bluuebunny/crossref_metadata_2025 huggingface dataset:
Aktuelles zu Alkoholkonsum- markern bei forensischen und suchtmedizinischen Fragestellungen
Authors: Skopp Gisela , Mußhoff Frank
Published: December 2020

Zusammenfassung. ﻿Abstract:﻿ ﻿Hintergrund:﻿ Direkte und indirekte Alkoholkonsummarker sind in forensischen und klinischen Kontexten wie riskantem oder schädlichem Trinken, Rückfall oder Abstinenz von Bedeutung. Hierbei können je nach Fragestellung einzelne oder auch eine Kombination von Markern hilfreich sein. ﻿Methode:﻿ Es wurde eine Literaturrecherche (PubMed) über die zurückliegenden 20 Jahre durchgeführt, zusätzlich flossen analytische und gutachterliche Erfahrungen der Autoren mit ein. ﻿Ergebnisse:﻿ Zu den gängigen indirekten Parametern zählen die Aktivität der gamma-Glutamyltransferase, der Aspartat- und Alaninaminotransferase, das mittlere korpuskuläre Volumen, das Kohlenhydrat-defiziente Transferrin und Methanol. Direkte Marker sind neben Ethanol seine Phase-II-Metaboliten Ethylglucuronid (EtG) und Ethylsulfat, Fettsäureethylester und Phosphatidylethanol (PEth). Die direkten Marker zeichnen sich durch deutlich höhere Sensitivitäten und Spezifitäten aus und sprechen bereits dann an, wenn ein Leberzellschaden noch nicht manifest geworden ist. Während Ethanol nur kurzfristig nachweisbar ist, eignet sich EtG im Urin und im Haar für einen mittel- und längerfristigen Nachweis. PEth scheint das bisherige Spektrum sinnvoll zu ergänzen; wie EtG im Haar lässt dieser Marker auch eine Einschätzung des Konsumverhaltens zu. ﻿Schlussfolgerungen:﻿ Insbesondere direkte Alkoholkonsummarker sind geeignet, den tatsächlichen Alkoholkonsum einzuschätzen, das Nachweisfenster zu erweitern, Interventionen zu ergreifen und abstinentes Verhalten bei Alkoholentzugs-/Entwöhnungsprogrammen und forensischen Fragestellungen zu überprüfen. Ein Analysenergebnis sollte allerdings nie isoliert, sondern immer im klinischen bzw. forensischen Kontext bewertet werden.
Escape of CO2+ and Other Heavy Minor Ions From the Ionosphere of Mars
Authors: Maes Lukas , Fraenz Markus , McFadden James P. , Benna Mehdi
Published: December 2020

Ionospheric escape from Mars is an important process for the erosion of the Martian atmosphere. The heavy ion outflow is dominated by and O+, however, the Martian ionosphere consists of many more ion species. In the dayside ionosphere below roughly 220 km altitude, is the second most dominant ion, and higher up and in the nightside ionosphere other ions species with a mass near but below that of (28–30 Atomic Mass Unit [AMU], e.g., CO+, , HCO+, NO+, etc.) gain in importance. However, their contribution to the ionospheric outflow is often obscured by the dominant ions and O+. Therefore, we perform a peak fitting to the mass spectrum of SupraThermal and Thermal Ion Composition onboard Mars Atmosphere and Volatile EvolutioN. This method is validated against the mass spectrum given by Neutral Gas and Ion Mass Spectrometer, and results in the ionosphere agree qualitatively very well. A statistical study is then performed to study the low‐energy (<100 eV) heavy ion outflow. We find that can be seen throughout the Martian magnetosphere, but it escapes only in small amounts at a mean rate of less than 1% of the rate. On the other hand, we find that the ions with a mass from 28 to 30 AMU, which were previously unknown in the Martian ion escape, are an important part of the ionospheric outflow, with a mean escape rate that reaches 32% of the rate.
Characteristics of Frequent Dynamic Triggering of Microearthquakes in Southern California
Authors: Fan Wenyuan , Barbour Andrew J. , Cochran Elizabeth S. , Lin Guoqing
Published: December 2020

Dynamic triggering of earthquakes has been reported at various fault systems. The triggered earthquakes are thought to be caused either directly by dynamic stress changes due to the passing seismic waves, or indirectly by other nonlinear processes that are initiated by the passing waves. Distinguishing these physical mechanisms is difficult because of the general lack of high‐resolution earthquake catalogs and robust means to quantitatively evaluate triggering responses, particularly, delayed responses. Here we use the high‐resolution Quake Template Matching catalog in Southern California to systematically evaluate teleseismic dynamic triggering patterns in the San Jacinto Fault Zone and the Salton Sea Geothermal Field from 2008 to 2017. We develop a new statistical approach to identify triggered cases, finding that approximately 1 out of every 5 globalMw ≥ 6 earthquakes dynamically trigger microearthquakes in Southern California. The triggering responses include both instantaneous and delayed triggering, showing a highly heterogeneous pattern and indicating possible evolving triggering thresholds. We do not observe a clear peak ground velocity triggering threshold that can differentiate triggering earthquakes from nontriggering events, but there are subtle differences in the frequency content of the ground motion that may differentiate the earthquakes. In contrast to the depth distribution of background seismicity, the identified triggered earthquakes tend to concentrate at the edges of the seismogenic zones. Although instantaneously triggered earthquakes are likely a result of dynamic Coulomb stress changes, the cases of delayed‐dynamic triggering are best explained by nonlinear triggering processes, including cyclic material fatigue, accelerated transient creep, and stochastic frictional heterogeneities.
Revealing Sediment Transport Pathways and Geomorphic Change in Washover Fans by Combining Drone‐Derived Digital Elevation Models and Single Grain Luminescence Data
Authors: May Simon Matthias , Callow John Nikolaus , Brill Dominik , Hoffmeister Dirk , May Jan‐Hendrik
Published: December 2020

Chronostratigraphic investigations on coastal sedimentary records such as washover fans or beach‐ridge sequences may be used to reconstruct storm chronologies on centennial to millennial time scales. However, modern analogs are pivotal in interpreting depositional processes and reducing uncertainty in evaluating the complex chronostratigraphic architecture of these landforms. Such a modern analog was provided by category 3 tropical cyclone (TC) Olwyn in 2015, which caused a significant storm surge in the Exmouth Gulf (Western Australia). Pre‐ and post‐TC Olwyn geomorphological surveys and high‐resolution drone‐derived topographical data of a large washover fan document a detailed history of erosion and deposition during the event. The modern analog deposits provided an excellent opportunity to evaluate the use of luminescence‐based proxies (luminescence inventories) for tracing event‐related sediment source environments and understanding transport processes. Sediments deposited during Olwyn show a systematic relationship between luminescence characteristics and washover fan position. Seaward and central washover sections are indicated by well‐bleached deposits due to the beach as the dominant source and/or long transport distances. Lateral washover deposits are characterized by rather local source areas and short transport distances, resulting in higher remnant ages of 70–140 a. Our data show that the combination of sediment source environments and sediment transport length across the fan represents the main control in resetting the luminescence signal and enabling reliable depositional ages to be calculated. It documents the benefit of investigating luminescence inventories when establishing chronologies from complex sedimentary records, thereby demanding a careful consideration of local processes and source areas when interpreting sedimentary TC records.
Distortions of the Rain Distribution With Warming, With and Without Self‐Aggregation
Authors: Fildier Benjamin , Collins William D. , Muller Caroline
Published: December 2020

We investigate how mesoscale circulations associated with convective aggregation can modulate the sensitivity of the hydrologic cycle to warming. We quantify changes in the full distribution of rain across radiative‐convective equilibrium states in a cloud‐resolving model. For a given Sea Surface Temperature (SST), the shift in mean rainfall between disorganized and organized states is associated with a shift in atmospheric radiative cooling, and is roughly analogous to the effect of a 4K SST increase. With rising temperatures, the increase in mean rain rate is insensitive to the presence of organization, while extremes can intensify faster in the aggregated state, leading to a faster amplification in the sporadic nature of rain. When convection aggregates, heavy rain is enhanced by 20%–30% and nonlinear behaviors are observed as a function of SST and strength of aggregation feedbacks. First, radiative‐ and surface‐flux aggregation feedbacks have multiplicative effects on extremes, illustrating a non‐trivial sensitivity to the degree of organization. Second, alternating Clausius‐Clapeyron and super‐Clausius‐Clapeyron regimes in extreme rainfall are found as a function of SST, corresponding to varying thermodynamic and dynamic contributions, and a large sensitivity to precipitation efficiency variations in some SST ranges.

The potential for mesoscale circulations in amplifying the hydrologic cycle is established. However, these nonlinear distortions question the quantitative relevance of idealized self‐aggregation. This calls for a deeper investigation of relationships which capture the coupling between global energetics, aggregation feedbacks and local convection, and for systematic tests of their sensitivity to domain configurations, surface boundary conditions, microphysics, and turbulence schemes.
Histone acylation marks respond to metabolic perturbations and enable cellular adaptation
Authors: Jo Chanhee , Park Seokjae , Oh Sungjoon , Choi Jinmi , Kim Eun-Kyoung , Youn Hong-Duk , Cho Eun-Jung
Published: December 2020

Acetylation is the most studied histone acyl modification and has been recognized as a fundamental player in metabolic gene regulation, whereas other short-chain acyl modifications have only been recently identified, and little is known about their dynamics or molecular functions at the intersection of metabolism and epigenetic gene regulation. In this study, we aimed to understand the link between nonacetyl histone acyl modification, metabolic transcriptional regulation, and cellular adaptation. Using antibodies specific for butyrylated, propionylated, and crotonylated H3K23, we analyzed dynamic changes of H3K23 acylation upon various metabolic challenges. Here, we show that H3K23 modifications were highly responsive and reversibly regulated by nutrient availability. These modifications were commonly downregulated by the depletion of glucose and recovered based on glucose or fatty acid availability. Depletion of metabolic enzymes, namely, ATP citrate lyase, carnitine acetyltransferase, and acetyl-CoA synthetase, which are involved in Ac-CoA synthesis, resulted in global loss of H3K23 butyrylation, crotonylation, propionylation, and acetylation, with a profound impact on gene expression and cellular metabolic states. Our data indicate that Ac-CoA/CoA and central metabolic inputs are important for the maintenance of histone acylation. Additionally, genome-wide analysis revealed that acyl modifications are associated with gene activation. Our study shows that histone acylation acts as an immediate and reversible metabolic sensor enabling cellular adaptation to metabolic stress by reprogramming gene expression.
A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1
Authors: Huang Zhenghui , Li Ruoxi , Tang Tongke , Ling Dazheng , Wang Manjiong , Xu Dandan , Sun Maoxin , Zheng Lulu , Zhu Feng , Min Hui , Boonhok Rachasak , Ding Yan , Wen Yuhao , Chen Yicong , Li Xiaokang , Chen Yuxi , Liu Taiping , Han Jiping , Miao Jun , Fang Qiang , Cao Yaming , Tang Yun , Cui Jie , Xu Wenyue , Cui Liwang , Zhu Jin , Wong Gary , Li Jian , Jiang Lubin
Published: December 2020

Although artemisinin combination therapies have succeeded in reducing the global burden of malaria, multidrug resistance of the deadliest malaria parasite, Plasmodium falciparum, is emerging worldwide. Innovative antimalarial drugs that kill all life-cycle stages of malaria parasites are urgently needed. Here, we report the discovery of the compound JX21108 with broad antiplasmodial activity against multiple life-cycle stages of malaria parasites. JX21108 was developed from chemical optimization of quisinostat, a histone deacetylase inhibitor. We identified P. falciparum histone deacetylase 1 (PfHDAC1), an epigenetic regulator essential for parasite growth and invasion, as a molecular target of JX21108. PfHDAC1 knockdown leads to the downregulation of essential parasite genes, which is highly consistent with the transcriptomic changes induced by JX21108 treatment. Collectively, our data support that PfHDAC1 is a potential drug target for overcoming multidrug resistance and that JX21108 treats malaria and blocks parasite transmission simultaneously.
Multipurpose self-configuration of programmable photonic circuits
Authors: Pérez-López Daniel , López Aitor , DasMahapatra Prometheus , Capmany José
Published: December 2020

Programmable integrated photonic circuits have been called upon to lead a new revolution in information systems by teaming up with high speed digital electronics and in this way, adding unique complementary features supported by their ability to provide bandwidth-unconstrained analog signal processing. Relying on a common hardware implemented by two-dimensional integrated photonic waveguide meshes, they can provide multiple functionalities by suitable programming of their control signals. Scalability, which is essential for increasing functional complexity and integration density, is currently limited by the need to precisely control and configure several hundreds of variables and simultaneously manage multiple configuration actions. Here we propose and experimentally demonstrate two different approaches towards management automation in programmable integrated photonic circuits. These enable the simultaneous handling of circuit self-characterization, auto-routing, self-configuration and optimization. By combining computational optimization and photonics, this work takes an important step towards the realization of high-density and complex integrated programmable photonics.
Exploring physics of ferroelectric domain walls via Bayesian analysis of atomically resolved STEM data
Authors: Nelson Christopher T. , Vasudevan Rama K. , Zhang Xiaohang , Ziatdinov Maxim , Eliseev Eugene A. , Takeuchi Ichiro , Morozovska Anna N. , Kalinin Sergei V.
Published: December 2020

The physics of ferroelectric domain walls is explored using the Bayesian inference analysis of atomically resolved STEM data. We demonstrate that domain wall profile shapes are ultimately sensitive to the nature of the order parameter in the material, including the functional form of Ginzburg-Landau-Devonshire expansion, and numerical value of the corresponding parameters. The preexisting materials knowledge naturally folds in the Bayesian framework in the form of prior distributions, with the different order parameters forming competing (or hierarchical) models. Here, we explore the physics of the ferroelectric domain walls in BiFeO3 using this method, and derive the posterior estimates of relevant parameters. More generally, this inference approach both allows learning materials physics from experimental data with associated uncertainty quantification, and establishing guidelines for instrumental development answering questions on what resolution and information limits are necessary for reliable observation of specific physical mechanisms of interest.
Bidirectional mid-infrared communications between two identical macroscopic graphene fibres
Authors: Fang Bo , Bodepudi Srikrishna Chanakya , Tian Feng , Liu Xinyu , Chang Dan , Du Sichao , Lv Jianhang , Zhong Jie , Zhu Haiming , Hu Huan , Xu Yang , Xu Zhen , Gao Weiwei , Gao Chao
Published: December 2020

Among light-based free-space communication platforms, mid-infrared (MIR) light pertains to important applications in biomedical engineering, environmental monitoring, and remote sensing systems. Integrating MIR generation and reception in a network using two identical devices is vital for the miniaturization and simplification of MIR communications. However, conventional MIR emitters and receivers are not bidirectional due to intrinsic limitations of low performance and often require cryogenic cooling. Here, we demonstrate that macroscopic graphene fibres (GFs) assembled from weakly-coupled graphene layers allow room-temperature MIR detection and emission with megahertz modulation frequencies due to the persistence of photo-thermoelectric effect in millimeter-length and the ability to rapidly modulate gray-body radiation. Based on the dual-functionality of GFs, we set up a system that conducts bidirectional data transmission by switching modes between two identical GFs. The room-temperature operation of our systems and the potential to produce GFs on industrial textile-scale offer opportunities for simplified and wearable optical communications.
Learning grain boundary segregation energy spectra in polycrystals
Authors: Wagih Malik , Larsen Peter M. , Schuh Christopher A.
Published: December 2020

The segregation of solute atoms at grain boundaries (GBs) can profoundly impact the structural properties of metallic alloys, and induce effects that range from strengthening to embrittlement. And, though known to be anisotropic, there is a limited understanding of the variation of solute segregation tendencies across the full, multidimensional GB space, which is critically important in polycrystals where much of that space is represented. Here we develop a machine learning framework that can accurately predict the segregation tendency—quantified by the segregation enthalpy spectrum—of solute atoms at GB sites in polycrystals, based solely on the undecorated (pre-segregation) local atomic environment of such sites. We proceed to use the learning framework to scan across the alloy space, and build an extensive database of segregation energy spectra for more than 250 metal-based binary alloys. The resulting machine learning models and segregation database are key to unlocking the full potential of GB segregation as an alloy design tool, and enable the design of microstructures that maximize the useful impacts of segregation.
A meta-learning approach for genomic survival analysis
Authors: Qiu Yeping Lina , Zheng Hong , Devos Arnout , Selby Heather , Gevaert Olivier
Published: December 2020

RNA sequencing has emerged as a promising approach in cancer prognosis as sequencing data becomes more easily and affordably accessible. However, it remains challenging to build good predictive models especially when the sample size is limited and the number of features is high, which is a common situation in biomedical settings. To address these limitations, we propose a meta-learning framework based on neural networks for survival analysis and evaluate it in a genomic cancer research setting. We demonstrate that, compared to regular transfer-learning, meta-learning is a significantly more effective paradigm to leverage high-dimensional data that is relevant but not directly related to the problem of interest. Specifically, meta-learning explicitly constructs a model, from abundant data of relevant tasks, to learn a new task with few samples effectively. For the application of predicting cancer survival outcome, we also show that the meta-learning framework with a few samples is able to achieve competitive performance with learning from scratch with a significantly larger number of samples. Finally, we demonstrate that the meta-learning model implicitly prioritizes genes based on their contribution to survival prediction and allows us to identify important pathways in cancer.
Sample spinning to mitigate polarization artifact and interstitial-vacancy imbalance in ion-beam irradiation
Authors: Ren Cui-Lan , Yang Yang , Li Yong-Gang , Huai Ping , Zhu Zhi-Yuan , Li Ju
Published: December 2020

Accelerator-based ion-beam irradiation has been widely used to mimic the effects of neutron radiation damage in nuclear reactors. However, ion radiation is most often monodisperse in the incoming ions’ momentum direction, leading to excessive polarization in defect distribution, while the scattering under neutron irradiation is often more isotropic and has less radiation-induced polarization. Mitigation of the excess-polarization as well as the damage non-uniformity artifact might be crucial for making the simulation of neutron radiation by ion-beam radiation more realistic. In this work, a general radiation polarization theory in treating radiation as external polar stimuli is established to understand the natural material responses in different contexts, and the possibility to correct the defect polarization artifact in ion-beam irradiation. Inspired by Magic Angle Spinning in Nuclear Magnetic Resonance, we present a precise sample spinning strategy to reduce the point-defect imbalance effect in ion-beam irradiation. It can be seen that with optimized surface inclination angle and the axis of sample rotation, the vacancy-interstitial population imbalance, as well as the damage profile non-uniformity in a designated region in the target are both reduced. It is estimated that sample spinning frequency on the order of kHz should be sufficient to scramble the ion momentum monodispersity for commonly taken ion fluxes and dose rates, which is experimentally feasible.
Segregation-assisted spinodal and transient spinodal phase separation at grain boundaries
Authors: Darvishi Kamachali Reza , Kwiatkowski da Silva Alisson , McEniry Eunan , Ponge Dirk , Gault Baptiste , Neugebauer Jörg , Raabe Dierk
Published: December 2020

Segregation to grain boundaries affects their cohesion, corrosion, and embrittlement and plays a critical role in heterogeneous nucleation. In order to quantitatively study segregation and low-dimensional phase separation at grain boundaries, here, we apply a density-based phase-field model. The current model describes the grain-boundary thermodynamic properties based on available bulk thermodynamic data, while the grain-boundary-density profile is obtained using atomistic simulations. To benchmark the performance of the model, Mn grain-boundary segregation in the Fe–Mn system is studied. 3D simulation results are compared against atom probe tomography measurements conducted for three alloy compositions. We show that a continuous increase in the alloy composition results in a discontinuous jump in the segregation isotherm. The jump corresponds to a spinodal phase separation at grain boundary. For alloy compositions above the jump, we reveal an interfacial transient spinodal phase separation. The transient spinodal phenomenon opens opportunities for knowledge-based microstructure design through the chemical manipulation of grain boundaries. The proposed density-based model provides a powerful tool to study thermodynamics and kinetics of segregation and phase changes at grain boundaries.
Quantum electromechanics with levitated nanoparticles
Authors: Martinetz Lukas , Hornberger Klaus , Millen James , Kim M. S. , Stickler Benjamin A.
Published: December 2020

Preparing and observing quantum states of nanoscale particles is a challenging task with great relevance for quantum technologies and tests of fundamental physics. In contrast to atomic systems with discrete transitions, nanoparticles exhibit a practically continuous absorption spectrum and thus their quantum dynamics cannot be easily manipulated. Here, we demonstrate that charged nanoscale dielectrics can be artificially endowed with a discrete level structure by coherently interfacing their rotational and translational motion with a superconducting qubit. We propose a pulsed scheme for the generation and read-out of motional quantum superpositions and entanglement between several levitated nanoparticles, providing an all-electric platform for networked hybrid quantum devices.
Side-stream products of malting: a neglected source of phytochemicals
Authors: Koistinen Ville M. , Tuomainen Marjo , Lehtinen Pekka , Peltola Petri , Auriola Seppo , Jonsson Karin , Hanhineva Kati
Published: December 2020

Whole grain consumption reduces the risk of several chronic diseases. A major contributor to the effect is the synergistic and additive effect of phytochemicals. Malting is an important technological method to process whole grains; the main product, malted grain, is used mainly for brewing, but the process also yields high amounts of side-stream products, such as rootlet. In this study, we comprehensively determined the phytochemical profile of barley, oats, rye, and wheat in different stages of malting and the subsequent extraction phases to assess the potential of malted products and side-streams as a dietary source of bioactive compounds. Utilizing semi-quantitative LC–MS metabolomics, we annotated 285 phytochemicals from the samples, belonging to more than 13 chemical classes. Malting significantly altered the levels of the compounds, many of which were highly increased in the rootlet. Whole grain cereals and the malting products were found to be a diverse and rich source of phytochemicals, highlighting the value of these whole foods as a staple. The characterization of phytochemicals from the 24 different sample types revealed previously unknown existence of some of the compound classes in certain species. The rootlet deserves more attention in human nutrition, rather than its current use mainly as feed, to benefit from its high content of bioactive components.
Elucidating the differences in oxidation of high-performance α- and β- diisobutylene biofuels via Synchrotron photoionization mass spectrometry
Authors: Terracciano Anthony Carmine , Neupane Sneha , Popolan-Vaida Denisia M. , Blair Richard G. , Hansen Nils , Vaghjiani Ghanshyam L. , Vasu Subith S.
Published: December 2020

Biofuels are a promising ecologically viable and renewable alternative to petroleum fuels, with the potential to reduce net greenhouse gas emissions. However, biomass sourced fuels are often produced as blends of hydrocarbons and their oxygenates. Such blending complicates the implementation of these fuels in combustion applications. Variations in a biofuel’s composition will dictate combustion properties such as auto ignition temperature, reaction delay time, and reaction pathways. A handful of novel drop-in replacement biofuels for conventional transportation fuels have recently been down selected from a list of over 10,000 potential candidates as part of the U.S. Department of Energy’s (DOE) Co-Optimization of Fuels and Engines (Co-Optima) initiative. Diisobutylene (DIB) is one such high-performing hydrocarbon which can readily be produced from the dehydration and dimerization of isobutanol, produced from the fermentation of biomass-derived sugars. The two most common isomers realized, from this process, are 2,4,4-trimethyl-1-pentene (α-DIB) and 2,4,4-trimethyl-2-pentene (β-DIB). Due to a difference in olefinic bond location, the α- and β- isomer exhibit dramatically different ignition temperatures at constant pressure and equivalence ratio. This may be attributed to different fragmentation pathways enabled by allylic versus vinylic carbons. For optimal implementation of these biofuel candidates, explicit identification of the intermediates formed during the combustion of each of the isomers is needed. To investigate the combustion pathways of these molecules, tunable vacuum ultraviolet (VUV) light (in the range 8.1–11.0 eV) available at the Lawrence Berkeley National Laboratory’s Advanced Light Source (ALS) has been used in conjunction with a jet stirred reactor (JSR) and time-of-flight mass spectrometry to probe intermediates formed. Relative intensity curves for intermediate mass fragments produced during this process were obtained. Several important unique intermediates were identified at the lowest observable combustion temperature with static pressure of 93,325 Pa and for 1.5 s residence time. As this relatively short residence time is just after ignition, this study is targeted at the fuels’ ignition events. Ignition characteristics for both isomers were found to be strongly dependent on the kinetics of C4 and C7 fragment production and decomposition, with the tert-butyl radical as a key intermediate species. However, the ignition of α-DIB exhibited larger concentrations of C4 compounds over C7, while the reverse was true for β-DIB. These identified species will allow for enhanced engineering modeling of fuel blending and engine design.
Author Correction: Aptamer-mediated survivin RNAi enables 5-fluorouracil to eliminate colorectal cancer stem cells
Authors: AlShamaileh Hadi , Wang Tao , Xiang Dongxi , Yin Wang , Tran Phuong Ha-Lien , Barrero Roberto A. , Zhang Pei-Zhuo , Li Yong , Kong Lingxue , Liu Ke , Zhou Shu-Feng , Hou Yingchun , Shigdar Sarah , Duan Wei
Published: December 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
In situ observations show vertical community structure of pelagic fauna in the eastern tropical North Atlantic off Cape Verde
Authors: Hoving H. J. T. , Neitzel P. , Hauss H. , Christiansen S. , Kiko R. , Robison B. H. , Silva P. , Körtzinger A.
Published: December 2020

Distribution patterns of fragile gelatinous fauna in the open ocean remain scarcely documented. Using epi-and mesopelagic video transects in the eastern tropical North Atlantic, which features a mild but intensifying midwater oxygen minimum zone (OMZ), we established one of the first regional observations of diversity and abundance of large gelatinous zooplankton. We quantified the day and night vertical distribution of 46 taxa in relation to environmental conditions. While distribution may be driven by multiple factors, abundance peaks of individual taxa were observed in the OMZ core, both above and below the OMZ, only above, or only below the OMZ whereas some taxa did not have an obvious distribution pattern. In the eastern eropical North Atlantic, OMZ expansion in the course of global climate change may detrimentally impact taxa that avoid low oxygen concentrations (Beroe, doliolids), but favour taxa that occur in the OMZ (Lilyopsis, phaeodarians, Cydippida, Colobonema, Haliscera conica and Halitrephes) as their habitat volume might increase. While future efforts need to focus on physiology and taxonomy of pelagic fauna in the study region, our study presents biodiversity and distribution data for the regional epi- and mesopelagic zones of Cape Verde providing a regional baseline to monitor how climate change may impact the largest habitat on the planet, the deep pelagic realm.
Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1
Authors: Molstad David H. H. , Zars Elizabeth , Norton Andrew , Mansky Kim C. , Westendorf Jennifer J. , Bradley Elizabeth W.
Published: December 2020

Previous studies examining the role of the histone deacetylase Hdac3 within myeloid cells demonstrated that Hdac3 promotes M2 activation and tissue healing in inflammatory conditions. Since myeloid lineage cells are required for proper bone formation and regeneration, in this study we examined the functions of Hdac3 during bone healing. Conditional deletion of Hdac3 within myeloid progenitors accelerates healing of cortical bone defects. Moreover, reduced osteoclast numbers within the defect site are correlated with Hdac3 suppression. Ex vivo osteoclastogenesis assays further demonstrate that Hdac3 deficiency limits osteoclastogenesis, the number of nuclei per cell and bone resorption, suggesting a defect in cell fusion. High throughput RNA sequencing identified the transmembrane protein Pmepa1 as a differentially expressed gene within osteoclast progenitor cells. Knockdown of Pmepa1 partially restores defects in osteoclastogenesis induced by Hdac3 deficiency. These results show that Hdac3 is required for optimal bone healing and osteoclast fusion, potentially via its regulation of Pmepa1 expression.
Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants
Authors: von Müller Christin , Bulman Fionnuala , Wagner Lysett , Rosenberger Daniel , Marolda Alessandra , Kurzai Oliver , Eißmann Petra , Jacobsen Ilse D. , Perner Birgit , Hemmerich Peter , Vylkova Slavena
Published: December 2020

Burn wounds are highly susceptible sites for colonization and infection by bacteria and fungi. Large wound surface, impaired local immunity, and broad-spectrum antibiotic therapy support growth of opportunistic fungi such as Candida albicans, which may lead to invasive candidiasis. Currently, it remains unknown whether depressed host defenses or fungal virulence drive the progression of burn wound candidiasis. Here we established an ex vivo burn wound model, where wounds were inflicted by applying preheated soldering iron to human skin explants, resulting in highly reproducible deep second-degree burn wounds. Eschar removal by debridement allowed for deeper C. albicans penetration into the burned tissue associated with prominent filamentation. Active migration of resident tissue neutrophils towards the damaged tissue and release of pro-inflammatory cytokine IL-1β accompanied the burn. The neutrophil recruitment was further increased upon supplementation of the model with fresh immune cells. Wound area and depth decreased over time, indicating healing of the damaged tissue. Importantly, prominent neutrophil presence at the infected site correlated to the limited penetration of C. albicans into the burned tissue. Altogether, we established a reproducible burn wound model of candidiasis using ex vivo human skin explants, where immune responses actively control the progression of infection and promote tissue healing.
Thermal stability of emission from single InGaAs/GaAs quantum dots at the telecom O-band
Authors: Holewa Paweł , Burakowski Marek , Musiał Anna , Srocka Nicole , Quandt David , Strittmatter André , Rodt Sven , Reitzenstein Stephan , Sęk Grzegorz
Published: December 2020

Single-photon sources are key building blocks in most of the emerging secure telecommunication and quantum information processing schemes. Semiconductor quantum dots (QD) have been proven to be the most prospective candidates. However, their practical use in fiber-based quantum communication depends heavily on the possibility of operation in the telecom bands and at temperatures not requiring extensive cryogenic systems. In this paper we present a temperature-dependent study on single QD emission and single-photon emission from metalorganic vapour-phase epitaxy-grown InGaAs/GaAs QDs emitting in the telecom O-band at 1.3 μm. Micro-photoluminescence studies reveal that trapped holes in the vicinity of a QD act as reservoir of carriers that can be exploited to enhance photoluminescence from trion states observed at elevated temperatures up to at least 80 K. The luminescence quenching is mainly related to the promotion of holes to higher states in the valence band and this aspect must be primarily addressed in order to further increase the thermal stability of emission. Photon autocorrelation measurements yield single-photon emission with a purity of $${g}_{50K}^{(2)}\left(0\right)=0.13$$

g

50
K

(
2
)

0

=
0.13

up to 50 K. Our results imply that these nanostructures are very promising candidates for single-photon sources at elevated (e.g., Stirling cryocooler compatible) temperatures in the telecom O-band and highlight means for improvements in their performance.
Cellular correlates of cortical thinning throughout the lifespan
Authors: Vidal-Pineiro Didac , Parker Nadine , Shin Jean , French Leon , Grydeland Håkon , Jackowski Andrea P. , Mowinckel Athanasia M. , Patel Yash , Pausova Zdenka , Salum Giovanni , Sørensen Øystein , Walhovd Kristine B. , Paus Tomas , Fjell Anders M. ,   the Alzheimer’s Disease Neuroimaging Initiative and the Australian Imaging Biomarkers and Lifestyle flagship study of ageing
Published: December 2020

Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 magnetic resonance images [MRIs]) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and, microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer’s Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.
Chloroform fraction of Chaetomorpha brachygona, a marine green alga from Indian Sundarbans inducing autophagy in cervical cancer cells in vitro
Authors: Majumder Indira , Paul Subhabrata , Nag Anish , Kundu Rita
Published: December 2020

Sundarbans Mangrove Ecosystem (SME) is a rich repository of bioactive natural compounds, with immense nutraceutical and therapeutic potential. Till date, the algal population of SME was not explored fully for their anticancer activities. Our aim is to explore the potential of these algal phytochemicals against the proliferation of cervical cancer cells (in vitro) and identify the mode of cell death induced in them. In the present work, the chloroform fraction of marine green alga,Chaetomorpha brachygonawas used on SiHa cell line. The algal phytochemicals were identified by GCMS, LCMS and column chromatography and some of the identified compounds, known for significant anticancer activities, have shown strong Bcl-2 binding capacity, as analyzed through molecular docking study. The extract showed cytostatic and cytotoxic activity on SiHa cells. Absence of fragmented DNA, and presence of increased number of acidic vacuoles in the treated cells indicate nonapoptotic cell death. The mode of cell death was likely to be autophagic, as indicated by the enhanced expression of Beclin 1 and LC3BII (considered as autophagic markers) observed by Western blotting. The study indicates that,C. brachygonacan successfully inhibit the proliferation of cervical cancer cells in vitro.
Three-dimensional in situ morphometrics of Mycobacterium tuberculosis infection within lesions by optical mesoscopy and novel acid-fast staining
Authors: Francis Robert J. , Robb Gillian , McCann Lee , Khatri Bhagwati , Keeble James , Dagg Belinda , Amos Brad , Salguero Francisco J. , Ho Mei Mei , Bullen Anwen , McConnell Gail , MacLellan-Gibson Kirsty
Published: December 2020

Tuberculosis (TB) preclinical testing relies on in vivo models including the mouse aerosol challenge model. The only method of determining colony morphometrics of TB infection in a tissue in situ is two-dimensional (2D) histopathology. 2D measurements consider heterogeneity within a single observable section but not above and below, which could contain critical information. Here we describe a novel approach, using optical clearing and a novel staining procedure with confocal microscopy and mesoscopy, for three-dimensional (3D) measurement of TB infection within lesions at sub-cellular resolution over a large field of view. We show TB morphometrics can be determined within lesion pathology, and differences in infection with different strains of Mycobacterium tuberculosis. Mesoscopy combined with the novel CUBIC Acid-Fast (CAF) staining procedure enables a quantitative approach to measure TB infection and allows 3D analysis of infection, providing a framework which could be used in the analysis of TB infection in situ.
Inter-individual predictors of pain inhibition during performance of a competing cognitive task
Authors: Tabry V. , Vogel T. A. , Lussier M. , Brouillard P. , Buhle J. , Rainville P. , Bherer L. , Roy M.
Published: December 2020

The main function of pain is to automatically draw attention towards sources of potential injury. However, pain sometimes needs to be inhibited in order to address or pursue more relevant tasks. Elucidating the factors that influence how people manage this relationship between pain and task performance is essential to understanding the disruptive nature of pain and its variability between individuals. Here, 41 healthy adults completed a challenging working memory task (2-back task) while receiving painful thermal stimulations. Examining the trial-by-trial relationship between pain perception and task performance revealed that pain’s disruptive effects on performance were mediated by self-reported pain intensity, and that the analgesic effects of a competing task were influenced by task performance. We found that higher pain catastrophizing, higher trait anxiety, and lower trait mindfulness were associated with larger trade-offs between pain perception and task performance, suggesting that these psychological factors can predict increased fluctuations between disruption by pain and analgesia from a competing task. Altogether these findings provide an important and novel perspective on our understanding of individual differences in the interplay between pain and ongoing task performance.
Liver lymphatic drainage patterns follow segmental anatomy in a murine model
Authors: Frenkel Nicola C. , Poghosyan Susanna , Verheem André , Padera Timothy P. , Rinkes Inne H. M. Borel , Kranenburg Onno , Hagendoorn Jeroen
Published: December 2020

The liver’s cellular functions are sustained by a hierarchical, segmentally-organized vascular system. Additionally, liver lymphatic vessels are thought to drain to perihepatic lymph nodes. Surprisingly, while recent findings highlight the importance of organ-specific lymphatics, the functional anatomy of liver lymphatics has not been mapped out. In literature, no segmental or preferential lymphatic drainage patterns are known to exist. We employ a novel murine model of liver lymphangiography and in vivo microscopy to delineate the lymphatic drainage patterns of individual liver lobes. Our data from blue dye liver lymphangiography show preferential lymphatic drainage patterns: Right lobe mainly to hepatoduodenal ligament lymph node 1 (LN1); left lobe to hepatoduodenal ligament LN1 + LN2 concurrently; median lobe showed a more variable LN1/LN2 drainage pattern with increased (sometimes exclusive) mediastinal thoracic lymph node involvement, indicating that part of the liver can drain directly to the mediastinum. Upon ferritin lymphangiography, we observed no functional communication between the lobar lymphatics. Altogether, these results show the existence of preferential lymphatic drainage patterns in the murine liver. Moreover, this drainage can occur directly to mediastinal lymph nodes and there is no interlobar lymphatic flow. Collectively, these data provide the first direct evidence that liver lymphatic drainage patterns follow segmental anatomy.
Cost-effectiveness of newer technologies for the diagnosis of Mycobacterium tuberculosis infection in Brazilian people living with HIV
Authors: Steffen Ricardo E. , Pinto Marcia , Kritski Afranio , Trajman Anete
Published: December 2020

Tuberculosis is the leading cause of death among people living with HIV (PLH). Preventive tuberculosis therapy reduces mortality in PLH, especially in those with a positive tuberculin skin test (TST). New, more specific technologies for detecting latent tuberculosis infection (LTBI) are now commercially available. We sought to analyse the cost-effectiveness of four different strategies for the diagnosis of LTBI in PLH in Brazil, from the Brazilian public health care system perspective. We developed a Markov state-transition model comparing four strategies for the diagnosis of LTBI over 20 years. The strategies consisted of TST with the currently used protein purified derivative (PPD RT 23), two novel skin tests using recombinant allergens (Diaskintest [Generium Pharmaceutical, Moscow, Russia] and EC [Zhifei Longcom Biologic Pharmacy Co., Anhui, China]), and the QuantiFERON-TB-Gold-Plus (Qiagen, Hilden, Germany). The main outcome was cost (in 2020 US dollars) per quality-adjusted life years (QALY). For the base case scenario, the Diaskintest was dominant over all other examined strategies. The cost saving estimate per QALY was US $1375. In sensitivity analyses, the Diaskintest and other newer tests remained cost-saving compared to TST. For PLH, TST could be replaced by more specific tests in Brazil, considering the current national recommendations.
Soy-tomato enriched diet reduces inflammation and disease severity in a pre-clinical model of chronic pancreatitis
Authors: Mukherjee Debasmita , DiVincenzo Mallory J. , Torok Molly , Choueiry Fouad , Kumar Rahul J. , Deems Anna , Miller Jenna L. , Hinton Alice , Geraghty Connor , Maranon Jose Angel , Kulp Samuel K. , Coss Christopher , Carson William E. , Conwell Darwin L. , Hart Phil A. , Cooperstone Jessica L. , Mace Thomas A.
Published: December 2020

Chronic pancreatitis (CP) is a fibro-inflammatory syndrome in individuals who develop persistent pathological responses to parenchymal injury or stress. Novel therapeutic or dietary interventions that could lessen inflammation in this disease could significantly improve quality of life in patients with CP. Complex dietary foods like soy and tomatoes are composed of active metabolites with anti-inflammatory effects. Data from our group reports that bioactive agents in soy and tomatoes can reduce pro-inflammatory cytokines and suppressive immune populations. Additionally, our team has developed a novel soy-tomato juice currently being studied in healthy individuals with no toxicities, and good compliance and bioavailability. Thus, we hypothesize that administration of a soy-tomato enriched diet can reduce inflammation and severity of CP. C57BL/6 mice were injected intraperitoneally with 50 μg/kg caeurlein (7 hourly injections, twice weekly) for 6 weeks to induce CP. After 4 weeks of caerulein injections, mice were administered a control or a soy-tomato enriched diet for 2 weeks. Disease severity was measured via immunohistochemical analysis of pancreata measuring loss of acini, fibrosis, inflammation, and necrosis. Serum lipase and amylase levels were analyzed at the end of the study. Inflammatory factors in the serum and pancreas, and immune populations in the spleen of mice were analyzed by cytokine multiplex detection, qRT-PCR, and flow cytometry respectively. Infra-red (IR) sensing of mice was used to monitor spontaneous activity and distress of mice. Mice fed a soy-tomato enriched diet had a significantly reduced level of inflammation and severity of CP (p = 0.032) compared to mice administered a control diet with restored serum lipase and amylase levels (p < 0.05). Mice with CP fed a soy-tomato diet had a reduction in inflammatory factors (TNF-α, IL-1β, IL-5) and suppressive immune populations (myeloid-derived suppressor cells; MDSC) compared to control diet fed mice (p < 0.05). Infra-red sensing to monitor spontaneous activity of mice showed that soy-tomato enriched diet improved total activity and overall health of mice with CP (p = 0.055) and CP mice on a control diet were determined to spend more time at rest (p = 0.053). These pre-clinical results indicate that a soy-tomato enriched diet may be a novel treatment approach to reduce inflammation and pain in patients with CP.