bluuebunny/crossref_metadata_2025 huggingface dataset:
Fanconi anemia pathway and its relationship with cancer
Authors: Dan Chenchen , Pei Hongjing , Zhang Buzhe , Zheng Xuan , Ran Dongmei , Du Changzheng
Published: June 2021

Fanconi Anemia (FA) is a rare inherited hematological disease, caused by mutations in genes involved in the DNA interstrand crosslink (ICL) repair. Up to date, 22 genes have been identified that encode a series of functionally associated proteins that recognize ICL lesion and mediate the activation of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. The FA pathway is strictly regulated by complex mechanisms such as ubiquitination, phosphorylation, and degradation signals that are essential for the maintenance of genome stability. Here, we summarize the discovery history and recent advances of the FA genes, and further discuss the role of FA pathway in carcinogenesis and cancer therapies.
How social innovations spread globally through the process of reverse innovation: a case-study from the South Korea
Authors: Cannavale Chiara , Claudio Lorenza , Simoni Michele
Published: June 2021

Nowadays, innovation is no longer a peculiarity of developed economies. Indeed, more frequently, it occurs that innovations born in the so called "emerging countries" spread in the advanced ones. This phenomenon is well known as Reverse innovation (RI), and within the global innovation literature about RI, some authors refer to these reversed innovations as developed in order to solve social or economic issues, specific of emerging contexts. However, scholars use to connect innovation with social goal as primary benefit to another phenomenon: i.e., Social innovation (SI). Within the Social innovation literature, there is a lack concerning how it should be undertaken to spread globally. Thus, we applied the Reverse innovation process to Social innovations: through a case-study analysis, we link the two phenomena which have never been explored together in previous studies. The paper aims at understanding how Social innovations spread from emerging to more advanced markets, while implementing this inversion of the flow. Further, we want to explore which is the potential that a Social innovation has in the host market: in other words, if SI could lose, hold, reduce, or increase their original social connotation.
Aerial Robotics: State-based Conflict Detection and Resolution (Detect and Avoid) in High Traffic Densities and Complexities
Authors: Hoekstra Jacco M. , Ellerbroek Joost
Published: June 2021

Purpose of Review

A lot of research into decentralised, state-based conflict detection and resolution, or detect and avoid algorithms has been executed. This paper explains the essential properties of state-based conflict detection and reviews the work in the context of applications for not only manned but also unmanned aerial vehicles, where this might be applied relatively soon.

Recent Findings

Lately, based on several reviews of a variety of published algorithms, a selection has been implemented and simulated in extremely high traffic densities for comparison.

The modified voltage potential has been surprisingly efficient, even compared with more complex algorithms or adaptations, as is apparent from looking at macroscopic metrics like domino effect, efficiency and safety. This indicates that to this date, it is so far the most suitable algorithm for the detect and avoid role for unmanned aerial vehicles in urban airspaces, or other areas where a high density is expected.
Socio-cognitive biases in folk AI ethics and risk discourse
Authors: Laakasuo Michael , Herzon Volo , Perander Silva , Drosinou Marianna , Sundvall Jukka , Palomäki Jussi , Visala Aku
Published: June 2021

The ongoing conversation on AI ethics and politics is in full swing and has spread to the general public. Rather than contributing by engaging with the issues and views discussed, we want to step back and comment on the widening conversation itself. We consider evolved human cognitive tendencies and biases, and how they frame and hinder the conversation on AI ethics. Primarily, we describe our innate human capacities known as folk theories and how we apply them to phenomena of different implicit categories. Through examples and empirical findings, we show that such tendencies specifically affect the key issues discussed in AI ethics. The central claim is that much of our mostly opaque intuitive thinking has not evolved to match the nature of AI, and this causes problems in democratizing AI ethics and politics. Developing awareness of how our intuitive thinking affects our more explicit views will add to the quality of the conversation.
Delayed Ejaculation Due to Improper Male Condom Size: A Case Report
Authors: Wainipitapong Sorawit , Wiwattarangkul Teeravut , Bumphenkiatikul Thanapob
Published: June 2021

Introduction

Delayed ejaculation (DE) is a poorly understood and uncommon male sexual dysfunction. The etiology of DE includes psychological and biological factors, which are usually combined. Herein, we report a case of acquired and situational DE due to improper male condom size.

Aims

To identify and correct the possible cause of acquired and situational DE.

Methods

A male patient presented with new-onset DE for 6 months. His physical and mental examination was unremarkable. Laboratory results were all normal. He was diagnosed with acquired, situational DE and received sessions of sexual counseling. However, his DE persisted until he accidentally used a larger condom. He then reported normal orgasm.

Main Outcome Measures

Resolution of acquired and situational DE.

Results

His DE was improved after using a more proper condom size.

Conclusion

Most patients are believed to have psychological problems and proper condom use is under-recognized. To the best of our knowledge, this is the first report of DE caused by this etiology.
A Philosopher Looks at Work
Authors: Geuss Raymond
Published: June 2021

Is work as we know it disappearing? And if so why should we care? These questions are explored by Raymond Geuss in this compact but sweeping survey which integrates conceptual analysis, historical reflection, autobiography and social commentary. Geuss explores our concept of work and its origins in industrial production, the incentives and compulsions which societies use to get us to work, and the powerful hold which the work ethic has over so many of us. He also looks at dissatisfaction with work - which is as old as work itself - and at various radical proposals for doing away with it, and at the seemingly irreversible growth of unemployment as a result of mechanisation. His book will interest anyone who wishes to understand the place of work in our world. This new series offers short and personal perspectives by expert thinkers on topics that we all encounter in our everyday lives.
Detecting the Ionospheric Disturbances in Japan Using the Three‐Dimensional Computerized Tomography
Authors: Song Rui , Hattori Katsumi , Zhang Xuemin , Liu Jann‐Yenq , Yoshino Chie
Published: June 2021

In this study, a three‐dimensional (3‐D) ionospheric tomography was developed in Japan using the constraint least‐square fitting algorithm, a model‐free method. Moreover, to make enough room for electron density (Ne) variations in the horizontal direction, only constraints on height were adopted. Slant total electron content data sets detected by 800 Global Positioning System (GPS) ground‐based receivers in 25°–50°N, 125°–150°E were selected. The spatial resolution was 1°, 1°, and 30 km in latitude, longitude, and altitude, respectively. The reconstructed performances concerning the quiet ionosphere, large‐scale traveling ionospheric disturbances on July 27, 2004, and nighttime medium‐scale traveling ionospheric disturbances on June 23, 2012, were verified successively. By comparing with Ne distributions from the International Reference Ionosphere model and GPS‐TEC mapping, the reconstructed results in both horizontal and vertical directions show good performance in imaging the ionospheric background and disturbed characteristics. The finding strongly indicates that retrieving Ne distributions by the improved constraint least‐square algorithm is promising for ionospheric studies and practical applications.
High Potential of Asian Dust to Act as Ice Nucleating Particles in Mixed‐Phase Clouds Simulated With a Global Aerosol‐Climate Model
Authors: Kawai Kei , Matsui Hitoshi , Tobo Yutaka
Published: June 2021

Mineral dust affects the microphysical and radiative properties of mixed‐phase clouds and hence the radiative balance of the Earth by acting as ice nucleating particles (INPs). However, the importance of Asian dust as INPs is not well understood. In this study, we examined the contribution of Asian dust to global dust INPs and its effect on cloud radiative forcing (CRF) using a global aerosol‐climate model with an ice nucleation parameterization that links INP number concentrations to ambient temperature and dust number concentrations. Our model well reproduces INP number concentrations measured over the Tokyo Metropolitan area in Japan during May 2017, when Asian dust was transported to Japan. Our simulation for the years 2013–2017 shows that Asian dust extends from its source regions (e.g., the Gobi and Taklimakan Deserts) to the North Pacific, North America, and the Arctic. Notably, Asian dust is transported to higher altitudes (i.e., to temperature regimes relevant for the formation of mixed‐phase clouds) more efficiently than dust from other regions. The annual‐mean simulated contribution of Asian dust to global dust INPs is 15%, which is 4.4 times higher than its contribution to global atmospheric dust loading (3.4%). These characteristics of Asian dust show its high potential to act as INPs in mixed‐phase clouds. Sensitivity simulations show that Asian dust INPs have a positive net CRF of 0.054–0.19 W m−2 in East Asia and the North Pacific during 2013–2017 (cf. 0.092–1.0 W m−2 for dust from other regions).
Quantifying the Stable Water Isotopologue Exchange Between the Snow Surface and Lower Atmosphere by Direct Flux Measurements
Authors: Wahl S. , Steen‐Larsen H. C. , Reuder J. , Hörhold M.
Published: June 2021

Surface processes in high latitudes play an important role in global climate and thus understanding the physics of these systems is critical for improving climate projections. The characterization of the stable water isotopologue flux between the surface and the atmosphere offers the potential to constrain parameterizations of these physical surface exchange processes in numerical models. In addition, observations of isotopologue surface fluxes allow the evaluation of surface fluxes as a process influencing the formation of the climate signal retrieved from ice core isotopologue records. Here, we present a record of stable water isotopologue surface fluxes measured in‐situ in the accumulation zone of the Greenland Ice Sheet at the East Greenland Ice Core Project site. We measured isotopologue fluxes above the snow surface directly by combining high‐frequency eddy covariance measurements with low‐frequency isotopologue measurements from a cavity ring‐down spectrometer (CRDS). We developed a method to correct for the high‐frequency loss of the CRDS by combining humidity measurements from both the CRDS and eddy covariance instruments. Using this approach our measurements provide the first direct observations of water isotopologue fluxes in polar areas. We observed a clear diurnal cycle in the fluxes of the different water isotopologues. The isotopic composition of the sublimation and deposition flux showed to be dependent on the snow and vapor isotopic composition, respectively. To a first order, the isotopic composition of the sublimation flux could be derived assuming equilibrium fractionation during sublimation.
Evaluation of CarbonTracker's Inverse Estimates of North American Net Ecosystem Exchange of CO2 From Different Observing Systems Using ACT‐America Airborne Observations
Authors: Cui Yu Yan , Jacobson Andrew R. , Feng Sha , Wesloh Daniel , Barkley Zachary R. , Zhang Li , Gerken Tobias , Keller Klaus , Baker David , Davis Kenneth J
Published: June 2021

Quantification of regional terrestrial carbon dioxide (CO2) fluxes is critical to our understanding of the carbon cycle. We evaluate inverse estimates of net ecosystem exchange (NEE) of CO2 fluxes in temperate North America, and their sensitivity to the observational data used to drive the inversions. Specifically, we consider the state‐of‐the‐science CarbonTracker global inversion system, which assimilates (a) in situ measurements (IS), (b) the Orbiting Carbon Observatory‐2 (OCO‐2) v9 column CO2 (XCO2) retrievals over land (LNLG), (c) OCO‐2 v9 XCO2 retrievals ocean‐glint (OG), and (d) a combination of all these observational constraints (LNLGOGIS). We use independent CO2 observations from the Atmospheric Carbon and Transport (ACT)—America aircraft mission to evaluate the inversions. We diagnose errors in the flux estimates using the differences between modeled and observed biogenic CO2 mole fractions, influence functions from a Lagrangian transport model, Bayesian inference, and root‐mean‐square error (RMSE) and bias metrics. The IS fluxes have the smallest RMSE among the four products, followed by LNLG. Both IS and LNLG outperform the OG and LNLGOGIS inversions with regard to RMSE. Regional errors do not differ markedly across the four sets of posterior fluxes. The CarbonTracker inversions appear to overestimate the seasonal cycle of NEE in the Midwest and Western Canada, and overestimate dormant season NEE across the Central and Eastern US. The CarbonTracker inversions may overestimate annual NEE in the Central and Eastern US. The success of the LNLG inversion with respect to independent observations bodes well for satellite‐based inversions in regions with more limited in situ observing networks.
Evaluating Freshwater Mussel Shell δ13C Values as a Proxy for Dissolved Inorganic Carbon δ13C Values in a Temperate River
Authors: Graniero L. E. , Gillikin D. P. , Surge D.
Published: June 2021

The stable isotope ratio of dissolved inorganic carbon (δ13CDIC) in rivers reflects the dominant vegetation type in the surrounding watershed, rates of chemical weathering, atmospheric CO2 fluxes, and the relative rates of photosynthesis and respiration. Reconstructing past δ13CDIC values may reveal changes in these characteristics before watersheds experience land‐use change and/or climate change. This study uses freshwater mussels, Elliptio complanata, and coeval environmental data to assess how high‐resolution changes in the oxygen and carbon isotope ratios of shell carbonate (δ18Oshell and δ13Cshell, respectively) can be used as proxies of paleotemperature and paleo‐DIC in rivers. To test our hypotheses, we analyzed time‐series δ18Oshell and δ13Cshell values, δ13C values in bivalve tissues, and environmental data collected fortnightly from the Neuse River, North Carolina. Shell microsamples milled every 150 μm along the maximum growth axis represent an average of 12 ± 5 days (n = 524; excluding periods of growth cessation of >30 days), which is similar to the environmental data resolution (∼14 days). Serially sampled δ18Oshell and δ13Cshell values did not capture the full range of environmental conditions due to growth cessation during winter shutdown and extreme weather events. Low water temperature and elevated turbidity appear to be significant drivers of growth cessation. Spatial and temporal differences in the amount of metabolic carbon incorporated in the shell (∼0%–44%) likely occur due to variable mussel metabolic rates within and among study sites. Though high‐resolution δ13Cshell values did not reflect variations in δ13CDIC values, average δ13Cshell values were indicative of average δ13CDIC values in the Neuse River.
A Tectonic Shift in Analytics and Computing Is Coming
Authors: Morra Gabriele , Bozdag Ebru , Knepley Matt , R�ss Ludovic , Vesselinov Velimir
Published: June 2021

Artificial intelligence combined with high-performance computing could trigger a fundamental change in how geoscientists extract knowledge from large volumes of data.
Intense Zonal Wind in the Martian Mesosphere During the 2018 Planet‐Encircling Dust Event Observed by Ground‐Based Infrared Heterodyne Spectroscopy
Authors: Miyamoto Akiho , Nakagawa Hiromu , Kuroda Takeshi , Takami Kosuke , Murata Isao , Medvedev Alexander S. , Yoshida Nao , Aoki Shohei , Sagawa Hideo , Kasaba Yasumasa , Terada Naoki
Published: June 2021

We report on the direct measurements of zonal winds around 80 km altitude during the 2018 planet‐encircling dust event (PEDE) by infrared (IR) heterodyne spectroscopy. The observed Doppler shifts assume intense retrograde (easterly) winds (208 ± 17 m s−1, 159 ± 20 m s−1, 211 ± 20 m s−1on June 21, June 27, August 31, 2018, respectively) in the equatorial region during the 2018 PEDE. This is significantly stronger than those during non‐storm conditions reported by the previous study (Sonnabend et al., 2012,https://doi.org/10.1016/j.icarus.2011.11.009). The substantial retrograde wind during the PEDE is qualitatively consistent with the predictions by the Mars general circulation models (MGCMs), however, the observed wind on 31, August, are of a larger magnitude. We evaluated the mechanism of acceleration using the output from a high‐resolution MGCM. We find out that the stronger winds are related to strengthening the meridional circulation across the equator and forcing by gravity waves.
How Do Weakening of the Stratospheric Polar Vortex in the Southern Hemisphere Affect Regional Antarctic Sea Ice Extent?
Authors: Wang Shaoyin , Liu Jiping , Cheng Xiao , Kerzenmacher Tobias , Hu Yongyun , Hui Fengming , Braesicke Peter
Published: June 2021

In the Southern Hemisphere, variability of the stratospheric polar vortex is an important driver of surface climate. In this study, we explore the influence of weakening and strengthening of the polar vortex on regional Antarctic sea ice in observations and model simulations. We propose a two‐stage mechanism that translates stratospheric harbingers to sea ice changes: (a) it starts with polar vortex variability that is highly correlated with the Amundsen Sea Low (ASL); through modulation of the ASL and thus surface winds, (b) weak polar vortex leads to statistically significant decrease of sea ice over the Ross Sea and increase of sea ice around the Antarctic Peninsula, and vice versa. The two‐stage mechanism can be detected in observations and state‐of‐the‐art model simulations, confirming a robust chain of response. This study underlines the importance of stratosphere‐troposphere coupling on the Antarctic sea ice variability and its seasonal predictability.
The Impact of Ocean‐Wave Coupling on the Upper Ocean Circulation During Storm Events
Authors: Bruciaferri D. , Tonani M. , Lewis H. W. , Siddorn J. R. , Saulter A. , Castillo Sanchez J. M. , Valiente N. G. , Conley D. , Sykes P. , Ascione I. , McConnell N.
Published: June 2021

Many human activities rely on accurate knowledge of the sea surface dynamics. This is especially true during storm events, when wave‐current interactions might represent a leading order process of the upper ocean. In this study, we assess and analyze the impact of including three wave‐dependent processes in the ocean momentum equation of the Met Office North West European Shelf ocean‐wave forecasting system on the accuracy of the simulated surface circulation. The analysis is conducted using ocean currents and Stokes drift data produced by different implementations of the coupled forecasting systems to simulate the trajectories of surface (iSphere) and 15 m drogued (SVP) drifters affected by four storms selected from winter 2016. Ocean and wave simulations differ only in the degree of coupling and the skills of the Lagrangian simulations are evaluated by comparing model results against the observed drifter tracks. Results show that, during extreme events, ocean‐wave coupling improves the accuracy of the surface dynamics by 4%. Improvements are larger for ocean currents on the shelf (8%) than in the open ocean (4%): this is thought to be due to the synergy between strong tidal currents and more mature decaying waves. We found that the Coriolis‐Stokes forcing is the dominant wave‐current interaction for both type of drifters; for iSpheres the secondary wave effect is the wave‐dependent sea surface roughness while for SVPs the wave‐modulated water‐side stress is more important. Our results indicate that coupled ocean‐wave systems may play a key role for improving the accuracy of particle transport simulations.
Factors Governing Cloud Growth and Entrainment Rates in Shallow Cumulus and Cumulus Congestus During GoAmazon2014/5
Authors: Eissner J. M. , Mechem D. B. , Jensen M. P. , Giangrande S. E.
Published: June 2021

Shallow cumulus and cumulus congestus clouds play an important role in the large‐scale tropical circulation by mixing heat and moisture vertically and preconditioning the environment for deeper convection. Different representations of these shallow clouds account for much of the spread in General Circulation Model (GCMs) climate sensitivity, potentially because of how entrainment is represented in GCM parameterizations. This study uses observations from the Department of Energy's Atmospheric Radiation Measurement (ARM) mobile facility deployed at Manacapuru, Brazil, during the Green Ocean Amazon (GoAmazon2014/5) Campaign. Environmental thermodynamic profiles and observations of cloud top height (CTH) are used to constrain an entraining plume model to estimate bulk entrainment rates (ERs). Estimates of CTH are obtained from a combination of vertically pointing W‐band ARM cloud radar and 1,290 MHz Radar Wind Profiler observations. A combination of radiosonde, microwave radiometer profiler, and microwave radiometer observations provides new best estimates of the environmental thermodynamic state. We quantify uncertainty in ERs considering uncertainties in estimated CTH, environmental thermodynamic properties, and assumed initial parcel characteristics. We find ERs ranging from 0.16 to 2.8 km−1 with an average of 0.58 ± 0.10 km−1 over a selected population of 469 shallow cumulus and cumulus congestus clouds. Using the retrieved estimates of ER, we evaluate several entrainment closures that are currently used in atmospheric models or have been proposed based on theory or large eddy simulation. Entrainment rates in cumulus clouds are weakly correlated with low‐level buoyancy, cloud depth, and cloud size.
Genetic variations influence brain changes in patients with attention-deficit hyperactivity disorder
Authors: Yadav Santosh K. , Bhat Ajaz A. , Hashem Sheema , Nisar Sabah , Kamal Madeeha , Syed Najeeb , Temanni Mohamed-Ramzi , Gupta Rakesh K. , Kamran Saddat , Azeem Muhammad Waqar , Srivastava Amit K. , Bagga Puneet , Chawla Sanjeev , Reddy Ravinder , Frenneaux Michael P. , Fakhro Khalid , Haris Mohammad
Published: June 2021

Attention-deficit hyperactivity disorder (ADHD) is a neurological and neurodevelopmental childhood-onset disorder characterized by a persistent pattern of inattentiveness, impulsiveness, restlessness, and hyperactivity. These symptoms may continue in 55–66% of cases from childhood into adulthood. Even though the precise etiology of ADHD is not fully understood, it is considered as a multifactorial and heterogeneous disorder with several contributing factors such as heritability, auxiliary to neurodevelopmental issues, severe brain injuries, neuroinflammation, consanguineous marriages, premature birth, and exposure to environmental toxins. Neuroimaging and neurodevelopmental assessments may help to explore the possible role of genetic variations on ADHD neuropsychobiology. Multiple genetic studies have observed a strong genetic association with various aspects of neuropsychobiological functions, including neural abnormalities and delayed neurodevelopment in ADHD. The advancement in neuroimaging and molecular genomics offers the opportunity to analyze the impact of genetic variations alongside its dysregulated pathways on structural and functional derived brain imaging phenotypes in various neurological and psychiatric disorders, including ADHD. Recently, neuroimaging genomic studies observed a significant association of brain imaging phenotypes with genetic susceptibility in ADHD. Integrating the neuroimaging-derived phenotypes with genomics deciphers various neurobiological pathways that can be leveraged for the development of novel clinical biomarkers, new treatment modalities as well as therapeutic interventions for ADHD patients. In this review, we discuss the neurobiology of ADHD with particular emphasis on structural and functional changes in the ADHD brain and their interactions with complex genomic variations utilizing imaging genetics methodologies. We also highlight the genetic variants supposedly allied with the development of ADHD and how these, in turn, may affect the brain circuit function and related behaviors. In addition to reviewing imaging genetic studies, we also examine the need for complementary approaches at various levels of biological complexity and emphasize the importance of combining and integrating results to explore biological pathways involved in ADHD disorder. These approaches include animal models, computational biology, bioinformatics analyses, and multimodal imaging genetics studies.
Methylome-wide change associated with response to electroconvulsive therapy in depressed patients
Authors: Sirignano Lea , Frank Josef , Kranaster Laura , Witt Stephanie H. , Streit Fabian , Zillich Lea , Sartorius Alexander , Rietschel Marcella , Foo Jerome C.
Published: June 2021

Electroconvulsive therapy (ECT) is a quick-acting and powerful antidepressant treatment considered to be effective in treating severe and pharmacotherapy-resistant forms of depression. Recent studies have suggested that epigenetic mechanisms can mediate treatment response and investigations about the relationship between the effects of ECT and DNA methylation have so far largely taken candidate approaches. In the present study, we examined the effects of ECT on the methylome associated with response in depressed patients (n = 34), testing for differentially methylated CpG sites before the first and after the last ECT treatment. We identified one differentially methylated CpG site associated with the effect of ECT response (defined as >50% decrease in Hamilton Depression Rating Scale score, HDRS), TNKS (q < 0.05; p = 7.15 × 10−8). When defining response continuously (ΔHDRS), the top suggestive differentially methylated CpG site was in FKBP5 (p = 3.94 × 10−7). Regional analyses identified two differentially methylated regions on chromosomes 8 (Šídák’s p = 0.0031) and 20 (Šídák’s p = 4.2 × 10−5) associated with ΔHDRS. Functional pathway analysis did not identify any significant pathways. A confirmatory look at candidates previously proposed to be involved in ECT mechanisms found CpG sites associated with response only at the nominally significant level (p < 0.05). Despite the limited sample size, the present study was able to identify epigenetic change associated with ECT response suggesting that this approach, especially when involving larger samples, has the potential to inform the study of mechanisms involved in ECT and severe and treatment-resistant depression.
Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3
Authors: Tang Peng , Virtue Sam , Goie Jian Yi Gerald , Png Chin Wen , Guo Jing , Li Ying , Jiao Huipeng , Chua Yen Leong , Campbell Mark , Moreno-Navarrete José Maria , Shabbir Asim , Fernández-Real José-Manuel , Gasser Stephan , Kemeny David Michael , Yang Henry , Vidal-Puig Antonio , Zhang Yongliang
Published: June 2021

Dysfunction of adipocytes and adipose tissue is a primary defect in obesity and obesity-associated metabolic diseases. Interferon regulatory factor 3 (IRF3) has been implicated in adipogenesis. However, the role of IRF3 in obesity and obesity-associated disorders remains unclear. Here, we show that IRF3 expression in human adipose tissues is positively associated with insulin sensitivity and negatively associated with type 2 diabetes. In mouse pre-adipocytes, deficiency of IRF3 results in increased expression of PPARγ and PPARγ-mediated adipogenic genes, leading to increased adipogenesis and altered adipocyte functionality. The IRF3 knockout (KO) mice develop obesity, insulin resistance, glucose intolerance, and eventually type 2 diabetes with aging, which is associated with the development of white adipose tissue (WAT) inflammation. Increased macrophage accumulation with M1 phenotype which is due to the loss of IFNβ-mediated IL-10 expression is observed in WAT of the KO mice compared to that in wild-type mice. Bone-marrow reconstitution experiments demonstrate that the nonhematopoietic cells are the primary contributors to the development of obesity and both hematopoietic and nonhematopoietic cells contribute to the development of obesity-related complications in IRF3 KO mice. This study demonstrates that IRF3 regulates the biology of multiple cell types including adipocytes and macrophages to prevent the development of obesity and obesity-related complications and hence, could be a potential target for therapeutic interventions for the prevention and treatment of obesity-associated metabolic disorders.
Adipocyte death triggers a pro-inflammatory response and induces metabolic activation of resident macrophages
Authors: Lindhorst Andreas , Raulien Nora , Wieghofer Peter , Eilers Jens , Rossi Fabio M. V. , Bechmann Ingo , Gericke Martin
Published: June 2021

A chronic low-grade inflammation within adipose tissue (AT) seems to be the link between obesity and some of its associated diseases. One hallmark of this AT inflammation is the accumulation of AT macrophages (ATMs) around dead or dying adipocytes, forming so-called crown-like structures (CLS). To investigate the dynamics of CLS and their direct impact on the activation state of ATMs, we established a laser injury model to deplete individual adipocytes in living AT from double reporter mice (GFP-labeled ATMs and tdTomato-labeled adipocytes). Hence, we were able to detect early ATM-adipocyte interactions by live imaging and to determine a precise timeline for CLS formation after adipocyte death. Further, our data indicate metabolic activation and increased lipid metabolism in ATMs upon forming CLS. Most importantly, adipocyte death, even in lean animals under homeostatic conditions, leads to a locally confined inflammation, which is in sharp contrast to other tissues. We identified cell size as cause for the described pro-inflammatory response, as the size of adipocytes is above a critical threshold size for efferocytosis, a process for anti-inflammatory removal of dead cells during tissue homeostasis. Finally, experiments on parabiotic mice verified that adipocyte death leads to a pro-inflammatory response of resident ATMs in vivo, without significant recruitment of blood monocytes. Our data indicate that adipocyte death triggers a unique degradation process and locally induces a metabolically activated ATM phenotype that is globally observed with obesity.
Cisplatin remodels the tumor immune microenvironment via the transcription factor EB in ovarian cancer
Authors: Liu Wei , Wang Yanqiu , Xie Yunkai , Dai Tianyu , Fan Mingjun , Li Changzhong , Zou Yonghui
Published: June 2021

The mortality rate of ovarian cancer (OC) remains the highest among all gynecological malignancies. Platinum-based chemotherapies are effective in treating most OC cases. However, chemoresistance is still a major challenge for successful OC treatments. Emerging evidence has highlighted that the modulation of the tumor immune microenvironment is involved in chemoresistance, but the mechanism remains unclear. This study aimed to investigate whether resistance to cisplatin (CDDP), the standard treatment for OC, is due to the remodeling of the tumor immune microenvironment by the transcription factor EB (TFEB). We hypothesized that TFEB is not essential for tumor survival but is associated with CDDP resistance. We collected 20 tissue samples of OC patients who had not undergone chemotherapy or radiotherapy prior to surgery. We cultured OC cell lines and performed cell transfection and assays as well as analytical, fluorescence microscopy, and immunohistochemical techniques to explore a novel function of TFEB in remodeling the tumor immune microenvironment in OC. We found a positive correlation between TFEB and programmed cell death-ligand 1 (PD-L1), PD-L2, and HLA-A expression in OC cells and tissues. We also found that CDDP treatment induced TFEB nuclear translocation, thus increasing PD-L1 and PD-L2 expression to foster an immunosuppressive tumor microenvironment, which mediates tumor immune evasion and drug resistance. Interestingly, TFEB also regulated HLA-A expression, which increases the tumor immunogenicity of OC. Finally, in a syngenic murine model of OC, we observed the therapeutic benefit of CDDP plus programmed cell death-1 (PD-1) inhibitor, which enhanced the cytolytic activity of CD8+ T cells and inhibited tumor growth. Our study illustrates the important role of TFEB in regulating the tumor immune microenvironment in OC.
Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1
Authors: Chang Yu-Chan , Chan Ming-Hsien , Li Chien-Hsiu , Yang Chih-Jen , Tseng Yu-Wen , Tsai Hsing-Fang , Chiou Jean , Hsiao Michael
Published: June 2021

Phosphoglycerate kinase (PGK) is involved in glycolytic and various metabolic events. Dysfunction of PGK may induce metabolic reprogramming and the Warburg effect. In this study, we demonstrated that PGK1, but not PGK2, may play a key role in tumorigenesis and is associated with metastasis. We observed an inverse correlation between PGK1 and the survival rate in several clinical cohorts through bioinformatics statistical and immunohistochemical staining analyses. Surprisingly, we found that PGK1 was significantly increased in adenocarcinoma compared with other subtypes. Thus, we established a PGK1-based proteomics dataset by a pull-down assay. We further investigated HIV-1 Tat Specific Factor 1 (HTATSF1), a potential binding partner, through protein–protein interactions. Then, we confirmed that PGK1 indeed bound to HTATSF1 by two-way immunoprecipitation experiments. In addition, we generated several mutant clones of PGK1 through site-directed mutagenesis, including mutagenesis of the N-terminal region, the enzyme catalytic domain, and the C-terminal region. We observed that even though the phosphoglycerate kinase activity had been inhibited, the migration ability induced by PGK1 was maintained. Moreover, our immunofluorescence staining also indicated the translocation of PGK1 from the cytoplasm to the nucleus and its colocalization with HTATSF1. From the results presented in this study, we propose a novel model in which the PGK1 binds to HTATSF1 and exerts functional control of cancer metastasis. In addition, we also showed a nonenzymatic function of PGK1.
Microbiota-related effects of prebiotic fibres in lipopolysaccharide-induced endotoxemic mice: short chain fatty acid production and gut commensal translocation
Authors: Fan Songtao , Zhang Zhihong , Zhong Yadong , Li Chang , Huang Xiaojun , Geng Fang , Nie Shaoping
Published: June 2021

Evidence on microbiota-related effects of prebiotic fibres in endotoxemic mice that were intervened by either a single gavage or the relative long-term intake.
MnO2/MXene–Ti3C2Tx flexible foam for use in lithium ion storage
Authors: Yan Jingze , Yu Lu , Wang Donghua , Zhang Wenyuan , Xiong Zhihao , Nie Tianshuo , Ji Zhen , Yan Xiaoqin
Published: June 2021

As a new two-dimensional material, MXene has attracted extensive attention because of its unique structure and electrochemical properties.
Lanthanide-doping enables kinetically controlled growth of deep-blue two-monolayer halide perovskite nanoplatelets
Authors: Cao Qinxuan , Ilyas Asif , Zhang Shuai , Ju Zhijie , Sun Fangling , Liu Tianyu , Yang Yang(Michael) , Lu Yunhao , Liu Xinfeng , Deng Renren
Published: June 2021

The doping of lanthanides enables the preparation of high-quality deep-blue emitting 2-monolayer CsPbBr3 nanoplatelets by enhancing the energy barrier for intermediates in the transformation of 2-monolayer to 3-monolayer CsPbBr3 nanoplatelets.
Catalyst-free arylation of sulfonamidesviavisible light-mediated deamination
Authors: Luo Yong , Ding Hao , Zhen Jing-Song , Du Xian , Xu Xiao-Hong , Yuan Han , Li Yi-Hui , Qi Wan-Ying , Liu Bing-Zhe , Lu Shi-Man , Xue Can , Ding Qiuping
Published: June 2021

The simple, catalyst-free sulfonylation of boronic acids with sulfonamidesviaa visible light-mediated N–S bond cleavage is described, affording diaryl sulfones with high efficiency. Late-stage functionalization of sulfonamide drugs was shown.
3D ordered macroporous copper nitride–titanium oxynitride as highly efficient electrocatalysts for universal-pH hydrogen evolution reaction
Authors: Wu Yuchen , Ning Fanghua , Wang Zhiwei , Saad Ali , Li Xiuting , Xia Dingguo
Published: June 2021

The Cu3N@TiOxNy electrocatalyst with 3D ordered macroporous nanostructure was prepared and its excellent electrocatalytical performance towards the hydrogen evolution reaction in all-pH electrolyte was demonstrated.
Promoted alkaline hydrogen evolution by an N-doped Pt–Ru single atom alloy
Authors: Luo Mi , Cai Jinyan , Zou Jiasui , Jiang Zheng , Wang Gongming , Kang Xiongwu
Published: June 2021

N incorporation induces d orbital tuning and promotes water dissociation on Ru, while single Pt atoms facilitate H desorption. The two effects synergistically enable the excellent alkaline HER performance on an N-doped Pt–Ru single atom alloy.
Photothermal treatment of oropharyngeal cancer with carbon-defective silicon carbide
Authors: Mu Haibin , Pang Haiyang , Zheng Ce , Wang Kaixin , Hu Narisu , Zhang Bin
Published: June 2021

Carbon-defective SiC1−x has been used for photothermal treatment of oral squamous carcinoma, which could meanwhile realize anti-wound infection.
Bearing estimation of low probability of intercept sources via polynomial matrices and sparse linear arrays
Authors: Coventry William , Clemente Carmine , Soraghan John , Cade Neil
Published: June 2021

Recent years have seen a steady convergence of Radar and Communications band Radio Frequency (RF) transceiver systems. Not only have Communications systems colonised large swathes of previously allocated Radar bands but there is also a convergence of technologies driven by the relatively low cost of software‐defined transceivers and solid‐sate RF sources. Thus, where conventional radar transmissions are characterised by short narrowband pulses with high peak power, new classes of ‘pulse‐compression’ radar are being developed to exploit this new technology. The resulting Low Probability of Intercept waveforms are designed to spread energy in both time and frequency, yielding a very low instantaneous power spectral density. Methods to detect, analyse and distinguish such sources require longer acquisition periods to collect more energy from the sources. Here, a novel solution is provided for detection and separation based on direction‐finding utilising polynomial matrix methods in conjunction with sparse array geometries. This approach provides enhanced detection, separation and direction finding while using relatively few antenna elements.
Cotton leaf curl Gezira virus.
Authors: Brown Judith K.
Published: June 2021

Cotton leaf curl Gezira virus (CLCuGV) is endemic to the African Sahel region (Idris et al., 2000). It is an economically important cotton-infecting begomovirus, and poses a serious threat to cotton production. It causes yield loss in all affected cotton-growing areas in Africa. Losses are difficult to assess, but estimates range up to 20% when infection occurs early in the growing season and/or with highly susceptible cultivars.
Changes in Young Adult Substance use during COVID-19 as a Function of ACEs, Depression, Prior Substance use and Resilience
Authors: Romm Katelyn F. , Patterson Brooke , Crawford Natalie D. , Posner Heather , West Carly D. , Wedding DeEnna , Horn Kimberly , Berg Carla J.
Published: June 2021

Background: Given the potential for increased substance use during COVID-19, we examined (1) young adults’ changes in cigarette, e-cigarette, marijuana, and alcohol use from pre- to during COVID-19; and (2) related risk/protective factors. These findings could inform intervention efforts aimed at curbing increases in substance use during periods of societal stress. Methods: We analyzed Wave 3 (W3; September–December 2019) and Wave 4 (W4; March–May 2020) from the Vape shop Advertising, Place characteristics and Effects Surveillance (VAPES), a 2-year, five-wave longitudinal study of young adults across six metropolitan areas. We examined risk/protective factors (i.e. adverse childhood experiences [ACEs], depressive symptoms, resilience) in relation to changes in past 30-day substance use frequency. Results: In this sample ( N = 1084, Mage=24.76, SD = 4.70; 51.8% female; 73.6% White; 12.5% Hispanic), W3/W4 past 30-day use prevalence was: 29.1% cigarettes (19.4% increased/26.4% decreased), 36.5% e-cigarettes (23.2% increased/28.6% decreased), 49.4% marijuana (27.2% increased/21.2% decreased), and 84.8% alcohol (32.9% increased/20.7% decreased). Multivariate regressions indicated that, greater increases were predicted by: for e-cigarettes, greater ACEs; and for alcohol, greater depression. Among those with low resilience, predictors included: for e-cigarettes, greater depression; and for marijuana, greater ACEs. Conclusions: Interventions to reduce substance use during societal stressors should target both risk and protective factors, particularly resilience.
Project ECHO and Primary Care Buprenorphine Treatment for Opioid use Disorder: Implementation and Clinical Outcomes
Authors: Anderson James B. , Martin Stephen A. , Gadomski Anne , Krupa Nicole , Mullin Daniel , Cahill Amber , Jenkins Paul
Published: June 2021

Background: Our rural health system sought to (1) increase the number of primary care clinicians waivered to prescribe buprenorphine for treatment of opioid use disorder (OUD) and (2) consequently increase the number of our patients receiving this treatment. Methods: We used the Project for Extension for Community Health Outcomes (ECHO) tele-education model as an implementation strategy. We examined the number of clinicians newly waivered, the number of patients treated with buprenorphine, the relationship between clinician engagement with ECHO training and rates of buprenorphine prescribing, and treatment retention at 180 days. Results: The number of clinicians with a waiver and number of patients treated increased during and after ECHO training. There was a moderate correlation between the number of ECHO sessions attended by a clinician and number of their buprenorphine prescriptions ( r = 0.50, p = 0.01). The 180-day retention rate was 80.7%. Conclusions: Project ECHO was highly effective for increasing access to this evidence-based treatment. The high retention rate in this rural context indicates that most patients are increasing their likelihood of favorable outcomes.
Interfacial microstructure and mechanical property in friction stir welded Mg/Al joints under low rotation speed
Authors: Fu Xuesong , Chen Ke , Zhang Zhen , Kondoh Katsuyoshi , Wang Min , Hua Xueming
Published: June 2021

The variation of interface microstructure along thickness direction and the associated effects on tensile strength were studied. Thin intermetallic compounds (IMC) layer, ranging from 700 nm to 2 μm, formed through solid-state diffusion instead of eutectic reaction under low rotation speed of 300 rev min−1. It was consisted of Al3Mg2 sublayer and Mg17Al12 sublayer, with Mg17Al12 sublayer thinner than Al3Mg2 sublayer. IMC layer in the upper part is thinner than that in the middle part, and it is continuous in the upper and middle part while discontinuous near the bottom surface. Despite the difference in interface microstructure, the bonding strengths of upper part and middle part are similar, proving the important effects of macroscopic geometrical configuration of the interface.
Governance of artificial intelligence
Authors: Taeihagh Araz
Published: June 2021

The rapid developments in Artificial Intelligence (AI) and the intensification in the adoption of AI in domains such as autonomous vehicles, lethal weapon systems, robotics and alike pose serious challenges to governments as they must manage the scale and speed of socio-technical transitions occurring. While there is considerable literature emerging on various aspects of AI, governance of AI is a significantly underdeveloped area. The new applications of AI offer opportunities for increasing economic efficiency and quality of life, but they also generate unexpected and unintended consequences and pose new forms of risks that need to be addressed. To enhance the benefits from AI while minimising the adverse risks, governments worldwide need to understand better the scope and depth of the risks posed and develop regulatory and governance processes and structures to address these challenges. This introductory article unpacks AI and describes why the Governance of AI should be gaining far more attention given the myriad of challenges it presents. It then summarises the special issue articles and highlights their key contributions. This special issue introduces the multifaceted challenges of governance of AI, including emerging governance approaches to AI, policy capacity building, exploring legal and regulatory challenges of AI and Robotics, and outstanding issues and gaps that need attention. The special issue showcases the state-of-the-art in the governance of AI, aiming to enable researchers and practitioners to appreciate the challenges and complexities of AI governance and highlight future avenues for exploration.
Pulling things together: regional policy coordination approaches and drivers in Europe
Authors: Ferry Martin
Published: June 2021

Coordination is a long-term issue for regional policy that has gained traction in academic and practitioner circles in recent years. The capacity challenges of responding to a broadening set of issues that cut across sectoral and administrative boundaries focus attention on regional policy coordination. Various concepts have emerged to study policy coordination processes, but efforts are ongoing to bring these together into overarching analytical frameworks. This paper contributes to these efforts by disaggregating coordination mechanisms according to different components of regional policy design and delivery (rule-based coordination, organisational arrangements, strategic policy coordination and policy instrument coordination) and by identifying cognitive, political and institutional factors that drive their use. The paper explores the relationship between coordination mechanisms and these drivers in the regional policy systems of three countries: Germany, Poland and the United Kingdom. It assesses the different dynamics at work and notes the importance of administrative capacity as a prerequisite for effective coordination.