bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Biomimicry to Support Resilient Infrastructure Design
Authors: Helmrich Alysha M. , Chester Mikhail V. , Hayes Samantha , Markolf Samuel A. , Desha Cheryl , Grimm Nancy B. 
Published: November 2020

AbstractInfrastructure must be resilient to both known and unknown disturbances. In the past, resilient infrastructure design efforts have tended to focus on principles of robustness and recovery against projected failures. This framing has developed independently from resilience principles in biological and ecological systems. As such, there are open questions as to whether the approaches of natural systems that lead to adaptation and transformation are relevant to engineered systems. To improve engineered system resilience, infrastructure managers may benefit from considering and applying a set of “Life's Principles”—design principles and patterns drawn from the field of biomimicry. Nature has long withstood disturbances within and beyond previous experience. Infrastructure resilience theory and practice are assessed against Life's Principles identifying alignments, contradictions, contentions, and gaps. Resilient infrastructure theory, which emphasizes a need for flexible and agile infrastructure, aligns well with Life's Principles, addressing each principle and most sub‐principles (excluding “breakdown products into benign components” and “do chemistry in water”). Meanwhile, resilient infrastructure practice only occasionally aligns with Life's Principles and contradicts five out of six principles. As resilience theory advances, Life's Principles offer support in broadening how infrastructure managers approach resilience, and by using biomimicry, infrastructure managers can be better equipped to deploy resilience for complexity and uncertainty.
The Coupled Impact of Emergency Responses and Population Flows on the COVID‐19 Pandemic in China
Authors: Cheng Changxiu , Zhang Tianyuan , Song Changqing , Shen Shi , Jiang Yifan , Zhang Xiangxue 
Published: November 2020

AbstractCoronavirus disease 2019 (COVID‐19) has spread around the world and requires effective control measures. Like the human‐to‐human transmission of the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2), the distribution of COVID‐19 was driven by population flow and required emergency response measures to slow down its spread and degrade the epidemic risk. The local epidemic risk of COVID‐19 is a combination of emergency response measures and population flow. Because of the spatial heterogeneity, the different impacts of coupled emergency responses and population flow on the COVID‐19 epidemic during the outbreak period and a control period are unclear. We examined and compared the impact of emergency response measures and population flow on China's epidemic risk after the Wuhan lockdown during the outbreak period and a control period. We found that the population flow out of Wuhan had a long‐term impact on the epidemic's spread. In the outbreak period, a large population flow out of Wuhan led to nationwide migration mobility, which directly increased the epidemic in each province. Meanwhile, quick emergency responses mitigated the spread. Although low population flow to provinces far from Hubei delayed the outbreak in those provinces, relatively delayed emergency response increased the epidemic in the control period. Consequently, due to the strong transmission ability of the SARS‐CoV‐2 virus, no region correctly estimated the epidemic, and the relaxed emergency response raised the epidemic risks in the context of the outbreak.
A Long‐Lasting Auroral Spiral Rotating Around Saturn's Pole
Authors: Palmaerts B. , Yao Z. H. , Sergis N. , Guo R. L. , Grodent D. , Dialynas K. , Gérard J.‐C. , Mitchell D. G. 
Published: November 2020

AbstractThe main ultraviolet auroral emission at Saturn consists of multiple structures forming a discontinuous ring of emission around the poles, occasionally organized in a global spiral. We present continuous observation of an auroral spiral rotating at ∼85% of rigid corotation during several hours. Simultaneously, energetic neutral atom (ENA) emissions revealed a hot magnetospheric plasma population located in the same local time sector as the ends of the rotating spiral. Following plasma theory, we propose that pressure gradients induced by the energized plasma distorted the magnetospheric current system, resulting in the spiral morphology of the aurora. The rotating hot plasma was several times reenergized in the dusk sector during at least 2 days, generating a long‐lasting auroral spiral. The ultraviolet spiral, the ENA emissions, and the ions revealed by this multi‐instrument data set are three signatures of a magnetosphere‐ionosphere coupling current system and of the associated hot plasma population rotating around Saturn.
Thunderstorm High‐Frequency Radio Bursts With Weak Low‐Frequency Radiation
Authors: Liu Ningyu Y. , Dwyer Joseph R. 
Published: November 2020

AbstractBrief bursts of high‐frequency (HF) and very high frequency (VHF) radio emissions unaccompanied by strong low‐frequency radiation have been observed during initiation and propagation of lightning or thunderstorm electrical breakdown without leading to fully fledged lightning. This paper investigates a physical mechanism to generate such radio bursts by electrical discharge activity inside a thundercloud. When a discharge consists of many high‐frequency emission sources, such as streamers, that generate currents in random directions, its radiation spectrum peaks in the HF and VHF bands, and the spectral magnitudes in low frequencies are much smaller or even negligible. Combined with recent observational findings, the present study suggests that lightning initiation may begin with a short burst of many randomly occurring small‐scale discharges in a localized thundercloud region.
Eddy‐Induced Transport and Kinetic Energy Budget in the Arabian Sea
Authors: Zhan Peng , Guo Daquan , Hoteit Ibrahim 
Published: November 2020

AbstractThis study investigates the vertical eddy structure, eddy‐induced transport, and eddy kinetic energy (EKE) budget in the Arabian Sea (AS) using an eddy‐resolving reanalysis product. The EKE intensifies during summer in the western AS. Anticyclonic eddies (AEs) and cyclonic eddies (CEs) present warm‐fresh and cold‐salty cores, respectively, with interleaved salinity structures. The eddy‐induced swirl transport is larger in the western AS and tends to compensate for heat transport by the mean flow. Zonal drift transport by AEs and CEs offset each other, and meridional transport is generally weaker. Eddies also produce notable upward heat flux during summer in the western AS, where ageostrophic circulations are induced to maintain a turbulent thermal wind balance. Plausible mechanisms for EKE production are governed by baroclinic and barotropic instabilities, which are enhanced in summer in the western basin, where signals are quantitatively one order larger than the turbulent wind inputs.
The Flux and Provenance of Dust Delivered to the SW Pacific During the Last Glacial Maximum
Authors: Trudgill M. D. , Shuttleworth R. , Bostock H. C. , Burke A. , Cooper M. J. , Greenop R. , Foster G. L. 
Published: November 2020

AbstractAtmospheric dust is a primary source of iron (Fe) to the open ocean, and its flux is particularly important in the high nutrient, low chlorophyll (HNLC) Southern Ocean where Fe currently limits productivity. Alleviation of this Fe limitation in the Subantarctic Zone of the Atlantic by increased dust‐borne Fe supply during glacial periods has been shown to increase primary productivity. However, previous work has found no such increase in productivity in the Pacific sector. In order to constrain the relative importance of Southern Ocean Fe fertilization on glacial‐interglacial carbon cycles, records of dust fluxes outside of the Atlantic sector of the Southern Ocean at the Last Glacial Maximum (LGM) are required. Here we use grain size and U‐series analyses to reconstruct lithogenic and CaCO3 fluxes and Nd, Sr, and Pb isotopes to ascertain the provenance of terrigenous material delivered to four deep water cores in the SW Pacific Ocean over the last ~30 kyr. We find evidence for an increase in the relative proportion of fine‐grained (0.5–12 μm) terrigenous sediment and higher detrital fluxes during the LGM compared to the Holocene. The provenance of the LGM dust varied spatially, with an older, more “continental” signature (low εNd, high 87Sr/86Sr) sourced from Australia in the northern cores, and a younger, more volcanogenic source in the southern cores (high εNd, low 87Sr/86Sr), likely sourced locally from New Zealand. Given this increase in lithogenic flux to the HNLC subantarctic Pacific Southern Ocean during the LGM, factors besides Fe supply must have regulated the biological productivity here.
A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumours
Authors: van Bussel Mark T. J. , Awada Ahmad , de Jonge Maja J. A. , Mau-Sørensen Morten , Nielsen Dorte , Schöffski Patrick , Verheul Henk M. W. , Sarholz Barbara , Berghoff Karin , El Bawab Samer , Kuipers Mirjam , Damstrup Lars , Diaz-Padilla Ivan , Schellens Jan H. M. 
Published: November 2020

AbstractBackgroundThis open-label, phase 1 trial (NCT02316197) aimed to determine the maximum-tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of peposertib (formerly M3814), a DNA-dependent protein kinase (DNA-PK) inhibitor in patients with advanced solid tumours. Secondary/exploratory objectives included safety/tolerability, pharmacokinetic/pharmacodynamic profiles and clinical activity.MethodsAdult patients with advanced solid tumours received peposertib 100–200 mg once daily or 150–400 mg twice daily (BID) in 21-day cycles.ResultsThirty-one patients were included (median age 66 years, 61% male). One dose-limiting toxicity, consisting of mainly gastrointestinal, non-serious adverse events (AEs) and long recovery duration, was reported at 300 mg BID. The most common peposertib-related AEs were nausea, vomiting, fatigue and pyrexia. The most common peposertib-related Grade 3 AEs were maculopapular rash and nausea. Peposertib was quickly absorbed systemically (medianTmax1.1–2.5 h). The p-DNA-PK/t-DNA-PK ratio decreased consistently in peripheral blood mononuclear cells 3–6 h after doses ≥100 mg. The best overall response was stable disease (12 patients), lasting for ≥12 weeks in seven patients.ConclusionsPeposertib was well-tolerated and demonstrated modest efficacy in unselected tumours. The MTD was not reached; the RP2D was declared as 400 mg BID. Further studies, mainly with peposertib/chemo-radiation, are ongoing.Clinical trial registrationNCT02316197
Autophagy-mediated metabolic effects of aspirin
Authors: Castoldi Francesca , Humeau Juliette , Martins Isabelle , Lachkar Sylvie , Loew Damarys , Dingli Florent , Durand Sylvère , Enot David , Bossut Noëlie , Chery Alexis , Aprahamian Fanny , Demont Yohann , Opolon Paule , Signolle Nicolas , Sauvat Allan , Semeraro Michaela , Bezu Lucillia , Baracco Elisa Elena , Vacchelli Erika , Pol Jonathan G. , Lévesque Sarah , Bloy Norma , Sica Valentina , Maiuri Maria Chiara , Kroemer Guido , Pietrocola Federico 
Published: November 2020

AbstractSalicylate, the active derivative of aspirin (acetylsalicylate), recapitulates the mode of action of caloric restriction inasmuch as it stimulates autophagy through the inhibition of the acetyltransferase activity of EP300. Here, we directly compared the metabolic effects of aspirin medication with those elicited by 48 h fasting in mice, revealing convergent alterations in the plasma and the heart metabolome. Aspirin caused a transient reduction of general protein acetylation in blood leukocytes, accompanied by the induction of autophagy. However, these effects on global protein acetylation could not be attributed to the mere inhibition of EP300, as determined by epistatic experiments and exploration of the acetyl-proteome from salicylate-treated EP300-deficient cells. Aspirin reduced high-fat diet-induced obesity, diabetes, and hepatosteatosis. These aspirin effects were observed in autophagy-competent mice but not in two different models of genetic (Atg4b−/− or Bcln1+/−) autophagy-deficiency. Aspirin also improved tumor control by immunogenic chemotherapeutics, and this effect was lost in T cell-deficient mice, as well as upon knockdown of an essential autophagy gene (Atg5) in cancer cells. Hence, the health-improving effects of aspirin depend on autophagy.
Structural insight into the assembly and conformational activation of human origin recognition complex
Authors: Cheng Jiaxuan , Li Ningning , Wang Xiaohan , Hu Jiazhi , Zhai Yuanliang , Gao Ning 
Published: November 2020

AbstractThe function of the origin recognition complex (ORC) in DNA replication is highly conserved in recognizing and marking the initiation sites. The detailed molecular mechanisms by which human ORC is reconfigured into a state competent for origin association remain largely unknown. Here, we present structural characterizations of human ORC1–5 and ORC2–5 assemblies. ORC2–5 exhibits a tightly autoinhibited conformation with the winged-helix domain of ORC2 completely blocking the central DNA-binding channel. The binding of ORC1 partially relieves the autoinhibitory effect of ORC2–5 through remodeling ORC2-WHD, which makes ORC2-WHD away from the central channel creating a still autoinhibited but more dynamic structure. In particular, the AAA+ domain of ORC1 is highly flexible to sample a variety of conformations from inactive to potentially active states. These results provide insights into the detailed mechanisms regulating the autoinhibition of human ORC and its subsequent activation for DNA binding.
A dose–response meta-analysis between serum concentration of 25-hydroxy vitamin D and risk of type 1 diabetes mellitus
Authors: Hou Yilin , Song An , Jin Yuxin , Xia Qiuyang , Song Guangyao , Xing Xiaoping 
Published: November 2020

AbstractIt remains debatable whether vitamin D plays any role as a risk factor for type 1 diabetes mellitus (T1DM). We have summarized the effect of circulating 25-hydroxy vitamin D [25(OH)D] concentration on the risk of developing T1DM via a dose–response meta-analysis. We undertook a database search on PubMed, Embase, and Cochrane Library from inception to January 2020. A meta-analysis based on random-effects model was applied. Subgroup analysis and meta-regression were performed to inspect the source of heterogeneity. Dose–response data were examined using the generalized least squares trend estimation method. This study was registered with the PROSPERO (ID: CRD42020166174). In total, 16 studies including 10,605 participants (3913 case patients) were included. The pooled odds ratios (OR) and 95% confidence intervals (95% CI) for the highest versus the lowest 25(OH)D concentration was 0.39 (0.27, 0.57), with a high heterogeneity (I2 = 76.7%, P < 0.001). Meta-regression analysis identified latitude (P = 0.02), adjustment for gender (P = 0.001), and 25(OH)D stratification (P < 0.001) as sources of heterogeneity. Furthermore, the nonlinear dose–response analysis determined the OR (95% CI) of T1DM to be 0.91 (0.90, 0.93) per 10 nmol/L increase in the 25(OH)D concentration. A ‘U’-shaped association was found between serum 25(OH)D concentration and risk of T1DM. The present study highlights the significant inverse association between the circulating 25(OH)D concentration and the risk of T1DM.
Biomineral armor in leaf-cutter ants
Authors: Li Hongjie , Sun Chang-Yu , Fang Yihang , Carlson Caitlin M. , Xu Huifang , Ješovnik Ana , Sosa-Calvo Jeffrey , Zarnowski Robert , Bechtel Hans A. , Fournelle John H. , Andes David R. , Schultz Ted R. , Gilbert Pupa U. P. A. , Currie Cameron R. 
Published: November 2020

AbstractAlthough calcareous anatomical structures have evolved in diverse animal groups, such structures have been unknown in insects. Here, we report the discovery of high-magnesium calcite [CaMg(CO3)2] armor overlaying the exoskeletons of major workers of the leaf-cutter ant Acromyrmex echinatior. Live-rearing and in vitro synthesis experiments indicate that the biomineral layer accumulates rapidly as ant workers mature, that the layer is continuously distributed, covering nearly the entire integument, and that the ant epicuticle catalyzes biomineral nucleation and growth. In situ nanoindentation demonstrates that the biomineral layer significantly hardens the exoskeleton. Increased survival of ant workers with biomineralized exoskeletons during aggressive encounters with other ants and reduced infection by entomopathogenic fungi demonstrate the protective role of the biomineral layer. The discovery of biogenic high-magnesium calcite in the relatively well-studied leaf-cutting ants suggests that calcareous biominerals enriched in magnesium may be more common in metazoans than previously recognized.
Recent evolution of a TET-controlled and DPPA3/STELLA-driven pathway of passive DNA demethylation in mammals
Authors: Mulholland Christopher B. , Nishiyama Atsuya , Ryan Joel , Nakamura Ryohei , Yiğit Merve , Glück Ivo M. , Trummer Carina , Qin Weihua , Bartoschek Michael D. , Traube Franziska R. , Parsa Edris , Ugur Enes , Modic Miha , Acharya Aishwarya , Stolz Paul , Ziegenhain Christoph , Wierer Michael , Enard Wolfgang , Carell Thomas , Lamb Don C. , Takeda Hiroyuki , Nakanishi Makoto , Bultmann Sebastian , Leonhardt Heinrich 
Published: November 2020

AbstractGenome-wide DNA demethylation is a unique feature of mammalian development and naïve pluripotent stem cells. Here, we describe a recently evolved pathway in which global hypomethylation is achieved by the coupling of active and passive demethylation. TET activity is required, albeit indirectly, for global demethylation, which mostly occurs at sites devoid of TET binding. Instead, TET-mediated active demethylation is locus-specific and necessary for activating a subset of genes, including the naïve pluripotency and germline markerDppa3(Stella, Pgc7). DPPA3 in turn drives large-scale passive demethylation by directly binding and displacing UHRF1 from chromatin, thereby inhibiting maintenance DNA methylation. Although unique to mammals, we show that DPPA3 alone is capable of inducing global DNA demethylation in non-mammalian species (Xenopus and medaka) despite their evolutionary divergence from mammals more than 300 million years ago. Our findings suggest that the evolution ofDppa3facilitated the emergence of global DNA demethylation in mammals.
Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR
Authors: Smith Alicia K. , Ratanatharathorn Andrew , Maihofer Adam X. , Naviaux Robert K. , Aiello Allison E. , Amstadter Ananda B. , Ashley-Koch Allison E. , Baker Dewleen G. , Beckham Jean C. , Boks Marco P. , Bromet Evelyn , Dennis Michelle , Galea Sandro , Garrett Melanie E. , Geuze Elbert , Guffanti Guia , Hauser Michael A. , Katrinli Seyma , Kilaru Varun , Kessler Ronald C. , Kimbrel Nathan A. , Koenen Karestan C. , Kuan Pei-Fen , Li Kefeng , Logue Mark W. , Lori Adriana , Luft Benjamin J. , Miller Mark W. , Naviaux Jane C. , Nugent Nicole R. , Qin Xuejun , Ressler Kerry J. , Risbrough Victoria B. , Rutten Bart P. F. , Stein Murray B. , Ursano Robert J. , Vermetten Eric , Vinkers Christiaan H. , Wang Lin , Youssef Nagy A. ,   INTRuST Clinical Consortium, Marx Christine , Grant Gerry , Stein Murray , Qin Xue-Jun , Jain Sonia , McAllister Thomas W. , Zafonte Ross , Lang Ariel , Coimbra Raul , Andaluz Norberto , Shutter Lori , George Mark S. ,   VA Mid-Atlantic MIRECC Workgroup, Brancu Mira , Calhoun Patrick S. , Dedert Eric , Elbogen Eric B. , Fairbank John A. , Hurley Robin A. , Kilts Jason D. , Kirby Angela , Marx Christine E. , McDonald Scott D. , Moore Scott D. , Morey Rajendra A. , Naylor Jennifer C. , Rowland Jared A. , Swinkels Cindy , Szabo Steven T. , Taber Katherine H. , Tupler Larry A. , Van Voorhees Elizabeth E. , Yoash-Gantz Ruth E. ,   PGC PTSD Epigenetics Workgroup, Basu Archana , Brick Leslie A. , Dalvie Shareefa , Daskalakis Nikolaos P. , Ensink Judith B. M. , Hemmings Sian M. J. , Herringa Ryan , Ikiyo Sylvanus , Koen Nastassja , Kuan Pei Fen , Montalvo-Ortiz Janitza , Nispeling Danny , Pfeiffer John , Qin XueJun , Ressler Kerry J. , Schijven Dick , Seedat Soraya , Shinozaki Gen , Sumner Jennifer A. , Swart Patricia , Tyrka Audrey , Van Zuiden Mirjam , Wani Agaz , Wolf Erika J. , Zannas Anthony , Uddin Monica , Nievergelt Caroline M. 
Published: November 2020

AbstractEpigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.
S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue
Authors: Jindal Sonali , Pennock Nathan D. , Klug Alex , Narasimhan Jayasri , Calhoun Andrea , Roberts Michelle R. , Tamimi Rulla M. , Eliassen A. Heather , Weinmann Sheila , Borges Virginia F. , Schedin Pepper 
Published: November 2020

AbstractImmunohistochemical (IHC) staining in breast cancer shows both gain and loss of COX2 expression with disease risk and progression. We investigated four common COX2 antibody clones and found high specificity for purified human COX2 for three clones; however, recognition of COX2 in cell lysates was clone dependent. Biochemical characterization revealed two distinct forms of COX2, with SP21 recognizing an S-nitrosylated form, and CX229 and CX294 recognizing non-nitrosylated COX2 antigen. We found S-nitrosylated and non-nitrosylated COX2 occupy different subcellular locations in normal and breast cancer tissue, implicating distinct synthetic/trafficking pathways and function. Dual stains of ~2000 breast cancer cases show early-onset breast cancer had increased expression of both forms of COX2 compared to postmenopausal cases. Our results highlight the strengths of using multiple, highly characterized antibody clones for COX2 IHC studies and raise the prospect that S-nitrosylation of COX2 may play a role in breast cancer biology.