as local museums and other youth and community organizations - including church youth groups, scout groups and local governments. One of the strengths of the manual is that it can be used in many ways, and is adaptable to the particular learning situation available. These opportunities can span the range from essentially uncontrolled interactibns with the general public, with its large age range and ability spectrum, to the very carefully structured setting of an ongoing, single-age class program.
The use of the Element “Passion” Applied to Microscopy
Authors: Smith N Crise
Published: July 2020

Of all the meanings and definitions of the word passion, the two that are applied here are “a pursuit to which one is devoted” and “excitement of the mind.” These are the emotional feelings that drive artists, musicians, writers, and scientists to fervently apply their skills. Within the field of microscopy, scientists and technologists display their zeal when they pursue the development of new techniques and methodologies, when they invite the world into their laboratories through telepresence microscopy, and when they use only the highest of standards to execute their studies. It is the ardor that drives retired microscopists to deliver microscopes to school children, and the joy that makes teachers of us all, as we are so desirous to share our knowledge. Passion is the deep feeling that can motivate a microscopist to produce imaginative IMAX movies and films for public television series.
Microscopy Milestones: Field Ion Microscopy, Atom Probe Field Ion Microscopy and Atom Probe Tomography
Authors: Miller M K , Panitz J A
Published: July 2020

Two of the most significant microscopy milestones that were achieved in the last century were the imaging of individual atoms and the identification of individual atoms. Both these remarkable achievements were due to Prof. E. W. Miiller and members of his group at Pennsylvania State University. Almost fifty years ago, Miiller introduced a new type of microscope in which a sharp needle-shaped specimen was pointed at a fluorescent screen, Fig. 1. By applying an appropriately high positive voltage to the specimen, image gas atoms near the apex of the specimen could be ionized and radially projected towards the screen where they produced highly magnified images of the specimen surface, Fig. 2. By cryogenically cooling the specimen and using helium as the image gas, the first images of individual atoms were obtained in a field ion microscope by Bahadur and Müller on October 11th, 1955.
Implications of Peat Soil Conceptualization for Groundwater Exfiltration in Numerical Modeling: A Study on a Hypothetical Peatland Hillslope
Authors: Autio Anna , Ala‐Aho Pertti , Ronkanen Anna‐Kaisa , Rossi Pekka M. , Kløve Bjørn
Published: July 2020

Fully integrated physically based hydrological modeling is an essential method for increasing hydrological understanding of groundwater‐surface water (GW‐SW) interactions in peatlands and for predicting anthropogenic impacts on these unique ecosystems. Modeling studies represent peat soil in a simplistic manner, as a homogeneous layer of uniform thickness, but field measurements consistently show pronounced spatial variability in peatlands. This study evaluated uncertainty in groundwater levels and exfiltration fluxes associated with the simplified representation of the peat soil layer. For transferability of the results, impacts of selected topographical and hydrogeological conceptual models on GW‐SW exchange fluxes were simulated in a hypothetical hillslope representing a typical aquifer‐mire transect. The results showed that peat soil layer geometry defined the simulated spatial GW‐SW exchange patterns and groundwater flow paths, whereas total groundwater exfiltration flux to the hillslope and groundwater level in the peatland were only subtly altered by different conceptual peat soil geometry models. GW‐SW interactions were further explored using different scenarios and dimensionless parameters for peat hydraulic conductivity and hillslope‐peatland system slope. The results indicated that accurate representation of physical peat soil properties and landscape topography is important when the main objective is to model spatial GW‐SW exchange. Groundwater level in virtual peatland was not greatly affected by groundwater drawdown in an adjacent aquifer, but the magnitude and spatial distribution of GW‐SW interactions was significantly altered. This means that commonly used groundwater depth observations near peat‐mineral soil interfaces and within peatlands may not be a suitable indicator for monitoring the hydrological state of groundwater‐dependent peatland ecosystems.
Developmental effects on sleep–wake patterns in infants receiving a cow’s milk-based infant formula with an added prebiotic blend: a Randomized Controlled Trial
Authors: Colombo John , Carlson Susan E. , Algarín Cecilia , Reyes Sussanne , Chichlowski Maciej , Harris Cheryl L. , Wampler Jennifer L. , Peirano Patricio , Berseth Carol Lynn
Published: July 2020

Background

Few studies have evaluated nutritive effects of prebiotics on infant behavior state, physiology, or metabolic status.

Methods

In this double-blind randomized study, infants (n = 161) received cow’s milk-based infant formula (Control) or similar formula with an added prebiotic blend (polydextrose and galactooligosaccharides [PDX/GOS]) from 14–35 to 112 days of age. Infant wake behavior (crying/fussing, awake/content) and 24-h sleep–wake actograms were analyzed (Baseline, Days 70 and 112). Salivary cortisol was immunoassayed (Days 70 and 112). In a subset, exploratory stool 16S ribosomal RNA-sequencing was analyzed (Baseline, Day 112).

Results

One hundred and thirty-one infants completed the study. Average duration of crying/fussing episodes was similar at Baseline, significantly shorter for PDX/GOS vs. Control at Day 70, and the trajectory continued at Day 112. Latency to first and second nap was significantly longer for PDX/GOS vs. Control at Day 112. Cortisol awakening response was demonstrated at Days 70 and 112. Significant stool microbiome beta-diversity and individual taxa abundance differences were observed in the PDX/GOS group.

Conclusions

Results indicate faster consolidation of daytime waking state in infants receiving prebiotics and support home-based actigraphy to assess early sleep–wake patterns. A prebiotic effect on wake organization is consistent with influence on the gut–brain axis and warrants further investigation.

Impact

Few studies have evaluated nutritive effects of prebiotics on infant behavior state, cortisol awakening response, sleep–wake entrainment, and gut microbiome.

Faster consolidation of daytime waking state was demonstrated in infants receiving a prebiotic blend in infant formula through ~4 months of age.

Shorter episodes of crying were demonstrated at ~2 months of age (time point corresponding to age/developmental range associated with peak crying) in infants receiving formula with added prebiotics.

Results support home-based actigraphy as a suitable method to assess early sleep–wake patterns.

Prebiotic effect on wake organization is consistent with influence on the gut–brain axis and warrants further investigation.
Pathogen-associated selection on innate immunity genes (TLR4, TLR7) in a neotropical rodent in landscapes differing in anthropogenic disturbance
Authors: Heni Alexander Christoph , Schmid Julian , Rasche Andrea , Corman Victor Max , Drosten Christian , Sommer Simone
Published: July 2020

Toll-like receptors (TLRs) form part of the innate immune system and can recognize structurally conserved pathogen-associated molecular pattern (PAMP) molecules. Their functional importance in the resistance to pathogens has been documented in laboratory experimental settings and in humans. TLR diversity, however, has been rarely investigated in wildlife species. How the genetic diversity of TLRs is associated with various pathogens and how it is shaped by habitat disturbance are understudied. Therefore, we investigated the role of genetic diversity in the functionally important parts of TLR4 and TLR7 genes in resistance towards gastrointestinal nematodes andHepacivirusinfection. We chose a generalist study species, the rodentProechimys semispinosus, because it is highly abundant in three Panamanian landscapes that differ in their degree of anthropogenic modification. We detected only two TLR7 haplotypes that differed by one synonymous single-nucleotide polymorphism (SNP) position. The TLR4 variability was higher, and we detected four TLR4 haplotypes that differed at one synonymous SNP and at three amino acid positions within the leucine-rich repeat region. Only TLR4 haplotypes had different frequencies in each landscape. Using generalized linear models, we found evidence that nematode loads and virus prevalence were influenced by both specific TLR4 haplotypes and landscape. Here, the variable “landscape” served as a surrogate for the important influential ecological factors distinguishing landscapes in our study, i.e. species diversity and host population density. Individuals carrying the common TLR4_Ht1 haplotype were less intensely infected by the most abundant strongyle nematode. Individuals carrying the rare TLR4_Ht3 haplotype were allHepacivirus-positive, where those carrying the rare haplotype TLR4_Ht4 were less often infected byHepacivirusthan individuals with other haplotypes. Our study highlights the role of TLR diversity in pathogen resistance and the importance of considering immune genetic as well as ecological factors in order to understand the effects of anthropogenic changes on wildlife health.
Synergistic reduction in albuminuria in type 2 diabetic mice by esaxerenone (CS-3150), a novel nonsteroidal selective mineralocorticoid receptor blocker, combined with an angiotensin II receptor blocker
Authors: Arai Kiyoshi , Morikawa Yuka , Ubukata Naoko , Sugimoto Kotaro
Published: July 2020

Esaxerenone is a novel selective mineralocorticoid receptor (MR) blocker that was recently approved in Japan to treat hypertension. In phase II and III studies, esaxerenone plus a renin–angiotensin system inhibitor markedly reduced the urinary albumin-to-creatinine ratio (UACR) in hypertensive patients with diabetic nephropathy. To evaluate a direct renoprotective effect by MR blockade independent of an antihypertensive effect in the context of diabetic nephropathy, esaxerenone (3 mg/kg), olmesartan (an angiotensin II receptor blocker; 1 mg/kg), or both were orally administered to KK-Ay mice, a type 2 diabetes model, once daily for 56 days. Urinary albumin (Ualb), UACR, and markers, such as podocalyxin, monocyte chemoattractant protein-1 (MCP-1), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), were measured, along with systolic blood pressure (SBP), fasting blood glucose, and serum K+ levels. Prior to the initiation of drug administration, KK-Ay mice showed higher blood glucose, insulin, Ualb excretion, and UACR levels than C57BL/6 J mice, a nondiabetic control, indicating the development of diabetic renal injury. Combined treatment with esaxerenone and olmesartan significantly reduced the change in UACR from baseline compared with the change associated with vehicle at week 8 (−1.750 vs. 0.339 g/gCre; P < 0.002) and significantly inhibited the change in Ualb from baseline compared with the change associated with vehicle at week 8 (P < 0.002). The combination treatment also reduced urinary excretion of podocalyxin and MCP-1, but did not influence 8-OHdG excretion, SBP, blood glucose, or serum K+ levels. Overall, esaxerenone plus olmesartan treatment ameliorated diabetic nephropathy in KK-Ay mice without affecting SBP, suggesting that the renoprotective effects of esaxerenone could be exerted independently of its antihypertensive effect.
The influence of postural threat on strategy selection in a stepping-down paradigm
Authors: Kluft Nick , Bruijn Sjoerd M. , Luu M. John , Dieën Jaap H. van , Carpenter Mark G. , Pijnappels Mirjam
Published: July 2020

To walk safely in their environment, people need to select adequate movement strategies during gait. In situations that are perceived as more threatening, older adults adopt more cautious strategies. For individuals with excessive fear, selecting adequate strategies might be troubling. We investigated how a postural threat affects the selection of strategies within and between older adults by using a stepping-down paradigm. In twenty-four older adults we determined the height at which they switched in stepping-down strategies from a less demanding but more balance threatening heel landing to a more demanding yet safer toe landing. We expected that this switching height would be lower in the high (0.78 m elevation) compared to low threat (floor level) condition. Furthermore, we investigated if older adults, for which the postural threat evoked an increase in the perceived fear, presented a different stepping down strategy due to the postural threat. Our results indicated that the postural threat changed older adults’ strategies selection towards a more conservative toe landing. Hence, despite the additional effort, older adults prefer more cautious strategies during a postural threat. No effects of perceived fear on strategy selection between individuals were observed, potentially due to relatively small differences in fear among participants.
Genome-wide identification and expression profiling of the YUCCA gene family in Malus domestica
Authors: Song Chunhui , Zhang Dong , Zheng Liwei , Shen Yawen , Zuo Xiya , Mao Jiangping , Meng Yuan , Wu Haiqin , Zhang Yike , Liu Xiaoyuan , Qian Ming , Zhang Jie , Li Gaochao , Zhao Caiping , Xing Libo , Ma Juanjuan , Han Mingyu , An Na
Published: July 2020

The plant hormone auxin is essential for plant growth and development. YUCCA proteins catalyse the rate-limiting step for endogenous auxin biosynthesis. In this study, we isolated 20 MdYUCCA genes from apple genome. MdYUCCA6a, MdYUCCA8a, and MdYUCCA10a were expressed in most organs and could support whole plant basal auxin synthesis. MdYUCCA4a, MdYUCCA10b, and MdYUCCA11a expression indicated roles for these genes in auxin biosynthesis in vegetative organs. MdYUCCA2b, MdYUCCA11b, and MdYUCCA11d were mainly expressed in flower organs. High temperature induced the expression of MdYUCCA4a, MdYUCCA6a, MdYUCCA8a, and MdYUCCA10a, and down-regulated the expression of MdYUCCA2b and MdYUCCA6b. Dual-luciferase assay indicated that MdPIF4 could trans-activate the MdYUCCA8a promoter. Overexpression of MdYUCCA8a increased IAA content, increased stem height, enhanced apical dominance, and led to silique malformation. These results provide a foundation for further investigation of the biological functions of apple MdYUCCAs.
Forest fragmentation modifies the composition of bumblebee communities and modulates their trophic and competitive interactions for pollination
Authors: Gómez-Martínez Carmelo , Aase Anne Lene T. O. , Totland Ørjan , Rodríguez-Pérez Javier , Birkemoe Tone , Sverdrup-Thygeson Anne , Lázaro Amparo
Published: July 2020

Understanding the effects of landscape fragmentation on global bumblebee declines requires going beyond estimates of abundance and richness and evaluating changes in community composition and trophic and competitive interactions. We studied the effects of forest fragmentation in a Scandinavian landscape that combines temperate forests and croplands. For that, we evaluated how forest fragmentation features (patch size, isolation and shape complexity, percentage of forest in the surroundings) as well as local flowering communities influenced bumblebee abundance, richness and community composition in 24 forest patches along a fragmentation gradient. In addition, we assessed the effect of fragmentation on bumblebee–plant network specialization (H2′), and potential inter- and intraspecific competition via shared plants. Patch isolation was associated with lower bumblebee abundance, whereas flower density was positively related to both bumblebee abundance and richness. Overall, forest fragmentation reduced the abundance of forest-specialists while increasing the abundance of open-habitat species. Patches with complex shapes and few flowers showed more generalized bumblebee–plant networks (i.e., fewer specific interactions). Patch shape complexity and the percentage of forest also modified inter- and intraspecific competitive interactions, with habitat generalists outcompeting forest specialists in fragmented areas. Understanding these mechanisms is necessary to anticipate to the impact of forest fragmentation on bumblebee decline.
Explosive Fibonacci-sequence growth into unusual sector-face morphology in poly(l-lactic acid) crystallized with polymeric diluents
Authors: Lugito Graecia , Nagarajan Selvaraj , Woo Eamor M.
Published: July 2020

Lamellar assembly in unusual sector-face PLLA spherulites from crystallization of poly(l-lactic acid) (PLLA) diluted with amorphous poly(methyl methacrylate) (PMMA). The growth and morphology of the crystalline structures is studied using polarized optical microscopy (POM), atomic-force and scanning electron microscopies (AFM, SEM). Crystals are also analyzed using differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS). The two alternate sectored faces differ dramatically in their optical birefringence and top-surface and interior lamellar assembly. By originating from the nucleus center, an explosive fan-like sector of high-birefringence lamellae is packed by fractal growth from an initial single stalk into hundreds of branches upon reaching the periphery, with the number of stalks increasing roughly by the Fibonacci sequence along the radial distance. The exploded pattern resembles a cross-hatch grating structure, and displays a cauliflower-like fractal-branching of optical birefringence blue/orange stripes. This finding suggests that growth with periodic branching is one of the main mechanisms to fill the ever-expanding space in the spherulitic 3D aggregates.
Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs
Authors: Kjærgaard Kristoffer , Weber Britta , Alstrup Aage Kristian Olsen , Petersen Jørgen Breede Baltzer , Hansen Rune , Hamilton-Dutoit Stephen Jacques , Mortensen Frank Viborg , Sørensen Michael
Published: July 2020

Normal liver tissue is highly vulnerable towards irradiation, which remains a challenge in radiotherapy of hepatic tumours. Here, we examined the effects of radiation-induced liver injury on two specific liver functions and hepatocellular regeneration in a minipig model. Five Göttingen minipigs were exposed to whole-liver stereotactic body radiation therapy (SBRT) in one fraction (14 Gy) and examined 4–5 weeks after; five pigs were used as controls. All pigs underwent in vivo positron emission tomography (PET) studies of the liver using the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine ([11C]CSar) and the galactose-analogue tracer [18F]fluoro-2-deoxy-d-galactose ([18F]FDGal). Liver tissue samples were evaluated histopathologically and by immunohistochemical assessment of hepatocellular mitosis, proliferation and apoptosis. Compared with controls, both the rate constant for secretion of [11C]CSar from hepatocytes into intrahepatic bile ducts as well as back into blood were doubled in irradiated pigs, which resulted in reduced residence time of [11C]CSar inside the hepatocytes. Also, the hepatic systemic clearance of [18F]FDGal in irradiated pigs was slightly increased, and hepatocellular regeneration was increased by a threefold. In conclusion, parenchymal injury and increased regeneration after whole-liver irradiation was associated with enhanced hepatobiliary secretion of bile acids. Whole-liver SBRT in minipigs ultimately represents a potential large animal model of radiation-induced liver injury and for testing of normal tissue protection methods.
Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry
Authors: Werdiger Freda , Donnelley Martin , Dubsky Stephen , Murrie Rhiannon P. , Carnibella Richard P. , Samarage Chaminda R. , How Ying Y. , Zosky Graeme R. , Fouras Andreas , Parsons David W. , Morgan Kaye S.
Published: July 2020

To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. This capability would enable any decline or improvement in health to be located and measured, allowing improved treatment options to be designed. Current lung function assessment methods have many limitations, including the inability to accurately localise the origin of global changes within the lung. However, X-ray velocimetry (XV) has recently been demonstrated to be a sophisticated and non-invasive lung function measurement tool that is able to display the full dynamics of airflow throughout the lung over the natural breathing cycle. In this study we present two developments in XV analysis. Firstly, we show the ability of laboratory-based XV to detect the patchy nature of cystic fibrosis (CF)-like disease in β-ENaC mice. Secondly, we present a technique for numerical quantification of CF-like disease in mice that can delineate between two major modes of disease symptoms. We propose this analytical model as a simple, easy-to-interpret approach, and one capable of being readily applied to large quantities of data generated in XV imaging. Together these advances show the power of XV for assessing local airflow changes. We propose that XV should be considered as a novel lung function measurement tool for lung therapeutics development in small animal models, for CF and for other muco-obstructive diseases.
Light-driven complex 3D shape morphing of glassy polymers by resolving spatio-temporal stress confliction
Authors: Lee Jong Hyeok , Choi Jun-Chan , Won Sukyoung , Lee Jae-Won , Lee Jae Gyeong , Kim Hak-Rin , Wie Jeong Jae
Published: July 2020

Programmable 3D shape morphing of hot-drawn polymeric sheets has been demonstrated using photothermal local shrinkage of patterned hinges. However, the hinge designs have been limited to simple linear hinges used to generate in-plane local folding or global curvature. Herein, we report an unprecedented design strategy to realize localized curvature engineering in 3D structures employing radial hinges and stress-releasing facets on 2D polymeric sheets. The shape and height of the 3D structures are readily controlled by varying the number of radial patterns. Moreover, they are numerically predictable by finite elemental modeling simulation with consideration of the spatio-temporal stress distribution, as well as of stress competition effects. Localized curvature engineering provides programming capabilities for various designs including soft-turtle-shell, sea-shell shapes, and saddle architectures with the desired chirality. The results of local curvilinear actuation with quantifiable stress implies options to advance the applicability of self-folded architectures embodying coexisting curved and linear geometric surfaces.
The impact of multidisciplinary team management on outcome of hepatic resection in liver-limited colorectal metastases
Authors: Basso Michele , Corallo Salvatore , Calegari Maria Alessandra , Zurlo Ina Valeria , Ardito Francesco , Vellone Maria , Marchesani Silvio , Orlandi Armando , Dadduzio Vincenzo , Fucà Giovanni , Di Dio Carmela , Mele Caterina , Barbaro Brunella , Strippoli Antonia , Coppola Alessandro , Cassano Alessandra , Bria Emilio , Barone Carlo Antonio , Giuliante Felice
Published: July 2020

Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88–1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p < 0.0001). The median duration of chemotherapy was lower in MDT patients (8 vs 10 cycles; p < 0.001). Post-operative morbidity was lower in the MDT cohort (6.2 vs 21.5%; p < 0.001). One hundred and ninety-seven patients in each group were matched by propensity score and no significant difference was observed between the two groups in terms of OS and DFS. Our study does not demonstrate a survival benefit from MDT management, but it allows surgery to patients with a more advanced disease. MDT assessment reduces the median duration of chemotherapy and post-operative morbidities.