bluuebunny/crossref_metadata_2025 huggingface dataset:
Literary Circles in Byzantine Iconoclasm
Authors: Prieto Domínguez Óscar
Published: January 2021

Iconoclasm was the name given to the stance of that portion of Eastern Christianity that rejected worshipping God through images (eikones) representing Christ, the Virgin or the saints and was the official doctrine of the Byzantine Empire for most of the period between 726 and 843. It was a period marked by violent passions on either side. This is the first comprehensive account of the extant contemporary texts relating to this phenomenon and their impact on society, politics and identity. By examining the literary circles emerging both during the time of persecution and immediately after the restoration of icons in 843, the volume casts new light on the striking (re)construction of Byzantine society, whose iconophile identity was biasedly redefined by the political parties led by Theodoros Stoudites, Gregorios Dekapolites and Empress Theodora or the patriarchs Methodios, Ignatios and Photios. It thereby offers an innovative paradigm for approaching Byzantine literature.
Thrive
Authors: Hannon Valerie , Peterson Amelia
Published: January 2021

Every generation faces challenges, but never before have young people been so aware of theirs. Whether due to school strikes for climate change, civil war, or pandemic lockdowns, almost every child in the world has experienced the interruption of their schooling by outside forces. When the world we have taken for granted proves so unstable, it gives rise to the question: what is schooling for? Thrive advocates a new purpose for education, in a rapidly changing world, and analyses the reasons why change is urgently needed in our education systems. The book identifies four levels of thriving: global – our place in the planet; societal – localities, communities, economies; interpersonal – our relationships; intrapersonal – the self. Chapters provide research-based theoretical evidence for each area, followed by practical international case studies showing how individual schools are addressing these considerable challenges. Humanity's challenges are shifting fast: schools need to be a part of the response.
The Virus Paradigm
Authors: Marchesini Roberto
Published: January 2021

In recent years, the word 'virus' has lost its biological perimeter of reference to acquire a much broader – could say 'paradigmatic' – meaning. The term 'virus' can be seen as a key word or an explanatory model also for processes that go beyond the infectious sphere. Every event appears to have a viral character: from the way information is transmitted to the processes of cultural globalization, from the impact of human beings on the planet to the subversion of ecosystems, from pandemic risks to the demographic increase on the planet. This seems to be indeed the Age of the Virus. Its model can be applied to most of the phenomena that characterize the twenty-first. Its profile – its looming and invisible nature, its ability to use other people's resources to spread and to transform into a dangerous doppelganger – is perfect to represent the fears of the contemporary age.
Survival Guide for Scientists
Authors: Lagendijk Ad
Published: January 2021

During the course of Dutch physicist and Spinoza Prize-winner Ad Lagendijk's long and influential career, he has published more than 300 articles, supervised over thirty doctoral dissertations, and given countless presentations and conference addresses. Over the years, his incisive consultations, tips, and rules for scientific study have proven themselves so beneficial to the emerging scientists under his watch that he has been inundated with requests for a written version. Aimed primarily at undergraduate, graduate, and postdoctoral students, this essential guide presents Lagendijk's practical how-to advice on topics such as writing scientific texts, presenting data and research information, and the writing and reading of collegial emails. Each section is organised by a collection of short rules, outlined and numbered in a logical order as selfexplanatory pieces of information - allowing the reader the freedom to study any number of them in any desired order. But it doesn't stop there: many of the hints, in particular those referring to presentations, are of invaluable use for a much broader audience of professionals, up to consultants and (public) managers. Survival Guide for Scientists is complimented by www.sciencesurvivalblog.com where Lagendijk and others explore ways of making scientific writing more effective.
Non-contact measurement system for hot water drilled ice boreholes
Authors: McAfee Carson W. I. , Rix Julius , Quirk Sean J. , Anker Paul G. D. , Brisbourne Alex M. , Makinson Keith
Published: January 2021

A programmable borehole measurement system was deployed in hot water drilled ice holes during the ‘Bed Access and Monitoring of Ice Sheet History’ (BEAMISH) project to drill to the bed of the Rutford Ice Stream in West Antarctica. This system operates autonomously (no live data) after deployment, and records borehole diameter (non-contact measurement), water column pressure, heading and inclination. Three cameras, two sideways looking and one vertical, are also included for visual inspection of hole integrity and sediments. The system is small, lightweight (~35.5 kg) and low power using only 6 ‘D’ cell sized lithium batteries, making it ideal for transport and use in remote field sites. The system is 2.81 m long and 165 mm in diameter, and can be deployed attached to the drill hose for measurements during drilling or on its own deployment line afterwards. The full system is discussed in detail, highlighting design strengths and weaknesses. Data from the BEAMISH project are also presented in the form of camera images showing hole integrity, and sensor data used to calculate borehole diameter through the full length of the hole. These data are used to show confidence in hole verticality and subsurface cavity development and connection.
Sofregaz v. NGSC (CA Paris)
Authors: Bizeau Marie-Laure
Published: January 2021

On June 3, 2020, the International Commercial Chamber of the Paris Court of Appeal (the Court or the Court of Appeal) dismissed the annulment application brought by the Société Française d'Etudes et de Réalisation d'Equipements Gaziers (Sofregaz, now called TCM FR) of an arbitral award rendered in Paris on December 27, 2018, in favor of the Iranian Natural Gas Storage Company (NGSC), pursuant to the Rules of Arbitration of the International Court of Arbitration of the International Chamber of Commerce (ICC Rules). The Court ruled in particular that U.S. sanctions against Iran do not form part of French international public order but that European Union (EU) and United Nations (UN) sanctions do. This ruling provides useful guidance on the interaction between international sanctions and international arbitration.
Gone and forgotten: Vinogradoff's historical jurisprudence
Authors: Eldridge Lorren
Published: January 2021

Sir Paul Vinogradoff was once well known for his historically contextualised approach to legal theory which held that legal ideas were the contingent products of social factors. Law was necessarily engaged with other subjects, and ‘historical jurisprudence’ could produce real insight into the nature of law – in part by placing theories such as analytical jurisprudence in context, evaluating and modifying theoretical models by reference to the contingent social facts of an era. This was part of the nineteenth-century turn to ‘science’ in history and a focus on methodology. Sir Henry Maine argued that legal history proved the insufficiency of analytic theories, but his method met with many criticisms, some of which Vinogradoff sought to address. However, Vinogradoff's insights have rarely been pursued or developed, with legal history favouring Maitland's more doctrinal approach, and legal theory rejecting historical jurisprudence – at least explicitly. Despite its imperfections, historical jurisprudence offers a rich and valuable way to understand law, including to evaluate analytical models such of those of HLA Hart, and as a methodology for dialogue between comparative and historical legal scholarship. It has, in fact, continued to do so without explicit recognition in the 100 years since Vinogradoff's death.
Military responses to COVID-19, emerging trends in global civil-military engagements
Authors: Gibson-Fall Fawzia
Published: January 2021

The COVID-19 pandemic is giving way to increases in military engagements in health-related activities at the domestic level. This article situates these engagements amid issues of continuity, change, and resistance in contemporary redefinitions of military health roles. It positions the COVID-19 pandemic as a pivotal moment in global health military practice. I identify three emerging trends within national military responses to COVID-19: (1) Minimal technical military support; (2) Blended civil-military responses; and (3) Military-led responses. The dynamics that underpin each type of military involvement follow context-specific military political legacies. These levels of involvement also relate to national public health approaches and the degree of capacity within health care systems. Each identified trend points towards specific trajectories for the future co-constitution of global and local civil-military engagements.
Effect of physical activity through virtual reality on design creativity
Authors: Fillingim Kenton B. , Shapiro Hannah , Reichling Catherine J. , Fu Katherine
Published: January 2021

A deeper understanding of creativity and design is essential for the development of tools to improve designers’ creative processes and drive future innovation. The objective of this research is to evaluate the effect of physical activity versus movement in a virtual environment on the creative output of industrial design students. This study contributes a novel assessment of whether the use of virtual reality can produce the same creative output within designers as physical activity has been shown to produce in prior studies. Eighteen industrial design students at the Georgia Institute of Technology completed nine design tasks across three conditions in a within-subjects experimental design. In each condition, participants independently experienced one of three interventions. Solutions were scored for novelty and feasibility, and self-reported mood data was correlated with performance. No significant differences were found in novelty or feasibility of solutions across the conditions. However, there are statistically significant correlations between mood, interventions, and peak performance to be discussed. The results show that participants who experienced movement in virtual reality prior to problem solving performed at an equal or higher level than physical walking for all design tasks and all designer moods. This serves as motivation for continuing to study how VR can provide an impact on a designer's creative output. Hypothesized creative performance with each mode is discussed using trends from four categories of mood, based on the combined mood characteristics of pleasantness (positive/negative) and activation (active/passive).
Historical and Projected Changes in the Southern Hemisphere Surface Westerlies
Authors: Goyal Rishav , Sen Gupta Alex , Jucker Martin , England Matthew H.
Published: January 2021

The Southern Hemisphere (SH) surface westerlies fundamentally control regional patterns of air temperature, storm tracks, and precipitation while also regulating ocean circulation, heat transport and carbon uptake. Wind‐forced ocean perturbation experiments commonly apply idealized poleward wind shifts ranging between 0.5 and 10 degrees of latitude and wind intensification factors of between 10% and 300%. In addition, changes in winds are often prescribed ad hoc as a zonally uniform anomaly that neglects important regional and seasonal differences. Here we quantify historical and projected SH westerly wind changes based on examination of CMIP5, CMIP6, and reanalysis data. We find a significant reduction in the location bias of the CMIP6 ensemble and an associated reduction in the projected poleward shift compared to CMIP5. Under a high emission scenario, we find a projected end of 21st Century ensemble mean wind increase of ∼10% and a poleward shift of ∼0.8° latitude, although there are important seasonal and regional variations.
Climate Change and Teleconnections Amplify Lake Stratification With Differential Local Controls of Surface Water Warming and Deep Water Cooling
Authors: Oleksy Isabella A. , Richardson David C.
Published: January 2021

Temperate lakes are experiencing increases in warming and stratification duration while global‐scale teleconnections potentially exacerbate effects of climate change. We examined interannual surface and deep water temperature change and stratification phenology in a long‐term, weekly data set (1985–2017) from a dimictic lake in New York State, USA. We developed a metric, called mixing action, to capture multiple facets about the stratified period. We found warming in surface waters and cooling in deep water. Surface warming was positively correlated with air temperature. Deep water cooling was positively correlated with spring mixing period length and deep water spring temperature, indicating a lag effect. Mixing action was correlated with global temperature anomaly and spring North Atlantic Oscillation index. With increasing summer stratification strength and length, dimictic lakes like Mohonk may continue shifting toward monomictic mixing regimes with increasing summer hypolimnetic anoxia and changing lake biogeochemistry, productivity, and habitat for aquatic organisms.
Identification of Short and Long‐Lived Atmospheric Trace Gases From IASI Space Observations
Authors: De Longueville Hélène , Clarisse Lieven , Whitburn Simon , Franco Bruno , Bauduin Sophie , Clerbaux Cathy , Camy‐Peyret Claude , Coheur Pierre‐François
Published: January 2021

In recent years, major progress has been made in measuring weakly absorbing atmospheric trace gases from high spectral resolution space observations. In this paper, we apply the so‐called whitening transformation on spectra of the Infrared Atmospheric Sounding Interferometer, and show that it allows removing most of the climatological background from spectra, leaving a residual that contains those spectral signatures that depart from normality. These can subsequently be attributed to changes in the abundance of trace species. This is illustrated for two diverging cases: (1) a biomass burning plume from the 2019/2020 Australian bushfires, leading to the unambiguous identification of nine reactive trace gases, including a first observation of glycolaldehyde; (2) spectra observed a decade apart, from which changes in eight long‐lived halogenated substances are identified; three of them never observed before by a nadir sounder.
Intense dB/dt Variations Driven by Near‐Earth Bursty Bulk Flows (BBFs): A Case Study
Authors: Wei Dong , Dunlop Malcolm W. , Yang Junying , Dong Xiangcheng , Yu Yiqun , Wang Tieyan
Published: January 2021

During geomagnetically disturbed times the surface geomagnetic field often changes abruptly, producing geomagnetically induced currents (GICs) in a number of ground‐based systems. There are, however, few studies reporting GIC effects which are driven directly by bursty bulk flows (BBFs) in the inner magnetosphere. In this study, we investigate the characteristics and responses of the magnetosphere‐ionosphere‐ground system during the January 7, 2015 storm by using a multipoint approach which combines space‐borne measurements and ground magnetic observations. During the event, multiple BBFs are detected in the inner magnetosphere while the magnetic footprints of both magnetospheric and ionospheric satellites map to the same conjugate region surrounded by a group of magnetometer ground stations. It is suggested that the observed, localized substorm currents are caused by the observed magnetospheric BBFs, giving rise to intense geomagnetic perturbations. Our results provide direct evidence that the wide‐range of intense dB/dt (and dH/dt) variations are associated with a large‐scale, substorm current system, driven by multiple BBFs.
Radio Frequency Emissions Associated With Multi‐Pulsed Terrestrial Gamma‐Ray Flashes
Authors: Mailyan B. , Stanbro M. , Briggs M. S. , Cummer S. , Dwyer J. R. , Roberts O. J. , Holzworth R.
Published: January 2021

Terrestrial Gamma‐ray Flashes (TGFs) with multiple pulses have been observed many times since their discovery in the 1990s. The BATSE sample of TGFs had a large fraction of multi‐pulsed TGFs. It was not until later instruments, such as RHESSI, that the sample of detected TGFs consisted mostly of single‐peaked, sub‐millisecond events. Recent research has focused chiefly on these common single pulsed events, but several questions can be answered by analyzing multi‐pulse TGFs. One is the relationship between very low frequency (VLF) radio signals and the gamma‐ray pulses of TGFs. This paper discusses multi‐pulsed TGFs observed by Fermi Gamma‐ray Burst Monitor and their associated radio frequency pulses. In our data set of 29 multi‐pulse TGFs, 22 have a VLF association only with the last gamma‐ray pulse. However, unlike previous studies, we identified several events having radio matches with the first or both gamma‐ray pulses of double‐pulse TGFs. The absence of a VLF signal can be due to detection efficiency. On the other hand, the lack of correlation between radio and gamma‐ray intensities for some TGFs, cannot be explained by existing models. The models should be revised taking into account recent observations.
Statistical Characteristics of Field‐Aligned Currents in the Plasma Sheet Boundary Layer
Authors: Chen Y. Q. , Wu M. , Zhang T. L. , Huang Y. , Wang G. Q. , Nakamura R. , Baumjohann W. , Russell C. T. , Giles B. J. , Burch J. L.
Published: January 2021

Energy and momentum can be transferred from the magnetosphere to the ionosphere through field‐aligned currents (FACs), which show seasonal variations due to seasonal variation of the ionospheric conductance. Using Magnetospheric Multiscale Mission observations, we investigate the characteristics of kinetic‐scale (close to local ion inertial length) FACs in the plasma sheet boundary layer (PSBL), such as occurrence rate, magnitude, and carriers. The results show that: (1) the occurrence rates of FACs exhibit a trident distribution; they are also larger in the northern hemisphere than in the southern hemisphere, especially for the earthward FACs. (2) Distribution patterns vs. plasma β are different for the beam‐type and the flow‐type FACs. Flow‐type FACs are observed closer to the central plasma sheet (higher β), and their occurrence rate decreases linearly toward the tail lobe (lower β), while the beam‐type FACs are mainly and equally distributed within 0.1 < β < 1.0. (3) The magnitude of FACs shows little dependence on β, and generally increases closer to the Earth. (4) Occurrence rate and magnitude of FACs both increase during active periods, consistent with ionospheric observations. (5) The main carriers for FACs in the PSBL are thermal electrons, while cold electrons also contribute occasionally, especially during active periods. Hemispheric asymmetry of occurrence rate and dependence on geomagnetic activity of the kinetic‐scale FACs in the PSBL are consistent with FACs at ionospheric altitudes. This fact demonstrates that kinetic‐scale FACs are significant in magnetosphere‐ionosphere coupling and illustrates the possible ionospheric feedback effects to the magnetosphere in the nightside.
Validation of a Multilayered Analog Model Integrating Crust‐Mantle Visco‐Elastic Coupling to Investigate Subduction Megathrust Earthquake Cycle
Authors: Caniven Yannick , Dominguez Stéphane
Published: January 2021

We have developed a scaled analog model of a subduction zone simulating seismic cycle deformation phases. Its rheology is based on multilayered visco‐elasto‐plastic materials to account for the mechanical behavior of a continental lithospheric plate overriding a subducting oceanic plate. The seismogenic zone displays unstable slip behavior, extending at depth into a weak interface with stable slip properties. The model succeeds in reproducing interseismic phases interrupted by coseismic ruptures and followed by after‐slip. The experimental data catalog shows a broad variability of slip events from aseismic slow slips to fast dynamic lab quakes. Results also show the occurrence of both isolated and precursory slow‐slip events arising before the mainshocks. Given the absence of fluids in the model, the broad variability in slip event velocity can be attributed to fault roughness complexity. The model rheology induces also a key visco‐elastic coupling between the elastic overriding plate and the mantle wedge allowing, for the first time, to reproduce experimentally a realistic postseismic visco‐elastic relaxation phase. Preliminary results reveal that the tectonic loading rate modulates this visco‐elastic coupling. A low loading rate weakens it, which increase the amount of storable interseismic elastic deformation, and favors the occurrence of large megathrust events. A high loading rate strengthens it, which minimize the accumulation of interseismic elastic deformation, the slip‐event sizes, and promote aseismic creep. This new scaled‐analog subduction model is a complementary tool to investigate earthquake mechanics and improve the interpretation of geodetic and seismological records.
A New Middle to Late Jurassic Geomagnetic Polarity Time Scale (GPTS) From a Multiscale Marine Magnetic Anomaly Survey of the Pacific Jurassic Quiet Zone
Authors: Tominaga Masako , Tivey Maurice A. , Sager William W.
Published: January 2021

The Geomagnetic Polarity Time Scale (GPTS) provides a basis for the geological timescale, quantifies geomagnetic field behavior, and gives a time framework for geologic studies. We build a revised Middle to Late Jurassic GPTS by using a new multiscale magnetic profile, combining sea surface, midwater, and autonomous underwater vehicle near‐bottom magnetic anomaly data from the Hawaiian lineation set in the Pacific Jurassic Quiet Zone (JQZ). We correlate the new profile with a previously published contemporaneous magnetic sequence from the Japanese lineation set. We then establish geomagnetic polarity block models as a basis for our interpretation of the origin and nature of JQZ magnetic anomalies and a GPTS. A significant level of coherency between short‐wavelength anomalies for both the Japanese and Hawaiian lineation magnetic anomaly sequences suggests the existence of a regionally coherent field during this period of rapid geomagnetic reversals. Our study implies the rapid onset of the Mesozoic Dipole Low from M42 through M39 and then a subsequent gradual recovery in field strength into the Cenozoic. The new GPTS, together with the Japanese sequence, extends the magnetic reversal history from M29 back in time to M44. We identify a zone of varying, difficult‐to‐correlate anomalies termed the Hawaiian Disturbed Zone, which is similar to the zone of low amplitude, difficult‐to‐correlate anomalies in the Japanese sequence termed the Low Amplitude Zone (LAZ). We suggest that the LAZ, bounded by M39–M41 isochrons, may in fact represent the core of what is more commonly known as the JQZ crust.
Precipitation Characteristics and Land Cover Control Wet Season Runoff Source and Rainfall Partitioning in Three Humid Tropical Catchments in Central Panama
Authors: Birch Andrew L. , Stallard Robert F. , Barnard Holly R.
Published: January 2021

Mechanisms of runoff generation in the humid tropics are poorly understood, particularly in the context of land‐use/land cover change. This study analyzed the results of 124 storm hydrographs from three humid tropical catchments of markedly different vegetation cover and land‐use history in central Panama during the 2017 wet season: actively grazed pasture, young secondary succession, and near‐mature forest. We used electrical conductivity to separate baseflow (old water) from storm‐event water (new‐water). In all three land covers, new‐water dominated storm runoff generation in 44% of the sampled storm events, indicating the dominance of fast shallow flow paths in the landscape. Activation of these flow paths was found to depend on a combination of maximum rainfall intensity and total storm rainfall, which, in turn, relates to markedly contrasting hydrograph separation results among land covers. Relationships between these rainfall characteristics and storm runoff generation were nonlinear, producing a threshold response with the exceedance of specific rainfall volumes and/or intensities. The pastoral catchment delivered order of magnitude more new‐water during storm events than the two forested catchments. Although new‐water contributed minimally (<10%) to total wet season runoff in the forested catchments, 43% of runoff generation in the pasture came from five large rainfall events where a threshold response produced substantial increases in total runoff and new‐runoff efficiency. Based on our results, we propose a conceptual model of hydrologic flow paths in humid tropical systems that can explain previously observed disparities in seasonal storage and runoff with respect to land use/land cover.
Towards efficient near-infrared fluorescent organic light-emitting diodes
Authors: Minotto Alessandro , Bulut Ibrahim , Rapidis Alexandros G. , Carnicella Giuseppe , Patrini Maddalena , Lunedei Eugenio , Anderson Harry L. , Cacialli Franco
Published: January 2021

The energy gap law (EG-law) and aggregation quenching are the main limitations to overcome in the design of near-infrared (NIR) organic emitters. Here, we achieve unprecedented results by synergistically addressing both of these limitations. First, we propose porphyrin oligomers with increasing length to attenuate the effects of the EG -law by suppressing the non-radiative rate growth, and to increase the radiative rate via enhancement of the oscillator strength. Second, we design side chains to suppress aggregation quenching. We find that the logarithmic rate of variation in the non-radiative rate vs. EG is suppressed by an order of magnitude with respect to previous studies, and we complement this breakthrough by demonstrating organic light-emitting diodes with an average external quantum efficiency of ~1.1%, which is very promising for a heavy-metal-free 850 nm emitter. We also present a novel quantitative model of the internal quantum efficiency for active layers supporting triplet-to-singlet conversion. These results provide a general strategy for designing high-luminance NIR emitters.
Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma
Authors: Ni Wei , Chen Zirong , Zhou Xin , Yang Rongqiang , Yu Mu , Lu Jianrong , Kaye Frederic J. , Wu Lizi
Published: January 2021

Mucoepidermoid carcinoma (MEC) is the most common type of salivary gland cancers and patients with advanced, metastatic, and recurrent MECs have limited therapeutic options and poor treatment outcomes. MEC is commonly associated with a chromosomal translocation t(11;19) (q14-21;p12-13) that encodes the CRTC1-MAML2 oncogenic fusion. The CRTC1-MAML2 fusion is required for MEC growth in part through inducing autocrine AREG-EGFR signaling. Growing evidence suggests that MEC malignancy is maintained by cancer stem-like cells. In this study, we aimed to determine critical signaling for maintaining MEC stem-like cells and the effect of combined targeting of stem cell signaling and CRTC1-MAML2-induced EGFR signaling on blocking MEC growth. First, we evaluated the significance of Notch signaling in regulating MEC stem-like cells. Aberrantly activated Notch signaling was detected in human fusion-positive MEC cells. The inhibition of Notch signaling with genetic or pharmacological inhibitors reduced oncosphere formation and ALDH-bright population in vitro and blocked the growth of MEC xenografts in vivo. Next, we investigated the effect of co-targeting Notch signaling and EGFR signaling, and observed enhanced inhibition on MEC growth in vivo. Collectively, this study identified a critical role of Notch signaling in maintaining MEC stem-like cells and tumor growth, and revealed a novel approach of co-targeting Notch and EGFR signaling as a potential effective anti-MEC treatment.
Inhibiting CBX4 efficiently protects hepatocellular carcinoma cells against sorafenib resistance
Authors: Zhao Wei , Ma Bo , Tian Zhihua , Han Haibo , Tang Jintian , Dong Bin , An Guo , Cao Baoshan , Wang Boqing
Published: January 2021

Background

This study aimed to investigate the possible role of inhibiting chromobox protein homologue 4 (CBX4) to deregulate of cancer stem cells (CSCs) and to evaluate the contribution of these molecules to sorafenib resistance in advanced hepatocellular carcinoma (HCC).

Methods

HCC cell lines and a xenograft mouse model with resistance to sorafenib were employed to analyse the effects of miR424 on CSC characteristics. RNA expression was analysed by RT-PCR and next-generation sequencing in a cohort of HCC cancer patients and sorafenib-resistant (SR) cell lines, respectively, to validate the key microRNAs and targets in the network.

Results

MicroRNA and mRNA profiles of SR cell lines identified miR424 and its direct target CBX4 as significantly associated with stem-cell-like properties, poor survival, and clinical characteristics. Functional experiments demonstrated that miR424 suppressed CBX4 and CBX4 induced nuclear translocation of YAP1 protein but was not associated with protein production. When YAP1 and CBX4 were modulated with CA3 and UNC3866, tumorigenicity and stem-like properties were extremely inhibited, thus indicating that these compounds exerted a strong anti-tumour effect in vivo against SR HCC cells.

Conclusions

Our results revealed that blocking CBX4 expression is critical in response to sorafenib resistance with advanced HCC.
Mesenchymal stem cells ameliorate lipid metabolism through reducing mitochondrial damage of hepatocytes in the treatment of post-hepatectomy liver failure
Authors: Wang Jing-lin , Ding Hao-ran , Pan Chen-yan , Shi Xiao-lei , Ren Hao-zhen
Published: January 2021

Hepatectomy is an effective therapeutic strategy for many benign and malignant liver diseases, while the complexity of liver anatomy and the difficulty of operation lead to complications after hepatectomy. Among them, post-hepatectomy liver failure (PHLF) is the main factor threatening the life of patients. At present, liver transplantation is an effective approach for PHLF. However, the application of liver transplantation has been largely limited due to the shortage of donors and the high cost of such operation. Therefore, it is urgently necessary to develop a new treatment for PHLF. Mesenchymal stem cells (MSCs) have become a new treatment regimen for liver diseases because of their easy access and low immunogenicity. Our study found that there were some subtle connections between MSCs and liver lipid metabolism in the PHLF model. We used MSC transplantation to treat PHLF induced by 90% hepatectomy. MSC transplantation could restore the mitochondrial function, promote the β-oxidation of fatty acid (FA), and reduce the lipid accumulation of hepatocytes. In addition, interleukin 10 (IL-10), a cytokine with immunoregulatory function, had an important role in lipid metabolism. We also found that MSCs transplantation activated the mammalian target of rapamycin (mTOR) pathway. Therefore, we explored the relationship between mitochondrial damage and lipid metabolism abnormality or PHLF. MSCs improved mitochondrial function and corrected abnormal lipid metabolism by affecting the mTOR pathway in the treatment of PHLF. Collectively, MSC transplantation could be used as a potential treatment for PHLF.
HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway
Authors: Lei Dan , Yang Wen-Ting , Zheng Peng-Sheng
Published: January 2021

Homeobox B4 (HOXB4), which belongs to the homeobox (HOX) family, possesses transcription factor activity and has a crucial role in stem cell self-renewal and tumorigenesis. However, its biological function and exact mechanism in cervical cancer remain unknown. Here, we found that HOXB4 was markedly downregulated in cervical cancer. We demonstrated that HOXB4 obviously suppressed cervical cancer cell proliferation and tumorigenic potential in nude mice. Additionally, HOXB4-induced cell cycle arrest at the transition from the G0/G1 phase to the S phase. Conversely, loss of HOXB4 promoted cervical cancer cell growth both in vitro and in vivo. Bioinformatics analyses and mechanistic studies revealed that HOXB4 inhibited the activity of the Wnt/β-catenin signaling pathway by direct transcriptional repression of β-catenin. Furthermore, β-catenin re-expression rescued HOXB4-induced cervical cancer cell defects. Taken together, these findings suggested that HOXB4 directly transcriptional repressed β-catenin and subsequently inactivated the Wnt/β-catenin signaling pathway, leading to significant inhibition of cervical cancer cell growth and tumor formation.
Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages
Authors: Wauters Els , Van Mol Pierre , Garg Abhishek Dinkarnath , Jansen Sander , Van Herck Yannick , Vanderbeke Lore , Bassez Ayse , Boeckx Bram , Malengier-Devlies Bert , Timmerman Anna , Van Brussel Thomas , Van Buyten Tina , Schepers Rogier , Heylen Elisabeth , Dauwe Dieter , Dooms Christophe , Gunst Jan , Hermans Greet , Meersseman Philippe , Testelmans Dries , Yserbyt Jonas , Tejpar Sabine , De Wever Walter , Matthys Patrick ,   CONTAGIOUS collaborators, Bosisio Maria , Casaer Michael , De Smet Frederik , De Munter Paul , Humblet-Baron Stephanie , Liston Adrian , Lorent Natalie , Martinod Kim , Proost Paul , Raes Jeroen , Thevissen Karin , Vos Robin , Weynand Birgit , Wouters Carine , Neyts Johan , Wauters Joost , Qian Junbin , Lambrechts Diether
Published: January 2021

How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4+ T-cells with T-helper-1 characteristics (TH1-like) and CD8+ T-cells expressing exhaustion markers (TEX-like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.
Sarcoma classification by DNA methylation profiling
Authors: Koelsche Christian , Schrimpf Daniel , Stichel Damian , Sill Martin , Sahm Felix , Reuss David E. , Blattner Mirjam , Worst Barbara , Heilig Christoph E. , Beck Katja , Horak Peter , Kreutzfeldt Simon , Paff Elke , Stark Sebastian , Johann Pascal , Selt Florian , Ecker Jonas , Sturm Dominik , Pajtler Kristian W. , Reinhardt Annekathrin , Wefers Annika K. , Sievers Philipp , Ebrahimi Azadeh , Suwala Abigail , Fernández-Klett Francisco , Casalini Belén , Korshunov Andrey , Hovestadt Volker , Kommoss Felix K. F. , Kriegsmann Mark , Schick Matthias , Bewerunge-Hudler Melanie , Milde Till , Witt Olaf , Kulozik Andreas E. , Kool Marcel , Romero-Pérez Laura , Grünewald Thomas G. P. , Kirchner Thomas , Wick Wolfgang , Platten Michael , Unterberg Andreas , Uhl Matthias , Abdollahi Amir , Debus Jürgen , Lehner Burkhard , Thomas Christian , Hasselblatt Martin , Paulus Werner , Hartmann Christian , Staszewski Ori , Prinz Marco , Hench Jürgen , Frank Stephan , Versleijen-Jonkers Yvonne M. H. , Weidema Marije E. , Mentzel Thomas , Griewank Klaus , de Álava Enrique , Martín Juan Díaz , Gastearena Miguel A. Idoate , Chang Kenneth Tou-En , Low Sharon Yin Yee , Cuevas-Bourdier Adrian , Mittelbronn Michel , Mynarek Martin , Rutkowski Stefan , Schüller Ulrich , Mautner Viktor F. , Schittenhelm Jens , Serrano Jonathan , Snuderl Matija , Büttner Reinhard , Klingebiel Thomas , Buslei Rolf , Gessler Manfred , Wesseling Pieter , Dinjens Winand N. M. , Brandner Sebastian , Jaunmuktane Zane , Lyskjær Iben , Schirmacher Peter , Stenzinger Albrecht , Brors Benedikt , Glimm Hanno , Heining Christoph , Tirado Oscar M. , Sáinz-Jaspeado Miguel , Mora Jaume , Alonso Javier , del Muro Xavier Garcia , Moran Sebastian , Esteller Manel , Benhamida Jamal K. , Ladanyi Marc , Wardelmann Eva , Antonescu Cristina , Flanagan Adrienne , Dirksen Uta , Hohenberger Peter , Baumhoer Daniel , Hartmann Wolfgang , Vokuhl Christian , Flucke Uta , Petersen Iver , Mechtersheimer Gunhild , Capper David , Jones David T. W. , Fröhling Stefan , Pfister Stefan M. , von Deimling Andreas
Published: January 2021

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.
Repeat DNA-PAINT suppresses background and non-specific signals in optical nanoscopy
Authors: Clowsley Alexander H. , Kaufhold William T. , Lutz Tobias , Meletiou Anna , Di Michele Lorenzo , Soeller Christian
Published: January 2021

DNA-PAINT is a versatile optical super-resolution technique relying on the transient binding of fluorescent DNA ‘imagers’ to target epitopes. Its performance in biological samples is often constrained by strong background signals and non-specific binding events, both exacerbated by high imager concentrations. Here we describe Repeat DNA-PAINT, a method that enables a substantial reduction in imager concentration, thus suppressing spurious signals. Additionally, Repeat DNA-PAINT reduces photoinduced target-site loss and can accelerate sampling, all without affecting spatial resolution.
GATA2 regulates mast cell identity and responsiveness to antigenic stimulation by promoting chromatin remodeling at super-enhancers
Authors: Li Yapeng , Gao Junfeng , Kamran Mohammad , Harmacek Laura , Danhorn Thomas , Leach Sonia M. , O’Connor Brian P. , Hagman James R. , Huang Hua
Published: January 2021

Mast cells are critical effectors of allergic inflammation and protection against parasitic infections. We previously demonstrated that transcription factors GATA2 and MITF are the mast cell lineage-determining factors. However, it is unclear whether these lineage-determining factors regulate chromatin accessibility at mast cell enhancer regions. In this study, we demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both typical and super-enhancers at genes that respond to antigenic stimulation. We find that the number and densities of GATA2- but not MITF-bound sites at the super-enhancers are several folds higher than that at the typical enhancers. Our studies reveal that GATA2 promotes robust gene transcription to maintain mast cell identity and respond to antigenic stimulation by binding to super-enhancer regions with dense GATA2 binding sites available at key mast cell genes.
Responses of soil microbiome to steel corrosion
Authors: Huang Ye , Xu Dake , Huang Lu-yao , Lou Yun-tian , Muhadesi Jiang-Baota , Qian Hong-chang , Zhou En-ze , Wang Bao-jun , Li Xiu-Tong , Jiang Zhen , Liu Shuang-Jiang , Zhang Da-wei , Jiang Cheng-Ying
Published: January 2021

The process of microbiologically influenced corrosion (MIC) in soils has received widespread attention. Herein, long-term outdoor soil burial experiments were conducted to elucidate the community composition and functional interaction of soil microorganisms associated with metal corrosion. The results indicated that iron-oxidizing (e.g.,Gallionella), nitrifying (e.g.,Nitrospira), and denitrifying (e.g.,Hydrogenophaga) microorganisms were significantly enriched in response to metal corrosion and were positively correlated with the metal mass loss. Corrosion process may promote the preferential growth of the abundant microbes. The functional annotation revealed that the metabolic processes of nitrogen cycling and electron transfer pathways were strengthened, and also that the corrosion of metals in soil was closely associated with the biogeochemical cycling of iron and nitrogen elements and extracellular electron transfer. Niche disturbance of microbial communities induced by the buried metals facilitated the synergetic effect of the major MIC participants. The co-occurrence network analysis suggested possible niche correlations among corrosion related bioindicators.
The genetic basis of inter-individual variation in recovery from traumatic brain injury
Authors: Cortes Daniel , Pera Martin F.
Published: January 2021

Traumatic brain injury (TBI) is one of the leading causes of death among young people, and is increasingly prevalent in the aging population. Survivors of TBI face a spectrum of outcomes from short-term non-incapacitating injuries to long-lasting serious and deteriorating sequelae. TBI is a highly complex condition to treat; many variables can account for the observed heterogeneity in patient outcome. The limited success of neuroprotection strategies in the clinic has led to a new emphasis on neurorestorative approaches. In TBI, it is well recognized clinically that patients with similar lesions, age, and health status often display differences in recovery of function after injury. Despite this heterogeneity of outcomes in TBI, restorative treatment has remained generic. There is now a new emphasis on developing a personalized medicine approach in TBI, and this will require an improved understanding of how genetics impacts on long-term outcomes. Studies in animal model systems indicate clearly that the genetic background plays a role in determining the extent of recovery following an insult. A candidate gene approach in human studies has led to the identification of factors that can influence recovery. Here we review studies of the genetic basis for individual differences in functional recovery in the CNS in animals and man. The application of in vitro modeling with human cells and organoid cultures, along with whole-organism studies, will help to identify genes and networks that account for individual variation in recovery from brain injury, and will point the way towards the development of new therapeutic approaches.
Phosphorus removal and recovery from wastewater via hybrid ion exchange nanotechnology: a study on sustainable regeneration chemistries
Authors: Ownby Miles , Desrosiers David-Alexandre , Vaneeckhaute Céline
Published: January 2021

Technologies that allow for removal and subsequent recovery and reuse of phosphorus from polluted streams are imperative. One such technology is hybrid ion exchange nanotechnology (HIX-Nano), which may allow to produce a valuable nutrient solution following phosphorus desorption of the saturated media. This study evaluated the potential of four regeneration chemistries to desorb phosphorus from a commercially available HIX-Nano resin hybridized with iron oxide nanoparticles using a design of experiments (DoE) approach. More sustainable and less harmful regeneration solutions using a KOH/K2SO4 blend or a recovered NH4OH alkaline solution, along with tap water instead of synthetic acid, were compared to a control solution of KOH and H2SO4. Among the four regeneration methods studied, using the combination of recovered NH4OH and tap water shows the highest phosphorus recovery potential because: (i) it involves low cost and sustainable products, (ii) it showed a relatively high recovery efficiency (75 ± 15% as compared to the control at 89 ± 13%), and (iii) it did not demonstrate any significant dampening of the resin longevity after five adsorption and desorption cycles. Based on the DoE data, a series of regression models was developed to generate understanding of the effect of important operational parameters (volume of the regenerant solution, rinse speed, strength of the alkaline solution) on the phosphorus concentration in the recovered nutrient solution. Overall, this study indicates that HIX-Nano may contribute to providing a cost-effective and sustainable technological solution to tackle the phosphorus problem in wastewater treatment applications across the globe.
Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma
Authors: Pedrosa Lucía , Fernández-Miranda Ismael , Pérez-Callejo David , Quero Cristina , Rodríguez Marta , Martín-Acosta Paloma , Gómez Sagrario , González-Rincón Julia , Santos Adrián , Tarin Carlos , García Juan F. , García-Arroyo Francisco R. , Rueda Antonio , Camacho Francisca I. , García-Cosío Mónica , Heredero Ana , Llanos Marta , Mollejo Manuela , Piris-Villaespesa Miguel , Gómez-Codina José , Yanguas-Casás Natalia , Sánchez Antonio , Piris Miguel A. , Provencio Mariano , Sánchez-Beato Margarita
Published: January 2021

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.