bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of food intake biomarkers in nutrition research
Authors: McNamara Aoife E. , Brennan Lorraine
Published: May 2020

The influence of dietary habits on health/disease is well-established. Accurate dietary assessment is essential to understand metabolic pathways/processes involved in this relationship. In recent years, biomarker discovery has become a major area of interest for improving dietary assessment. Well-established nutrient intake biomarkers exist; however, there is growing interest in identifying and using biomarkers for more accurate and objective measurements of food intake. Metabolomics has emerged as a key tool used for biomarker discovery, employing techniques such as NMR spectroscopy, or MS. To date, a number of putatively identified biomarkers were discovered for foods including meat, cruciferous vegetables and legumes. However, many of the results are associations only and lack the desired validation including dose–response studies. Food intake biomarkers can be employed to classify individuals into consumers/non-consumers of specific foods, or into dietary patterns. Food intake biomarkers can also play a role in correcting self-reported measurement error, thus improving dietary intake estimates. Quantification of food intake was previously performed for citrus (proline betaine), chicken (guanidoacetate) and grape (tartaric acid) intake. However, this area still requires more investigation and expansion to a range of foods. The present review will assess the current literature of identified specific food intake biomarkers, their validation and the variety of biomarker uses. Addressing the utility of biomarkers and highlighting gaps in this area is important to advance the field in the context of nutrition research.
Speaking With the Other and Not Only About the Other: Reflections for a Postcolonial Archaeology
Authors: Campos Akinruli Luana Carla Martins
Published: May 2020

This text proposes to provoke an interdisciplinary reflection on alterity as challenged through investigations in archaeology. It intends to analyse the process of archaeological practice in a contemporary Latin American context. Archaeological practice configures criteria for selecting a specific cultural heritage collection, and in turn, this reflects what should be forgotten or what has the right to be remembered by the society. It also aims to contribute to the speech practice and audience of the subjects, in order to problematize the experience of research and the researcher through ethnography and discussions in the postcolonial archaeology; these could promote a point of schism where paradigms for archaeological studies may reach a breaking point.
The origins of the Asia dollar market 1968–1986: regulatory competition and complementarity in Singapore and Hong Kong
Authors: Schenk Catherine R.
Published: May 2020

Offshore financial centres have attracted considerable critical attention over the past few decades as havens for lightly taxed funds that circulate outside the regulatory oversight of major financial centres. This article addresses the emergence of an offshore market in US dollars in Singapore from the late 1960s using a range of archival sources to identify the motivations of the host, participant banks and regional rivals. The development of the Asia dollar market is particularly striking because Singapore was not the most likely venue for an Asian offshore financial centre. The main regional financial centre was Hong Kong, but the Hong Kong authorities made a deliberate choice not to host an offshore market in Hong Kong, a decision that was initially supported both by the state and by incumbent banks, although the banks later changed their view as the Singapore market grew. This case thus opens up discussion of the influence market actors exert over regulators when they are engaged in regulatory arbitrage as well as regulatory competition between states. Evidence is also presented about the efforts of the Bank for International Settlements to encourage greater transparency in offshore financial centres in the 1980s.
On‐Shelf Nutrient Trapping Enhances the Fertility of the Southern Benguela Upwelling System
Authors: Flynn R. F. , Granger J. , Veitch J. A. , Siedlecki S. , Burger J. M. , Pillay K. , Fawcett S. E.
Published: May 2020

The southern Benguela upwelling system (SBUS) supports high rates of primary productivity that sustain important commercial fisheries. The exceptional fertility of this system is reportedly fueled not only by upwelled nutrients but also by nutrients regenerated on the broad and shallow continental shelf. We measured nutrient concentrations and the nitrogen (N) and oxygen (O) isotope ratios (δ15N and δ18O) of nitrate along four zonal lines in the SBUS in late summer and early winter to evaluate the extent to which regenerated nutrients augment the upwelled nutrient reservoir originating offshore. During summer upwelling, a decrease in on‐shelf nitrate δ18O revealed that 0–48% of the subsurface nutrients derived from in situ remineralization. The nitrate regenerated on‐shelf in the more quiescent winter (0–63% of total nitrate) extended further offshore along the mid‐shelf. A shoreward increase in subsurface nitrate δ15N and a greater N deficit in on‐shelf bottom waters further indicated N loss to benthic (and at times, watercolumn) denitrification coincident with the on‐shelf remineralization. Our data show that remineralized nutrients get trapped on the SBUS shelf in summer through early winter, enhancing the nutrient pool that can be upwelled to support surface production. We hypothesize that this process is aided by a number of equatorward‐flowing hydrographic fronts that impede the lateral exchange of surface waters. The extent to which nutrients remain trapped on the shelf has implications for the occurrence of hypoxic events in the SBUS.
Pliocene‐Pleistocene Stratigraphy and Sea‐Level Estimates, Republic of South Africa With Implications for a 400 ppmv CO2 World
Authors: Hearty P. J. , Rovere A. , Sandstrom M. R. , O'Leary M. J. , Roberts D. , Raymo M. E.
Published: May 2020

The Mid‐Pliocene Warm Period (MPWP, 2.9 to 3.3 Ma), along with older Pliocene (3.2 to 5.3 Ma) records, offers potential past analogues for our 400‐ppmv world. The coastal geology of western and southern coasts of the Republic of South Africa exposes an abundance of marine deposits of Pliocene and Pleistocene age. In this study, we report differential GPS elevations, detailed stratigraphic descriptions, standardized interpretations, and dating of relative sea‐level indicators measured across ~700 km from the western and southern coasts of the Cape Provinces. Wave abrasion surfaces on bedrock, intertidal sedimentary structures, and in situ marine invertebrates including oysters and barnacles provide precise indicators of past sea levels. Multiple sea‐level highstands imprinted at different elevations along South African coastlines were identified. Zone I sites average +32 ± 5 m (six sites). A lower topographic Zone II of sea stands were measured at several sites around +17 ± 5 m. Middle and late Pleistocene sites are included in Zone III. Shoreline chronologies using 87Sr/86Sr ages on shells from these zones yield ages from Zone I at 4.6 and 3.0 Ma and Zone II at 1.04 Ma. Our results show that polar ice sheets during the Plio‐Pleistocene were dynamic and subject to significant melting under modestly warmer global temperatures. These processes occurred during a period when CO2 concentrations were comparable to our current and rapidly rising values above 400 ppmv.
Resilience to Large, “Catastrophic” Wildfires in North America's Grassland Biome
Authors: Donovan Victoria M. , Twidwell Dirac , Uden Daniel R. , Tadesse Tsegaye , Wardlow Brian D. , Bielski Christine H. , Jones Matthew O. , Allred Brady W. , Naugle David E. , Allen Craig R.
Published: May 2020

Wildfires are ecosystem‐level drivers of structure and function in many vegetated biomes. While numerous studies have emphasized the benefits of fire to ecosystems, large wildfires have also been associated with the loss of ecosystem services and shifts in vegetation abundance. The size and number of wildfires are increasing across a number of regions, and yet the outcomes of large wildfire on vegetation at large‐scales are still largely unknown. We introduce an exhaustive analysis of wildfire‐scale vegetation response to large wildfires across North America's grassland biome. We use 18 years of a newly released vegetation data set combined with 1,390 geospatial wildfire perimeters and drought data to detect large‐scale vegetation response among multiple vegetation functional groups. We found no evidence of persistent declines in vegetation driven by wildfire at the biome level. All vegetation functional groups exhibited relatively rapid recovery to pre wildfire ranges of variation across the Great Plains ecoregions, with the exception being a persistent decrease in the abundance of trees in the Northwestern Great Plains. Drought intensity magnified immediate vegetation response to wildfire. Persistent declines in vegetation cover were observed at the scale of single pixels (30 m), suggesting that these responses were localized and represent extreme cases within larger wildfires. Our findings echo over a century of research demonstrating a biome resilient to wildfire.
Silicon‐Depleted Present‐Day Earth's Outer Core Revealed by Sound Velocity Measurements of Liquid Fe‐Si Alloy
Authors: Nakajima Yoichi , Kawaguchi Saori I. , Hirose Kei , Tateno Shigehiko , Kuwayama Yasuhiro , Sinmyo Ryosuke , Ozawa Haruka , Tsutsui Satoshi , Uchiyama Hiroshi , Baron Alfred Q. R.
Published: May 2020

Here we determined the P wave velocity of liquid Fe84Si16 up to 56 GPa based on inelastic X‐ray scattering measurements in a laser‐heated diamond‐anvil cell. We found that silicon significantly increases the P wave velocity of liquid iron under high pressure. The equation of state (EoS) of liquid Fe‐Si is obtained from the present sound velocity measurements. When extrapolating the present data to core pressures with the EoS, the silicon concentration must be limited to less than
 wt.% in the outer core to explain its P wave velocity. In contrast, if silicon is the sole light element,
to
 wt.% is necessary to account for the outer core density deficit. Thus, a liquid Fe‐Si cannot explain both the density and sound velocity simultaneously, suggesting that silicon is not the predominant light element in the core. Recent core formation models have predicted that the initial core contained 2 to 9 wt.% Si, which makes the P wave velocity much faster than that observed in the present‐day outer core. The core may have changed its composition by crystallizing SiO2 or (Mg,Fe)SiO3. It is possible that the initial core with <4 wt.% Si and ~5 wt.% O segregated from silicate under moderately oxidizing conditions and its composition evolved into a silicon‐poor one (<1.9 wt.% Si), which is compatible with the seismological observations. Such moderate Si content in the original core could also account for the high MgO/SiO2 and 30Si/28Si ratios in Earth's mantle relative to chondritic values.
T-cells in chronic lymphocytic leukemia: Guardians or drivers of disease?
Authors: Roessner Philipp M. , Seiffert Martina
Published: May 2020

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy, which is associated with profound alterations and defects in the immune system and a prevalent dependency on the microenvironmental niche. An abnormal T-cell compartment in the blood of CLL patients was already reported 40 years ago. Since then, our knowledge of T-cell characteristics in CLL has grown steadily, but the question of whether T-cells act as pro-tumoral bystander cells or possess anti-tumoral activity is still under debate. Increased numbers of CD4+ T-helper cell subsets are present in the blood of CLL patients, and T-helper cell cytokines have been shown to stimulate CLL cell survival and proliferation in vitro. In line with this, survival and growth of CLL cells in murine xenograft models have been shown to rely on activated CD4+ T-cells. This led to the hypothesis that T-cells are tumor-supportive in CLL. In recent years, evidence for an enrichment of antigen-experienced CD8+ T-cells in CLL has accumulated, and these cells have been shown to control leukemia in a CLL mouse model. Based on this, it was suggested that CD8+ T-cells recognize CLL-specific antigens and exert an anti-leukemia function. As described for other cancer entities, T-cells in CLL express multiple inhibitory receptors, such as PD-1, and lose their functional capacity, leading to an exhaustion phenotype which has been shown to be more severe in T-cells from secondary lymphoid organs compared with peripheral blood. This exhausted phenotype has been suggested to be causative for the poor response of CLL patients to CAR T-cell therapies. In addition, T-cells have been shown to be affected by drugs that are used to treat CLL, which likely impacts therapy response. This review provides an overview of the current knowledge about alterations of T-cells in CLL, including their distribution, function, and exhaustion state in blood and lymphoid organs, and touches also on the topic of how CLL drugs impact on the T-cell compartment and recent results of T-cell-based immunotherapy. We will discuss potential pathological roles of T-cell subsets in CLL and address the question of whether they foster progression or control of disease.
Fine tuning of the unfolded protein response by ISRIB improves neuronal survival in a model of amyotrophic lateral sclerosis
Authors: Bugallo Ricardo , Marlin Elías , Baltanás Ana , Toledo Estefanía , Ferrero Roberto , Vinueza-Gavilanes Rodrigo , Larrea Laura , Arrasate Montserrat , Aragón Tomás
Published: May 2020

Loss of protein folding homeostasis features many of the most prevalent neurodegenerative disorders. As coping mechanism to folding stress within the endoplasmic reticulum (ER), the unfolded protein response (UPR) comprises a set of signaling mechanisms that initiate a gene expression program to restore proteostasis, or when stress is chronic or overwhelming promote neuronal death. This fate-defining capacity of the UPR has been proposed to play a key role in amyotrophic lateral sclerosis (ALS). However, the several genetic or pharmacological attempts to explore the therapeutic potential of UPR modulation have produced conflicting observations. In order to establish the precise relationship between UPR signaling and neuronal death in ALS, we have developed a neuronal model where the toxicity of a familial ALS-causing allele (mutant G93A SOD1) and UPR activation can be longitudinally monitored in single neurons over the process of neurodegeneration by automated microscopy. Using fluorescent UPR reporters we established the temporal and causal relationship between UPR and neuronal death by Cox regression models. Pharmacological inhibition of discrete UPR processes allowed us to establish the contribution of PERK (PKR-like ER kinase) and IRE1 (inositol-requiring enzyme-1) mechanisms to neuronal fate. Importantly, inhibition of PERK signaling with its downstream inhibitor ISRIB, but not with the direct PERK kinase inhibitor GSK2606414, significantly enhanced the survival of G93A SOD1-expressing neurons. Characterization of the inhibitory properties of both drugs under ER stress revealed that in neurons (but not in glial cells) ISRIB overruled only part of the translational program imposed by PERK, relieving the general inhibition of translation, but maintaining the privileged translation of ATF4 (activating transcription factor 4) messenger RNA. Surprisingly, the fine-tuning of the PERK output in G93A SOD1-expressing neurons led to a reduction of IRE1-dependent signaling. Together, our findings identify ISRIB-mediated translational reprogramming as a new potential ALS therapy.
P2Y14 receptor has a critical role in acute gouty arthritis by regulating pyroptosis of macrophages
Authors: Li Hanwen , Jiang Wenjiao , Ye Shumin , Zhou Mengze , Liu Chunxiao , Yang Xiping , Hao Kun , Hu Qinghua
Published: May 2020

Nod-like receptor protein 3 (NLRP3)-mediated pyroptosis has a causal role in the pathogenesis of gout. P2Y14 receptor (P2Y14R) distributed in immune cells including macrophages is a Gi-coupled receptor that inhibits the synthesis of cAMP, which has been regarded as a potential regulator of inflammatory response. Nevertheless, the role of P2Y14R in MSU-induced pyroptosis of macrophages involved in acute gouty arthritis is still unclear. In our present study, P2Y14R knockout (P2Y14R-KO) disrupted MSU-induced histopathologic changes in rat synoviums, accompanied with a significant inhibition of pyroptotic cell death characterized by Caspase-1/PI double-positive and blockade of NLRP3 inflammasome activation in synovial tissues, which was consistent with that observed in in vitro studies. Owing to the interaction of NLRP3 inflammasome and cAMP, we then investigated the effect of adenylate cyclase activator (Forskolin) on macrophage pyroptosis and gout flare caused by MSU stimulation. The reversal effect of Forskolin verified the negative regulatory role of cAMP in MSU-induced pyroptosis. More importantly, adenylate cyclase inhibitor (SQ22536) intervention led to a reversal of protection attributed to P2Y14R deficiency. Findings in air pouch animal models also verified aforementioned experimental results. Our study first identified the role of P2Y14R/cAMP/NLRP3 signaling pathway in acute gouty arthritis, which provides a novel insight into the pathological mechanisms of pyroptosis-related diseases.
Novel LAMA2 variants identified in a patient with white matter abnormalities
Authors: Yamamoto-Shimojima Keiko , Ono Hiroaki , Imaizumi Taichi , Yamamoto Toshiyuki
Published: May 2020

Comprehensive genomic analysis was performed in a patient with mild psychomotor developmental delay, elevated creatine kinase, and white matter abnormalities. The results revealed biallelic pathogenic variants in the gene related to merosin-deficient congenital muscular dystrophy, NM_000426.3(LAMA2):c.1338_1339del [p.Gly447Phefs*7] and c.2749 + 2dup, which consist of compound heterozygous involvement with predicted loss-of-function and splicing abnormalities.
Light-switchable propulsion of active particles with reversible interactions
Authors: Vutukuri Hanumantha Rao , Lisicki Maciej , Lauga Eric , Vermant Jan
Published: May 2020

Active systems such as microorganisms and self-propelled particles show a plethora of collective phenomena, including swarming, clustering, and phase separation. Control over the propulsion direction and switchability of the interactions between the individual self-propelled units may open new avenues in designing of materials from within. Here, we present a self-propelled particle system, consisting of half-gold-coated titania (TiO2) particles, in which we can quickly and on-demand reverse the propulsion direction, by exploiting the different photocatalytic activities on both sides. We demonstrate that the reversal in propulsion direction changes the nature of the hydrodynamic interaction from attractive to repulsive and can drive the particle assemblies to undergo both fusion and fission transitions. Moreover, we show these active colloids can act as nucleation sites, and switch rapidly the interactions between active and passive particles, leading to reconfigurable assembly and disassembly. Our experiments are qualitatively described by a minimal hydrodynamic model.
Sources of path integration error in young and aging humans
Authors: Stangl Matthias , Kanitscheider Ingmar , Riemer Martin , Fiete Ila , Wolbers Thomas
Published: May 2020

Path integration plays a vital role in navigation: it enables the continuous tracking of one's position in space by integrating self-motion cues. Path integration abilities vary widely across individuals, and tend to deteriorate in old age. The specific causes of path integration errors, however, remain poorly characterized. Here, we combine tests of path integration performance in participants of different ages with an analysis based on the Langevin equation for diffusive dynamics, which allows us to decompose errors into distinct causes that can corrupt path integration computations. We show that, across age groups, the dominant error source is unbiased noise that accumulates with travel distance not elapsed time, suggesting that the noise originates in the velocity input rather than within the integrator. Age-related declines are primarily traced to a growth in this noise. These findings shed light on the contributors to path integration error and the mechanisms underlying age-related navigational deficits.
The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions
Authors: Littlejohns Thomas J. , Holliday Jo , Gibson Lorna M. , Garratt Steve , Oesingmann Niels , Alfaro-Almagro Fidel , Bell Jimmy D. , Boultwood Chris , Collins Rory , Conroy Megan C. , Crabtree Nicola , Doherty Nicola , Frangi Alejandro F. , Harvey Nicholas C. , Leeson Paul , Miller Karla L. , Neubauer Stefan , Petersen Steffen E. , Sellors Jonathan , Sheard Simon , Smith Stephen M. , Sudlow Cathie L. M. , Matthews Paul M. , Allen Naomi E.
Published: May 2020

UK Biobank is a population-based cohort of half a million participants aged 40–69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world’s largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.
Mode-resolved reciprocal space mapping of electron-phonon interaction in the Weyl semimetal candidate Td-WTe2
Authors: Hein Petra , Jauernik Stephan , Erk Hermann , Yang Lexian , Qi Yanpeng , Sun Yan , Felser Claudia , Bauer Michael
Published: May 2020

The excitation of coherent phonons provides unique capabilities to control fundamental properties of quantum materials on ultrafast time scales. Recently, it was predicted that a topologically protected Weyl semimetal phase in the transition metal dichalcogenide Td-WTe2 can be controlled and, ultimately, be destroyed upon the coherent excitation of an interlayer shear mode. By monitoring electronic structure changes with femtosecond resolution, we provide here direct experimental evidence that the shear mode acts on the electronic states near the phase-defining Weyl points. Furthermore, we observe a periodic reduction in the spin splitting of bands, a distinct electronic signature of the Weyl phase-stabilizing non-centrosymmetric Td ground state of WTe2. The comparison with higher-frequency coherent phonon modes finally proves the shear mode-selectivity of the observed changes in the electronic structure. Our real-time observations reveal direct experimental insights into electronic processes that are of vital importance for a coherent phonon-induced topological phase transition in Td-WTe2.
Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program
Authors: Karagiannis Tanya T. , Cleary John P. , Gok Busra , Henderson Andrew J. , Martin Nicholas G. , Yajima Masanao , Nelson Elliot C. , Cheng Christine S.
Published: May 2020

Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system. However, how opioid impacts the immune system is still barely characterized systematically. In order to understand the immune modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evokes widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide. Furthermore, scRNA-seq reveals the same phenomenon after a short in vitro morphine treatment. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program. Our results suggest that further characterization of the immune modulatory effects of opioid is critical to ensure the safety of clinical opioids.
Search and rescue at sea aided by hidden flow structures
Authors: Serra Mattia , Sathe Pratik , Rypina Irina , Kirincich Anthony , Ross Shane D. , Lermusiaux Pierre , Allen Arthur , Peacock Thomas , Haller George
Published: May 2020

Every year, hundreds of people die at sea because of vessel and airplane accidents. A key challenge in reducing the number of these fatalities is to make Search and Rescue (SAR) algorithms more efficient. Here, we address this challenge by uncovering hidden TRansient Attracting Profiles (TRAPs) in ocean-surface velocity data. Computable from a single velocity-field snapshot, TRAPs act as short-term attractors for all floating objects. In three different ocean field experiments, we show that TRAPs computed from measured as well as modeled velocities attract deployed drifters and manikins emulating people fallen in the water. TRAPs, which remain hidden to prior flow diagnostics, thus provide critical information for hazard responses, such as SAR and oil spill containment, and hence have the potential to save lives and limit environmental disasters.
Parkinson’s disease associated mutation E46K of α-synuclein triggers the formation of a distinct fibril structure
Authors: Zhao Kun , Li Yaowang , Liu Zhenying , Long Houfang , Zhao Chunyu , Luo Feng , Sun Yunpeng , Tao Youqi , Su Xiao-dong , Li Dan , Li Xueming , Liu Cong
Published: May 2020

Amyloid aggregation of α-synuclein (α-syn) is closely associated with Parkinson’s disease (PD) and other synucleinopathies. Several single amino-acid mutations (e.g. E46K) of α-syn have been identified causative to the early onset of familial PD. Here, we report the cryo-EM structure of an α-syn fibril formed by N-terminally acetylated E46K mutant α-syn (Ac-E46K). The fibril structure represents a distinct fold of α-syn, which demonstrates that the E46K mutation breaks the electrostatic interactions in the wild type (WT) α-syn fibril and thus triggers the rearrangement of the overall structure. Furthermore, we show that the Ac-E46K fibril is less resistant to harsh conditions and protease cleavage, and more prone to be fragmented with an enhanced seeding capability than that of the WT fibril. Our work provides a structural view to the severe pathology of the PD familial mutation E46K of α-syn and highlights the importance of electrostatic interactions in defining the fibril polymorphs.
CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer
Authors: Sanij Elaine , Hannan Katherine M. , Xuan Jiachen , Yan Shunfei , Ahern Jessica E. , Trigos Anna S. , Brajanovski Natalie , Son Jinbae , Chan Keefe T. , Kondrashova Olga , Lieschke Elizabeth , Wakefield Matthew J. , Frank Daniel , Ellis Sarah , Cullinane Carleen , Kang Jian , Poortinga Gretchen , Nag Purba , Deans Andrew J. , Khanna Kum Kum , Mileshkin Linda , McArthur Grant A. , Soong John , Berns Els M. J. J. , Hannan Ross D. , Scott Clare L. , Sheppard Karen E. , Pearson Richard B.
Published: May 2020

Acquired resistance to PARP inhibitors (PARPi) is a major challenge for the clinical management of high grade serous ovarian cancer (HGSOC). Here, we demonstrate CX-5461, the first-in-class inhibitor of RNA polymerase I transcription of ribosomal RNA genes (rDNA), induces replication stress and activates the DNA damage response. CX-5461 co-operates with PARPi in exacerbating replication stress and enhances therapeutic efficacy against homologous recombination (HR) DNA repair-deficient HGSOC-patient-derived xenograft (PDX) in vivo. We demonstrate CX-5461 has a different sensitivity spectrum to PARPi involving MRE11-dependent degradation of replication forks. Importantly, CX-5461 exhibits in vivo single agent efficacy in a HGSOC-PDX with reduced sensitivity to PARPi by overcoming replication fork protection. Further, we identify CX-5461-sensitivity gene expression signatures in primary and relapsed HGSOC. We propose CX-5461 is a promising therapy in combination with PARPi in HR-deficient HGSOC and also as a single agent for the treatment of relapsed disease.
UDP-glucosyltransferase regulates grain size and abiotic stress tolerance associated with metabolic flux redirection in rice
Authors: Dong Nai-Qian , Sun Yuwei , Guo Tao , Shi Chuan-Lin , Zhang Yi-Min , Kan Yi , Xiang You-Huang , Zhang Hai , Yang Yi-Bing , Li Ya-Chao , Zhao Huai-Yu , Yu Hong-Xiao , Lu Zi-Qi , Wang Yong , Ye Wang-Wei , Shan Jun-Xiang , Lin Hong-Xuan
Published: May 2020

Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.
Causal mechanism of injection-induced earthquakes through the Mw 5.5 Pohang earthquake case study
Authors: Yeo I. W. , Brown M. R. M. , Ge S. , Lee K. K.
Published: May 2020

Causal mechanisms for fluid injection-induced earthquakes remain a challenge to identify. Past studies largely established spatiotemporal correlations. Here, we propose a multi-process causal mechanism for injection-induced earthquakes through a case study of the 2017 Mw 5.5 induced earthquake near Pohang Enhanced Geothermal System, Korea, where detailed hydraulic stimulation and on-site seismicity monitoring data provide an unprecedented opportunity. Pore pressure modeling reveals that pore pressure changes initiate seismicity on critically stressed faults and Coulomb static stress transfer modeling reveals that earthquake interactions promote continued seismicity, leading to larger events. On the basis of these results, we propose the following causal mechanism for induced seismicity: pore pressure increase and earthquake interactions lead to fault weakening and ultimately triggering larger earthquakes later in the process. We suggest that it is prudent that pore pressure change, initial seismicity locations, and Coulomb static stress transfer from seismicity earlier in the sequence are assessed in real-time.
Tuning molecular emission of organic emitters from fluorescence to phosphorescence through push-pull electronic effects
Authors: Feng Hai-Tao , Zeng Jiajie , Yin Ping-An , Wang Xue-Dong , Peng Qian , Zhao Zujin , Lam Jacky W. Y. , Tang Ben Zhong
Published: May 2020

Organic emitters with persistent phosphorescence have shown potential application in optoelectronic devices. However, rational design and phosphorescence tuning are still challenging. Here, a series of metal-free luminophores without heavy atoms and carbonyl groups from commercial/lab-synthesized carbazole and benzene were synthesized to realize tunable molecular emission from fluorescence to phosphorescence by simply substituent variation. All the molecules emit blue fluorescence in both solution and solid state. Upon removal of excitation source, the fluorinated luminophores show obvious phosphorescence. The lab-synthesized carbazole based molecules exhibit a huge lifetime difference to the commercially purchased ones due to the existence of isomer in the latter samples. The small energy gap between singlet and triplet state and low reorganization energy help enhance intersystem crossing to contribute to a more competitive radiative process from triplet to ground state. Blue and white organic light-emitting devices are fabricated by using fluorinated luminophore as emitting layer.
Electrical switching between exciton dissociation to exciton funneling in MoSe2/WS2 heterostructure
Authors: Meng Yuze , Wang Tianmeng , Jin Chenhao , Li Zhipeng , Miao Shengnan , Lian Zhen , Taniguchi Takashi , Watanabe Kenji , Song Fengqi , Shi Su-Fei
Published: May 2020

The heterostructure of monolayer transition metal dichalcogenides (TMDCs) provides a unique platform to manipulate exciton dynamics. The ultrafast carrier transfer across the van der Waals interface of the TMDC hetero-bilayer can efficiently separate electrons and holes in the intralayer excitons with a type II alignment, but it will funnel excitons into one layer with a type I alignment. In this work, we demonstrate the reversible switch from exciton dissociation to exciton funneling in a MoSe2/WS2 heterostructure, which manifests itself as the photoluminescence (PL) quenching to PL enhancement transition. This transition was realized through effectively controlling the quantum capacitance of both MoSe2 and WS2 layers with gating. PL excitation spectroscopy study unveils that PL enhancement arises from the blockage of the optically excited electron transfer from MoSe2 to WS2. Our work demonstrates electrical control of photoexcited carrier transfer across the van der Waals interface, the understanding of which promises applications in quantum optoelectronics.
Causal effects of population dynamics and environmental changes on spatial variability of marine fishes
Authors: Wang Jheng-Yu , Kuo Ting-Chun , Hsieh Chih-hao
Published: May 2020

Populations with homogeneous distributions have better bet-hedging capacity than more heterogeneously distributed populations. Both population dynamics and environmental factors may influence the spatial variability of a population, but clear empirical evidence of such causal linkages is sparse. Using 25-year fish survey data from the North Sea, we quantify causal effects of age structure, abundance, and environment on nine fish species. We use empirical dynamic modeling—an approach based on state-space reconstruction rather than correlation—to demonstrate causal effects of those factors on population spatial variability. The causal effects are detected in most study species, though direction and strength vary. Specifically, truncated age structure elevates population spatial variability. Warming and spatially heterogeneous temperatures may enhance population spatial variability, whereas abundance and large-scale environmental effects are inconclusive. Fishing may affect population spatial variability directly or indirectly by altering age structure or abundance. We infer potential harmful effects of fishing and environmental changes on fish population stability, highlighting the importance of considering spatial dynamics in fisheries management.
Enabling safe aqueous lithium ion open batteries by suppressing oxygen reduction reaction
Authors: Chen Long , Cao Longsheng , Ji Xiao , Hou Singyuk , Li Qin , Chen Ji , Yang Chongyin , Eidson Nico , Wang Chunsheng
Published: May 2020

Due to the non-flammable nature of water-based electrolytes, aqueous lithium-ion batteries are resistant to catching fire. However, they are not immune to the risk of explosion, since the sealing structure adopted by current batteries limits the dissipation of heat and pressure within the cells. Here, we report a safe aqueous lithium-ion battery with an open configuration using water-in-salt electrolytes and aluminum oxide coated anodes. The design can inhibit the self-discharge by substantially suppressing the oxygen reduction reaction on lithiated anodes and enable good cycle performance over 1000 times. Our study may open a pathway towards safer lithium-ion battery designs.
Soil fungal networks maintain local dominance of ectomycorrhizal trees
Authors: Liang Minxia , Johnson David , Burslem David F. R. P. , Yu Shixiao , Fang Miao , Taylor Joe D. , Taylor Andy F. S. , Helgason Thorunn , Liu Xubing
Published: May 2020

The mechanisms regulating community composition and local dominance of trees in species-rich forests are poorly resolved, but the importance of interactions with soil microbes is increasingly acknowledged. Here, we show that tree seedlings that interact via root-associated fungal hyphae with soils beneath neighbouring adult trees grow faster and have greater survival than seedlings that are isolated from external fungal mycelia, but these effects are observed for species possessing ectomycorrhizas (ECM) and not arbuscular mycorrhizal (AM) fungi. Moreover, survival of naturally-regenerating AM seedlings over ten years is negatively related to the density of surrounding conspecific plants, while survival of ECM tree seedlings displays positive density dependence over this interval, and AM seedling roots contain greater abundance of pathogenic fungi than roots of ECM seedlings. Our findings show that neighbourhood interactions mediated by beneficial and pathogenic soil fungi regulate plant demography and community structure in hyperdiverse forests.
Author Correction: Mutualist and pathogen traits interact to affect plant community structure in a spatially explicit model
Authors: Schroeder John W. , Dobson Andrew , Mangan Scott A. , Petticord Daniel F. , Herre Edward Allen
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response
Authors: Szewczyk Magdalena M. , Ishikawa Yoshinori , Organ Shawna , Sakai Nozomu , Li Fengling , Halabelian Levon , Ackloo Suzanne , Couzens Amber L. , Eram Mohammad , Dilworth David , Fukushi Hideto , Harding Rachel , dela Seña Carlo C. , Sugo Tsukasa , Hayashi Kozo , McLeod David , Zepeda Carlos , Aman Ahmed , Sánchez-Osuna Maria , Bonneil Eric , Takagi Shinji , Al-Awar Rima , Tyers Mike , Richard Stephane , Takizawa Masayuki , Gingras Anne-Claude , Arrowsmith Cheryl H. , Vedadi Masoud , Brown Peter J. , Nara Hiroshi , Barsyte-Lovejoy Dalia
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Temperatures, diagnostics and treatment in pediatric cancer patients with fever in neutropenia, NCT01683370
Authors: Brack Eva , Wagner Stéphanie , Stutz-Grunder Eveline , Agyeman Philipp K. A. , Ammann Roland A.
Published: May 2020

In pediatric oncology, there is no evidence-based definition of the temperature limit defining fever (TLDF), which itself is essential for the definition of fever in chemotherapy-induced severe neutropenia (FN). Lowering the TLDF can increase the number of FN episodes diagnosed. This prospective, single center observational study collected data on all temperature measurements, complete blood counts (CBCs), and measures of diagnostics and therapy performed at and after FN diagnosis in pediatric oncology patients using a high standard TLDF (39 °C ear temperature). In 45 FN episodes in 20 patients, 3391 temperature measurements and 318 CBCs, plus information on antibiotics, anti-fungal therapy, antipyretics, blood cultures taken and on discharge were collected. These data can mainly be used to study the influence of virtually lowering the TLDF on diagnostic measures, treatment and length of hospitalization in pediatric FN, which in turn are directly related to costs of FN therapy, and quality of life. This approach can be expanded to include as well different definitions of neutropenia.
Multi-beam two-photon polymerization for fast large area 3D periodic structure fabrication for bioapplications
Authors: Maibohm Christian , Silvestre Oscar F. , Borme Jérôme , Sinou Maina , Heggarty Kevin , Nieder Jana B.
Published: May 2020

Two-photon polymerization (TPP) is capable of fabricating 3D structures with dimensions from sub-µm to a few hundred µm. As a direct laser writing (DLW) process, fabrication time of 3D TPP structures scale with the third order, limiting its use in large volume fabrication. Here, we report on a scalable fabrication method that cuts fabrication time to a fraction. A parallelized 9 multi-beamlets DLW process, created by a fixed diffraction optical element (DOE) and subsequent stitching are used to fabricate large periodic high aspect ratio 3D microstructured arrays with sub-micron features spanning several hundred of µm2. The wall structure in the array is designed with a minimum of traced lines and is created by a low numerical aperture (NA) microscope objective, leading to self-supporting lines omitting the need for line-hatching. The fabricated periodic arrays are applied in a cell – 3D microstructure interaction study using living HeLa cells. First indications of increased cell proliferation in the presence of 3D microstructures compared to planar surfaces are obtained. Furthermore, the cells adopt an elongated morphology when attached to the 3D microstructured surfaces. Both results constitute promising findings rendering the 3D microstructures a suited tool for cell interaction experiments, e.g. for cell migration, separation or even tissue engineering studies.
Beyond Forcing Scenarios: Predicting Climate Change through Response Operators in a Coupled General Circulation Model
Authors: Lembo Valerio , Lucarini Valerio , Ragone Francesco
Published: May 2020

Global Climate Models are key tools for predicting the future response of the climate system to a variety of natural and anthropogenic forcings. Here we show how to use statistical mechanics to construct operators able to flexibly predict climate change. We perform our study using a fully coupled model - MPI-ESM v.1.2 - and for the first time we prove the effectiveness of response theory in predicting future climate response to CO2 increase on a vast range of temporal scales, from inter-annual to centennial, and for very diverse climatic variables. We investigate within a unified perspective the transient climate response and the equilibrium climate sensitivity, and assess the role of fast and slow processes. The prediction of the ocean heat uptake highlights the very slow relaxation to a newly established steady state. The change in the Atlantic Meridional Overturning Circulation (AMOC) and of the Antarctic Circumpolar Current (ACC) is accurately predicted. The AMOC strength is initially reduced and then undergoes a slow and partial recovery. The ACC strength initially increases due to changes in the wind stress, then undergoes a slowdown, followed by a recovery leading to a overshoot with respect to the initial value. Finally, we are able to predict accurately the temperature change in the North Atlantic.
Monti Sabatini and Colli Albani: the dormant twin volcanoes at the gates of Rome
Authors: Marra F. , Castellano C. , Cucci L. , Florindo F. , Gaeta M. , Jicha B. R. , Palladino D. M. , Sottili G. , Tertulliani A. , Tolomei C.
Published: May 2020

This multi-disciplinary work provides an updated assessment of possible future eruptive scenarios for the city of Rome. Seven new 40Ar/39Ar ages from selected products of the Monti Sabatini and Vulsini volcanic districts, along with a compilation of all the literature ages on the Colli Albani and Vico products, are used to reconstruct and compare the eruptive histories of the Monti Sabatini and Colli Albani over the last 900 ka, in order to define their present state of activity. Petrographic analyses of the dated units characterize the crystal cargo, and Advanced-InSAR analysis highlights active deformation in the MS. We also review the historical and instrumental seismicity affecting this region. Based on the chronology of the most recent phases and the time elapsed between the last eruptions, we conclude that the waning/extinguishment of eruptive activity shifted progressively from NW to SE, from northern Latium toward the Neapolitan area, crossing the city of Rome. Although Monti Sabatini is unaffected by the unrest indicators presently occurring at the Colli Albani, it should be regarded as a dormant volcanic district, as the time of 70 kyr elapsed since the last eruption is of the same order of the longest dormancies occurred in the past.
A deep learning approach for designed diffraction-based acoustic patterning in microchannels
Authors: Raymond Samuel J. , Collins David J. , O’Rorke Richard , Tayebi Mahnoush , Ai Ye , Williams John
Published: May 2020

Acoustic waves can be used to accurately position cells and particles and are appropriate for this activity owing to their biocompatibility and ability to generate microscale force gradients. Such fields, however, typically take the form of only periodic one or two-dimensional grids, limiting the scope of patterning activities that can be performed. Recent work has demonstrated that the interaction between microfluidic channel walls and travelling surface acoustic waves can generate spatially variable acoustic fields, opening the possibility that the channel geometry can be used to control the pressure field that develops. In this work we utilize this approach to create novel acoustic fields. Designing the channel that results in a desired acoustic field, however, is a non-trivial task. To rapidly generate designed acoustic fields from microchannel elements we utilize a deep learning approach based on a deep neural network (DNN) that is trained on images of pre-solved acoustic fields. We use then this trained DNN to create novel microchannel architectures for designed microparticle patterning.
Instrumentation for quantitative analysis of volatile compounds emission at elevated temperatures. Part 2: Analysis of carbon fibre reinforced epoxy composite
Authors: Lourenço Célia , Francis Daniel , Fowler Dawn P. , Staines Stephen E. , Hodgkinson Jane , Walton Christopher , Bergin Sarah , Tatam Ralph P.
Published: May 2020

We have investigated the release of gases and volatile organic compounds (VOCs) from a carbon fibre reinforced epoxy composite matrix used in aircraft structural components. Analysis was performed at several temperatures both up to and above the recommended operating temperature (121 °C) for the material, to a maximum of 250 °C. Gas chromatography-mass spectrometry (GC-MS) combined with thermal desorption (TD-GC-MS) was used to identify and quantify VOCs, and in parallel real-time gas detection with commercial off-the-shelf (COTS) gas sensors. Under hydrocarbon free air, CO, SO2, NO, NO2and VOCs (mainly aldehydes, ketones and a carboxylic acid) were detected as the gaseous products released during the thermal exposure of the material up to 250 °C, accompanied by increased relative humidity (4%). At temperatures up to 150 °C, gas and volatile emission was limited.