bluuebunny/crossref_metadata_2025 huggingface dataset:
In-host evolution of Staphylococcus epidermidis in a pacemaker-associated endocarditis resulting in increased antibiotic tolerance
Authors: Dengler Haunreiter Vanina , Boumasmoud Mathilde , Häffner Nicola , Wipfli Dennis , Leimer Nadja , Rachmühl Carole , Kühnert Denise , Achermann Yvonne , Zbinden Reinhard , Benussi Stefano , Vulin Clement , Zinkernagel Annelies S.
Published: March 2019

Treatment failure in biofilm-associated bacterial infections is an important healthcare issue. In vitro studies and mouse models suggest that bacteria enter a slow-growing/non-growing state that results in transient tolerance to antibiotics in the absence of a specific resistance mechanism. However, little clinical confirmation of antibiotic tolerant bacteria in patients exists. In this study we investigate a Staphylococcus epidermidis pacemaker-associated endocarditis, in a patient who developed a break-through bacteremia despite taking antibiotics to which the S. epidermidis isolate is fully susceptible in vitro. Characterization of the clinical S. epidermidis isolates reveals in-host evolution over the 16-week infection period, resulting in increased antibiotic tolerance of the entire population due to a prolonged lag time until growth resumption and a reduced growth rate. Furthermore, we observe adaptation towards an increased biofilm formation capacity and genetic diversification of the S. epidermidis isolates within the patient.
Targeting of dermal myofibroblasts through death receptor 5 arrests fibrosis in mouse models of scleroderma
Authors: Park Jong-Sung , Oh Yumin , Park Yong Joo , Park Ogyi , Yang Hoseong , Slania Stephanie , Hummers Laura K. , Shah Ami A. , An Hyoung-Tae , Jang Jiyeon , Horton Maureen R. , Shin Joseph , Dietz Harry C. , Song Eric , Na Dong Hee , Park Eun Ji , Kim Kwangmeyung , Lee Kang Choon , Roschke Viktor V. , Hanes Justin , Pomper Martin G. , Lee Seulki
Published: March 2019

Scleroderma is an autoimmune rheumatic disorder accompanied by severe fibrosis in skin and other internal organs. During scleroderma progression, resident fibroblasts undergo activation and convert to α-smooth muscle actin (α-SMA) expressing myofibroblasts (MFBs) with increased capacity to synthesize collagens and fibrogenic components. Accordingly, MFBs are a major therapeutic target for fibrosis in scleroderma and treatment with blocking MFBs could produce anti-fibrotic effects. TLY012 is an engineered human TNF-related apoptosis-inducing ligand (TRAIL) which induces selective apoptosis in transformed cells expressing its cognate death receptors (DRs). Here we report that TLY012 selectively blocks activation of dermal fibroblasts and induces DR-mediated apoptosis in α-SMA+ MFBs through upregulated DR5 during its activation. In vivo, TLY012 reverses established skin fibrosis to near-normal skin architecture in mouse models of scleroderma. Thus, the TRAIL pathway plays a critical role in tissue remodeling and targeting upregulated DR5 in α-SMA+ MFBs is a viable therapy for fibrosis in scleroderma.
Small contact resistance and high-frequency operation of flexible low-voltage inverted coplanar organic transistors
Authors: Borchert James W. , Peng Boyu , Letzkus Florian , Burghartz Joachim N. , Chan Paddy K. L. , Zojer Karin , Ludwigs Sabine , Klauk Hagen
Published: March 2019

The contact resistance in organic thin-film transistors (TFTs) is the limiting factor in the development of high-frequency organic TFTs. In devices fabricated in the inverted (bottom-gate) device architecture, staggered (top-contact) organic TFTs have usually shown or are predicted to show lower contact resistance than coplanar (bottom-contact) organic TFTs. However, through comparison of organic TFTs with different gate-dielectric thicknesses based on the small-molecule organic semiconductor 2,9-diphenyl-dinaphtho[2,3-b:2’,3’-f]thieno[3,2-b]thiophene, we show the potential for bottom-contact TFTs to have lower contact resistance than top-contact TFTs, provided the gate dielectric is sufficiently thin and an interface layer such as pentafluorobenzenethiol is used to treat the surface of the source and drain contacts. We demonstrate bottom-contact TFTs fabricated on flexible plastic substrates with record-low contact resistance (29 Ωcm), record subthreshold swing (62 mV/decade), and signal-propagation delays in 11-stage unipolar ring oscillators as short as 138 ns per stage, all at operating voltages of about 3 V.
Enterovirus particles expel capsid pentamers to enable genome release
Authors: Buchta David , Füzik Tibor , Hrebík Dominik , Levdansky Yevgen , Sukeník Lukáš , Mukhamedova Liya , Moravcová Jana , Vácha Robert , Plevka Pavel
Published: March 2019

Viruses from the genus Enterovirus are important human pathogens. Receptor binding or exposure to acidic pH in endosomes converts enterovirus particles to an activated state that is required for genome release. However, the mechanism of enterovirus uncoating is not well understood. Here, we use cryo-electron microscopy to visualize virions of human echovirus 18 in the process of genome release. We discover that the exit of the RNA from the particle of echovirus 18 results in a loss of one, two, or three adjacent capsid-protein pentamers. The opening in the capsid, which is more than 120 Å in diameter, enables the release of the genome without the need to unwind its putative double-stranded RNA segments. We also detect capsids lacking pentamers during genome release from echovirus 30. Thus, our findings uncover a mechanism of enterovirus genome release that could become target for antiviral drugs.
Terrain uplift due to natural hydrologic overpressure in karstic conduits
Authors: Braitenberg Carla , Pivetta Tommaso , Barbolla Dora Francesca , Gabrovšek Franci , Devoti Roberto , Nagy Ildikó
Published: March 2019

Water supply from karst sources is a worldwide natural resource and the exploitation is tied to the knowledge of the positions of the hydrologic channels. We show that surface deformation induced by flood events in karst conduits is observable, and consists in uplift and outward movement from the hydraulic channel. Precipitation events produce the natural occurrence of subsurface hydraulic overpressure up to 1 MPa. Numerical modeling shows that the stresses are so strong to uplift and dislocate the surface by several mm and induce tilts in the order of microradians. The naturally induced deformation is compatible with a transient internal pressure loading of a channel. The results can be used to find new channels with dense GNSS networks. Sea water incursion and channels accessed for tourism could be monitored. Seismicity has been shown to have a seasonal variation in some areas, which could be explained by the subsurface stresses induced by the natural subsurface overpressure. The pressure induced deformation is expected to be observed in all karstic systems worldwide.
Black carbon and other light-absorbing impurities in snow in the Chilean Andes
Authors: Rowe Penny M. , Cordero Raul R. , Warren Stephen G. , Stewart Emily , Doherty Sarah J. , Pankow Alec , Schrempf Michael , Casassa Gino , Carrasco Jorge , Pizarro Jaime , MacDonell Shelley , Damiani Alessandro , Lambert Fabrice , Rondanelli Roberto , Huneeus Nicolas , Fernandoy Francisco , Neshyba Steven
Published: March 2019

Vertical profiles of black carbon (BC) and other light-absorbing impurities were measured in seasonal snow and permanent snowfields in the Chilean Andes during Austral winters 2015 and 2016, at 22 sites between latitudes 18°S and 41°S. The samples were analyzed for spectrally-resolved visible light absorption. For surface snow, the average mass mixing ratio of BC was 15 ng/g in northern Chile (18–33°S), 28 ng/g near Santiago (a major city near latitude 33°S, where urban pollution plays a significant role), and 13 ng/g in southern Chile (33–41°S). The regional average vertically-integrated loading of BC was 207 µg/m2 in the north, 780 µg/m2 near Santiago, and 2500 µg/m2 in the south, where the snow season was longer and the snow was deeper. For samples collected at locations where there had been no new snowfall for a week or more, the BC concentration in surface snow was high (~10–100 ng/g) and the sub-surface snow was comparatively clean, indicating the dominance of dry deposition of BC. Mean albedo reductions due to light-absorbing impurities were 0.0150, 0.0160, and 0.0077 for snow grain radii of 100 µm for northern Chile, the region near Santiago, and southern Chile; respective mean radiative forcings for the winter months were 2.8, 1.4, and 0.6 W/m2. In northern Chile, our measurements indicate that light-absorption by impurities in snow was dominated by dust rather than BC.
Coevolution of visual behaviour, the material world and social complexity, depicted by the eye-tracking of archaeological objects in humans
Authors: Criado-Boado Felipe , Alonso-Pablos Diego , Blanco Manuel J. , Porto Yolanda , Rodríguez-Paz Anxo , Cabrejas Elena , del Barrio-Álvarez Elena , Martínez Luis M.
Published: March 2019

We live in a cluttered visual world that is overflowing with information, the continuous processing of which would be a truly daunting task. Nevertheless, our brains have evolved to select which part of a visual scene is to be prioritized and analysed in detail, and which parts can be discarded or analysed at a later stage. This selection is in part determined by the visual stimuli themselves, and is known as “selective attention”, which, in turn, determines how we explore and interact with our environment, including the distinct human artefacts produced in different socio-cultural contexts. Here we hypothesize that visual responses and material objects should therefore co-evolve to reflect changes in social complexity and culture throughout history. Using eye-tracking, we analysed the eye scan paths in response to prehistoric pottery ranging from the Neolithic through to the Iron Age (ca 6000–2000 BP), finding that each ceramic style caused a particular pattern of visual exploration. Horizontal movements become dominant in earlier periods, while vertical movements are more frequent in later periods that were marked by greater social complexity.
Fusion proteins consisting of Bet v 1 and Phl p 5 form IgE-reactive aggregates with reduced allergenic activity
Authors: Najafi N. , Hofer G. , Gattinger P. , Smiljkovic D. , Blatt K. , Selb R. , Stoecklinger A. , Keller W. , Valent P. , Niederberger V. , Thalhamer J. , Valenta R. , Flicker S.
Published: March 2019

The cross-linking of effector cell-bound IgE antibodies by allergens induces the release of inflammatory mediators which are responsible for the symptoms of allergy. We demonstrate that a recombinant hybrid molecule consisting of the major birch (Bet v 1) and grass (Phl p 5) pollen allergen exhibited reduced allergenic activity as compared to equimolar mixes of the isolated allergens in basophil activation experiments. The reduced allergenic activity of the hybrid was not due to reduced IgE reactivity as demonstrated by IgE binding experiments using sera from allergic patients. Physicochemical characterization of the hybrid by size exclusion chromatography, dynamic light scattering, negative-stain electron microscopy and circular dichroism showed that the hybrid occurred as folded aggregate whereas the isolated allergens were folded monomeric proteins. IgG antibodies raised in rabbits against epitopes of Bet v 1 and Phl p 5 showed reduced reactivity with the hybrid compared to the monomeric allergens. Our results thus demonstrate that aggregation can induce changes in the conformation of allergens and lead to the reduction of allergenic activity. This is a new mechanism for reducing the allergenic activity of allergens which may be important for modifying allergens to exhibit reduced side effects when used for allergen-specific immunotherapy.
Lifespan Changes of the Human Brain In Alzheimer’s Disease
Authors: Coupé Pierrick , Manjón José Vicente , Lanuza Enrique , Catheline Gwenaelle
Published: March 2019

Brain imaging studies have shown that slow and progressive cerebral atrophy characterized the development of Alzheimer’s Disease (AD). Despite a large number of studies dedicated to AD, key questions about the lifespan evolution of AD biomarkers remain open. When does the AD model diverge from the normal aging model? What is the lifespan trajectory of imaging biomarkers for AD? How do the trajectories of biomarkers in AD differ from normal aging? To answer these questions, we proposed an innovative way by inferring brain structure model across the entire lifespan using a massive number of MRI (N = 4329). We compared the normal model based on 2944 control subjects with the pathological model based on 3262 patients (AD + Mild cognitive Impaired subjects) older than 55 years and controls younger than 55 years. Our study provides evidences of early divergence of the AD models from the normal aging trajectory before 40 years for the hippocampus, followed by the lateral ventricles and the amygdala around 40 years. Moreover, our lifespan model reveals the evolution of these biomarkers and suggests close abnormality evolution for the hippocampus and the amygdala, whereas trajectory of ventricular enlargement appears to follow an inverted U-shape. Finally, our models indicate that medial temporal lobe atrophy and ventricular enlargement are two mid-life physiopathological events characterizing AD brain.
Exploration of the Structure and Recognition of a G-quadruplex in the her2 Proto-oncogene Promoter and Its Transcriptional Regulation
Authors: Cui Xiaojie , Chen Han , Zhang Qiang , Xu Ming , Yuan Gu , Zhou Jiang
Published: March 2019

G-quadruplexes in oncogene promoters provide putative targets for transcriptional regulation. The structure of a putative G-quadruplex sequence (S1: GGAGAAGGAGGAGGTGGAGGAGGAGGG) in potassium solution in the her2 promoter has been resolved mainly through nuclear magnetic resonance (NMR) spectroscopy. By application of various NMR spectra, we proved the formation of a four-layer G-quadruplex composing of two G-tetrads and two G/A-mixed planes with a four-residues loop (A3-G4-A5-A6). Further evidence from a luciferase reporter assay, Q-RT-PCR and Western blotting indicates that S1 G-quadruplex formation can repress her2 promoter activity, and a selected G-quadruplex ligand cβ can enhance the repression by down regulating her2 transcription and expression. These findings provide a G-quadruplex target and perspective implications in her2 transcriptional regulation.
Vibration induced refrigeration using ferroelectric materials
Authors: Kumar Anuruddh , Chauhan Aditya , Patel Satyanarayan , Novak Nikola , Kumar Rajeev , Vaish Rahul
Published: March 2019

This article aims to propose a cantilever based cooling device employing non-axis symmetric placement of bulk ferroelectric patches. Ambient mechanical vibrations produce large stresses in cantilevers resulting in elastocaloric effect associated with ferroelectrics. Further, design allows cascading of several cantilevers to achieve large cooling response. A finite element analysis of the system was performed using material properties of bulk 0.50Ba(Zr0.2Ti0.8)O3−0.50(Ba0.7Ca0.3)TiO3. An individual element could produce a peak elastocaloric effect of 0.02 K (324 K); whereas the proposed system could achieve a temperature drop of 0.2 K within 50 seconds (10 elements, 1.5 Hz). Furthermore, net cooling can be further improved about ~2 K (using 10 cantilevers) for a starting temperature of 358 K. This study shows that elastocaloric effect in ferroelectric materials is capable of converting waste mechanical vibration into refrigeration effect which is not reported so far.
Parasitoid envenomation alters the Galleria mellonella midgut microbiota and immunity, thereby promoting fungal infection
Authors: Polenogova Olga V. , Kabilov Marsel R. , Tyurin Maksim V. , Rotskaya Ulyana N. , Krivopalov Anton V. , Morozova Vera V. , Mozhaitseva Kseniya , Kryukova Nataliya A. , Alikina Tatyana , Kryukov Vadim Yu. , Glupov Viktor V.
Published: March 2019

Gut bacteria influence the development of different pathologies caused by bacteria, fungi and parasitoids in insects. Wax moth larvae became more susceptible to fungal infections after envenomation by the ectoparasitoid Habrobracon hebetor. In addition, spontaneous bacterioses occurred more often in envenomated larvae. We analyzed alterations in the midgut microbiota and immunity of the wax moth in response to H. hebetor envenomation and topical fungal infection (Beauveria bassiana) alone or in combination using 16S rRNA sequencing, an analysis of cultivable bacteria and a qPCR analysis of immunity- and stress-related genes. Envenomation led to a predominance shift from enterococci to enterobacteria, an increase in CFUs and the upregulation of AMPs in wax moth midguts. Furthermore, mycosis nonsignificantly increased the abundance of enterobacteria and the expression of AMPs in the midgut. Combined treatment led to a significant increase in the abundance of Serratia and a greater upregulation of gloverin. The oral administration of predominant bacteria (Enterococcus faecalis, Enterobacter sp. and Serratia marcescens) to wax moth larvae synergistically increased fungal susceptibility. Thus, the activation of midgut immunity might prevent the bacterial decomposition of envenomated larvae, thus permitting the development of fungal infections. Moreover, changes in the midgut bacterial community may promote fungal killing.
Plastics in sea surface waters around the Antarctic Peninsula
Authors: Lacerda Ana L. d. F. , Rodrigues Lucas dos S. , van Sebille Erik , Rodrigues Fábio L. , Ribeiro Lourenço , Secchi Eduardo R. , Kessler Felipe , Proietti Maíra C.
Published: March 2019

Although marine plastic pollution has been the focus of several studies, there are still many gaps in our understanding of the concentrations, characteristics and impacts of plastics in the oceans. This study aimed to quantify and characterize plastic debris in oceanic surface waters of the Antarctic Peninsula. Sampling was done through surface trawls, and mean debris concentration was estimated at 1,794 items.km−2 with an average weight of 27.8 g.km−2. No statistical difference was found between the amount of mesoplastics (46%) and microplastics (54%). We found hard and flexible fragments, spheres and lines, in nine colors, composed mostly of polyurethane, polyamide, and polyethylene. An oceanographic dispersal model showed that, for at least seven years, sampled plastics likely did not originate from latitudes lower than 58°S. Analysis of epiplastic community diversity revealed bacteria, microalgae, and invertebrate groups adhered to debris. Paint fragments were present at all sampling stations and were approximately 30 times more abundant than plastics. Although paint particles were not included in plastic concentration estimates, we highlight that they could have similar impacts as marine plastics. We call for urgent action to avoid and mitigate plastic and paint fragment inputs to the Southern Ocean.
Prenatal treatment with EGCG enriched green tea extract rescues GAD67 related developmental and cognitive defects in Down syndrome mouse models
Authors: Souchet Benoit , Duchon Arnaud , Gu Yuchen , Dairou Julien , Chevalier Claire , Daubigney Fabrice , Nalesso Valérie , Créau Nicole , Yu Yuejin , Janel Nathalie , Herault Yann , Delabar Jean Maurice
Published: March 2019

Down syndrome is a common genetic disorder caused by trisomy of chromosome 21. Brain development in affected foetuses might be improved through prenatal treatment. One potential target is DYRK1A, a multifunctional kinase encoded by chromosome 21 that, when overexpressed, alters neuronal excitation–inhibition balance and increases GAD67 interneuron density. We used a green tea extract enriched in EGCG to inhibit DYRK1A function only during gestation of transgenic mice overexpressing Dyrk1a (mBACtgDyrk1a). Adult mice treated prenatally displayed reduced levels of inhibitory markers, restored VGAT1/VGLUT1 balance, and rescued density of GAD67 interneurons. Similar results for gabaergic and glutamatergic markers and interneuron density were obtained in Dp(16)1Yey mice, trisomic for 140 chromosome 21 orthologs; thus, prenatal EGCG exhibits efficacy in a more complex DS model. Finally, cognitive and behaviour testing showed that adult Dp(16)1Yey mice treated prenatally had improved novel object recognition memory but do not show improvement with Y maze paradigm. These findings provide empirical support for a prenatal intervention that targets specific neural circuitries.
E-syt1 Re-arranges STIM1 Clusters to Stabilize Ring-shaped ER-PM Contact Sites and Accelerate Ca2+ Store Replenishment
Authors: Kang Fei , Zhou Mengxuan , Huang Xiaoshuai , Fan Junchao , Wei Lisi , Boulanger Jerome , Liu Zengzhen , Salamero Jean , Liu Yanmei , Chen Liangyi
Published: March 2019

In many non-excitable cells, the depletion of endoplasmic reticulum (ER) Ca2+ stores leads to the dynamic formation of membrane contact sites (MCSs) between the ER and the plasma membrane (PM), which activates the store-operated Ca2+ entry (SOCE) to refill the ER store. Two different Ca2+-sensitive proteins, STIM1 and extended synaptotagmin-1 (E-syt1), are activated during this process. Due to the lack of live cell super-resolution imaging, how MCSs are dynamically regulated by STIM1 and E-syt1 coordinately during ER Ca2+ store depletion and replenishment remain unknown. With home-built super-resolution microscopes that provide superior axial and lateral resolution in live cells, we revealed that extracellular Ca2+ influx via SOCE activated E-syt1s to move towards the PM by ~12 nm. Unexpectedly, activated E-syt1s did not constitute the MCSs per se, but re-arranged neighboring ER structures into ring-shaped MCSs (230~280 nm in diameter) enclosing E-syt1 puncta, which helped to stabilize MCSs and accelerate local ER Ca2+ replenishment. Overall, we have demonstrated different roles of STIM1 and E-syt1 in MCS formation regulation, SOCE activation and ER Ca2+ store replenishment.
Mxenes Derived Laminated and Magnetic Composites with Excellent Microwave Absorbing Performance
Authors: Feng Wanlin , Luo Heng , Wang Yu , Zeng Sifan , Tan Yongqiang , Deng Lianwen , Zhou Xiaosong , Zhang Haibin , Peng Shuming
Published: March 2019

Two dimensional materials have been widely identified as promising microwave absorbers, owing to their large surface area and abundant interfaces. Here, a novel laminated and magnetic composite derived from Mxene was designed and successfully synthesized via facile hydrothermal oxidization of nickel ion intercalated Ti3C2. Highly disordered carbon sheets were obtained by low temperature hydrothermal oxidization, and the in-situ produced TiO2 and NiO nanoparticles embedded closely between them. This layered hybrid exhibits excellent microwave absorbing performance with an effective absorbing bandwidth as high as 11.1 GHz (6.9–18 GHz) and 9 GHz (9–18 GHz) when the thickness is 3 and 2 mm, respectively. Besides the high dielectric loss, magnetic loss and ohmic loss of the composite, the amorphous nature of obtained carbon sheets and multi-reflections between them are believed to play a decisive role in achieving such superior microwave absorbing performance.
The relevance of Brownian relaxation as power absorption mechanism in Magnetic Hyperthermia
Authors: Torres Teobaldo E. , Lima Enio , Calatayud M. Pilar , Sanz Beatriz , Ibarra Alfonso , Fernández-Pacheco Rodrigo , Mayoral Alvaro , Marquina Clara , Ibarra M. Ricardo , Goya Gerardo F.
Published: March 2019

The Linear Response Theory (LRT) is a widely accepted framework to analyze the power absorption of magnetic nanoparticles for magnetic fluid hyperthermia. Its validity is restricted to low applied fields and/or to highly anisotropic magnetic nanoparticles. Here, we present a systematic experimental analysis and numerical calculations of the specific power absorption for highly anisotropic cobalt ferrite (CoFe2O4) magnetic nanoparticles with different average sizes and in different viscous media. The predominance of Brownian relaxation as the origin of the magnetic losses in these particles is established, and the changes of the Specific Power Absorption (SPA) with the viscosity of the carrier liquid are consistent with the LRT approximation. The impact of viscosity on SPA is relevant for the design of MNPs to heat the intracellular medium during in vitro and in vivo experiments. The combined numerical and experimental analyses presented here shed light on the underlying mechanisms that make highly anisotropic MNPs unsuitable for magnetic hyperthermia.
Degradation kinetics of cold plasma-treated antibiotics and their antimicrobial activity
Authors: Sarangapani Chaitanya , Ziuzina Dana , Behan Patrice , Boehm Daniela , Gilmore Brendan F. , Cullen P. J. , Bourke Paula
Published: March 2019

Antibiotics, such as ofloxacin (OFX) and ciprofloxacin (CFX), are often detected in considerable concentrations in both wastewater effluents and surface water. This poses a risk to non-target organisms and to human health. The aim of this work was to study atmospheric cold plasma (ACP) degradation of antibiotics in water and meat effluent and to explore any residual antimicrobial activity of samples submitted to the plasma process. The results revealed that ACP successfully degraded the studied antibiotics and that the reaction mechanism is principally related to attack by hydroxyl radicals and ozone. According to the disk diffusion assay, the activity of both antibiotics was considerably reduced by the plasma treatment. However, a microdilution method demonstrated that CFX exhibited higher antimicrobial activity after ACP treatment than the corresponding control revealing a potentially new platform for future research to improve the efficiency of conventional antibiotic treatments. Importantly, short-term exposures to sub-lethal concentrations of the antibiotic equally reduced bacterial susceptibility to both ACP treated and untreated CFX. As a remediation process, ACP removal of antibiotics in complex wastewater effluents is possible. However, it is recommended that plasma encompass degradant structure activity relationships to ensure that biological activity is eliminated against non-target organisms and that life cycle safety of antibiotic compounds is achieved.
Spontaneous center formation in Dictyostelium discoideum
Authors: Vidal-Henriquez Estefania , Gholami Azam
Published: March 2019

Dictyostelium discoideum (D.d.) is a widely studied amoeba due to its capabilities of development, survival, and self-organization. During aggregation it produces and relays a chemical signal (cAMP) which shows spirals and target centers. Nevertheless, the natural emergence of these structures is still not well understood. We present a mechanism for creation of centers and target waves of cAMP in D.d. by adding cell inhomogeneity to a well known reaction-diffusion model of cAMP waves and we characterize its properties. We show how stable activity centers appear spontaneously in areas of higher cell density with the oscillation frequency of these centers depending on their density. The cAMP waves have the characteristic dispersion relation of trigger waves and a velocity which increases with cell density. Chemotactically competent cells react to these waves and create aggregation streams even with very simple movement rules. Finally we argue in favor of the existence of bounded phosphodiesterase to maintain the wave properties once small cell clusters appear.
Spontaneous Parametric Down-Conversion Induced by Non-Degenerate Three-Wave Mixing in a Scanning MEMS Micro Mirror
Authors: Nabholz Ulrike , Schatz Frank , Mehner Jan E. , Degenfeld-Schonburg Peter
Published: March 2019

Scanning micro-mirror actuators are silicon-based oscillatory micro-electro-mechanical systems (MEMS). They enable laser distance measurements for automotive LIDAR applications as well as projection modules for the consumer market. For MEMS applications, the geometric structure is typically designed to serve a number of functional requirements. Most importantly, the mode spectrum contains a single high-Q mode, the drive mode, which per design is expected to yield the only resonantly excited geometric motion during operation. Yet here, we report on the observation of a resonant three-mode excitation via a process known as spontaneous parametric down-conversion. We show that this phenomenon, most extensively studied in the field of nonlinear optics, originates from three-wave coupling induced by geometric nonlinearities. In combination with further Duffing-type nonlinearities, the micro mirror displays a variety of nonlinear dynamical behaviour ranging from stationary state bifurcations to dynamical instabilities observable via amplitude modulations. We are able to explain and emulate all experimental observations using a single fundamental model. In particular, our analysis allows us to understand the conditions for the onset of three-wave down-conversion which if not accounted for in the design of the MEMS structure, can have drastic impact on its functionality even leading to fracture.
Thermally-responsive Virus-like Particle for Targeted Delivery of Cancer Drug
Authors: Thong Qiu Xian , Biabanikhankahdani Roya , Ho Kok Lian , Alitheen Noorjahan Banu , Tan Wen Siang
Published: March 2019

Multifunctional nanocarriers displaying specific ligands and simultaneously response to stimuli offer great potentials for targeted and controlled drug delivery. Several synthetic thermally-responsive nanocarriers have been studied extensively for hyperthermia incorporated chemotherapy. However, no information is available on the application of virus-like particle (VLP) in thermally-controlled drug delivery systems. Here, we describe the development of a novel multifunctional nanovehicle based on the VLP of Macrobrachium rosenbergii nodavirus (MrNVLP). Folic acid (FA) was covalently conjugated to lysine residues located on the surface of MrNVLP, while doxorubicin (Dox) was loaded inside the VLP using an infusion method. This thermally-responsive nanovehicle, namely FA-MrNVLP-Dox, released Dox in a sustained manner and the rate of drug release increased in response to a hyperthermia temperature at 43 °C. The FA-MrNVLP-Dox enhanced the delivery of Dox to HT29 cancer cells expressing high level of folate receptor (FR) as compared to CCD841CoN normal cells and HepG2 cancer cells, which express low levels of FR. As a result, FA-MrNVLP-Dox increased the cytotoxicity of Dox on HT29 cells, and decreased the drug’s cytotoxicity on CCD841CoN and HepG2 cells. This study demonstrated the potential of FA-MrNVLP-Dox as a thermally-responsive nanovehicle for targeted delivery of Dox to cancer cells rich in FR.
Generalizing the first-difference correlated random walk for marine animal movement data
Authors: Albertsen Christoffer Moesgaard
Published: March 2019

Animal telemetry data are often analysed with discrete time movement models. These models are defined with regular time steps. However, telemetry data from marine animals are observed irregularly. To account for irregular data, a time-irregularised first-difference correlated random walk model with drift is introduced. The model generalizes the commonly used first-difference correlated random walk with regular time steps by allowing irregular time steps, including a drift term, and by allowing different autocorrelation in the two coordinates. The model is applied to data from a ringed seal collected through the Argos satellite system, and is compared to related movement models through simulations. Accounting for irregular data in the movement model results in accurate parameter estimates and reconstruction of movement paths. Further, the introduced model can provide more accurate movement paths than the regular time counterpart. Extracting accurate movement paths from uncertain telemetry data is important for evaluating space use patterns for marine animals, which in turn is crucial for management. Further, handling irregular data directly in the movement model allows efficient simultaneous analyses of several animals.
Atomic Resolution Defocused Electron Ptychography at Low Dose with a Fast, Direct Electron Detector
Authors: Song Jiamei , Allen Christopher S. , Gao Si , Huang Chen , Sawada Hidetaka , Pan Xiaoqing , Warner Jamie , Wang Peng , Kirkland Angus I.
Published: March 2019

Electron ptychography has recently attracted considerable interest for high resolution phase-sensitive imaging. However, to date studies have been mainly limited to radiation resistant samples as the electron dose required to record a ptychographic dataset is too high for use with beam-sensitive materials. Here we report defocused electron ptychography using a fast, direct-counting detector to reconstruct the transmission function, which is in turn related to the electrostatic potential of a two-dimensional material at atomic resolution under various low dose conditions.
Capturing 3D large-strain Euler-bending filament dynamics in fibrous media simulations; sample case of compression collapse in dendritic actin network
Authors: Simhadri Jyothirmai J. , Chandran Preethi L.
Published: March 2019

Cytoskeletal networks to transmission towers are comprised of slender elements. Slender filaments bend and buckle more easily than stretch. Therefore a deforming network is expected to exhaust all possible bending-based modes before engaging filament stretch. While the large-strain bending critically determines fibrous-media response, simulations use small-strain and jointed approximations. At low resolution, these approximations inflate bending resistance and delay buckling onset. The proposed string-of-continuous-beams (SOCB) approach captures 3D nonlinear Euler bending of filaments with high fidelity at low cost. Bending geometry (i.e. angles and its differentials) is solved as primary variables, to fit a 5thorder polynomial of the contour angle. Displacement, solved simultaneously as length conservation, is predicted with C3 and C6 smoothness between and within segments, using only 2 nodes. In the chosen analysis frame, in-plane and out-plane moments can be decoupled for arbitrarily-curved segments. Complex crosslink force-transfers can be specified. Simulations show that when a daughter branch is appended, the buckling resistance of a filament changes from linear to nonlinear before reversible collapse. An actin outcrop with 8 generations of mother-daughter branching produced the linear, nonlinear, and collapse regimes observed in compression experiments. ‘Collapse’ was a redistribution of outcrop forces following the buckling of few strands.
Circuit-Based Quantum Random Access Memory for Classical Data
Authors: Park Daniel K. , Petruccione Francesco , Rhee June-Koo Kevin
Published: March 2019

A prerequisite for many quantum information processing tasks to truly surpass classical approaches is an efficient procedure to encode classical data in quantum superposition states. In this work, we present a circuit-based flip-flop quantum random access memory to construct a quantum database of classical information in a systematic and flexible way. For registering or updating classical data consisting of M entries, each represented by n bits, the method requires O(n) qubits and O(Mn) steps. With post-selection at an additional cost, our method can also store continuous data as probability amplitudes. As an example, we present a procedure to convert classical training data for a quantum supervised learning algorithm to a quantum state. Further improvements can be achieved by reducing the number of state preparation queries with the introduction of quantum forking.
Correcting locomotion dependent observation biases in thermal preference of Drosophila
Authors: Giraldo Diego , Adden Andrea , Kuhlemann Ilyas , Gras Heribert , Geurten Bart R. H.
Published: March 2019

Sensing environmental temperatures is essential for the survival of ectothermic organisms. InDrosophila, two of the most used methodologies to study temperature preferences (TP) and the genes involved in thermosensation are two-choice assays and temperature gradients. Whereas two-choice assays reveal a relative TP, temperature gradients can identify the absolute Tp. One drawback of gradients is that small ectothermic animals are susceptible to cold-trapping: a physiological inability to move at the cold area of the gradient. Often cold-trapping cannot be avoided, biasing the resulting TPto lower temperatures. Two mathematical models were previously developed to correct for cold-trapping. These models, however, focus on group behaviour which can lead to overestimation of cold-trapping due to group aggregation. Here we present a mathematical model that simulates the behaviour of individualDrosophilain temperature gradients. The model takes the spatial dimension and temperature difference of the gradient into account, as well as the rearing temperature of the flies. Furthermore, it allows the quantification of cold-trapping and reveals unbiased TP.Additionally, our model reveals that flies have a range of tolerable temperatures, and this measure is more informative about the behaviour than commonly used TP. Online simulation is hosted athttp://igloo.uni-goettingen.de. The code can be accessed athttps://github.com/zerotonin/igloo.
Limits of Babinet’s principle for solid and hollow plasmonic antennas
Authors: Horák M. , Křápek V. , Hrtoň M. , Konečná A. , Ligmajer F. , Stöger-Pollach M. , Šamořil T. , Paták A. , Édes Z. , Metelka O. , Babocký J. , Šikola T.
Published: March 2019

We present an experimental and theoretical study of Babinet’s principle of complementarity in plasmonics. We have used spatially-resolved electron energy loss spectroscopy and cathodoluminescence to investigate electromagnetic response of elementary plasmonic antenna: gold discs and complementary disc-shaped apertures in a gold layer. We have also calculated their response to the plane wave illumination. While the qualitative validity of Babinet’s principle has been confirmed, quantitative differences have been found related to the energy and quality factor of the resonances and the magnitude of related near fields. In particular, apertures were found to exhibit stronger interaction with the electron beam than solid antennas, which makes them a remarkable alternative of the usual plasmonic-antennas design. We also examine the possibility of magnetic near field imaging based on the Babinet’s principle.
Prelimbic and infralimbic cortical inactivations attenuate contextually driven discriminative responding for reward
Authors: Riaz Sadia , Puveendrakumaran Pugaliya , Khan Dinat , Yoon Sharon , Hamel Laurie , Ito Rutsuko
Published: March 2019

The infralimbic (IL) and prelimbic (PL) cortices of the medial prefrontal cortex (mPFC) have been shown to differentially control context-dependent behavior, with the PL implicated in the expression of contextually conditioned fear and drug-seeking, and the IL in the suppression of these behaviors. However, the roles of these subregions in contextually driven natural reward-seeking remain relatively underexplored. The present study further examined the functional dichotomy within the mPFC in the contextual control over cued reward-seeking, using a contextual biconditional discrimination (CBD) task. Rats were first trained to emit a nose poke response to the presentation of an auditory stimulus (e.g., X) for the delivery of sucrose reward, and to withhold a nose poke response to the presentation of another auditory stimulus (e.g., Y) in a context-specific manner (e.g. Context A: X+, Y−; Context B: X−, Y+). Following acquisition, rats received bilateral microinjections of GABA receptor agonists (muscimol and baclofen), or saline into the IL or PL, prior to a CBD training session and a probe test (under extinction conditions). Both IL and PL inactivation resulted in robust impairment in CBD performance, indicating that both subregions are involved in the processing of appetitively motivated contextual memories in reward-seeking.
Carboxyl-terminal modulator protein regulates Akt signaling during skeletal muscle atrophy in vitro and a mouse model of amyotrophic lateral sclerosis
Authors: Wang Junmei , Fry Colin M. E. , Walker Chandler L.
Published: March 2019

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease involving motor neuron death, paralysis and, ultimately, respiratory failure. Motor neuron dysfunction leads to target skeletal muscle atrophy involving dysregulation of downstream cell survival, growth and metabolic signaling. Decreased Akt activity is linked to muscle atrophy in ALS and is associated with increased atrophy gene expression. Unfortunately, the regulating mechanism of Akt activity in atrophic muscle remains unclear. Recent research indicates a role of carboxyl-terminal modulator protein (CTMP) in Akt-signaling related neurologic dysfunction and skeletal muscle metabolism. CTMP is known to bind and reduce Akt phosphorylation and activation. We hypothesized that CTMP expression might progressively increase in ALS skeletal muscle as the disease progresses, downregulating Akt activity. We found that CTMP protein expression significantly increased in hindlimb skeletal muscle in the mSOD1G93A mouse model of ALS in late stages of the disease (P < 0.05), which negatively correlated with Akt phosphorylation over this period (R2 = −0.77). Co-immunoprecipitation of Akt revealed CTMP binding in pre-symptomatic and end-stage skeletal muscle, suggesting a possible direct role in reduced Akt signaling during disease progression. Inflammatory TNFα and downstream cellular degradation process markers for autophagy, lysosome production, and atrophy significantly increased in a pattern corresponding to increased CTMP expression and reduced Akt phosphorylation. In an in vitro model of skeletal muscle atrophy, differentiated C2C12 cells exhibited reduced Akt activity and decreased FOXO1 phosphorylation, a process known to promote transcription of atrophy genes in skeletal muscle. These results corresponded with  increased  Atrogin-1 expression  compared to healthy control cells  (P < 0.05). Transfection with CTMP siRNA significantly increased Akt phosphorylation in atrophic C2C12 cells, corresponding to significantly decreased CTMP expression. In conclusion, this is the first study to provide evidence for a link between elevated CTMP expression, downregulated Akt phosphorylation and muscle atrophy in ALS and clearly demonstrates a direct influence of CTMP on Akt phosphorylation in an in vitro muscle cell atrophy model.
Spatio-temporal patterns and characteristics of swine shipments in the U.S. based on Interstate Certificates of Veterinary Inspection
Authors: Gorsich Erin E. , Miller Ryan S. , Mask Holly M. , Hallman Clayton , Portacci Katie , Webb Colleen T.
Published: March 2019

Domestic swine production in the United States is a critical economic and food security industry, yet there is currently no large-scale quantitative assessment of swine shipments available to support risk assessments. In this study, we provide a national-level characterization of the swine industry by quantifying the demographic (i.e. age, sex) patterns, spatio-temporal patterns, and the production diversity within swine shipments. We characterize annual networks of swine shipments using a 30% stratified sample of Interstate Certificates of Veterinary Inspection (ICVI), which are required for the interstate movement of agricultural animals. We used ICVIs in 2010 and 2011 from eight states that represent 36% of swine operations and 63% of the U.S. swine industry. Our analyses reflect an integrated and spatially structured industry with high levels of spatial heterogeneity. Most shipments carried young swine for feeding or breeding purposes and carried a median of 330 head (range: 1–6,500). Geographically, most shipments went to and were shipped from Iowa, Minnesota, and Nebraska. This work, therefore, suggests that although the swine industry is variable in terms of its size and type of swine, counties in states historically known for breeding and feeding operations are consistently more central to the shipment network.
Clinical and endoscopic characteristics of sessile serrated adenomas/polyps with dysplasia/adenocarcinoma in a Korean population: A Korean Association for the Study of Intestinal Diseases (KASID) multicenter study
Authors: Kim Ki-Hyun , Kim Kyeong-Ok , Jung Yunho , Lee Jun , Kim Sang-Wook , Kim Jae-Hyun , Kim Tae-Jun , Cho Young-Seok , Joo Young-Eun
Published: March 2019

Sessile serrated adenomas/polyps (SSA/Ps) are precancerous lesions that account for one-third of colorectal cancers. The endoscopic and pathologic differentiation between SSA/Ps without dysplasia (SSA/POs) and SSA/Ps with dysplasia or adenocarcinoma (SSA/PDAs) can be difficult. This study aimed to assess the clinical characteristics of SSA/PDs. This multicenter retrospective cohort study included 532 patients who underwent endoscopic resection and were pathologically diagnosed with SSA/POs and SSA/PDAs. Initially, medical, endoscopic, and histopathological records of patients who underwent endoscopic resection of SSA/POs and SSA/PDAs at eight university hospitals in Korea between January 2005 and December 2015 were reviewed. A total of 307 (57.7%) patients were detected in men and 319 (60.0%) were located in the proximal colon. Most SSA/Ps had a flat, slightly elevated, or sessile morphology. The most prevalent endoscopic findings of SSA/Ps were nodular surface (244, 45.9%), disrupted vascular pattern (232, 43.6%), altered fold contour (141, 26.5%), dome-shaped morphology (135, 25.4%), and pale color (115, 21.6%). SSA/POs were more commonly found in the proximal colon, compared to SSA/PDAs. SSA/PDAs displayed 0-Ip, Isp, IIb or IIa + IIc morphologies more frequently, while SSA/POs displayed 0-Is or IIa morphology more frequently. The frequency of a rim of debris/bubbles was significantly higher in SSA/POs, while nodular surface and disrupted vascular pattern were significantly higher in SSA/PDAs. In the univariate analysis of endoscopic features, SSA/PDAs were significantly associated with the distal colon location, 0-Isp and IIb morphologies, nodular surface, and disrupted vascular pattern. In the multivariate analysis, 0-IIb, nodular surface, and disrupted vascular pattern were significantly associated with SSA/PDAs. SSA/Ps with 0-IIb morphology, nodular surface and disrupted vascular pattern are associated with an increased risk of dysplasia or adenocarcinoma.
Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States
Authors: Chen Fangzhou , Knutson Todd P. , Rossow Stephanie , Saif Linda J. , Marthaler Douglas G.
Published: March 2019

The epidemiology and genetic diversity oftransmissible gastroenteritis virus(TGEV) in the United States (US) was investigated by testing clinical cases for TGEV by real time RT-PCR between January 2008 and November 2016. Prevalence of TGEV ranged between 3.8–6.8% and peaked during cold months until March 2013, in which prevalence decreased to < 0.1%. Nineteen complete TGEV genomes and a single strain ofporcine respiratory coronavirus(PRCV) from the US were generated and compared to historical strains to investigate the evolution of these endemic coronaviruses. Sixteen of our TGEV strains share 8 unique deletions and 119 distinct amino acid changes, which might greatly affect the biological characteristics of the variant TGEV, and resulted in a “variant” genotype of TGEV. The “variant” genotype shared similar unique deletions and amino acid changes with the recent PRCV strain identified in this study, suggesting a recombination event occurred between the ‘‘variant’’ TGEV and PRCV. Moreover, the results indicate the “variant” genotype is the dominant genotype circulating in the US. Therefore, this study provides insight into the occurrence, origin, genetic characteristics, and evolution of TGEV and PRCV circulating in the US.