bluuebunny/crossref_metadata_2025 huggingface dataset:
A Gold Nanocage/Cluster Hybrid Structure for Whole‐Body Multispectral Optoacoustic Tomography Imaging, EGFR Inhibitor Delivery, and Photothermal Therapy
Authors: Zhan Chenyue , Huang Yong , Lin Guifang , Huang Shuailing , Zeng Fang , Wu Shuizhu
Published: June 2019

Gold nanocages (AuNCs) and gold nanoclusters (AuClusters) are two classes of advantageous nanostructures with special optical properties, and many other attractive properties. Integrating them into one nanosystem may achieve greater and smarter performance. Herein, a hybrid gold nanostructure for fluorescent and optoacoustic tomography imaging, controlled release of drugs, and photothermal therapy (PTT) is demonstrated. For this nanodrug (EA–AB), an epidermal growth factor receptor (EGFR) inhibitor erlotinib (EB) is loaded into AuNCs, which are then capped and functionalized by biocompatible AuCluster@BSA (BSA = bovine serum albumin) conjugates via electrostatic interaction. Upon cell internalization, the lysosomal proteases and low pH cause the release of EB from EA–AB, and also induce fluorescence restoration of the AuCluster for imaging. Irradiation with near‐infrared light further promotes the drug release and affords a PTT effect as well. The AuNC‐based nanodrug is optoacoustically active, and its biodistribution and metabolic process have been successfully monitored by whole‐body and 3D multispectral optoacoustic tomography imaging. Owing to the combined actions of PTT and EGFR pathway blockage, EA–AB exhibits marked tumor inhibition efficacy in vivo.
Energy‐based predictive algorithm for semi‐active tuned mass dampers
Authors: Zelleke Daniel H. , Matsagar Vasant A.
Published: June 2019

There are various control strategies proposed and implemented for the protection of structures against different types of dynamic excitations. Currently, semi‐active control devices are very popular due to their adaptability and low power requirement. In this paper, a novel energy‐based predictive (EBP) algorithm is proposed, and its effectiveness is studied when applied to semi‐active tuned mass damper (SATMD). The mechanical energy of the primary structure is taken as the key parameter to be used by the algorithm to predict a suitable value of the manipulated variable, the damping of the tuned mass damper (TMD). The choice of the damping is made such that the damping used at a time interval leads to the least possible mechanical energy of the primary structure. The efficacy of the proposed control algorithm is studied by employing the EBP algorithm on single‐story and multistory structures equipped with the SATMD. The performance of the proposed algorithm when applied to the SATMD is also compared with that with the passive TMD for similar parameters. The results of the study show that the implementation of the EBP algorithm leads to significantly reduced dynamic response as compared with the passive TMD. Furthermore, numerical studies are conducted to gain insight into the effect of various parameters such as the mass ratio, the TMD damping ratio, and the flexibility of the structure.
Observation of radiative double electron capture for
Authors: Kumara Nuwan , La Mantia David S. , Buglione Stephanie L. , McCoy Craig P. , Taylor Charles J. , White Jacob S. , Kayani Asghar , Tanis John A.
Published: June 2019

Radiative double electron capture (RDEC), occurring when two electrons are captured to a projectile ion with the simultaneous emission of a single photon, has been investigated. RDEC can be considered as the time inverse process of double photoionization. Strong evidence for RDEC is found in F9+ + N2 collisions and additionally for one‐electron F8+ for which the probability for the process is expected to be considerably smaller. Preliminary values for the cross sections for RDEC have been determined. A significant advantage of the gas target is that multiple‐collision effects seen for a solid target are avoided due to the single‐collision conditions that prevail for gas targets.
Spin 2 operators in holographic 4d $$ \mathcal{N}=2 $$ SCFTs
Authors: Chen Kevin , Gutperle Michael , Uhlemann Christoph F.
Published: June 2019

Abstract

A broad class of holographic duals for 4d

$$ \mathcal{N}=2 $$

N
=
2

SCFTs is based on the general half-BPS AdS
5 solutions to M-theory constructed by Lin, Lunin and Maldacena, and their Kaluza-Klein reductions to Type IIA. We derive the equations governing spin 2 fluctuations around these solutions. The resulting partial differential equations admit families of universal solutions which are constructed entirely out of the generic data characterizing the background. This implies the existence of families of spin 2 operators in the dual SCFTs, in short superconformal multiplets which we identify.
Improved EEMD-based standardization method for developing long tree-ring chronologies
Authors: Zhang Xianliang , Li Junxia , Liu Xiaobo , Chen Zhenju
Published: June 2019

Long tree-ring chronologies can be developed by overlapping data from living trees with data from fossil trees through cross-dating. However, low-frequency climate signals are lost when standardizing tree-ring series due to the “segment length curse”. To alleviate the segment length curse and thus improve the standardization method for developing long tree-ring chronologies, here we first calculated a mean value for all the tree ring series by overlapping all of the tree ring series. The growth trend of the mean tree ring width (i.e., cumulated average growth trend of all the series) was determined using ensemble empirical mode decomposition. Then the chronology was developed by dividing the mean value by the growth trend of the mean value. Our improved method alleviated the problem of trend distortion. Long-term signals were better preserved using the improved method than in previous detrending methods. The chronologies developed using the improved method were better correlated with climate than those developed using conservative methods. The improved standardization method alleviates trend distortion and retains more of the low-frequency climate signals.
A singular vorticity wave packet within a rapidly rotating vortex: spiralling versus oscillating motions
Authors: Caillol Philippe
Published: June 2019

This paper considers a free vorticity wave packet propagating within a rapidly rotating vortex in the quasi-steady regime, a long time after the wave packet strongly and unsteadily interacted with the vortex. We study a singular, nonlinear, helical and asymmetric shear mode inside a linearly stable, columnar and axisymmetric vortex on the $f$-plane. The amplitude-modulated mode enters resonance with the vortex at a certain radius $r_{c}$, where the phase angular speed is equal to the rotation frequency. The singularity in the modal equation at $r_{c}$ strongly modifies the flow in the three-dimensional helical critical layer, the region around $r_{c}$ where the wave/vortex interaction occurs. This interaction generates a vertically sheared three-dimensional mean flow of higher amplitude than the wave packet. The chosen envelope regime assumes the formation of a mean radial velocity of the same order as the wave packet amplitude, leading to the streamlines exhibiting a spiral motion in the neighbourhood of the critical layer. Radar images frequently show such spiral bands in tropical cyclones or tornadoes. Through matched asymptotic expansions, we find an analytical solution of the leading-order equations inside the critical layer. The generalized Batchelor integral condition applied to the quasi-steady, three-dimensional motion inside the separatrices yields a leading-order, non-uniform three-dimensional vorticity. The critical-layer pattern, strongly deformed by the mean radial velocity, loses its symmetries with respect to the azimuthal and radial directions, which makes the leading-order mean radial wave fluxes non-zero. Finally, a stronger wave/vortex interaction occurs with respect to previous studies where a steady neutral vortical mode or an envelope of larger extent was involved.
VARIETIES OF BURDEN IN RELIGIOUS ACCOMMODATIONS
Authors: Su Anna
Published: June 2019

Religious accommodation analysis often takes the form of a tripartite test. One of the factors in such a test is the presence of burden, the current judicial understandings of which have been inadequate to capture a wide range of impact that government regulations have on the individual or community practice of religion. This article considers and compares the jurisprudence of the high courts of the United States and Canada and the European Court of Human Rights and argues for an expansive understanding of the burden requirement in the evaluation of religious accommodation claims, namely to consider burden as (1) coercion, (2) impact, and (3) ratification. I argue that it is imperative to acknowledge different kinds of burden before proceeding to determine its gravity. This approach takes religion more seriously than prevailing approaches and provides for a more equitable distribution of the burden of proof in religious accommodation claims.
A macro- and micronutrient-fortified complementary food supplement reduced acute infection, improved haemoglobin and showed a dose–response effect in improving linear growth: a 12-month cluster randomised trial
Authors: Ghosh Shibani A. , Strutt Nicholas R. , Otoo Gloria E. , Suri Devika J. , Ankrah Judith , Johnson Thomas , Nsiah Paul , Furuta Chie , Murakami Hitoshi , Perera Gillian , Chui Kenneth , Bomfeh Kennedy , Amonoo-Kuofi Harold , Tano-Debrah Kwaku , Uauy Ricardo
Published: June 2019

Inadequate protein quality may be a risk factor for poor growth. To examine the effect of a macronutrient–micronutrient supplement KOKO Plus (KP), provided to infants from 6 to 18 months of age, on linear growth, a single-blind cluster-randomised study was implemented in Ghana. A total of thirty-eight communities were randomly allocated to receive KP (fourteen communities,n322), a micronutrient powder (MN, thirteen communities,n329) and nutrition education (NE, eleven communities,n319). A comparison group was followed cross-sectionally (n303). Supplement delivery and morbidity were measured weekly and anthropometry monthly. NE education was provided monthly. Baseline, midline and endline measurements at 6, 12 and 18 months included venous blood draws, diet, anthropometry, morbidity, food security and socio-economics. Length-for-ageZ-score (LAZ) was the primary outcome. Analyses were intent-to-treat using mixed-effects regressions adjusted for clustering, sex, age and baseline. No differences existed in mean LAZ scores at endline (−1·219 (sd0·06) KP, −1·211 (sd0·03) MN, −1·266 (sd0·03) NE). Acute infection prevalence was lower in the KP than NE group (P= 0·043). Mean serum Hb was higher in KP infants free from acute infection (114·02 (sd1·87) g/l) than MN (107·8 (sd2·5) g/l;P= 0·047) and NE (108·8 (sd0·99) g/l;P= 0·051). Compliance was 84·9 % (KP) and 87·2 % (MN) but delivery 60 %. Adjusting for delivery and compliance, LAZ score at endline was significantly higher in the KPv.MN group (+0·2 LAZ;P= 0·026). A macro- and micronutrient-fortified supplement KP reduced acute infection, improved Hb and demonstrated a dose–response effect on LAZ adjusting consumption for delivery.
The iconicity toolbox: empirical approaches to measuring iconicity
Authors: MOTAMEDI YASAMIN , LITTLE HANNAH , NIELSEN ALAN , SULIK JUSTIN
Published: June 2019

abstract

Growing evidence from across the cognitive sciences indicates that iconicity plays an important role in a number of fundamental language processes, spanning learning, comprehension, and online use. One benefit of this recent upsurge in empirical work is the diversification of methods available for measuring iconicity. In this paper, we provide an overview of methods in the form of a ‘toolbox’. We lay out empirical methods for measuring iconicity at a behavioural level, in the perception, production, and comprehension of iconic forms. We also discuss large-scale studies that look at iconicity on a system-wide level, based on objective measures of similarity between signals and meanings. We give a detailed overview of how different measures of iconicity can better address specific hypotheses, providing greater clarity when choosing testing methods.
Desde la perspectiva de la isla: el ordenamiento territorial incaico en la transecta andina Arica-Carangas (18° S)
Authors: Saintenoy Thibault , González Estefane Federico , Uribe Rodríguez Mauricio
Published: June 2019

Estudiamos el imperialismo incaico en el contexto de las formaciones socioterritoriales del Colesuyu durante la época prehispánica tardía (siglos quince y dieciséis). Por su poblamiento con alto grado de multietnicidad e imbricación socioterritorial, además de su heterogeneidad biogeográfica entre el Pacífico y el Altiplano, esta región de los Valles Occidentales de los Andes Centro-Sur planteó un reto geopolítico para su integración imperial. Nos interesamos aquí por el caso de los Altos de Arica, que los archivos coloniales describen como un espacio multiétnico, con complejos sistemas de asentamiento interdigitados, extendidos entre el altiplano de Carangas y el litoral de Arica. A partir de un catastro arqueogeográfico, complementado con datos de excavaciones y dataciones, analizamos el proceso de ordenamiento incaico del valle precordillerano de Belén (ca. 3.000 m snm), el cual era conocido como Tocoroma en los archivos coloniales y constituía la principal isla del archipiélago carangas en la vertiente occidental andina del 18° S. Evidenciamos la producción de un paisaje agrícola imperial en el valle y discutimos la función nodal de Tocoroma-Belén en el contexto de la integración socioterritorial de la transecta Arica-Carangas. Asimismo, el estudio confirma el protagonismo del Tawantinsuyu en la estructuración de los archipiélagos verticales de los Andes Centro-Sur, además de documentar la diversidad de los dispositivos de hegemonía imperial implementados para este fin.
Geological and geophysical study of a thin-skinned tectonic wedge formed during an early collisional stage: the Trasimeno Tectonic Wedge (Northern Apennines, Italy)
Authors: Carboni Filippo , Brozzetti Francesco , Mirabella Francesco , Cruciani Francesco , Porreca Massimiliano , Ercoli Maurizio , Back Stefan , Barchi Massimiliano R.
Published: June 2019

The presence of a set of well-known turbidite successions, deposited in progressively E-migrating foredeep basins and subsequently piled up with east vergence, makes the Northern Apennines of Italy paradigmatic of the evolution of deepwater fold-and-thrust belts. This study focuses on the early Apenninic collisional stage, early Miocene in age, which led to the accretion of the turbidites of the Trasimeno Tectonic Wedge (TTW), in the central part of the Northern Apennines. Based on the interpretation of previously unpublished seismic reflection profiles with new surface geology data and tectonic balancing, we present a detailed tectonic reconstruction of the TTW. In the study area, the TTW is characterized by a W-dipping shaly basal décollement located at a depth of 1–5 km. The tectonic wedge isc. 5 km thick at its central-western part and tapers progressively eastwards toc. 1 km. The total shortening, balanced along a 33 km long cross-section, isc. 60 km, including 20 km (40%) of internal imbrication,c. 23 km of horizontal ENE-wards translation along the basal décollement andc. 17 km of passive translation caused by the later shortening of footwall units. Deformation balancing, constrained through upper Aquitanian – upper Burdigalian (c. 21–16 Ma) biostratigraphy, provides an average shortening rate ofc. 8.6 mm a–1. Internal shortening of the TTW shows an average shortening rate ofc. 4 mm a–1for this period.
Saritā and the 1950s Hindi Middlebrow Reader
Authors: MANDHWANI AAKRITI
Published: June 2019

The article discusses Saritā, one of the best-selling Hindi magazines of the 1950s, and the part it played in the establishment of the Hindi ‘middlebrow’ reader. While a rich and vibrant journal culture in Hindi had existed since the nineteenth century, what distinguishes the post-1947 Hindi popular magazine is the emergence of the middle class as a burgeoning consumer. Saritā defied prescriptions of Nehruvian state building, as well as the right-wing discourses of nationalism and national language prevalent in the post-Independence space. In addition, it reconfigured biases towards gendered reading and consumption processes, as well as encouraging increased reader participation. This article argues for Saritā’s role in the creation of a middlebrow reading space in the period immediately following Independence, since it not only packaged what was deemed wholesome and educational for the family as a unit, but also, most significantly, promoted readership in segments, with a focus on each individual's reading desires.
Potential role of arteether on N-methyl-D-aspartate (NMDA) receptor expression in experimental cerebral malaria mice and extension of their survival
Authors: Singh Sunil Kumar , Dwivedi Hemlata , Gunjan Sarika , Chauhan Bhavana Singh , Pandey Swaroop Kumar , Tripathi Renu
Published: June 2019

Cerebral malaria (CM) is the severe neurological complication causing acute non-traumatic encephalopathy in tropical countries. The mechanisms underlying the fatal cerebral complications are still not fully understood. Glutamate, a major excitatory neurotransmitter in the central nervous system of the mammalian brain, plays a key role in the development of neuronal cells, motor function, synaptic plasticity, learning and memory processes under normal physiological conditions. The subtypes of ionotropic glutamate receptor are N-methyl-D-aspartate receptors (NMDARs) which are involved in cellular mechanisms of learning and memory, synaptic plasticity and also mediate excitotoxic neuronal injury. In the present study, we found that glutamate level in synaptosomes, as well as expression of NMDAR, was elevated during the extreme condition of CM in C57BL6 mice. Arteether at 50 mg kg−1× 1, 25 mg kg−1× 2, days decreased the NMDAR expression and increased the overall survival of the experimental CM mice.
Therapie alkoholbezogener Störungen im Alter: Ergebnisse der deutschen Stichprobe der randomisiert-kontrollierten ELDERLY-Studie bis zum 12-Monats-Follow-up
Authors: Braun Barbara , Behrendt Silke , Piontek Daniela , Kraus Ludwig , Bühringer Gerhard
Published: June 2019

Zusammenfassung. Zielsetzung: Der demographische Wandel lässt eine höhere Anzahl älterer Personen mit Alkoholproblemen erwarten, deren therapeutische Versorgung bislang unzureichend ist. Mit der internationalen, randomisiert-kontrollierten ELDERLY-Studie wurden zwei Varianten einer ambulanten psychotherapeutischen Behandlung für Personen ab 60 Jahren mit einer Alkoholkonsumstörung nach DSM-5 (AS) in drei Ländern erprobt. Methodik: Nach der Baseline-Befragung wurden die zufällig zugeordneten Behandlungsgruppen nach 1, 3, 6 und 12 Monaten erneut untersucht. Erfasst wurden Veränderungen (Zeit und Gruppe) hinsichtlich Trinkmenge, Anzahl abstinenter Tage, Anzahl Tage Rauschtrinken und Tage risikoarmen Konsums sowie Anzahl zutreffender DSM-5-Kriterien für AS. Complete-Case- und Intention-to-treat-Analysen werden für die deutsche Teilstichprobe vorgestellt (n=203). Ergebnisse: Für beide Behandlungsgruppen ergaben sich stabil bis zu 12 Monate nach Baseline ein Anstieg der Abstinenzrate (18 %; t0: 4 %), des Anteils der Personen ohne einen Tag mit riskantem Konsum (45 %, t0: 4 %) sowie ohne Rauschtrinken (68 %, t0: 15 %). Auch zeigte sich eine Verringerung der Trinkmenge (Median bei 27 g Reinalkohol pro Trinktag; t0: 58 g) und Anzahl erfüllter AS-Kriterien (Median bei 2; t0: 5). Schlussfolgerungen: Die Verbesserungen des Trinkverhaltens und der AS-Symptome waren trotz relativ kurzer Behandlungsdauer stabil. Motivierende Interventionen, insbesondere die persönliche Rückmeldung zum Trinkverhalten, bewirken auch bei älteren Personen mit alkoholbezogenen Störungen Verhaltensänderungen. Ein therapeutischer Nihilismus ist unangebracht; vielmehr sollten spezifische Bedürfnisse der Zielgruppe beachtet und in passenden Versorgungsangeboten umgesetzt werden.
Mobilization of Attached Clustered Colloids in Porous Media
Authors: Chequer Larissa , Bedrikovetsky Pavel , Carageorgos Themis , Badalyan Alexander , Gitis Vitaly
Published: June 2019

The models for colloidal mobilization in porous media are often based on Derjaguin‐Landau‐Verwey‐Overbeek interaction energy profiles. Despite abundant evidence on mobilization of particle clusters, the models to date have been limited to single colloid‐surface Derjaguin‐Landau‐Verwey‐Overbeek calculations. We show through visualization tests, qualitative and quantitative modeling, and data evaluation, that the widely accepted single colloid‐single surface isolation does not always adequately describe colloid behavior. The experiments were performed with kaolinite and latex particles mobilized from sand grains and glass beads in a transparent visualization cell. The particles were mobilized under increasing velocity and pH and decreasing salinity. The detachment conditions were determined by a torque balance of electrostatic, drag, lifting, and gravity forces, combined with a theory of a contact area between a single soft particle and a plane surface. The tests show that the calculations based on the mechanical equilibrium of a single particle on a plane surface significantly underestimate the critical detachment velocity. A better prediction is obtained using a cluster approximation. High‐resolution images taken during mobilization tests show 2‐12 particle clusters on media surface and in its proximity. The mechanical‐equilibrium calculations show that the attaching torque for clusters with assumed size and cylindrical shape is significantly higher than that for single particles. The critical detachment velocity of clusters, derived from the mechanical‐equilibrium force and torque balances, is higher than for single particles and provides a better fit to the experimental data. Our study suggests that a cluster approximation can accurately predict the mobilization of colloids in porous media.
Designing the Global Observing System for Marine Life
Authors: Miloslavich Patricia , Bax Nicholas , Satterthwaite Erin
Published: June 2019

Identifying the Backbone of a Global Observing System for Marine Life and Planning Its Implementation for the Next Decade; Santa Barbara, California, 5–7 March 2019
The Climate Data Toolbox for MATLAB
Authors: Greene Chad A. , Thirumalai Kaustubh , Kearney Kelly A. , Delgado José Miguel , Schwanghart Wolfgang , Wolfenbarger Natalie S. , Thyng Kristen M. , Gwyther David E. , Gardner Alex S. , Blankenship Donald D.
Published: June 2019

Climate science is highly interdisciplinary by nature, so understanding interactions between Earth processes inherently warrants the use of analytical software that can operate across the disciplines of Earth science. Toward this end, we present the Climate Data Toolbox for MATLAB, which contains more than 100 functions that span the major climate‐related disciplines of Earth science. The toolbox enables streamlined, entirely scriptable workflows that are intuitive to write and easy to share. Included are functions to evaluate uncertainty, perform matrix operations, calculate climate indices, and generate common data displays. Documentation is presented pedagogically, with thorough explanations of how each function works and tutorials showing how the toolbox can be used to replicate results of published studies. As a well‐tested, well‐documented platform for interdisciplinary collaborations, the Climate Data Toolbox for MATLAB aims to reduce time spent writing low‐level code, let researchers focus on physics rather than coding and encourage more efficacious code sharing.
ReishiMax inhibits mTORC1/2 by activating AMPK and inhibiting IGFR/PI3K/Rheb in tumor cells
Authors: Sohretoglu Didem , Zhang Chao , Luo Jun , Huang Shile
Published: June 2019

Ganoderma lucidum (G. lucidum) extracts, as dietary supplements, have been found to exert potent anticancer activity, which is attributed to the presence of polysaccharides and triterpenes. However, the molecular mechanism underlying the anticancer action of G. lucidum extracts remains to be investigated. Here, we show that ReishiMax GLp, containing G. lucidum polysaccharides and triterpenes (GLPT), inhibited cell proliferation and induced cell death in human lung cancer cells (A549 and A427) and simultaneously suppressed the signaling pathways of mammalian target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2), respectively. Mechanistically, GLPT downregulated the phosphorylation and protein levels of insulin-like growth factor 1 receptor (IGFR) and phosphoinositide 3-kinase (PI3K) as well as the protein level of RAS homolog enriched in brain (Rheb). In addition, GLPT also activated the AMP-activated protein kinase (AMPK) network. This was evidenced by observations that GLPT increased the phosphorylation of AMPKα (T172) and its substrates tuberous sclerosis complex 2 (TSC2, S1387) and regulatory-associated protein of mTOR (raptor, S792). Ectopic expression of dominant-negative AMPKα partially mitigated the inhibitory effect of GLPT on mTORC1, indicating that GLPT inhibits mTORC1 partly by activating AMPK. The results suggest that G. lucidum extracts exert anticancer action at least partly by suppressing mTORC1/2 signaling via activation of AMPK and inhibition of IGFR/PI3K/Rheb in tumor cells.
Modulation of extrasynaptic GABAA alpha 5 receptors in the ventral hippocampus normalizes physiological and behavioral deficits in a circuit specific manner
Authors: Donegan J. J. , Boley A. M. , Yamaguchi J. , Toney G. M. , Lodge D. J.
Published: June 2019

Hippocampal hyperactivity is correlated with psychosis in schizophrenia patients and likely attributable to deficits in GABAergic signaling. Here we attempt to reverse this deficit by overexpression of the α5-GABAA receptor within the ventral hippocampus (vHipp). Indeed, this is sufficient to normalize vHipp activity and downstream alterations in dopamine neuron function in the MAM rodent model. This approach also attenuated behavioral deficits in cognitive flexibility. To understand the specific pathways that mediate these effects, we used chemogenetics to manipulate discrete projections from the vHipp to the nucleus accumbens (NAc) or prefrontal cortex (mPFC). We found that inhibition of the vHipp-NAc, but not the vHipp-mPFC pathway, normalized aberrant dopamine neuron activity. Conversely, inhibition of the vHipp-mPFC improved cognitive function. Taken together, these results demonstrate that restoring GABAergic signaling in the vHipp improves schizophrenia-like deficits and that distinct behavioral alterations are mediated by discrete projections from the vHipp to the NAc and mPFC.
FGFR4 overexpression and hotspot mutations in metastatic ER+ breast cancer are enriched in the lobular subtype
Authors: Levine Kevin M. , Priedigkeit Nolan , Basudan Ahmed , Tasdemir Nilgun , Sikora Matthew J. , Sokol Ethan S. , Hartmaier Ryan J. , Ding Kai , Ahmad Nedah Z. , Watters Rebecca J. , Weiss Kurt R. , Blohmer Jens-Uwe , Denkert Carsten , Machleidt Anna , Karsten Maria M. , Boisen Michelle M. , Elishaev Esther , Lucas Peter C. , Lee Adrian V. , Oesterreich Steffi
Published: June 2019

Invasive lobular carcinoma (ILC) is an understudied subtype of breast cancer that requires novel therapies in the advanced setting. To study acquired resistance to endocrine therapy in ILC, we have recently performed RNA-Sequencing on long-term estrogen deprived cell lines and identified FGFR4 overexpression as a top druggable target. Here, we show that FGFR4 expression also increases dramatically in endocrine-treated distant metastases, with an average fold change of 4.8 relative to the paired primary breast tumor for ILC, and 2.4-fold for invasive ductal carcinoma (IDC). In addition, we now report that FGFR4 hotspot mutations are enriched in metastatic breast cancer, with an additional enrichment for ILC, suggesting a multimodal selection of FGFR4 activation. These data collectively support the notion that FGFR4 is an important mediator of endocrine resistance in ILC, warranting future mechanistic studies on downstream signaling of overexpressed wild-type and mutant FGFR4.
DNA extraction and amplicon production strategies deeply inf luence the outcome of gut mycobiome studies
Authors: Frau Alessandra , Kenny John G. , Lenzi Luca , Campbell Barry J. , Ijaz Umer Z. , Duckworth Carrie A. , Burkitt Michael D. , Hall Neil , Anson Jim , Darby Alistair C. , Probert Christopher S. J.
Published: June 2019

Microbial ecology studies are often performed through extraction of metagenomic DNA followed by amplification and sequencing of a marker. It is known that each step may bias the results. These biases have been explored for the study of bacterial communities, but rarely for fungi. Our aim was therefore to evaluate methods for the study of the gut mycobiome. We first evaluated DNA extraction methods in fungal cultures relevant to the gut. Afterwards, to assess how these methods would behave with an actual sample, stool from a donor was spiked with cells from the same cultures. We found that different extraction kits favour some species and bias against others. In terms of amplicon sequencing, we evaluated five primer sets, two for ITS2 and one for ITS1, 18S and 28S rRNA. Results showed that 18S rRNA outperformed the other markers: it was able to amplify all the species in the mock community and to discriminate among them. ITS primers showed both amplification and sequencing biases, the latter related to the variable length of the product. We identified several biases in the characterisation of the gut mycobiome and showed how crucial it is to be aware of these before drawing conclusions from the results of these studies.
Untargeted metabolomics unveil alterations of biomembranes permeability in human HaCaT keratinocytes upon 60 GHz millimeter-wave exposure
Authors: Le Pogam Pierre , Le Page Yann , Habauzit Denis , Doué Mickael , Zhadobov Maxim , Sauleau Ronan , Le Dréan Yves , Rondeau David
Published: June 2019

A joint metabolomic and lipidomic workflow is used to account for a potential effect of millimeter waves (MMW) around 60 GHz on biological tissues. For this purpose, HaCaT human keratinocytes were exposed at 60.4 GHz with an incident power density of 20 mW/cm², this value corresponding to the upper local exposure limit for general public in the context of a wide scale deployment of MMW technologies and devices. After a 24h-exposure, endo- and extracellular extracts were recovered to be submitted to an integrative UPLC-Q-Exactive metabolomic and lipidomic workflow. R-XCMS data processing and subsequent statistical treatment led to emphasize a limited number of altered features in lipidomic sequences and in intracellular metabolomic analyses, whatever the ionization mode (i.e 0 to 6 dysregulated features). Conversely, important dysregulations could be reported in extracellular metabolomic profiles with 111 and 99 frames being altered upon MMW exposure in positive and negative polarities, respectively. This unexpected extent of modifications can hardly stem from the mild changes that could be reported throughout transcriptomics studies, leading us to hypothesize that MMW might alter the permeability of cell membranes, as reported elsewhere.
Author Correction: A rare genetic variant of BPIFB4 predisposes to high blood pressure via impairment of nitric oxide signaling
Authors: Vecchione Carmine , Villa Francesco , Carrizzo Albino , Spinelli Chiara Carmela , Damato Antonio , Ambrosio Mariateresa , Ferrario Anna , Madonna Michele , Uccellatore Annachiara , Lupini Silvia , Maciag Anna , Ryskalin Larisa , Milanesi Luciano , Frati Giacomo , Sciarretta Sebastiano , Bellazzi Riccardo , Genovese Stefano , Ceriello Antonio , Auricchio Alberto , Malovini Alberto , Puca Annibale Alessandro
Published: June 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper
Task-dependent functional organizations of the visual ventral stream
Authors: Jo Han-Gue , Ito Junji , Schulte Holthausen Barbara , Baumann Conrad , Grün Sonja , Habel Ute , Kellermann Thilo
Published: June 2019

The visual hierarchy of the ventral stream has been widely studied. However, it remains unclear how the hierarchical system organizes its functional coupling during top-down cognitive process. The present fMRI study investigated task-dependent functional connectivity along the ventral stream, while twenty-eight participants performed object recognition tasks that required different types of visual processing: i) searching or ii) memorizing visual objects embedded in natural scene images or iii) free viewing of the same images. Utilizing a seed-based approach that explicitly compared task-specific BOLD time-series, we identified task-dependent functional connectivity of the visual ventral stream, demonstrating different correlation structures. Searching for a target object manifested both correlated and anti-correlated structures, separating the visual areas V1 and V4 from the posterior part of the inferior temporal cortex (PIT). In contrast, the ventral stream structure remained correlated during memorizing objects, but increased the correlation between the right V4 and PIT. On the other hand, V1 and V4 showed task-dependent activation, whereas PIT was deactivated. These results highlight the context-dependent nature of the visual ventral stream and shed light on how the visual hierarchy is selectively organized to bias object recognition toward features of interest.
Skin Carotenoid Index in a large Japanese population sample
Authors: Obana Akira , Gohto Yuko , Gellermann Werner , Ermakov Igor V. , Sasano Hiroyuki , Seto Takahiko , Bernstein Paul S.
Published: June 2019

Carotenoids are anti-oxidative agents. Human skin and eyes contain specific carotenoid species known to prevent various pathologies caused by oxidative stress. We quantified skin and eye carotenoid levels and investigated their potential correlation in a population including 985 Japanese patients and staff members of an ophthalmology clinic (577 men, 408 women, mean age of 69.7 ± 13.6 [SD]). Skin carotenoid (SC) and macular pigment (MP) levels were measured with reflection spectroscopy and autofluorescence imaging methods, respectively. The mean SC index was 343.1 ± 142.1 (SD). SC indices for women were higher than for men (382 vs 315, p < 0.001). Smokers and overweight subjects (BMI ≥ 25) had lower SC indices. Subjects taking lutein supplements had higher SC indices than non-supplementing subjects (415 vs 325, p < 0.001). SC and MP indices were significantly correlated. The obtained data set can be used for reference purposes by Japanese subjects and researchers interested in tissue responses to diets high in carotenoids and lutein supplementation.
A novel host-adapted strain of Salmonella Typhimurium causes renal disease in olive ridley turtles (Lepidochelys olivacea) in the Pacific
Authors: Work Thierry M. , Dagenais Julie , Stacy Brian A. , Ladner Jason T. , Lorch Jeffrey M. , Balazs George H. , Barquero-Calvo Elías , Berlowski-Zier Brenda M. , Breeden Renee , Corrales-Gómez Natalia , Gonzalez-Barrientos Rocio , Harris Heather S. , Hernández-Mora Gabriela , Herrera-Ulloa Ángel , Hesami Shoreh , Jones T. Todd , Morales Juan Alberto , Norton Terry M. , Rameyer Robert A. , Taylor Daniel R. , Waltzek Thomas B.
Published: June 2019

Salmonella spp. are frequently shed by wildlife including turtles, but S. enterica subsp. enterica serovar Typhimurium or lesions associated with Salmonella are rare in turtles. Between 1996 and 2016, we necropsied 127 apparently healthy pelagic olive ridley turtles (Lepidochelys olivacea) that died from drowning bycatch in fisheries and 44 live or freshly dead stranded turtles from the west coast of North and Central America and Hawaii. Seven percent (9/127) of pelagic and 47% (21/44) of stranded turtles had renal granulomas associated with S. Typhimurium. Stranded animals were 12 times more likely than pelagic animals to have Salmonella-induced nephritis suggesting that Salmonella may have been a contributing cause of stranding. S. Typhimurium was the only Salmonella serovar detected in L. olivacea, and phylogenetic analysis from whole genome sequencing showed that the isolates from L. olivacea formed a single clade distinct from other S. Typhimurium. Molecular clock analysis revealed that this novel clade may have originated as recently as a few decades ago. The phylogenetic lineage leading to this group is enriched for non-synonymous changes within the genomic area of Salmonella pathogenicity island 1 suggesting that these genes are important for host adaptation.
Carbon cycle instability and orbital forcing during the Middle Eocene Climatic Optimum
Authors: Giorgioni Martino , Jovane Luigi , Rego Eric S. , Rodelli Daniel , Frontalini Fabrizio , Coccioni Rodolfo , Catanzariti Rita , Özcan Ercan
Published: June 2019

The Middle Eocene Climatic Optimum (MECO) is a global warming event that occurred at about 40 Ma. In comparison to the most known global warming events of the Paleogene, the MECO has some peculiar features that make its interpretation controversial. The main peculiarities of the MECO are a duration of ~500 kyr and a carbon isotope signature that varies from site to site. Here we present new carbon and oxygen stable isotopes records (δ13C and δ18O) from three foraminiferal genera dwelling at different depths throughout the water column and the sea bottom during the middle Eocene, from eastern Turkey. We document that the MECO is related to major oceanographic and climatic changes in the Neo-Tethys and also in other oceanic basins. The carbon isotope signature of the MECO is difficult to interpret because it is highly variable from site to site. We hypothesize that such δ13C signature indicates highly unstable oceanographic and carbon cycle conditions, which may have been forced by the coincidence between a 400 kyr and a 2.4 Myr orbital eccentricity minimum. Such forcing has been also suggested for the Cretaceous Oceanic Anoxic Events, which resemble the MECO event more than the Cenozoic hyperthermals.
Multiple hollow-core anti-resonant fiber as a supermodal fiber interferometer
Authors: Huang Xiaosheng , Zang Jichao , Yoo Seongwoo
Published: June 2019

Hollow-core anti-resonant fiber technology has made a rapid progress in low loss broadband transmission, enabled by its much reduced light-material overlap. This unique characteristic has driven emerging of new applications spanning from extreme wavelength generation to beam delivery. The successful demonstrations appear to suggest progression of the technology toward device level development and all-fiberized systems. We investigate this opportunity and report an in-fiber interferometer built in a dual hollow-core anti-resonant fiber. By placing multiple air cores in a single fiber, coherently interacting transverse modes are excited, which becomes a basis of an interferometer. We use this hollow core based inherent supermodal interaction to demonstrate highly sensitive in-fiber interferometer. Unique combination of the air guidance and the supermodal interaction offers robust, simple yet highly sensitive interferometer with suppressed temperature cross-talk that has been an enduring problem in fiber strain sensing applications. The in-fiber interferometer is further investigated as a sensing element for pressure measurement based on an interferometric phase change upon external strain. The interferometer features 39.3 nm/MPa of ultrahigh sensitivity with 0.14 KPa/°C of negligible gas pressure temperature crosstalk. The performance, which is much improved from prior fiber sensors, testifies advances of hollow core fiber technology toward a device level.
Evaluation of Candida peritonitis with underlying peritoneal fibrosis and efficacy of micafungin in murine models of intra-abdominal candidiasis
Authors: Ashizawa Nobuyuki , Miyazaki Taiga , Abe Shinichi , Takazono Takahiro , Saijo Tomomi , Obata Yoko , Shimamura Shintaro , Yamamoto Kazuko , Imamura Yoshifumi , Koji Takehiko , Nishino Tomoya , Izumikawa Koichi , Yanagihara Katsunori , Kohno Shigeru , Mukae Hiroshi
Published: June 2019

Candida peritonitis is a crucial disease, however the optimal antifungal therapy regimen has not been clearly defined. Peritoneal fibrosis (PF) can be caused by abdominal surgery, intra-abdominal infection, and malignant diseases, and is also widely recognized as a crucial complication of long-term peritoneal dialysis. However, the influence of PF on Candida peritonitis prognosis remains unknown. Here, we evaluated the severity of Candida peritonitis within the context of PF and the efficacy of micafungin using mice. A PF mouse model was generated by intraperitoneally administering chlorhexidine gluconate. Candida peritonitis, induced by intraperitoneal inoculation of Candida albicans, was treated with a 7-day consecutive subcutaneous administration of micafungin. Candida infection caused a higher mortality rate in the PF mice compared with the control mice on day 7. Proliferative Candida invasion into the peritoneum and intra-abdominal organs was confirmed pathologically only in the PF mice. However, all mice in both groups treated with micafungin survived until day 20. Micafungin treatment tends to suppress inflammatory cytokines in the plasma 12 h after infection in both groups. Our results suggest that PF enhances early mortality in Candida peritonitis. Prompt initiation and sufficient doses of micafungin had good efficacy for Candida peritonitis, irrespective of the underlying PF.
Animal Study to Evaluate the Effect of Carbon Dioxide Insufflation on Recurrent Laryngeal Nerve Function in Transoral Endoscopic Thyroidectomy
Authors: Zhang Daqi , Li Shijie , Dionigi Gianlorenzo , Zhang Jiao , Niu Chunbo , Wang Tie , Liang Nan , Sun Hui
Published: June 2019

Data with regard to potential recurrent laryngeal nerve (RLN) compromise caused by intra-neck CO2 insufflation during transoral endoscopic thyroidectomy vestibular approach (TOETVA) are missing. RLN electromyographic (EMG) profiles, metabolic and hemodynamic parameters (oxygen saturation, heart rate, blood pressure, experimental time, CO2 partial pressure, pH, O2 partial pressure), central venous pressure (CVP), airpocket temperature and pressure were recorded in a TOETVA animal model. Twelve pigs were randomly divided into different groups according to increasing CO2 insufflation pressures. Nerves segments were then collected for histopathology. Significant variation of metabolic and hemodynamic parameters were registered when CO2 insufflation pressures increased x3 and x5 the baseline parameters. Combined EMG amplitude drop and latency increase also were documented. There was no significant change in the intraluminal temperature. RLNs structure were preserved with normal axons, no fibrosis, and no vacuolization and without loss of myelinated fibers during the experiment. RLN EMG profiles (but not histology) were altered when CO2 insufflation pressures increased.
Limited evidence of hierarchical encoding in the cheerleader effect
Authors: Carragher Daniel J. , Thomas Nicole A. , Gwinn O. Scott , Nicholls Mike E. R.
Published: June 2019

“The cheerleader effect” refers to the increase in attractiveness that an individual face experiences when seen in a group of other faces. It has been proposed that the cheerleader effect occurs because (a) the visual system rapidly summarises a group of faces into an ensemble representation, (b) which is hypothesised to be highly attractive because of its average facial characteristics, and (c) observers remember individual faces to be more alike the ensemble representation than they were, due to hierarchical structure of visual working memory. Across three experiments, we investigated whether the cheerleader effect is consistent with hierarchical encoding, by asking observers to give attractiveness ratings to the same target faces shown in groups and alone. Consistent with hierarchical encoding, the largest attractiveness increases of 1.5–2.0% occurred when target faces were presented in groups of faces that could be mentally summarised to create an ensemble representation with average facial characteristics. Surprisingly, smaller cheerleader effects still occurred in conditions that were incompatible with hierarchical encoding (i.e., groups with non-human images). Together, these results offer only limited evidence for the role of hierarchical encoding in the cheerleader effect, suggesting that alternative mechanisms must be explored in future research.
The two faces of titanium dioxide nanoparticles bio-camouflage in 3D bone spheroids
Authors: Souza W. , Piperni S. G. , Laviola P. , Rossi A. L. , Rossi Maria Isabel D. , Archanjo Bráulio S. , Leite P. E. , Fernandes M. H. , Rocha L. A. , Granjeiro J. M. , Ribeiro A. R.
Published: June 2019

Titanium (Ti) and its alloys are widely used in dental implants and hip-prostheses due to their excellent biocompatibility. Growing evidence support that surface degradation due to corrosion and wear processes, contribute to implant failure, since the release of metallic ions and wear particles generate local tissue reactions (peri-implant inflammatory reactions). The generated ions and wear debris (particles at the micron and nanoscale) stay, in a first moment, at the interface implant-bone. However, depending on their size, they can enter blood circulation possibly contributing to systemic reactions and toxicities. Most of the nanotoxicological studies with titanium dioxide nanoparticles (TiO2NPs) use conventional two-dimensional cell culture monolayers to explore macrophage and monocyte activation, where limited information regarding bone cells is available. Recently three-dimensional models have been gaining prominence since they present a greater anatomical and physiological relevance. Taking this into consideration, in this work we developed a human osteoblast-like spheroid model, which closely mimics bone cell-cell interactions, providing a more realistic scenario for nanotoxicological studies. The treatment of spheroids with different concentrations of TiO2NPs during 72 h did not change their viability significantly. Though, higher concentrations of TiO2NPs influenced osteoblast cell cycle without interfering in their ability to differentiate and mineralize. For higher concentration of TiO2NPs, collagen deposition and pro-inflammatory cytokine, chemokine and growth factor secretion (involved in osteolysis and bone homeostasis) increased. These results raise the possible use of this model in nanotoxicological studies of osseointegrated devices and demonstrate a possible therapeutic potential of this TiO2NPs to prevent or reverse bone resorption.
Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain
Authors: Dean Jon G. , Liu Tiecheng , Huff Sean , Sheler Ben , Barker Steven A. , Strassman Rick J. , Wang Michael M. , Borjigin Jimo
Published: June 2019

N,N-dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic-L-amino acid decarboxylase (AADC) and indolethylamine-N-methyltransferase (INMT). Whether DMT is biosynthesized in the mammalian brain is unknown. We investigated brain expression of INMT transcript in rats and humans, co-expression of INMT and AADC mRNA in rat brain and periphery, and brain concentrations of DMT in rats. INMT transcripts were identified in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans viain situhybridization. Notably, INMT mRNA was colocalized with AADC transcript in rat brain tissues, in contrast to rat peripheral tissues where there existed little overlapping expression of INMT with AADC transcripts. Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin. A significant increase of DMT levels in the rat visual cortex was observed following induction of experimental cardiac arrest, a finding independent of an intact pineal gland. These results show for the first time that the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters and raise the possibility that this phenomenon may occur similarly in human brains.