bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Model for Nowcasting the Aviation Radiation Environment With Comparisons to In Situ Measurements During GLEs
Authors: Hands A. D. P. , Lei F. , Davis C. S. , Clewer B. J. , Dyer C. S. , Ryden K. A.
Published: July 2022

Significant increases to the atmospheric radiation environment are recorded by a network of ground level neutron monitors as ground level enhancements (GLEs). These space weather phenomena pose a risk to aviation via single event effects in aircraft electronics and ionizing dose to passengers and crew. Under the UK Space Weather Instrumentation, Measurement, Modeling and Risk programme, we have developed a new model to provide nowcasts of the aviation radiation environment, including both the galactic cosmic ray (GCR) background and during GLE events. The Model for Atmospheric Ionising Radiation Effects (MAIRE+) uses multiple data sources to characterize primary GCR and GLE particle spectra and combines these with precalculated geomagnetic and atmospheric response matrices to predict particle fluxes from ground level to 20 km altitude across the entire globe. Two European neutron monitors (located at Oulu in Finland and Dourbes in Belgium) are used as the primary indicators of GLE intensity in order to maximize accuracy over UK airspace. Outputs from MAIRE+ for the historical GLEs in September and October 1989 are compared to recalibrated empirical data from a solid‐state detector that was carried on Concorde in that period. The model will be hosted in the UK and will provide additional capability to the Met Office Space Weather Operations Center (MOSWOC).
Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1
Authors: Jin Yu , Liu Zhen , Li Zhenxia , Li Hairui , Zhu Cheng , Li Ruomei , Zhou Ting , Fang Bing
Published: July 2022

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.
TM4SF1 promotes esophageal squamous cell carcinoma metastasis by interacting with integrin α6
Authors: Hou Sicong , Hao Xin , Li Jiajia , Weng Siwei , Wang Jiaxin , Zhao Tiantian , Li Wenqian , Hu Xiaolin , Deng Bing , Gu Jianguo , Hang Qinglei
Published: July 2022

Transmembrane-4 L-six family member-1 (TM4SF1) is a member of the L6 family and functions as a signal transducer to regulate tumor cell behaviors. However, the function and mechanism of TM4SF1 in esophageal squamous cell carcinoma (ESCC) metastasis remains unclear. Here, we find that TM4SF1 expression is increased and positively correlated with clinical TNM stage, N classification, differentiation, tumor size, and poor prognosis in ESCC patients. Interestingly, we demonstrate that TM4SF1 promotes ESCC cell adhesion, spreading, migration, and invasion, but not cell proliferation, in a laminin-dependent manner by interacting with integrin α6. Mechanistically, the TM4SF1/integrin α6/FAK axis signal pathway mediates cell migration under laminin-coating condition. Inhibiting FAK or knocking down TM4SF1 can attenuate TM4SF1-mediated cell migration and lung metastasis. Clinically, the TM4SF1/integrin α6/FAK axis positively correlates with ESCC. Altogether, these findings reveal a new mechanism of TM4SF1 in promoting ESCC metastasis via binding to integrin α6 and suggest that the cross-talk between TM4SF1 and integrin α6 may serve as a therapeutic target for ESCC.
Equilibrated evolution of the mixed auto-/allopolyploid haplotype-resolved genome of the invasive hexaploid Prussian carp
Authors: Kuhl Heiner , Du Kang , Schartl Manfred , Kalous Lukáš , Stöck Matthias , Lamatsch Dunja K.
Published: July 2022

Understanding genome evolution of polyploids requires dissection of their often highly similar subgenomes and haplotypes. Polyploid animal genome assemblies so far restricted homologous chromosomes to a ‘collapsed’ representation. Here, we sequenced the genome of the asexual Prussian carp, which is a close relative of the goldfish, and present a haplotype-resolved chromosome-scale assembly of a hexaploid animal. Genome-wide comparisons of the 150 chromosomes with those of two ancestral diploid cyprinids and the allotetraploid goldfish and common carp revealed the genomic structure, phylogeny and genome duplication history of its genome. It consists of 25 syntenic, homeologous chromosome groups and evolved by a recent autoploid addition to an allotetraploid ancestor. We show that de-polyploidization of the alloploid subgenomes on the individual gene level occurred in an equilibrated fashion. Analysis of the highly conserved actinopterygian gene set uncovered a subgenome dominance in duplicate gene loss of one ancestral chromosome set.
Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity
Authors: Gilchrist James J. , Makino Seiko , Naranbhai Vivek , Sharma Piyush K. , Koturan Surya , Tong Orion , Taylor Chelsea A. , Watson Robert A. , de los Aires Alba Verge , Cooper Rosalin , Lau Evelyn , Danielli Sara , Hameiri-Bowen Dan , Lee Wanseon , Ng Esther , Whalley Justin , Knight Julian C. , Fairfax Benjamin P.
Published: July 2022

Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.
Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria
Authors: Musasia Fauzia K. , Nkumama Irene N. , Frank Roland , Kipkemboi Victor , Schneider Martin , Mwai Kennedy , Odera Dennis O. , Rosenkranz Micha , Fürle Kristin , Kimani Domitila , Tuju James , Njuguna Patricia , Hamaluba Mainga , Kapulu Melissa C. , Wardemann Hedda ,   CHMI-SIKA Study Team, Abdi Abdirahman I. , Abebe Yonas , Bejon Philip , Billingsley Peter F. , Bull Peter C. , de Laurent Zaydah , Hoffman Stephen L. , James Eric R. , Kariuki Silvia , Kimathi Rinter , Kinyanjui Sam , Kivisi Cheryl , Makale Johnstone , Marsh Kevin , Mohammed Khadija Said , Mosobo Moses , Musembi Janet , Musyoki Jennifer , Muthui Michelle , Mwacharo Jedidah , Ndungu Francis , Ngoi Joyce M. , Ngoto Omar , Ogutu Bernhards , Olewe Fredrick , Omuoyo Donwilliams , Ong’echa John , Otieno Edward , Shangala Jimmy , Sim Betty Kim Lee , Richie Thomas L. , Wambua Juliana , Williams Thomas N. , Osier Faith H. A.
Published: July 2022

Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study. Antibody-dependent phagocytosis of both ring-infected and uninfected erythrocytes from parasite cultures was strongly correlated with protection. A surface proteomic analysis revealed the presence of merozoite proteins including erythrocyte binding antigen-175 and −140 on ring-infected and uninfected erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition phagocytosis assays support the hypothesis that merozoite antigens are the key mediators of this functional activity. Targeting ring-stage parasites may contribute to the control of parasitaemia and prevention of clinical malaria.
HRS phosphorylation drives immunosuppressive exosome secretion and restricts CD8+ T-cell infiltration into tumors
Authors: Guan Lei , Wu Bin , Li Ting , Beer Lynn A. , Sharma Gaurav , Li Mingyue , Lee Chin Nien , Liu Shujing , Yang Changsong , Huang Lili , Frederick Dennie T. , Boland Genevieve M. , Shao Guangcan , Svitkina Tatyana M. , Cai Kathy Q. , Chen Fangping , Dong Meng-Qiu , Mills Gordon B. , Schuchter Lynn M. , Karakousis Giorgos C. , Mitchell Tara C. , Flaherty Keith T. , Speicher David W. , Chen Youhai H. , Herlyn Meenhard , Amaravadi Ravi K. , Xu Xiaowei , Guo Wei
Published: July 2022

The lack of tumor infiltration by CD8+ T cells is associated with poor patient response to anti-PD-1 therapy. Understanding how tumor infiltration is regulated is key to improving treatment efficacy. Here, we report that phosphorylation of HRS, a pivotal component of the ESCRT complex involved in exosome biogenesis, restricts tumor infiltration of cytolytic CD8+ T cells. Following ERK-mediated phosphorylation, HRS interacts with and mediates the selective loading of PD-L1 to exosomes, which inhibits the migration of CD8+ T cells into tumors. In tissue samples from patients with melanoma, CD8+ T cells are excluded from the regions where tumor cells contain high levels of phosphorylated HRS. In murine tumor models, overexpression of phosphorylated HRS increases resistance to anti-PD-1 treatment, whereas inhibition of HRS phosphorylation enhances treatment efficacy. Our study reveals a mechanism by which phosphorylation of HRS in tumor cells regulates anti-tumor immunity by inducing PD-L1+ immunosuppressive exosomes, and suggests HRS phosphorylation blockade as a potential strategy to improve the efficacy of cancer immunotherapy.
Sub-nanometer mapping of strain-induced band structure variations in planar nanowire core-shell heterostructures
Authors: Martí-Sánchez Sara , Botifoll Marc , Oksenberg Eitan , Koch Christian , Borja Carla , Spadaro Maria Chiara , Di Giulio Valerio , Ramasse Quentin , García de Abajo F. Javier , Joselevich Ernesto , Arbiol Jordi
Published: July 2022

Strain relaxation mechanisms during epitaxial growth of core-shell nanostructures play a key role in determining their morphologies, crystal structure and properties. To unveil those mechanisms, we perform atomic-scale aberration-corrected scanning transmission electron microscopy studies on planar core-shell ZnSe@ZnTe nanowires on α-Al2O3 substrates. The core morphology affects the shell structure involving plane bending and the formation of low-angle polar boundaries. The origin of this phenomenon and its consequences on the electronic band structure are discussed. We further use monochromated valence electron energy-loss spectroscopy to obtain spatially resolved band-gap maps of the heterostructure with sub-nanometer spatial resolution. A decrease in band-gap energy at highly strained core-shell interfacial regions is found, along with a switch from direct to indirect band-gap. These findings represent an advance in the sub-nanometer-scale understanding of the interplay between structure and electronic properties associated with highly mismatched semiconductor heterostructures, especially with those related to the planar growth of heterostructured nanowire networks.
Electric-field control of nonlinear THz spintronic emitters
Authors: Agarwal Piyush , Huang Lisen , Ter Lim Sze , Singh Ranjan
Published: July 2022

Energy-efficient spintronic technology holds tremendous potential for the design of next-generation processors to operate at terahertz frequencies. Femtosecond photoexcitation of spintronic materials generates sub-picosecond spin currents and emission of terahertz radiation with broad bandwidth. However, terahertz spintronic emitters lack an active material platform for electric-field control. Here, we demonstrate a nonlinear electric-field control of terahertz spin current-based emitters using a single crystal piezoelectric Pb(Mg1/3Nb2/3)O3–PbTiO3 (PMN–PT) that endows artificial magnetoelectric coupling onto a spintronic terahertz emitter and provides 270% modulation of the terahertz field at remnant magnetization. The nonlinear electric-field control of the spins occurs due to the strain-induced change in magnetic energy of the ferromagnet thin-film. Results also reveal a robust and repeatable switching of the phase of the terahertz spin current. Electric-field control of terahertz spintronic emitters with multiferroics and strain engineering offers opportunities for the on-chip realization of tunable energy-efficient spintronic-photonic integrated platforms.
Adipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism
Authors: Cho Yoon Keun , Yoon Young Cheol , Im Hyeonyeong , Son Yeonho , Kim Minsu , Saha Abhirup , Choi Cheoljun , Lee Jaewon , Lee Sumin , Kim Jae Hyun , Kang Yun Pyo , Jung Young-Suk , Ha Hong Koo , Seong Je Kyung , Granneman James G. , Kwon Sung Won , Lee Yun-Hee
Published: July 2022

Dysregulation of adipose tissue plasmalogen metabolism is associated with obesity-related metabolic diseases. We report that feeding mice a high-fat diet reduces adipose tissue lysoplasmalogen levels and increases transmembrane protein 86 A (TMEM86A), a putative lysoplasmalogenase. Untargeted lipidomic analysis demonstrates that adipocyte-specific TMEM86A-knockout (AKO) increases lysoplasmalogen content in adipose tissue, including plasmenyl lysophosphatidylethanolamine 18:0 (LPE P-18:0). Surprisingly, TMEM86A AKO increases protein kinase A signalling pathways owing to inhibition of phosphodiesterase 3B and elevation of cyclic adenosine monophosphate. TMEM86A AKO upregulates mitochondrial oxidative metabolism, elevates energy expenditure, and protects mice from metabolic dysfunction induced by high-fat feeding. Importantly, the effects of TMEM86A AKO are largely reproduced in vitro and in vivo by LPE P-18:0 supplementation. LPE P-18:0 levels are significantly lower in adipose tissue of human patients with obesity, suggesting that TMEM86A inhibition or lysoplasmalogen supplementation might be therapeutic approaches for preventing or treating obesity-related metabolic diseases.
Auxotrophic and prototrophic conditional genetic networks reveal the rewiring of transcription factors in Escherichia coli
Authors: Gagarinova Alla , Hosseinnia Ali , Rahmatbakhsh Matineh , Istace Zoe , Phanse Sadhna , Moutaoufik Mohamed Taha , Zilocchi Mara , Zhang Qingzhou , Aoki Hiroyuki , Jessulat Matthew , Kim Sunyoung , Aly Khaled A. , Babu Mohan
Published: July 2022

Bacterial transcription factors (TFs) are widely studied inEscherichia coli. Yet it remains unclear how individual genes in the underlying pathways of TF machinery operate together during environmental challenge. Here, we address this by applying an unbiased, quantitative synthetic genetic interaction (GI) approach to measure pairwise GIs among all TF genes inE. coliunder auxotrophic (rich medium) and prototrophic (minimal medium) static growth conditions. The resulting static and differential GI networks reveal condition-dependent GIs, widespread changes among TF genes in metabolism, and new roles for uncharacterized TFs (yjdC,yneJ,ydiP) as regulators of cell division, putrescine utilization pathway, and cold shock adaptation. Pan-bacterial conservation suggests TF genes with GIs are co-conserved in evolution. Together, our results illuminate the global organization ofE. coliTFs, and remodeling of genetic backup systems for TFs under environmental change, which is essential for controlling the bacterial transcriptional regulatory circuits.
Ultraviolet supercontinuum generation driven by ionic coherence in a strong laser field
Authors: Lei Hongbin , Yao Jinping , Zhao Jing , Xie Hongqiang , Zhang Fangbo , Zhang He , Zhang Ning , Li Guihua , Zhang Qian , Wang Xiaowei , Yang Yan , Yuan Luqi , Cheng Ya , Zhao Zengxiu
Published: July 2022

Supercontinuum (SC) light sources hold versatile applications in many fields ranging from imaging microscopic structural dynamics to achieving frequency comb metrology. Although such broadband light sources are readily accessible in the visible and near infrared regime, the ultraviolet (UV) extension of SC spectrum is still challenging. Here, we demonstrate that the joint contribution of strong field ionization and quantum resonance leads to the unexpected UV continuum radiation spanning the 100 nm bandwidth in molecular nitrogen ions. Quantum coherences in a bunch of ionic levels are found to be created by dynamic Stark-assisted multiphoton resonances following tunneling ionization. We show that the dynamical evolution of the coherence-enhanced polarization wave gives rise to laser-assisted continuum emission inside the laser field and free-induction decay after the laser field, which jointly contribute to the SC generation together with fifth harmonics. As proof of principle, we also show the application of the SC radiation in the absorption spectroscopy. This work offers an alternative scheme for constructing exotic SC sources, and opens up the territory of ionic quantum optics in the strong-field regime.
Rising ecosystem water demand exacerbates the lengthening of tropical dry seasons
Authors: Xu Hao , Lian Xu , Slette Ingrid J. , Yang Hui , Zhang Yuan , Chen Anping , Piao Shilong
Published: July 2022

Precipitation-based assessments show a lengthening of tropical dry seasons under climate change, without considering simultaneous changes in ecosystem water demand. Here, we compare changes in tropical dry season length and timing when dry season is defined as the period when precipitation is less than: its climatological average, potential evapotranspiration, or actual evapotranspiration. While all definitions show more widespread tropical drying than wetting for 1983-2016, we find the largest fraction (48.7%) of tropical land probably experiencing longer dry seasons when dry season is defined as the period when precipitation cannot meet the need of actual evapotranspiration. Southern Amazonia (due to delayed end) and central Africa (due to earlier onset and delayed end) are hotspots of dry season lengthening, with greater certainty when accounting for water demand changes. Therefore, it is necessary to account for changing water demand when characterizing changes in tropical dry periods and ecosystem water deficits.
Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries
Authors: Banday A. Rouf , Stanifer Megan L. , Florez-Vargas Oscar , Onabajo Olusegun O. , Papenberg Brenen W. , Zahoor Muhammad A. , Mirabello Lisa , Ring Timothy J. , Lee Chia-Han , Albert Paul S. , Andreakos Evangelos , Arons Evgeny , Barsh Greg , Biesecker Leslie G. , Boyle David L. , Brahier Mark S. , Burnett-Hartman Andrea , Carrington Mary , Chang Euijin , Choe Pyoeng Gyun , Chisholm Rex L. , Colli Leandro M. , Dalgard Clifton L. , Dude Carolynn M. , Edberg Jeff , Erdmann Nathan , Feigelson Heather S. , Fonseca Benedito A. , Firestein Gary S. , Gehring Adam J. , Guo Cuncai , Ho Michelle , Holland Steven , Hutchinson Amy A. , Im Hogune , Irby Les’Shon , Ison Michael G. , Joseph Naima T. , Kim Hong Bin , Kreitman Robert J. , Korf Bruce R. , Lipkin Steven M. , Mahgoub Siham M. , Mohammed Iman , Paschoalini Guilherme L. , Pacheco Jennifer A. , Peluso Michael J. , Rader Daniel J. , Redden David T. , Ritchie Marylyn D. , Rosenblum Brooke , Ross M. Elizabeth , Anna Hanaisa P. Sant , Savage Sharon A. , Sharma Sudha , Siouti Eleni , Smith Alicia K. , Triantafyllia Vasiliki , Vargas Joselin M. , Vargas Jose D. , Verma Anurag , Vij Vibha , Wesemann Duane R. , Yeager Meredith , Yu Xu , Zhang Yu , Boulant Steeve , Chanock Stephen J. , Feld Jordan J. , Prokunina-Olsson Ludmila
Published: July 2022

The chr12q24.13 locus encoding OAS1–OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454-A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.
CRISPR–Cas12a-mediated DNA clamping triggers target-strand cleavage
Authors: Naqvi Mohsin M. , Lee Laura , Montaguth Oscar E. Torres , Diffin Fiona M. , Szczelkun Mark D.
Published: July 2022

Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas12a is widely used for genome editing and diagnostics, so it is important to understand how RNA-guided DNA recognition activates the cleavage of the target strand (TS) following non-target-strand (NTS) cleavage. Here we used single-molecule magnetic tweezers, gel-based assays and nanopore sequencing to explore DNA unwinding and cleavage. In addition to dynamic and heterogenous R-loop formation, we also directly observed transient double-stranded DNA unwinding downstream of the 20-bp heteroduplex and, following NTS cleavage, formation of a hyperstable ‘clamped’ Cas12a–DNA intermediate necessary for TS cleavage. Annealing of a 4-nucleotide 3′ CRISPR RNA overhang to the unwound TS downstream of the heteroduplex inhibited clamping and slowed TS cleavage by ~16-fold. Alanine substitution of a conserved aromatic amino acid in the REC2 subdomain that normally caps the R-loop relieved this inhibition but favoured stabilisation of unwound states, suggesting that the REC2 subdomain regulates access of the 3′ CRISPR RNA to downstream DNA.
A europium metal–organic framework for dual Fe3+ ion and pH sensing
Authors: Rozenberga Linda , Skinner William , Lancaster David G. , Bloch Witold M. , Blencowe Anton , Krasowska M. , Beattie David A.
Published: July 2022

Metal–organic frameworks (MOFs) with ratiometric sensing properties are desirable for many applications due to their intrinsic self-calibration. We report the re-assessment of the sensing properties of a MOF, originally reported as containing europium(III) and 2-hydroxyterephtalic acid, and having fluorescent ratiometric iron(III) sensing properties. Synchrotron single-crystal X-ray diffraction and proton nuclear magnetic resonance (1H NMR) spectroscopy revealed that the MOF is composed of 2-methoxyterephthalate, not 2-hydroxyterephthalate as originally reported. We found that the MOF exhibits a sensor turn-off response towards Fe3+ ion concentrations in the range 0.5–3.7 ppm (band 425 nm), and a turn-on response towards a decrease of pH from 5.4 to 3.0 (band 375 nm), both resulting from the addition of acidic Fe3+ salt solution to a MOF suspension. Thus, the ratiometric sensing properties and the originally proposed mechanism no longer apply; our work reveals a dynamic quenching mechanism for the fluorescence turn-off response due to the presence of Fe3+ ions, and a ligand protonation mechanism for the turn-on response to a decrease in pH. Our work highlights the importance of a thorough investigation of the structure of any newly synthesized MOF, and, in the case of potential sensors, their selectivity and any environmental effects on their sensing behavior.
Plant rarity in fire-prone dry sclerophyll communities
Authors: Sritharan Meena S. , Scheele Ben C. , Blanchard Wade , Foster Claire N. , Werner Patricia A. , Lindenmayer David B.
Published: July 2022

Understanding the responses of rare species to altered fire disturbance regimes is an ongoing challenge for ecologists. We asked: are there associations between fire regimes and plant rarity across different vegetation communities? We combined 62 years of fire history records with vegetation surveys of 86 sites across three different dry sclerophyll vegetation communities in Booderee National Park, south-east Australia to: (1) compare associations between species richness and rare species richness with fire regimes, (2) test whether fire regimes influence the proportion of rare species present in an assemblage, and (3) examine whether rare species are associated with particular fire response traits and life history. We also sought to determine if different rarity categorisations influence the associations between fire regimes and plant rarity. We categorised plant rarity using three standard definitions; species' abundance, species' distribution, and Rabinowitz's measure of rarity, which considers a species' abundance, distribution and habitat specificity. We found that total species richness was negatively associated with short fire intervals but positively associated with time since fire and fire frequency in woodland communities. Total species richness was also positively associated with short fire intervals in forest communities. However, rare species richness was not associated with fire when categorised via abundance or distribution. Using Rabinowitz's measure of rarity, the proportion of rare species present was negatively associated with fire frequency in forest communities but positively associated with fire frequency in woodland communities. We found that rare species classified by all three measures of rarity exhibited no difference in fire response traits and serotiny compared to species not classified as rare. Rare species based on abundance differed to species not classified as rare across each life history category, while species rare by distribution differed in preferences for seed storage location. Our findings suggest that species categorised as rare by Rabinowitz's definition of rarity are the most sensitive to the effects of fire regimes. Nevertheless, the paucity of responses observed between rare species with fire regimes in a fire-prone ecosystem suggests that other biotic drivers may play a greater role in influencing the rarity of a species in this system.
Effectiveness of controlling COVID-19 epidemic by implementing soft lockdown policy and extensive community screening in Taiwan
Authors: Chan Ta-Chien , Chou Ching-Chi , Chu Yi-Chi , Tang Jia-Hong , Chen Li-Chi , Lin Hsien-Ho , Chen Kevin J. , Chen Ran-Chou
Published: July 2022

Strict and repeated lockdowns have caused public fatigue regarding policy compliance and had a large impact on several countries’ economies. We aimed to evaluate the effectiveness of a soft lockdown policy and the strategy of active community screening for controlling COVID-19 in Taiwan. We used village-based daily confirmed COVID-19 statistics in Taipei City and New Taipei City, between May 2, 2021, and July 17, 2021. The temporal Gi* statistic was used to compute the spatiotemporal hotspots. Simple linear regression was used to evaluate the trend of the epidemic, positivity rate from community screening, and mobility changes in COVID-19 cases and incidence before and after a level three alert in both cities. We used a Bayesian hierarchical zero-inflated Poisson model to estimate the daily infection risk. The cities accounted for 11,403 (81.17%) of 14,048 locally confirmed cases. The mean effective reproduction number (Re) surged before the level three alert and peaked on May 16, 2021, the day after the level three alert in Taipei City (Re = 3.66) and New Taipei City (Re = 3.37). Mobility reduction and a lower positive rate were positively associated with a lower number of cases and incidence. In the spatiotemporal view, seven major districts were identified with a radial spreading pattern from one hard-hit district. Villages with a higher inflow degree centrality among people aged ≥ 60 years, having confirmed cases, specific land-use types, and with a higher aging index had higher infection risks than other villages. Early soft lockdown policy and detection of infected patients showed an effective strategy to control COVID-19 in Taiwan.
Broadband metasurface superstrate for polarization-independent wave focusing and gain enhancement at Ka-band
Authors: Lee Kanghyeok , Hong Ha Young , Lee Wonwoo , Jo Semin , Park Hong Soo , Yang Junhyuk , Park Changkun , Lee Hojin , Hong Sun K.
Published: July 2022

A broadband metasurface flat lens is proposed as a polarization-independent wideband superstrate for wave focusing and gain enhancement at Ka-band. The proposed metasurface structure consists of four metal layers and is designed with diagonally symmetric unit cells to accommodate both the vertical and horizontal polarizations. The focusing ability of the proposed metasurface flat lens is validated via simulation and measurement, where normally incident plane waves are shown to be enhanced by up to 11 dB as a result of wave focusing. Also, the radiation gain enhancement due to the proposed metasurface flat lens is demonstrated via simulation and measurement, where a gain enhancement of up to 10.5 dB is achieved. The results show that the proposed structure maintains the wave focusing and gain enhancement characteristics over a bandwidth of 28–32 GHz. Furthermore, to demonstrate the utility of the proposed metasurface for circular polarization (CP), the gain enhancement of a CP patch antenna as a result of implementing the proposed metasurface as a superstrate is demonstrated via simulation and measurement. It is shown that the proposed metasurface superstrate provides a CP gain enhancement of nearly 10 dB.
Generalized monodromy method in gauge/gravity duality
Authors: Hou Yuanpeng
Published: July 2022

The method of monodromy is an important tool for computing Virasoro conformal blocks in a two-dimensional Conformal Field Theory (2d CFT) at large central charge and external dimensions. In deriving the form of the monodromy problem, which defines the method, one needs to insert a degenerate operator, usually a level-two operator, into the corresponding correlation function. It can be observed that the choice of which degenerate operator to insert is arbitrary, and they shall reveal the same physical principles underlying the method. In this paper, we exploit this freedom and generalize the method of monodromy by inserting higher-level degenerate operators. We illustrate the case with a level-three operator, and derive the corresponding form of the monodromy problem. We solve the monodromy problem perturbatively and numerically; and check that it agrees with the standard monodromy method, despite the fact that the two versions of the monodromy problem do not seem to be related in any obvious way. The forms corresponding to other higher-level degenerate operators are also discussed. We explain the physical origin of the coincidence and discuss its implication from a mathematical perspective.
GM-CSF derived from the inflammatory microenvironment potentially enhanced PD-L1 expression on tumor-associated macrophages in human breast cancer
Authors: Yonemitsu Kimihiro , Pan Cheng , Fujiwara Yukio , Miyasato Yuko , Shiota Takuya , Yano Hiromu , Hosaka Seiji , Tamada Koji , Yamamoto Yutaka , Komohara Yoshihiro
Published: July 2022

Ever since immune checkpoint inhibitors have been approved for anti-cancer therapy in several cancers, including triple-negative breast cancer, the significance of programmed death-1 ligand 1 (PD-L1) expression in the tumor immune microenvironment has been a topic of interest. In the present study, we investigated the detailed mechanisms of PD-L1 overexpression on tumor-associated macrophages (TAMs) in breast cancer. In in vitro culture studies using human monocyte-derived macrophages, lymphocytes, and breast cancer cell lines, PD-L1 overexpression on macrophages was induced by the conditioned medium (CM) of activated lymphocytes, but not that of cancer cells. Granulocyte–macrophage colony-stimulating factor (GM-CSF) derived from activated lymphocytes was found to be involved in PD-L1 overexpression, in addition to interferon (IFN)-γ, via STAT3 pathway activation. Macrophages suppressed lymphocyte activation, and this inhibition was impaired by PD-1 blocking. The CM of activated lymphocytes also induced the overexpression of PD-L2, but GM-CSF did not affect PD-L2 expression. In the murine E0771 breast cancer model, anti-GM-CSF therapy did not affect PD-L1 expression on TAMs, and the mechanisms of PD-L1 expression on TAMs might differ between humans and mice. However, not only PD-L1, but also PD-L2 was overexpressed on TAMs in the E0771 tumor model, and their expression levels were significantly lower in the tumors in nude mice than in wild-type mice. Anti-PD-L1 antibody and anti-PD-L2 antibody synergistically inhibited E0771 tumor development. In conclusion, PD-L1 and PD-L2 were overexpressed on TAMs, and they potentially contributed to immunosuppression. The GM-CSF-STAT3 pathway is thought to represent a new mechanism of PD-L1 overexpression on TAMs in human breast cancer microenvironment.
Speciation and transformation of nitrogen for swine manure thermochemical liquefaction
Authors: Liu Zhuangzhuang , Yan Zhiwei , Liu Fen , Fang Jun
Published: July 2022

The nitrogen conversion mechanism of swine manure by thermochemical liquefaction with ethanol as solvent was investigated at a lower temperature range (180–300 °C). The fate of nitrogen in liquid phase products, bio-oil and biochar was evaluated by XPS, GC–MS and other methods. After thermochemical liquefaction, most of the nitrogen in swine manure was transferred to biochar (63.75%). As the temperature increased to 220 °C, the biochar-N yields decreased to 43.29%, accompanied by an increase in bio-oil-N and liquid phase product-N by 7.99% and 1.26% respectively. The results indicated that increasing the temperature could facilitate solid nitrogen structure cracking into bio-oil-N. Amines and heterocyclic nitrogen from protein peptide bond cracking and Maillard reactions made up the main nitrogen compounds in bio-oil, and high temperatures favored the further cyclization and condensation of heterocyclic nitrogen (e.g., indole, quinoline). In the case of biochar, the inorganic nitrogen disappeared at 260 °C and was obviously transformed into liquid phase products. The rising temperature promoted the polymerization of pyridine nitrogen and pyrrole nitrogen, which formed more stabilized nitrogen formation (such as quaternary nitrogen). Nitrogen conversion and possible reaction schematics during swine manure thermochemical liquefaction were explored in this study.
COVID-19 increases the risk for the onset of atrial fibrillation in hospitalized patients
Authors: Wollborn Jakob , Karamnov Sergey , Fields Kara G. , Yeh Tiffany , Muehlschlegel Jochen D.
Published: July 2022

COVID-19 is associated with significant extrapulmonary symptoms. Myocardial involvement has been described for infections with SARS-CoV-2 which may lead to an increase in morbidity and mortality. The objective of our study was to investigate the association of COVID-19 and atrial fibrillation (AF) or atrial flutter (AFl) in hospitalized patients. This retrospective study used electronic medical records to detect patients with COVID-19 and their comorbidities within the Mass General Brigham hospital system. All patients ≥ 18 years who were hospitalized and received a PCR test for SARS-CoV-2 were screened for inclusion as well as patients from a pre-pandemic cohort. We matched on common risk factors for AF and then used multivariable logistic regression to estimate the odds for AF or AFl. Of 78,725 patients eligible for analysis, 11,004 COVID-19 negative patients were matched to 3,090 COVID-19 positive patients and 5005 pre-pandemic patients were matched to 2283 COVID-19 positive patients. After adjusting for demographics and comorbidities, COVID-19 positive patients had 1.19 times the odds (95% CI 1.00, 1.41) of developing AF compared to COVID-19 negative patients and 1.57 times the odds (95% CI 1.23, 2.00) of developing AF compared to pre-pandemic patients. Our study demonstrated an increased risk for AF, directing the attention for improved screening and treatment regimens for the sequelae of COVID-19. While COVID-19 continues to affect many people around the world, AF may be a significant cause for morbidity and mortality. Adequate detection and treatment of AF is essential to reduce the burden of disease.
Area-based breast percentage density estimation in mammograms using weight-adaptive multitask learning
Authors: Gudhe Naga Raju , Behravan Hamid , Sudah Mazen , Okuma Hidemi , Vanninen Ritva , Kosma Veli-Matti , Mannermaa Arto
Published: July 2022

Breast density, which is a measure of the relative amount of fibroglandular tissue within the breast area, is one of the most important breast cancer risk factors. Accurate segmentation of fibroglandular tissues and breast area is crucial for computing the breast density. Semiautomatic and fully automatic computer-aided design tools have been developed to estimate the percentage of breast density in mammograms. However, the available approaches are usually limited to specific mammogram views and are inadequate for complete delineation of the pectoral muscle. These tools also perform poorly in cases of data variability and often require an experienced radiologist to adjust the segmentation threshold for fibroglandular tissue within the breast area. This study proposes a new deep learning architecture that automatically estimates the area-based breast percentage density from mammograms using a weight-adaptive multitask learning approach. The proposed approach simultaneously segments the breast and dense tissues and further estimates the breast percentage density. We evaluate the performance of the proposed model in both segmentation and density estimation on an independent evaluation set of 7500 craniocaudal and mediolateral oblique-view mammograms from Kuopio University Hospital, Finland. The proposed multitask segmentation approach outperforms and achieves average relative improvements of 2.88% and 9.78% in terms of F-score compared to the multitask U-net and a fully convolutional neural network, respectively. The estimated breast density values using our approach strongly correlate with radiologists’ assessments with a Pearson’s correlation of$$r = 0.90$$r=0.90(95% confidence interval [0.89, 0.91]). We conclude that our approach greatly improves the segmentation accuracy of the breast area and dense tissues; thus, it can play a vital role in accurately computing the breast density. Our density estimation model considerably reduces the time and effort needed to estimate density values from mammograms by radiologists and therefore, decreases inter- and intra-reader variability.
LRP-1 receptor combines EGFR signalling and eHsp90α autocrine to support constitutive breast cancer cell motility in absence of blood supply
Authors: Chang Cheng , Tang Xin , Mosallaei Daniel , Chen Mei , Woodley David T. , Schönthal Axel H. , Li Wei
Published: July 2022

Tumor cells face constant stress of ischemic (nutrient paucity and hypoxia) environment when they migrate and invade too fast to outgrow the nearest blood vessels. During the temporary loss of support from circulation, the tumor cells must act self-sufficient to survive and then to migrate to re-connect with the nearest blood supply or die. We have previously reported that ablation of the low-density lipoprotein receptor-related protein 1 (LRP-1) completely nullified the ability of tumour cells to migrate and invade under serum-free conditions in vitro and to form tumours in vivo. The mechanism behind the important function by cell surface LRP-1 was not fully understood. Herein we show that LRP-1 orchestrates two parallel cell surface signalling pathways to support the full constitutive tumour cell migration. First, LRP-1 stabilizes activated epidermal growth factor receptor (EGFR) to contribute half of the pro-motility signalling. Second, LRP-1 mediates secreted Hsp90α autocrine signalling to bring the other half of pro-motility signalling. Only combined inhibitions of the EGFR signalling and the eHsp90α autocrine signalling led to the full blockade of the tumour cell migration as the LRP-1 depletion did. This finding uncovers a novel mechanism by which certain breast cancer cells use LRP-1 to engage parallel signalling pathways to move when they lose contact with blood support.
Urban tropical forest islets as hotspots of ants in general and invasive ants in particular
Authors: Rajesh T. P. , Manoj K. , Prashanth Ballullaya U. , Shibil V. K. , Asha G. , Varma Sangeetha , Mohan Prabitha , Sinu Palatty Allesh
Published: July 2022

Urbanization is a crucial driver of environmental and biodiversity change. It is suggested that urbanization favours generalist and invasive species and might harm specialists of natural and semi-natural habitats. In this study, we examined how an urbanization gradient and environmental gradients in the habitat area, habitat diversity, elevation, and proportion of built-up area influenced the abundance and richness of ants within tropical forest islet habitat in south India. We used abundance (proportional trap incidence) of overall ants, native ants, invasive ants, and Anoplolepis gracilipes—a globally notorious invasive ant of possible south Asian origin—and rarefied richness as the response variables. We found that native ant abundance was greater and A. gracilipes abundance was lesser in less-urbanized landscape compared to moderately-urbanized and highly-urbanized landscape. The richness of ants and abundance of overall and invasive ants were unaffected by the urbanization. We also found that none of the measured environmental gradients but habitat diversity influenced abundance of overall ants, native ants, overall invasive ants, and richness of ants; however, A. gracilipes abundance was negatively correlated with habitat diversity. Ant species composition of less-urbanized landscape was distinct from that of higher urbanization levels. The richness and abundance of native ants and abundance of non-A. gracilipes invasive ants decreased with the abundance of A. gracilipes. Because the forest islets of all three urbanization levels supported similar richness of native ants, the urbanization seems not to have an adverse effect for the native ants of native forest islets. The increasing population of A. gracilipes in urban green islets, however, is a concern. Future studies might investigate its effect on other invertebrates of epigeal and soil strata.
Noncovalent functionalization of carbon nanotubes as a scaffold for tissue engineering
Authors: Assali Mohyeddin , Kittana Naim , Alhaj-Qasem Sahar , Hajjyahya Muna , Abu-Rass Hanood , Alshaer Walhan , Al-Buqain Rula
Published: July 2022

Tissue engineering is one of the hot topics in recent research that needs special requirements. It depends on the development of scaffolds that allow tissue formation with certain characteristics, carbon nanotubes (CNTs)-collagen composite attracted the attention of the researchers with this respect. However, CNTs suffer from low water dispersibility, which hampered their utilization. Therefore, we aim to functionalize CNTs non-covalently with pyrene moiety using an appropriate hydrophilic linker derivatized from polyethylene glycol (PEG) terminated with hydroxyl or carboxyl group to disperse them in water. The functionalization of the CNTs is successfully confirmed by TEM, absorption spectroscopy, TGA, and zeta potential analysis. 3T3 cells-based engineered connective tissues (ECTs) are generated with different concentrations of the functionalized CNTs (f-CNTs). These tissues show a significant enhancement in electrical conductivity at a concentration of 0.025%, however, the cell viability is reduced by about 10 to 20%. All ECTs containing f-CNTs show a significant reduction in tissue fibrosis and matrix porosity relative to the control tissues. Taken together, the developed constructs show great potential for further in vivo studies as engineered tissue.
How well have CMIP3, CMIP5 and CMIP6 future climate projections portrayed the recently observed warming
Authors: Carvalho D. , Rafael S. , Monteiro A. , Rodrigues V. , Lopes M. , Rocha A.
Published: July 2022

Despite the dire conclusions of the Intergovernmental Panel on Climate Change (IPCC) Assessment Reports in terms of global warming and its impacts on Earth’s climate, ecosystems and human society, a skepticism claiming that the projected global warming is alarmist or, at least, overestimated, still persists. Given the years passed since the future climate projections that served as basis for the IPCC 4th, 5th and 6th Assessment Reports were released, it is now possible to answer this fundamental question if the projected global warming has been over or underestimated. This study presents a comparison between CMIP3, CMIP5 and CMIP6 future temperature projections and observations. The results show that the global warming projected by all CMIPs and future climate scenarios here analyzed project a global warming slightly lower than the observed one. The observed warming is closer to the upper level of the projected ones, revealing that CMIPs future climate scenarios with higher GHG emissions appear to be the most realistic ones. These results show that CMIPs future warming projections have been slightly conservative up to 2020, which could suggest a similar cold bias in their warming projections up to the end of the current century. However, given the short future periods here analyzed, inferences about warming at longer timescales cannot be done with confidence, since the models internal variability can play a relevant role on timescales of 20 years and less.