bluuebunny/crossref_metadata_2025 huggingface dataset:
Scintillators for the SEM - A Practical Guide
Authors: Taylor Gene
Published: March 2018

The scintillator Is a part of the electron collection system in most SEMs and other types of electron imaging systems. Without a properly functioning scintillator, images may be noisy, weak, or exhibit other signs of degradation.

There are three types of scintillators generally used in the SEM: organic/polymeric, phosphor powder, and crystalline (single or poly).

Plastic scintillators are currently used less frequently, mainly because they are subject to radiation damage (i.e., short lifetime). This type of scintillator has the shortest decay time (~2.2 - 5 ns) and very low noise. We still have many customers who prefer this type of scintillator even though they have to change it more frequently (∼2 - 6 month lifetime with average use is our experience).
Comparison of Commercial Microvacuum Sampling Cassettes for Settled Dust Analysis
Authors: Millette James R
Published: March 2018

Three commercially available vacuum samplers (also known as microvacuum samplers or microvacs) were examined for compliance with the Standard ASTM Methods for asbestos in settled dust. The American Society for Testing and Materials (ASTM) Standard Test Method (D5755-95) for Microvacuum Sampling and Indirect Analysis of Dust by Transmission Electron Microscopy for Asbestos Structure Number Concentration and the similar Method (D5756-95) for mass require that a sample be collected by vacuuming a known surface area with a standard 25 or 37 mm air sampling cassette using a plastic tube that is attached to the inlet orifice which acts as a nozzle.
Imaging with Photoelectrons
Authors: Carmichael Stephen W
Published: March 2018

Most of us have used fluorescence microscopy and are all too familiar with the advantages and disadvantages of this tool: easy identification of one or more labels that fluoresce at different wavelengths (color) against the relatively dark background of the biologic substrate, but we can't always get the spatial resolution that is needed to answer our questions. Electron microscopy, both transmission and scanning modes, offer much better spatial resolution, but present problems in localizing a label, particularly on the surface of a cell. Wouldn't it be great if an imaging technique were available that gave us the possibility of localizing one or more labels on the surface of a cell with resolution approaching electron microscopy. Karen Hedberg, Bruce Birrel, Douglas Habliston, and Hayes Griffith at the University of Oregon describe photoelectron imaging as the electron optical analogue of fluorescence microscopy, offering some of the advantages of both methods.
Beam Skirt Effects When Doing EDS In An Low-Vacuum SEM
Authors: Blide-Soerensen JB
Published: March 2018

Approximately 75 % of the primary electrons will be scattered when you use a working distance of 12 mm and a pressure of 3.5 torr, and a significant fraction of these scattered electrons will hit the sample farther away from the beam target than 50 pm. (The scattered intensity is approximately given by Is/ lo = 1 – exp(-ρσL/kT) where p is the pressure, σ the total scattering cross section for electron scattering on the gas used, L the distance between the last pressure limiting aperture and the sample, k the Boltzmann constant and T the absolute temperature).
The Effect of Gas Type on Beam Scatter
Authors: Chernoff Don
Published: March 2018

Last month I addressed the phenomena of beam scatter in the environmental and low vacuum SEM. In that article I covered how beam scatter is affected by chamber pressure, working distance, and accelerating voltage. To briefly summarize, beam scatter becomes worse at higher chamber pressure, longer working distance, and lower accelerating voltages. As the beam scatters, electrons strike the sample some distance away from the primary beam and as a result, generate X-rays from unwanted areas of the sample. It is advantageous for the analyst to keep beam scatter to a minimum to reduce the generation of these X-ray signals. Under conditions of high chamber pressure, long working distance, and low accelerating voltage, it is possible for electrons from the beam to strike the sample on the order of a millimeter or more from the primary beam.
Limits of SEM Resolution
Authors: Joy David C
Published: March 2018

Over the past decade the achievable resolution of the scanning electron microscope (SEM) in secondary electron (SE) imaging mode has improved by about one order of magnitude. In fact, instruments capable of demonstrating a resolution of one nanometer and exhibiting a probe size of less than 0.6 nm are not available. Continued improvements in electronoptics, electron sources, and in electronic and mechanical stability promise even smaller probe sizes that still contain adequate current for imaging, it is therefore relevant to consider what resolution might ultimately be achievable with an SEM in SE mode.
Home Made Silicone Rubber Embedding Molds
Authors: Muss Wolfgang
Published: March 2018

Silicone rubber embedding molds may be inexpensive In North America, but are not necessarily so elsewhere in the world. Further, commercial molds are available only in standard sizes and only with standard sizes and shapes of cavities for specimen embedding, If, however, one needs to embed specimens of n on standard size or shape, wants more embedding cavities per mold than usually available, or is working where commercial molds are expensive or not easily available, then all is not lost, Embedding molds for specimen blocks can easily be made in the lab from silicone rubber. Further, making embedding blocks allows the use of different silicone rubbers which would be of value with unusual embedding resins, or when embedding must be done in unusual environments (such as extreme cold or heat).
Scanning Electron Microscope EDucatorS
Authors: Williams Joseph P
Published: March 2018

Can you imagine the motivational value of a young adult being exposed to images of common day objects that they have an interest in, magnified ten, one hundred, or one thousand times? Then imagine the student learning the theory and operation of a scanning electron microscope. Finally, imagine walking into a laboratory to see these same students operating an SEM and taking their own micrographs.

For the past three years I have had the pleasure of teaching the laboratory portion of the SEMEDS program. The program's goal is not just to motivate high school students in science, but to expose them to the wonders of microscopy and how it affects their everyday life.

The program currently has three phases. During phase one, teachers from local high schools are contracted about the program. The teachers volunteer at the beginning of the school year then become students themselves during a four hour class.
Low Pressure Nitrogen Purge Stops Oil Contamination
Authors: Vane Ronald A
Published: March 2018

Oil contamination in SEMs is a common problem. It manifests itself as dark spots and carton buildup in low KV scans and oil condensation on EDX detector windows. While one of the most common sources of this contamination is oil backstreamed from the roughing pump, other sources include pump oils, lubricants, seals, fingerprints, and the samples themselves. Depending upon severity, this effect ranges from a minor irritation to a very major problem.

Historical solutions to this problem have included turbomolecular pumps (TMP), cryopumps, drag pumps, traps, better pump oils, cooler running roughing pumps, double diffusion pumps and fractionating diffusion pumps. Many of these solutions have proved to be costly, require much maintenance and/or have not been very effective.
High Pressure Freezing; Benefits and Limitations
Authors: Wise Robert R
Published: March 2018

Rapid freezing of biological samples for subsequent processing and examination in the TEM has been around since the 1960's. Freezing in general, is advantageous because it can provide an instantaneous cessation of all biological activity and hall ultrastructural rearrangement The freezing ‘fixes” biological structures in water ice until such time that the ice can be substituted for a chemical fixative. Freezing is typically conducted at liquid nitrogen temperatures (-196°C), and freeze substitution (FS) is then carried out over days to weeks on dry ice (-80°C) (Severs el. al., 1995).
A Stable, Adjustable Voltage Source to Replace Mercury Batteries in EMs and Other Instruments
Authors: (Woody) White N W
Published: March 2018

From time to time, a stable but adjustable voltage source can be quite handy. This article was prompted by a request for a replacement for mercury battery collage references which are not only difficult to find, but are rot environmentally friendly. Another application could be powering a 3 to 9 volt disk-man (or whatever) from a nominal 12 volt source such as an automobile. In fact, the circuit can be set to supply any collage From 3 to 38 volts.
Measuring, Stopping and Preventing Vibration in Microscopes and Other Laboratory Equipment
Authors: Leidich Richard , Listner Gregory
Published: March 2018

Vibration in microscopes may seem a bit baffling, but we have found that solutions to vibration problems are usually quite simple. Vibration is the result of an object being moved until it collides with another object and bounces back. Yes, it can be as simple as shaking, but the normal definition involves collisions. Some source must continuously supply energy to the moving part(s). As long as energy is supplied to the moving part(s) and the part(s) collide, bouncing can occur at a constant frequency. If the parts can be moved so they do not collide or if the energy can be absorbed, the frequency of the bouncing can be changed or stopped.
Pioloform F Instead of Formvar as a Support Film for TEM
Authors: Madden Victoria J
Published: March 2018

Pioloform F (Wacker Chemie Co., Munich, Germany) is an excellent plastic for use as a support film for electron microscopy. The advantages of Pioloform F are high mechanical and thermal stability, and low material bulk (Stockem, 1970). Because of these properties, thinner films than Formvar or collodion may be used and remain stable under the electron beam without subsequent stabilization by carton coating. Thin support films of gray interference color are prepared by dissolving 0.5 grams of Pioloform F powder in 100 milliliters of anhydrous chloroform (Stockem, 1970), using the dip method described by Reimer (1967).
How Good is Your Glut?
Authors: Compton Bob
Published: March 2018

Gluteraldehyde (GA) has proven to be an extraordinarily versatile product. Its many uses range from softening leather and paper to disinfecting and sterilizing hospital instruments. It is used, of course, as a fixative in preparing biological samples for microscopic investigations that most readers of this publication will be familiar with. Even though quality questions relating to GA have been well researched and documented, there is still enough disagreement between industry experts to stimulate an enthusiastic discussion on microscopic list servers.
He who borrows lenses borrows trouble
Authors: Newberry Sterling
Published: March 2018

This adage for my students was obviously inspired by "He who steals my purse steals trash" but the lens borrower may be in for more serious trouble than the purse snatcher. This comes about because the eyepiece fit and the objective threads are standardized to a couple of standards so that the mechanical interchange of components between different optical microscopes is easily accomplished, while the incompatibility of the optical components is not usually apparent. This incompatibility can range from easily recognized blurring of the image to only slight loss of resolution which leads to inferior work or much wasted time before the problem is recognized.
Microscopy In Forensic Science
Authors: Houck Max M
Published: March 2018

This article is the first in a series relating to the application of microscopy to forensic science. As such, the article is intended to be purely introductory in nature. Future articles will be specific both as to the forensic challenge and the solution as allowed by the creative application of microscopy.

Microscopy has played an integral part in forensic science since the early part of this century. In 1928, E. Locard established the practical and theoretical underpinnings of the microscopic examination of trace amounts of evidence. The “exchange principle of evidence” was so developed:

Whenever two objects come into contact there is always a transfer of material. The methods of detection may not be sensitive enough to demonstrate this or the decay rate may be so rapid that all evidence of transfer has vanished after a given time. Nonetheless, the transfer has taken place.
Evolution and Revolution in Microscopy - I
Authors: Revel Jean-Paul
Published: March 2018

Disney, Hill and Baker in their 1928 booh on the Origin and Development of the Microscope, quote the 1829 article on Optics of the London Encyclopedia as saying; “Microscopes, though but toys compared with telescopes, nevertheless deserve to be rendered as perfect as possible; for they yield not to them in the quantity and variety of rational amusement which they are capable of introducing to us (though not of the sublime description of the wonders of the heavens). Compound microscopes, though not so much to be depended upon for the purposes of discovery and philosophical investigation as single lenses, are still the best adapted for recreation”. It is hard to imagine that this was written at about the time when Robert Brown of motion fame, was discovering the celt nucleus (1831), the repository of the genetic code and thus arguably laying the foundations for all of modern biology. The sentence quoted might be taken to suggest that there was no evolutionary connection between hand lenses and compound microscopes, since as late as the 1830s the two still competed.

In trying to follow the evolution of microscopes it is trite to state that lenses had to come first. It was known for a long time that objects seen through a glass bulb full of water appeared enlarged, but the water was thought the important factor and it was not until the time of Alhazen (962-1038) that the action of a lens was understood. Roger Bacon (1242-1292) wrote “if one looks at letters and other minute things though the medium of a crystal or glass or other lens put over the letters... he will see the letters much better and they will appear much larger to him... and therefore this instrument is useful to old men and to those having feeble sight” Spectacles seem to have been invented by Salvano d'Aramento degli Arrtati of Florence who died in 1317, the secret process of how to make them being revealed by a contemporary, Alessandro della Spina of Pisa. The use of lenses in visualizing small objects made slow progress at first but eventually led to “macroscopy”, in the form of spectacles and then to microscopy.
The Transmission Confocal Laser Scanning Microscope
Authors: Carter David
Published: March 2018

A confocal laser scanning microscope which can collect images in both transmission and reflection modes has been installed and is being tested in the Imaging Laboratories of the John P. Roberts Research Institute, London, Ontario. Designed by Dr. Ted Dixon at the University of Waterloo, it is being developed by a multi-disciplinary research group which includes the Ontario Lasers and Lightwaves Research Centre and the Department of Physiology, University of Toronto; the Radiology, Physics, and Pathology Departments, MacMaster University; and the Zoology Department, University of Western Ontario.

Commercial confacal microscopes operate by reflectance or epifluorescence. A pair of scanning mirrors direct a diffuse laser beam in a raster pattern through an objective lens, which focuses it on the specimen. Reflected light passes back along the same light path, being “de-scanned” by the moving mirrors and then diverted by a beam splitter into a detector. On its return to the detector, light from the focal plane is focussed through a pinhole, which blocks light from out-of-focus regions of the spectrum The microscope stage is moved up and down by a stepping motor to collect images at different depths.
How Accurate is Your SEM’s Magnification?
Authors: Geller Joseph D
Published: March 2018

With such topics as ISO-9000, TQM (Total Quality Management) and with the Maicolm Baldridge Quality Award being mentioned these days, it may not be long before instrument calibration becomes an issue in your laboratory. Among the many important areas governed will be magnification accuracy of optical microscopes, TEMs, and SEMs, The following brief discussion probes the rather complex subject of SEM magnification accuracy.
Meconium proteins as a source of biomarkers for the assessment of the intrauterine environment of the fetus
Authors: Lisowska-Myjak B. , Skarżyńska E. , Bakun M.
Published: March 2018

Intrauterine environmental factors can be associated with perinatal complications and long-term health outcomes although the underlying mechanisms remain poorly defined. Meconium formed exclusively in utero and passed naturally by a neonate may contain proteins which characterise the intrauterine environment. The aim of the study was proteomic analysis of the composition of meconium proteins and their classification by biological function. Proteomic techniques combining isoelectrofocussing fractionation and LC-MS/MS analysis were used to study the protein composition of a meconium sample obtained by pooling 50 serial meconium portions from 10 healthy full-term neonates. The proteins were classified by function based on the literature search for each protein in the PubMed database. A total of 946 proteins were identified in the meconium, including 430 proteins represented by two or more peptides. When the proteins were classified by their biological function the following were identified: immunoglobulin fragments and enzymatic, neutrophil-derived, structural and fetal intestine-specific proteins. Meconium is a rich source of proteins deposited in the fetal intestine during its development in utero. A better understanding of their specific biological functions in the intrauterine environment may help to identify these proteins which may serve as biomarkers associated with specific clinical conditions/diseases with the possible impact on the fetal development and further health consequences in infants, older children and adults.
CME: Anorexia nervosa: eine enigmatische Krankheit besser verstehen und angehen
Authors: Milos Gabriella , Brunner Eleonora
Published: March 2018

Zusammenfassung. Anorexia nervosa ist eine Erkrankung mit potenziell schwerwiegenden Auswirkungen auf Körper, Psyche und soziale Situation. In schweren Fällen führt sie bis zu Invalidität und Tod. Die Betroffenen fühlen sich oft nicht krank und sind uneinsichtig gegenüber der Therapie, wobei das Verhalten der Kranken oft zu Konଂikten mit Nahestehenden führt. Ängste und Zwänge hindern die Erkrankten, sich normal zu verhalten und zu ernähren. Wichtig sind ein frühes Erkennen sowie Verständnis für die Anorexia nervosa, damit diese möglichst schnell und krankheitsspeziଁsch behandelt werden kann, da dies die Prognose verbessert. Die Aufklärung der Betroffenen und Angehörigen über Erkrankung, Komplikationen und Behandlungsmöglichkeiten ist Bestandteil der interdisziplinären Therapie.
Lerngeschichten für Kinder in den ersten drei Lebensjahren
Authors: Knauf Helen
Published: March 2018

Zusammenfassung. Die hier vorgestellte Studie untersucht theoretisch und empirisch, ob sich das in Neuseeland von Margaret Carr entwickelte Konzept der Lerngeschichten als Instrument der Bildungsdokumentation für Kinder in den ersten drei Lebensjahren eignet. Die theoretische Analyse kommt zu dem Schluss, dass es deutliche Übereinstimmungen des in der Frühpädagogik vorherrschenden Bildungsverständnisses für die ersten drei Lebensjahre mit dem Konzept der Lerngeschichten gibt. Dementsprechend werden sieben für die Bildungsarbeit mit 0- bis 3-jährigen Kindern besonders relevante Kategorien im Konzept der Lerngeschichten (u.a. Fokus auf Lerndispositionen) herausgearbeitet. Auf dieser Basis wurden 111 Lerngeschichten aus deutschen Kindertagesstätten in einer explorativen Studie untersucht. Die empirische Analyse zeigt, dass ein großer Teil der Lerngeschichten die an sie gestellten theoretischen Ansprüche einlöst. Doch es zeigen sich auch Diskrepanzen zwischen Anspruch und Realisierung. So wird der subjektive Charakter dieser Dokumentationsform oftmals nicht deutlich gemacht, viele Lerngeschichten sind zudem sprachlich sehr anspruchsvoll und daher für Kinder und Eltern potenziell nur schwer verständlich.
Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis
Authors: Lee Cheol-Jung , Moon Su-Jin , Jeong Jeong-Hee , Lee Sangbae , Lee Mee-Hyun , Yoo Sun-Mi , Lee Hye Suk , Kang Han Chang , Lee Joo Young , Lee Weon Sun , Lee Hee-Jin , Kim Eun-Kyung , Jhun Joo-Yeon , Cho Mi-La , Min Jun-Ki , Cho Yong-Yeon
Published: March 2018

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3–RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68+macrophages with high frequency, while pRSK2-expressing CD4+T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin β3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3–RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.
Microscopic mechanisms of deformation transfer in high dynamic range branched nanoparticle deformation sensors
Authors: Raja Shilpa N. , Ye Xingchen , Jones Matthew R. , Lin Liwei , Govindjee Sanjay , Ritchie Robert O.
Published: March 2018

Nanoscale stress sensing is of crucial importance to biomechanics and other fields. An ideal stress sensor would have a large dynamic range to function in a variety of materials spanning orders of magnitude of local stresses. Here we show that tetrapod quantum dots (tQDs) exhibit excellent sensing versatility with stress-correlated signatures in a multitude of polymers. We further show that tQDs exhibit pressure coefficients, which increase with decreasing polymer stiffness, and vary >3 orders of magnitude. This high dynamic range allows tQDs to sense in matrices spanning >4 orders of magnitude in Young’s modulus, ranging from compliant biological levels (~100 kPa) to stiffer structural polymers (~5 GPa). We use ligand exchange to tune filler-matrix interfaces, revealing that inverse sensor response scaling is maintained upon significant changes to polymer-tQD interface chemistry. We quantify and explore mechanisms of polymer-tQD strain transfer. An analytical model based on Mori-Tanaka theory presents agreement with observed trends.
Photonic chip-based soliton frequency combs covering the biological imaging window
Authors: Karpov Maxim , Pfeiffer Martin H. P. , Liu Junqiu , Lukashchuk Anton , Kippenberg Tobias J.
Published: March 2018

Dissipative Kerr solitons (DKS) in optical microresonators provide a highly miniaturised, chip-integrated frequency comb source with unprecedentedly high repetition rates and spectral bandwidth. To date, such frequency comb sources have been successfully applied in the optical telecommunication band for dual-comb spectroscopy, coherent telecommunications, counting of optical frequencies and distance measurements. Yet, the range of applications could be significantly extended by operating in the near-infrared spectral domain, which is a prerequisite for biomedical and Raman imaging applications, and hosts commonly used optical atomic transitions. Here we show the operation of photonic-chip-based soliton Kerr combs driven with 1 micron laser light. By engineering the dispersion properties of a Si3N4 microring resonator, octave-spanning soliton Kerr combs extending to 776 nm are attained, thereby covering the optical biological imaging window. Moreover, we show that soliton states can be generated in normal group–velocity dispersion regions when exploiting mode hybridisation with other mode families.
Explosive dissolution and trapping of block copolymer seed crystallites
Authors: Guerin Gerald , Rupar Paul A. , Manners Ian , Winnik Mitchell A.
Published: March 2018

Enhanced control over crystallization-driven self-assembly (CDSA) of coil-crystalline block copolymers has led to the formation of intricate structures with well-defined morphology and dimensions. While approaches to build those sophisticated structures may strongly differ from each other, they all share a key cornerstone: a polymer crystallite. Here we report a trapping technique that enables tracking of the change in length of one-dimensional (1D) polymer crystallites as they are annealed in solution at different temperatures. Using the similarities between 1D polymeric micelles and bottle-brush polymers, we developed a model explaining how the dissolving crystallites reach a critical size independent of the annealing temperature, and then explode in a cooperative process involving the remaining polymer chains of the crystallites. This model also allows us to demonstrate the role of the distribution in seed core crystallinity on the dissolution of the crystallites.
Spatial variation of the rain–snow temperature threshold across the Northern Hemisphere
Authors: Jennings Keith S. , Winchell Taylor S. , Livneh Ben , Molotch Noah P.
Published: March 2018

Despite the importance of precipitation phase to global hydroclimate simulations, many land surface models use spatially uniform air temperature thresholds to partition rain and snow. Here we show, through the analysis of a 29-year observational dataset (n = 17.8 million), that the air temperature at which rain and snow fall in equal frequency varies significantly across the Northern Hemisphere, averaging 1.0 °C and ranging from –0.4 to 2.4 °C for 95% of the stations. Continental climates generally exhibit the warmest rain–snow thresholds and maritime the coolest. Simulations show precipitation phase methods incorporating humidity perform better than air temperature-only methods, particularly at relative humidity values below saturation and air temperatures between 0.6 and 3.4 °C. We also present the first continuous Northern Hemisphere map of rain–snow thresholds, underlining the spatial variability of precipitation phase partitioning. These results suggest precipitation phase could be better predicted using humidity and air temperature in large-scale land surface model runs.
Improving imputation in disease-relevant regions: lessons from cystic fibrosis
Authors: Panjwani Naim , Xiao Bowei , Xu Lizhen , Gong Jiafen , Keenan Katherine , Lin Fan , He Gengming , Baskurt Zeynep , Kim Sangook , Zhang Lin , Esmaeili Mohsen , Blackman Scott , Scherer Stephen W. , Corvol Harriet , Drumm Mitchell , Knowles Michael , Cutting Garry , Rommens Johanna M. , Sun Lei , Strug Lisa J.
Published: March 2018

Does genotype imputation with public reference panels identify variants contributing to disease? Genotype imputation using the 1000 Genomes Project (1KG; 2504 individuals) displayed poor coverage at the causal cystic fibrosis (CF) transmembrane conductance regulator (CFTR) locus for the International CF Gene Modifier Consortium. Imputation with the larger Haplotype Reference Consortium (HRC; 32,470 individuals) displayed improved coverage but low sensitivity of variants clinically relevant for CF. A hybrid reference that combined whole genome sequencing (WGS) from 101 CF individuals with the 1KG imputed a greater number of single-nucleotide variants (SNVs) that would be analyzed in a genetic association study (r2 ≥ 0.3 and MAF ≥ 0.5%) than imputation with the HRC, while the HRC excelled in the lower frequency spectrum. Using the 1KG or HRC as reference panels missed the most common CF-causing variants or displayed low imputation accuracy. Designs that incorporate population-specific WGS can improve imputation accuracy at disease-specific loci, while imputation using public data sets can omit disease-relevant genotypes.
Baseline mapping of Lassa fever virology, epidemiology and vaccine research and development
Authors: Hallam Hoai J. , Hallam Steven , Rodriguez Sergio E. , Barrett Alan D. T. , Beasley David W. C. , Chua Arlene , Ksiazek Thomas G. , Milligan Gregg N. , Sathiyamoorthy Vaseeharan , Reece Lisa M.
Published: March 2018

Lassa fever (LF) is a zoonotic disease associated with acute and potentially fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the family Arenaviridae. It is generally assumed that a single infection with LASV will produce life-long protective immunity. This suggests that protective immunity induced by vaccination is an achievable goal and that cell-mediated immunity may play a more important role in protection, at least following natural infection. Seropositive individuals in endemic regions have been shown to have LASV-specific T cells recognizing epitopes for nucleocapsid protein (NP) and glycoprotein precursor (GPC), suggesting that these will be important vaccine immunogens. The role of neutralizing antibodies in protective immunity is still equivocal as recent studies suggest a role for neutralizing antibodies. There is extensive genetic heterogeneity among LASV strains that is of concern in the development of assays to detect and identify all four LASV lineages. Furthermore, the gene disparity may complicate the synthesis of effective vaccines that will provide protection across multiple lineages. Non-human primate models of LASV infection are considered the gold standard for recapitulation of human LF. The most promising vaccine candidates to date are the ML29 (a live attenuated reassortant of Mopeia and LASV), vesicular stomatitis virus (VSV) and vaccinia-vectored platforms based on their ability to induce protection following single doses, high rates of survival following challenge, and the use of live virus platforms. To date no LASV vaccine candidates have undergone clinical evaluation.
Plasmon induced modification of silicon nanocrystals photoluminescence in presence of gold nanostripes
Authors: Dyakov S. A. , Zhigunov D. M. , Marinins A. , Shalygina O. A. , Vabishchevich P. P. , Shcherbakov M. R. , Presnov D. E. , Fedyanin A. A. , Kashkarov P. K. , Popov S. , Gippius N. A. , Tikhodeev S. G.
Published: March 2018

We report on the results of theoretical and experimental studies of photoluminescense of silicon nanocrystals in the proximity to plasmonic modes of different types. In the studied samples, the type of plasmonic mode is determined by the filling ratio of a one-dimensional array of gold stripes which covers the thin film with silicon nanocrystals on a quartz substrate. We analyze the extinction, photoluminesce spectra and decay kinetics of silicon nanocrystals and show that the incident and emitted light is coupled to the corresponding plasmonic mode. We demonstrate the modification of the extinction and photoluminesce spectra under the transition from wide to narrow gold stripes. The experimental extinction and photoluminescense spectra are in good agreement with theoretical calculations performed by the rigorous coupled wave analysis. We study the contribution of individual silicon nanocrystals to the overall photoluminescense intensity, depending on their spacial position inside the structure.
Intrinsic Frequency Analysis and Fast Algorithms
Authors: Tavallali Peyman , Koorehdavoudi Hana , Krupa Joanna
Published: March 2018

Intrinsic Frequency (IF) has recently been introduced as an ample signal processing method for analyzing carotid and aortic pulse pressure tracings. The IF method has also been introduced as an effective approach for the analysis of cardiovascular system dynamics. The physiological significance, convergence and accuracy of the IF algorithm has been established in prior works. In this paper, we show that the IF method could be derived by appropriate mathematical approximations from the Navier-Stokes and elasticity equations. We further introduce a fast algorithm for the IF method based on the mathematical analysis of this method. In particular, we demonstrate that the IF algorithm can be made faster, by a factor or more than 100 times, using a proper set of initial guesses based on the topology of the problem, fast analytical solution at each point iteration, and substituting the brute force algorithm with a pattern search method. Statistically, we observe that the algorithm presented in this article complies well with its brute-force counterpart. Furthermore, we will show that on a real dataset, the fast IF method can draw correlations between the extracted intrinsic frequency features and the infusion of certain drugs.
Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5
Authors: Yabuta Norikazu , Ota Chie , Sasakura Towa , Naito Yoko , Okuzaki Daisuke , Fukushima Kohshiro , Nojima Hiroshi
Published: March 2018

p63, a transcriptional factor that belongs to the p53 family, regulates epidermal differentiation, stemness, cell death, tumorigenesis, metastasis, and senescence. However, its molecular mechanism remains elusive. We report here that TAp63 phosphorylated at T46/T281 specifically upregulates the late cornified envelope 1C (LCE1C) gene that is essential at a relatively late stage of epithelial development. We identified these phosphorylation sites during a search for the targets of Cyclin G-associated kinase (GAK) in vitro. LCE1C was drastically upregulated by doxycycline-dependent expression of Myc-TAp63 wild-type protein. Luciferase reporter assays using the promoter region of the LCE1C gene confirmed that the phosphorylations of TAp63-T46/T281 contributed to full transcriptional activation of the LCE1C gene. LCE1C interacted with protein arginine methyltransferase 5 (PRMT5) and translocated it from the nucleus to the cytoplasm. Mass spectrometry and co-immunoprecipitation identified importin-α as one of the association partners of LCE1C. In summary, we propose that the GAK_TAp63-pT46/pT281_LCE1C axis plays an important role in preventing the nuclear function of PRMT5.
Tidal and diel orchestration of behaviour and gene expression in an intertidal mollusc
Authors: Schnytzer Y. , Simon-Blecher N. , Li J. , Waldman Ben-Asher H. , Salmon-Divon M. , Achituv Y. , Hughes M. E. , Levy O.
Published: March 2018

Intertidal inhabitants are exposed to the 24-hour solar day, and the 12.4 hour rising and falling of the tides. One or both of these cycles govern intertidal organisms’ behaviour and physiology, yet little is known about the molecular clockworks of tidal rhythmicity. Here, we show that the limpet Cellana rota exhibits robust tidally rhythmic behaviour and gene expression. We assembled a de-novo transcriptome, identifying novel tidal, along with known circadian clock genes. Surprisingly, most of the putative circadian clock genes, lack a typical rhythmicity. We identified numerous tidally rhythmic genes and pathways commonly associated with the circadian clock. We show that not only is the behaviour of an intertidal organism in tune with the tides, but so too are many of its genes and pathways. These findings highlight the plasticity of biological timekeeping in nature, strengthening the growing notion that the role of ‘canonical’ circadian clock genes may be more fluid than previously thought, as exhibited in an organism which has evolved in an environment where tidal oscillations are the dominant driving force.
Complement C1q stimulates the progression of hepatocellular tumor through the activation of discoidin domain receptor 1
Authors: Lee Ji-Hyun , Poudel Barun , Ki Hyeon-Hui , Nepali Sarmila , Lee Young-Mi , Shin Jeon-Soo , Kim Dae-Ki
Published: March 2018

C1q is known to perform several functions in addition to the role it plays in complement activation. C1q contains a collagen-like portion and DDR1 (discoidin domain receptor 1) is a well-known collagen receptor. Accordingly, we hypothesized C1q might be a novel ligand of DDR1. This study shows for the first time C1q directly induces the activation and upregulation of DDR1, and that this leads to enhanced migration and invasion of HepG2 cells. In addition, C1q was found to induce the activations of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/Akt signaling, and to increase the expressions of matrix metalloproteinases (MMP2 and 9). Our results reveal a relationship between C1q and DDR1 and suggest C1q-induced DDR1 activation signaling may be involved in the progression of hepatocellular carcinoma.
Identification of new inhibitors against human Great wall kinase using in silico approaches
Authors: Ammarah Ummi , Kumar Amit , Pal Rajesh , Bal Naresh C. , Misra Gauri
Published: March 2018

Microtubule associated serine/threonine kinase (MASTL) is an important Ser/Thr kinase belonging to the family of AGC kinases. It is the human orthologue of Greatwall kinase (Gwl) that plays a significant role in mitotic progression and cell cycle regulation. Upregulation of MASTL in various cancers and its association with poor patient survival establishes it as an important drug target in cancer therapy. Nevertheless, the target remains unexplored with the paucity of studies focused on identification of inhibitors against MASTL, which emphasizes the relevance of our present study. We explored various drug databases and performed virtual screening of compounds from both natural and synthetic sources. A list of promising compounds displaying high binding characteristics towards MASTL protein is reported. Among the natural compounds, we found a 6-hydroxynaphthalene derivative ZINC85597499 to display best binding energy value of −9.32 kcal/mol. While among synthetic compounds, a thieno-pyrimidinone based tricyclic derivative ZINC53845290 compound exhibited best binding affinity of value −7.85 kcal/mol. MASTL interactions with these two compounds were further explored using molecular dynamics simulations. Altogether, this study identifies potential inhibitors of human Gwl kinase from both natural and synthetic origin and calls for studying these compounds as potential drugs for cancer therapy.
Microbiome-metabolome signatures in mice genetically prone to develop dementia, fed a normal or fatty diet
Authors: Sanguinetti Elena , Collado Maria Carmen , Marrachelli Vannina G. , Monleon Daniel , Selma-Royo Marta , Pardo-Tendero Mercedes M. , Burchielli Silvia , Iozzo Patricia
Published: March 2018

Cognitive decline, obesity and gut dysfunction or microbial dysbiosis occur in association. Our aim was to identify gut microbiota-metabolomics signatures preceding dementia in genetically prone (3xtg) mice, with and without superimposed high-fat diet. We examined the composition and diversity of their gut microbiota, and serum and faecal metabolites. 3xtg mice showed brain hypometabolism typical of pre-demented stage, and lacked the physiological bacterial diversity between caecum and colon seen in controls. Cluster analyses revealed distinct profiles of microbiota, and serum and fecal metabolome across groups. Elevation in Firmicutes-to-Bacteroidetes abundance, and exclusive presence of Turicibacteraceae, Christensenellaceae, Anaeroplasmataceae and Ruminococcaceae, and lack of Bifidobacteriaceae, were also observed. Metabolome analysis revealed a deficiency in unsaturated fatty acids and choline, and an overabundance in ketone bodies, lactate, amino acids, TMA and TMAO in 3xtg mice, with additive effects of high-fat diet. These metabolic alterations were correlated with high prevalence of Enterococcaceae, Staphylococcus, Roseburia, Coprobacillus and Dorea, and low prevalence of S24.7, rc4.4 and Bifidobacterium, which in turn related to cognitive impairment and cerebral hypometabolism. Our results indicate an effect of transgenic background on gut microbiome-metabolome, enhanced by high-fat diet. The resulting profiles may precede overt cognitive impairment, suggesting their predictive or risk-stratifying potential.
The tobacco carcinogen NNK drives accumulation of DNMT1 at the GR promoter thereby reducing GR expression in untransformed lung fibroblasts
Authors: Taylor Kerryn M. , Wheeler Roxanne , Singh Nimisha , Vosloo Dalene , Ray David W. , Sommer Paula
Published: March 2018

Small cell lung cancer (SCLC) is a highly aggressive, predominantly cigarette smoke-induced tumour with poor prognosis. The glucocorticoid receptor (GR), a SCLC tumour suppressor gene, is typically reduced in SCLC. We now show that SCLC cells express high levels of DNA methyltransferase 1 (DNMT1) which accumulates at the GR promoter. DNMT1 expression is further increased by exposure to the tobacco carcinogen NNK. In the untransformed human lung fibroblast cell line, MRC-5, short term NNK treatment decreases GRα mRNA and protein expression due to accumulation of DNMT1 at the GR promoter. Long term NNK treatment results in persistently augmented DNMT1 levels with lowered GR levels. Long term exposure to NNK slows cell proliferation and induces DNA damage, while the GR antagonist RU486 stimulates proliferation and protects against DNA damage. Although both NNK and RU486 treatment increases methylation at the GR promoter, neither are sufficient to prevent senescence in this context. NNK exposure results in accumulation of DNMT1 at the GR promoter in untransformed lung cells mimicking SCLC cells, directly linking tobacco smoke exposure to silencing of the GR, an important step in SCLC carcinogenesis.
Direct synthesis and in situ characterization of monolayer parallelogrammic rhenium diselenide on gold foil
Authors: Jiang Shaolong , Hong Min , Wei Wei , Zhao Liyun , Zhang Na , Zhang Zhepeng , Yang Pengfei , Gao Nan , Zhou Xiebo , Xie Chunyu , Shi Jianping , Huan Yahuan , Tong Lianming , Zhao Jijun , Zhang Qing , Fu Qiang , Zhang Yanfeng
Published: March 2018

Rhenium diselenide (ReSe2) has recently garnered great research interest due to its distorted 1T structure, anisotropic physical properties, and applications in polarization-sensitive photodetectors. However, ReSe2 synthesized by chemical vapor deposition (CVD) is usually a multilayer/polycrystalline material containing numerous grain boundaries, thereby hindering its further applications. Here we describe the direct CVD growth of high-quality monolayer ReSe2 single crystals with a parallelogram shape arising from its anisotropic structure on a gold foil substrate. In particular, we use low-energy electron microscopy/diffraction combined with scanning tunneling microscopy/spectroscopy to determine the atomic-scale structure, domain orientation/boundaries, and band features of monolayer ReSe2 flakes grown directly on gold foils. This work may open new opportunities for the direct synthesis and in situ characterization of CVD-grown monolayer ReSe2.
A theoretical study on mixtures of amino acid-based ionic liquids
Authors: Herrera Cesar , Atilhan Mert , Aparicio Santiago
Published: March 2018

Ionic liquid mixtures containing amino acid anions are studied at the microscopic level using molecular dynamics simulations.
Dietary impact on esophageal cancer in humans: a review
Authors: Sardana Rachna Khosla , Chhikara Navnidhi , Tanwar Beenu , Panghal Anil
Published: March 2018

Foods and the risk of esophageal cancer.
Citrus medica: nutritional, phytochemical composition and health benefits – a review
Authors: Chhikara Navnidhi , Kour Ragni , Jaglan Sundeep , Gupta Pawan , Gat Yogesh , Panghal Anil
Published: March 2018

Health benefits and products ofCitrus medica.
Microfluidic determination of lymphocyte vascular deformability: effects of intracellular complexity and early immune activation
Authors: Kang Ning , Guo Quan , Islamzada Emel , Ma Hongshen , Scott Mark D.
Published: March 2018

Despite the critical importance of mechanical (rheological + extrudability) deformability in the vascular flow of lymphocytes, it has been poorly investigated due to the limitations of existing technological tools.
Bright monolayer tungsten disulfide via exciton and trion chemical modulations
Authors: Tao Ye , Yu Xuechao , Li Jiewei , Liang Houkun , Zhang Ying , Huang Wei , Wang Qi Jie
Published: March 2018

An efficient exciton/trion modulation approach of organic p-type molecule doping via drop casting is proposed for tuning the optical properties of WS2.
Facile synthesis of 3D flower-like Pt nanostructures on polypyrrole nanowire matrix for enhanced methanol oxidation
Authors: Mazzotta E. , Caroli A. , Pennetta A. , De Benedetto G. E. , Primiceri E. , Monteduro A. G. , Maruccio G. , Malitesta C.
Published: March 2018

Platinum nanoflowers on polymer nanowires exhibit catalytic properties ascribed to the effect of high surface area flower-like structures and polymer 3D structure.
Composite-dissolving microneedle patches for chemotherapy and photothermal therapy in superficial tumor treatment
Authors: Pei Peng , Yang Fan , Liu Jiaxing , Hu Haoran , Du Xiaoyu , Hanagata Nobutaka , Zhao Shichang , Zhu Yufang
Published: March 2018

Doxorubicin hydrochloride (DOX)- and indocyanine green (ICG)-loaded microneedle (MN) patches (PVP@DOX/MSN@ICG) were successfully fabricated using a two-step casting process, which is a promising strategy for synergistic therapy of superficial tumors.
Synergistic effects of hyaluronate – epidermal growth factor conjugate patch on chronic wound healing
Authors: Kim Yun Seop , Sung Dong Kyung , Kong Won Ho , Kim Hyemin , Hahn Sei Kwang
Published: March 2018

A HA–EGF conjugate patch was developed for the treatment of diabetic chronic wounds with advantages such as facilitating topical delivery and interaction with dual receptors, and alleviating the degradation of EGF.
Oligothienyl catenated germanes and silanes: synthesis, structure, and properties
Authors: Zaitsev Kirill V. , Lam Kevin , Poleshchuk Oleg Kh. , Kuz'mina Lyudmila G. , Churakov Andrei V.
Published: March 2018

A series of catenated terminal and internal Group 14 oligothienyl derivatives was obtained; their structural, electrochemical, and optical properties were investigated.
Lantern-like bismuth oxyiodide embedded typha-based carbon via in situ self-template and ion exchange–recrystallization for high-performance photocatalysis
Authors: Hou Jianhua , Wei Rui , Wu Xiaoge , Tahir Muhammad , Wang Xiaozhi , Butt Faheem K. , Cao Chuanbao
Published: March 2018

Well-defined lantern-like hierarchical Bi7O9I3/NTC with superior photocatalytic activity is successfully obtained via a one-step route using in situ ion exchange–recrystallization.
Rapid and controlled photo-induced thiol–ene wrinkle formationviaflowcoating
Authors: Ma Stephen J. , Wagner Norman J. , Kloxin Christopher J.
Published: March 2018

Spatially controlled wrinkle formation on an elastomeric substrate is achieved through flowcoating of a nanometer thick, high modulus thiol–ene film laminated on a millimeter-thick thiol–ene elastomer.