bluuebunny/crossref_metadata_2025 huggingface dataset:
Distanzunterricht und E-Learning in der beruflichen Fort- und Weiterbildung
Authors: Heislbetz Claus , Götz Vanadis
Published: January 2022

Zusammenfassung. Die Prognose, dass die Digitalisierung die Praxis in der beruflichen Fort- und Weiterbildung verändern wird, ist nicht neu. Dennoch gibt es bislang wenig Erkenntnis zu den Erwartungen der Teilnehmer_innen nach digital unterstützten Lernformen. Auf Grundlage von Erhebungen zu zwei Zeitpunkten vergleicht dieser Beitrag, wie sich die diesbezüglichen Erwartungen in der beruflichen Fort- und Weiterbildung im Sozial- und Gesundheitswesen vor und während des Ausbruchs der Corona-Pandemie verändert haben.
Gesundheit pflegender Mütter
Authors: Büker Christa , Streicher Bianca , Scheerbaum Laura
Published: January 2022

Zusammenfassung. Mütter mit einem pflegebedürftigen Kind haben zahlreiche Herausforderungen und Belastungen zu bewältigen. Damit gehören sie zu einer Risikogruppe für eigene gesundheitliche Beeinträchtigungen. Die professionelle Pflege kann wirksame Unterstützung durch Information, Schulung und Beratung leisten.
Creative Self and Fear of Rejection
Authors: Sordia Natia , Martskvishvili Khatuna
Published: January 2022

Abstract. Realization of creative potential in everyday life, sharing an original product or idea with others involves the risk of being rejected. In the current study, we explored the factors affecting the process of realization of creative potential in creative activities and creative achievements. We examined whether creative self-efficacy and creative personal identity, on the one hand, and fear of negative evaluation and rejection sensitivity, on the other hand, moderate the relationship between creative potential and real-life creativity (i.e., creative activities and achievements). According to the results, the relationship between creative potential and real-life creativity is stronger when people with creative potential have high creative personal identity and fear of negative evaluation scores. However, the relationship between creative potential and real-life creativity is not significant when people with creative potential have high scores on the creative self-efficacy and rejection expectancy scales (a cognitive aspect of rejection sensitivity). Possible explanations of the different results related to the different indicators of creativity and implications for future research are discussed.
Can IMERG Data Capture the Scaling of Precipitation Extremes With Temperature at Different Time Scales?
Authors: Hosseini‐Moghari Seyed‐Mohammad , Tang Qiuhong
Published: January 2022

This study evaluates the validity of the Integrated Multisatellite Retrievals for Global Precipitation Measurement (IMERG) in scaling extreme precipitation with temperature (termed scaling factor, SF). To this end, we use Hadley‐Integrated Surface Database (HadISD) data set at 1‐hourly, 6‐hourly, and 24‐hourly scales between 2000 and 2020 over the contiguous United States (CONUS) as a reference data set. Our findings reveal that IMERG can capture changes in precipitation extremes with the temperature at 6‐hourly, and 24‐hourly scales, especially over dry regions. The difference between IMERG's SF and HadISD's SF at 6‐hourly scale is less than 0.3%/°C in dry areas. However, IMERG underestimates SF in wet regions, especially at 1‐hourly scale, up to ∼5%/°C. It is found that IMERG's performance is dependent on temperature, particularly at 1‐hourly scale. IMERG overestimates extreme precipitations when temperatures are below 5°–11°C while the opposite is true at higher temperatures, indicating the need for considering temperature in adjusting IMERG.
On the Processes Sustaining Biological Production in the Offshore Propagating Eddies of the Northern Canary Upwelling System
Authors: Lovecchio Elisa , Gruber Nicolas , Münnich Matthias , Frenger Ivy
Published: January 2022

Oceanic mesoscale eddies constitute ephemeral hotspots for marine life and are pivotal for the lateral transport of nutrients and organic matter. Here, we use a high‐resolution coupled physical‐biogeochemical model to study the processes sustaining biological production and export in long‐living cyclonic (CE) and anticyclonic (AE) eddies of the northern Canary Upwelling System (CanUS). We track the eddies for 18 months as they propagate offshore, and study their composite properties in time in a Lagrangian manner. Our model shows that long‐living CEs sustain their production with the nitrogen that they initially trap in the nearshore nutrient‐rich waters and keep isolated in their cores. The vertical input of nitrate from below tends to be comparatively small, and is mostly driven by mixing. In contrast, AEs tend to start with low nutrient concentrations in their core as they do not trap coastal waters, but have elevated concentrations at their periphery. In AEs, stirring is responsible for both the building up of the positive nitrate anomaly at depth and the enhanced lateral input of organic nitrogen in the near‐surface. Compared to CEs, the input of nitrate into the euphotic zone by vertical mixing is substantially more important. Though regenerated production dominates in both types of eddies, new production is higher than the regional average in CE cores and at the rim of AEs, partially compensating for the intense losses due to sinking. Both cyclonic trapping and transport and anticyclonic stirring shape the regional pattern of organic matter and nutrients in the northern CanUS.
Water Oxygen Consumption Rather Than Sediment Oxygen Consumption Drives the Variation of Hypoxia on the East China Sea Shelf
Authors: Meng Qicheng , Zhang Wenyan , Zhou Feng , Liao Yibo , Yu Peisong , Tang Yanbin , Ma Xiao , Tian Di , Ding Ruibin , Ni Xiaobo , Zeng Dingyong , Schrum Corinna
Published: January 2022

Sediment oxygen consumption (SOC) is important in modulating the oxygen budget in the East China Sea where seasonal hypoxia occurs. Porewater advection, molecular diffusion and bioturbation supply oxygen for sedimentary organic matter degradation. A pelagic‐benthic coupled model was applied to quantify the SOC. A comparison with observations showed good model performance in reproducing the hydrographic and ecological environments, particularly for the interannual variation in the hypoxic zone. Simulation results show that porewater‐advection‐induced flux is the predominant component of the SOC in sandy areas on the Changjiang bank and outer shelves, while the bioturbation‐induced flux is predominant at mud depocenters. By comparing SOC to the water oxygen consumption (WOC) below the pycnocline, the contribution of SOC is generally below ∼40% in the hypoxic zone. The spatial distribution of SOC in summer is relatively steady from year to year, while the high WOC patches explain more about the interannual variation in the hypoxic zone. WOC rather than SOC drives the variation of hypoxia. Particularly on the Changjiang bank, milder hydrodynamics are favorable for both the higher WOC and bioturbation‐induced benthic oxygen flux but substantially suppress the porewater advective flux, which results in the net lower contribution of SOC to hypoxia. This finding may shed light on other pelagic‐benthic coupling processes in coastal shelf seas where hypoxia occurs on permeable sediments.
Hydro‐Morphological Disturbance and Suitability for Temporary Agriculture of Riverine Islands in a Tropical Wandering River
Authors: Serrao Livia , Brentari Luca , Balcazar Terrones Luz Elita , Huamaní Yupanqui Hugo Alfredo , Rengifo Trigoso Juan Pablo , Zolezzi Guido
Published: January 2022

Fluvial islands define fundamental interfaces between the aquatic and terrestrial environment in river corridors, have unique environmental value, and represent a place of interest for human communities worldwide. Temporary agriculture occurs in many riverine islands in tropical regions of the planet, but this has received little attention so far. By integrating remote sensing, field and laboratory investigations, hydrological and hydraulic analysis, we quantified controls on their agricultural suitability in terms of fluvial disturbance, morphological stability, soils characteristics, and selection of flood‐resistant crops. A highly dynamic foothill reach of the wandering Huallaga River (Peruvian Amazon) where temporary agriculture is practiced by local farmers is used as a case study. Islands show rapid turnover rates, with their number and total area tripling in the 1986‐2019 period, in association with recent river corridor widening. Simulated disturbance‐free windows of opportunity can be long enough (up to 230 days, for plantain) to cultivate on the most elevated portions of the largest islands, about 3 m above the thalweg. A gradient of increasing agricultural suitability paralleled that of decreasing fluvial disturbance from the most recently developed island (e.g., organic matter 0.2%–1.2%) to the more stable one (0.1%–2.6%) to the established floodplain (0.5%–3.5%). While the floodplain is more suitable for farming, we quantified how suitable islands are for temporary food production. Our results are generalized through a conceptual model for fluvial islands' agricultural suitability, thus filling an important knowledge gap about the characteristics of those highly sensitive environments within floodplains still moderately affected by human activities.
Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis
Authors: Lin Jun , Li Qinfeng , Jin Tingting , Wang Jiacheng , Gong Yingchao , Lv Qingbo , Wang Meihui , Chen Jiawen , Shang Min , Zhao Yanbo , Fu Guosheng
Published: January 2022

Myocardial ischemia reperfusion (I/R) injury is a complex process with intense inflammatory response and cardiomyocyte apoptosis. As a decoy receptor of IL-1β, Interleukin-1 receptor type 2 (IL-1R2) inhibits IL-1β signaling. However, its role in I/R injury remains unknown. Here we found that the serum levels of IL-1R2 were significantly increased in patients with acute myocardial infarction (AMI) following interventional therapy. Similarly, after myocardial I/R surgery, IL-1R2 expression was significantly increased in heart of wild-type mice. In addition, IL-1R2-deficient mice heart showed enlarged infarct size, increased cardiomyocyte apoptosis together with reduced cardiac systolic function. Following exposure to hypoxia and reoxygenation (H/R), neonatal rat ventricular myocytes (NRVM) significantly increased IL-1R2 expression relying on NF-κB activation. Consistently, IL-1R2-deficient mice increased immune cells infiltrating into heart after surgery, which was relevant with cardiac damage. Additionally, IL-1R2 overexpression in cardiomyocyte protected cardiomyocyte against apoptosis through reducing the IL-17RA expression both in vivo and in vitro. Our results indicate that IL-1R2 protects cardiomyocytes from apoptosis, which provides a therapeutic approach to turn down myocardial I/R injury.
Machine learning-informed and synthetic biology-enabled semi-continuous algal cultivation to unleash renewable fuel productivity
Authors: Long Bin , Fischer Bart , Zeng Yining , Amerigian Zoe , Li Qiang , Bryant Henry , Li Man , Dai Susie Y. , Yuan Joshua S.
Published: January 2022

Algal biofuel is regarded as one of the ultimate solutions for renewable energy, but its commercialization is hindered by growth limitations caused by mutual shading and high harvest costs. We overcome these challenges by advancing machine learning to inform the design of a semi-continuous algal cultivation (SAC) to sustain optimal cell growth and minimize mutual shading. An aggregation-based sedimentation (ABS) strategy is then designed to achieve low-cost biomass harvesting and economical SAC. The ABS is achieved by engineering a fast-growing strain, Synechococcus elongatus UTEX 2973, to produce limonene, which increases cyanobacterial cell surface hydrophobicity and enables efficient cell aggregation and sedimentation. SAC unleashes cyanobacterial growth potential with 0.1 g/L/hour biomass productivity and 0.2 mg/L/hour limonene productivity over a sustained period in photobioreactors. Scaling-up the SAC with an outdoor pond system achieves a biomass yield of 43.3 g/m2/day, bringing the minimum biomass selling price down to approximately $281 per ton.
Control of electronic band profiles through depletion layer engineering in core–shell nanocrystals
Authors: Ghini Michele , Curreli Nicola , Lodi Matteo B. , Petrini Nicolò , Wang Mengjiao , Prato Mirko , Fanti Alessandro , Manna Liberato , Kriegel Ilka
Published: January 2022

Fermi level pinning in doped metal oxide (MO) nanocrystals (NCs) results in the formation of depletion layers, which affect their optical and electronic properties, and ultimately their application in smart optoelectronics, photocatalysis, or energy storage. For a precise control over functionality, it is important to understand and control their electronic bands at the nanoscale. Here, we show that depletion layer engineering allows designing the energetic band profiles and predicting the optoelectronic properties of MO NCs. This is achieved by shell thickness tuning of core–shell Sn:In2O3–In2O3 NCs, resulting in multiple band bending and multi-modal plasmonic response. We identify the modification of the band profiles after the light-induced accumulation of extra electrons as the main mechanism of photodoping and enhance the charge storage capability up to hundreds of electrons per NC through depletion layer engineering. Our experimental results are supported by theoretical models and are transferable to other core-multishell systems as well.
The neglected role of relative humidity in the interannual variability of urban malaria in Indian cities
Authors: Santos-Vega M. , Martinez P. P. , Vaishnav K. G. , Kohli V. , Desai V. , Bouma M. J. , Pascual M.
Published: January 2022

The rapid pace of urbanization makes it imperative that we better understand the influence of climate forcing on urban malaria transmission. Despite extensive study of temperature effects in vector-borne infections in general, consideration of relative humidity remains limited. With process-based dynamical models informed by almost two decades of monthly surveillance data, we address the role of relative humidity in the interannual variability of epidemic malaria in two semi-arid cities of India. We show a strong and significant effect of humidity during the pre-transmission season on malaria burden in coastal Surat and more arid inland Ahmedabad. Simulations of the climate-driven transmission model with the MLE (Maximum Likelihood Estimates) of the parameters retrospectively capture the observed variability of disease incidence, and also prospectively predict that of ‘out-of-fit’ cases in more recent years, with high accuracy. Our findings indicate that relative humidity is a critical factor in the spread of urban malaria and potentially other vector-borne epidemics, and that climate change and lack of hydrological planning in cities might jeopardize malaria elimination efforts.
Carbohydrate-aromatic interface and molecular architecture of lignocellulose
Authors: Kirui Alex , Zhao Wancheng , Deligey Fabien , Yang Hui , Kang Xue , Mentink-Vigier Frederic , Wang Tuo
Published: January 2022

Plant cell walls constitute the majority of lignocellulosic biomass and serve as a renewable resource of biomaterials and biofuel. Extensive interactions between polysaccharides and the aromatic polymer lignin make lignocellulose recalcitrant to enzymatic hydrolysis, but this polymer network remains poorly understood. Here we interrogate the nanoscale assembly of lignocellulosic components in plant stems using solid-state nuclear magnetic resonance and dynamic nuclear polarization approaches. We show that the extent of glycan-aromatic association increases sequentially across grasses, hardwoods, and softwoods. Lignin principally packs with the xylan in a non-flat conformation via non-covalent interactions and partially binds the junction of flat-ribbon xylan and cellulose surface as a secondary site. All molecules are homogeneously mixed in softwoods; this unique feature enables water retention even around the hydrophobic aromatics. These findings unveil the principles of polymer interactions underlying the heterogeneous architecture of lignocellulose, which may guide the rational design of more digestible plants and more efficient biomass-conversion pathways.
Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis
Authors: Fielding Claire , García-García Andrés , Korn Claudia , Gadomski Stephen , Fang Zijian , Reguera Juan L. , Pérez-Simón José A. , Göttgens Berthold , Méndez-Ferrer Simón
Published: January 2022

The sympathetic nervous system has been evolutionary selected to respond to stress and activates haematopoietic stem cells via noradrenergic signals. However, the pathways preserving haematopoietic stem cell quiescence and maintenance under proliferative stress remain largely unknown. Here we found that cholinergic signals preserve haematopoietic stem cell quiescence in bone-associated (endosteal) bone marrow niches. Bone marrow cholinergic neural signals increase during stress haematopoiesis and are amplified through cholinergic osteoprogenitors. Lack of cholinergic innervation impairs balanced responses to chemotherapy or irradiation and reduces haematopoietic stem cell quiescence and self-renewal. Cholinergic signals activate α7 nicotinic receptor in bone marrow mesenchymal stromal cells leading to increased CXCL12 expression and haematopoietic stem cell quiescence. Consequently, nicotine exposure increases endosteal haematopoietic stem cell quiescence in vivo and impairs hematopoietic regeneration after haematopoietic stem cell transplantation in mice. In humans, smoking history is associated with delayed normalisation of platelet counts after allogeneic haematopoietic stem cell transplantation. These results suggest that cholinergic signals preserve stem cell quiescence under proliferative stress.
Structural basis for safe and efficient energy conversion in a respiratory supercomplex
Authors: Kao Wei-Chun , Ortmann de Percin Northumberland Claire , Cheng Tat Cheung , Ortiz Julio , Durand Alexandre , von Loeffelholz Ottilie , Schilling Oliver , Biniossek Martin L. , Klaholz Bruno P. , Hunte Carola
Published: January 2022

Proton-translocating respiratory complexes assemble into supercomplexes that are proposed to increase the efficiency of energy conversion and limit the production of harmful reactive oxygen species during aerobic cellular respiration. Cytochrome bc complexes and cytochrome aa3 oxidases are major drivers of the proton motive force that fuels ATP generation via respiration, but how wasteful electron- and proton transfer is controlled to enhance safety and efficiency in the context of supercomplexes is not known. Here, we address this question with the 2.8 Å resolution cryo-EM structure of the cytochrome bcc-aa3 (III2-IV2) supercomplex from the actinobacterium Corynebacterium glutamicum. Menaquinone, substrate mimics, lycopene, an unexpected Qc site, dioxygen, proton transfer routes, and conformational states of key protonable residues are resolved. Our results show how safe and efficient energy conversion is achieved in a respiratory supercomplex through controlled electron and proton transfer. The structure may guide the rational design of drugs against actinobacteria that cause diphtheria and tuberculosis.
Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis
Authors: Lopez-Fabuel Irene , Garcia-Macia Marina , Buondelmonte Costantina , Burmistrova Olga , Bonora Nicolo , Alonso-Batan Paula , Morant-Ferrando Brenda , Vicente-Gutierrez Carlos , Jimenez-Blasco Daniel , Quintana-Cabrera Ruben , Fernandez Emilio , Llop Jordi , Ramos-Cabrer Pedro , Sharaireh Aseel , Guevara-Ferrer Marta , Fitzpatrick Lorna , Thompton Christopher D. , McKay Tristan R. , Storch Stephan , Medina Diego L. , Mole Sara E. , Fedichev Peter O. , Almeida Angeles , Bolaños Juan P.
Published: January 2022

CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage neurodegenerative disease highly prevalent in children.CLN7/MFSD8gene encodes a lysosomal membrane glycoprotein, but the biochemical processes affected by CLN7-loss of function are unexplored thus preventing development of potential treatments. Here, we found, in theCln7∆ex2mouse model of CLN7 disease, that failure in autophagy causes accumulation of structurally and bioenergetically impaired neuronal mitochondria. In vivo genetic approach reveals elevated mitochondrial reactive oxygen species (mROS) inCln7∆ex2neurons that mediates glycolytic enzyme PFKFB3 activation and contributes to CLN7 pathogenesis. Mechanistically, mROS sustains a signaling cascade leading to protein stabilization of PFKFB3, normally unstable in healthy neurons. Administration of the highly selective PFKFB3 inhibitor AZ67 inCln7∆ex2mouse brain in vivo and in CLN7 patients-derived cells rectifies key disease hallmarks. Thus, aberrant upregulation of the glycolytic enzyme PFKFB3 in neurons may contribute to CLN7 pathogenesis and targeting PFKFB3 could alleviate this and other lysosomal storage diseases.
Emerging experience-dependent dynamics in primary somatosensory cortex reflect behavioral adaptation
Authors: Waiblinger Christian , McDonnell Megan E. , Reedy April R. , Borden Peter Y. , Stanley Garrett B.
Published: January 2022

Behavioral experience and flexibility are crucial for survival in a constantly changing environment. Despite evolutionary pressures to develop adaptive behavioral strategies in a dynamically changing sensory landscape, the underlying neural correlates have not been well explored. Here, we use genetically encoded voltage imaging to measure signals in primary somatosensory cortex (S1) during sensory learning and behavioral adaptation in the mouse. In response to changing stimulus statistics, mice adopt a strategy that modifies their detection behavior in a context dependent manner as to maintain reward expectation. Surprisingly, neuronal activity in S1 shifts from simply representing stimulus properties to transducing signals necessary for adaptive behavior in an experience dependent manner. Our results suggest that neuronal signals in S1 are part of an adaptive framework that facilitates flexible behavior as individuals gain experience, which could be part of a general scheme that dynamically distributes the neural correlates of behavior during learning.
Structures and function of a tailoring oxidase in complex with a nonribosomal peptide synthetase module
Authors: Fortinez Camille Marie , Bloudoff Kristjan , Harrigan Connor , Sharon Itai , Strauss Mike , Schmeing T. Martin
Published: January 2022

Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that synthesize secondary metabolites and natural product therapeutics. Most NRPS biosynthetic pathways include an NRPS and additional proteins that introduce chemical modifications before, during or after assembly-line synthesis. The bacillamide biosynthetic pathway is a common, three-protein system, with a decarboxylase that prepares an NRPS substrate, an NRPS, and an oxidase. Here, the pathway is reconstituted in vitro. The oxidase is shown to perform dehydrogenation of the thiazoline in the peptide intermediate while it is covalently attached to the NRPS, as the penultimate step in bacillamide D synthesis. Structural analysis of the oxidase reveals a dimeric, two-lobed architecture with a remnant RiPP recognition element and a dramatic wrapping loop. The oxidase forms a stable complex with the NRPS and dimerizes it. We visualized co-complexes of the oxidase bound to the elongation module of the NRPS using X-ray crystallography and cryo-EM. The three active sites (for adenylation, condensation/cyclization, and oxidation) form an elegant arc to facilitate substrate delivery. The structures enabled a proof-of-principle bioengineering experiment in which the BmdC oxidase domain is embedded into the NRPS.
Operando monitoring of ion activities in aqueous batteries with plasmonic fiber-optic sensors
Authors: Wang Runlin , Zhang Haozhe , Liu Qiyu , Liu Fu , Han Xile , Liu Xiaoqing , Li Kaiwei , Xiao Gaozhi , Albert Jacques , Lu Xihong , Guo Tuan
Published: January 2022

Understanding ion transport kinetics and electrolyte-electrode interactions at electrode surfaces of batteries in operation is essential to determine their performance and state of health. However, it remains a challenging task to capture in real time the details of surface-localized and rapid ion transport at the microscale. To address this, a promising approach based on an optical fiber plasmonic sensor capable of being inserted near the electrode surface of a working battery to monitor its electrochemical kinetics without disturbing its operation is demonstrated using aqueous Zn-ion batteries as an example. The miniature and chemically inert sensor detects perturbations of surface plasmon waves propagating on its surface to rapidly screen localized electrochemical events on a sub-μm-scale thickness adjacent to the electrode interface. A stable and reproducible correlation between the real-time ion insertions over charge-discharge cycles and the optical plasmon response has been observed and quantified. This new operando measurement tool will provide crucial additional capabilities to battery monitoring methods and help guide the design of better batteries with improved electro-chemistries.
Atherosclerosis amelioration by allicin in raw garlic through gut microbiota and trimethylamine-N-oxide modulation
Authors: Panyod Suraphan , Wu Wei-Kai , Chen Pei-Chen , Chong Kent-Vui , Yang Yu-Tang , Chuang Hsiao-Li , Chen Chieh-Chang , Chen Rou-An , Liu Po-Yu , Chung Ching-Hu , Huang Huai-Syuan , Lin Angela Yu-Chen , Shen Ting-Chin David , Yang Kai-Chien , Huang Tur-Fu , Hsu Cheng-Chih , Ho Chi-Tang , Kao Hsien-Li , Orekhov Alexander N. , Wu Ming-Shiang , Sheen Lee-Yan
Published: January 2022

Cardiovascular disease (CVD) is strongly associated with the gut microbiota and its metabolites, including trimethylamine-N-oxide (TMAO), formed from metaorganismal metabolism of ʟ-carnitine. Raw garlic juice, with allicin as its primary compound, exhibits considerable effects on the gut microbiota. This study validated the benefits of raw garlic juice against CVD risk via modulation of the gut microbiota and its metabolites. Allicin supplementation significantly decreased serum TMAO in ʟ-carnitine-fed C57BL/6 J mice, reduced aortic lesions, and altered the fecal microbiota in carnitine-induced, atherosclerosis-prone, apolipoprotein E-deficient (ApoE−/−) mice. In human subjects exhibiting high-TMAO production, raw garlic juice intake for a week reduced TMAO formation, improved gut microbial diversity, and increased the relative abundances of beneficial bacteria. In in vitro and ex vivo studies, raw garlic juice and allicin inhibited γ-butyrobetaine (γBB) and trimethylamine production by the gut microbiota. Thus, raw garlic juice and allicin can potentially prevent cardiovascular disease by decreasing TMAO production via gut microbiota modulation.
Increased trunk fat is associated with altered gene expression in breast tissue of normal weight women
Authors: Cho Byuri Angela , Iyengar Neil M. , Zhou Xi Kathy , Mendieta Hillary , Winston Lisle , Falcone Domenick J. , Landa Jonathan , Morrow Monica , Dannenberg Andrew J.
Published: January 2022

Increased trunk fat is associated with an elevated risk of breast cancer in normal-weight postmenopausal women. The main objective of this study was to determine whether levels of trunk fat are associated with changes in breast gene expression in normal-weight women. Non-tumorous breast tissue was collected from 32 normal BMI women who underwent mastectomy for breast cancer risk reduction or treatment. Body composition was measured by dual-energy x-ray absorptiometry. High levels of trunk fat were associated with a large number of differentially expressed genes and changes in multiple pathways and processes potentially linked to breast cancer pathogenesis. High levels of trunk fat were also associated with an elevated immune score and increased levels of leptin, CCL2, VEGF-C, IL6, and aromatase. Collectively, these results help to explain why high levels of trunk fat are associated with an increased risk of breast cancer in normal BMI women.
Mechanism of keyhole pore formation in metal additive manufacturing
Authors: Wang Lu , Zhang Yanming , Chia Hou Yi , Yan Wentao
Published: January 2022

During metal additive manufacturing, the porosity of the as-built part deteriorates the mechanical property and even hinders the further application of metal additive manufacturing. Particularly, the mechanisms of keyhole pores associated with the keyhole fluctuation are not fully understood. To reveal the mechanisms of the keyhole pores formation, we adopt a multiphysics thermal-fluid flow model incorporating heat transfer, liquid flow, metal evaporation, Marangoni effect, and Darcy’s law to simulate the keyhole pore formation process, and the results are validated with the in situ X-ray images. The simulation results present the instant bubble formation due to the keyhole instability and motion of the instant bubble pinning on the solidification front. Furthermore, comparing the keyhole pore formation under different laser scanning speeds shows that the keyhole pore is sensitive to the manufacturing parameters. Additionally, the simulation under a low ambient pressure shows the feasibility of improving the keyhole stability to reduce and even avoid the formation of keyhole pores.
Supramolecular gating of guest release from cucurbit[7]uril using de novo design
Authors: Lambert Hugues , Castillo Bonillo Alvaro , Zhu Qiang , Zhang Yong-Wei , Lee Tung-Chun
Published: January 2022

Herein we computationally explore the modulation of the release kinetics of an encapsulated guest molecule from the cucurbit[7]uril (CB7) cavity by ligands binding to the host portal. We uncovered a correlation between the ligand-binding affinity with CB7 and the guest residence time, allowing us to rapidly predict the release kinetics through straightforward energy minimization calculations. These high-throughput predictions in turn enable a Monte-Carlo Tree Search (MCTS) to de novo design a series of cap-shaped ligand molecules with large binding affinities and boosting guest residence times by up to 7 orders of magnitude. Notably, halogenated aromatic compounds emerge as top-ranking ligands. Detailed modeling suggests the presence of halogen-bonding between the ligands and the CB7 portal. Meanwhile, the binding of top-ranked ligands is supported by 1H NMR and 2D DOSY-NMR. Our findings open up possibilities in gating of molecular transport through a nanoscale cavity with potential applications in nanopore technology and controlled drug release.
Intriguing magnetoelectric effect in two-dimensional ferromagnetic/perovskite oxide ferroelectric heterostructure
Authors: Li Ping , Zhou Xue-Song , Guo Zhi-Xin
Published: January 2022

Two-dimensional (2D) magnets have broad application prospects in the spintronics, but how to effectively control them with a small electric field is still an issue. Here we propose that 2D magnets can be efficiently controlled in a multiferroic heterostructure composed of 2D magnetic material and perovskite oxide ferroelectric (POF) whose dielectric polarization is easily flipped under a small electric field. We illustrate the feasibility of such strategy in the bilayer CrI3/BiFeO3(001) heterostructure by using the first-principles calculations. Different from the traditional POF multiferroic heterostructures which have strong interface interactions, we find that the interface interaction between CrI3 and BiFeO3(001) is van der Waals type. Whereas, the heterostructure has particular strong magnetoelectric coupling where the bilayer CrI3 can be efficiently switched between ferromagnetic and antiferromagnetic types by the polarized states P↑ and P↓ of BiFeO3(001). We also discover the competing effect between electron doping and the additional electric field on the interlayer exchange coupling interaction of CrI3, which is responsible to the magnetic phase transition. Our results provide a avenue for the tuning of 2D magnets with a small electric field.
A two-way photonic quantum entanglement transfer interface
Authors: Huang Yiwen , Li Yuanhua , Qi Zhantong , Feng Juan , Zheng Yuanlin , Chen Xianfeng
Published: January 2022

A quantum interface for two-way entanglement transfer, e.g., between orbital angular momentum degree of freedom in free space and time-energy degree of freedom in optical fibers, provides a way toward establishing entanglement between remote heterogeneous quantum nodes. Here, we experimentally demonstrate this kind of transfer interface by using two interferometric cyclic gates. By using this quantum interface, we perform two-way entanglement transfer for the two degrees of freedom. The results show that the quantum entangled state can be switched back and forth between orbital angular momentum and time-energy degrees of freedom, and the fidelity of the state before and after switching is higher than 90%. Our work demonstrates the feasibility and high performance of our proposed transfer interface, and paves a route toward building a large-scale quantum communication network.
Optimal control of stimulated Raman adiabatic passage in a superconducting qudit
Authors: Zheng Wen , Zhang Yu , Dong Yuqian , Xu Jianwen , Wang Zhimin , Wang Xiaohan , Li Yong , Lan Dong , Zhao Jie , Li Shaoxiong , Tan Xinsheng , Yu Yang
Published: January 2022

Stimulated Raman adiabatic passage (STIRAP) is a widely used protocol to realize high-fidelity and robust quantum control in various quantum systems. However, further application of this protocol in superconducting qubits is limited by population leakage caused by the only weak anharmonicity. Here, we introduce an optimally controlled shortcut-to-adiabatic (STA) technique to speed-up the STIRAP protocol in a superconducting qudit. By modifying the shapes of the STIRAP pulses, we experimentally realize a fast (32 ns) and high-fidelity (0.996 ± 0.005) quantum state transfer. In addition, we demonstrate that our protocol is robust against control parameter perturbations. Our stimulated Raman shortcut-to-adiabatic passage transition provides an efficient and practical approach for quantum information processing.
Hippo-Yap/Taz signalling in zebrafish regeneration
Authors: Riley Susanna E. , Feng Yi , Hansen Carsten Gram
Published: January 2022

The extent of tissue regeneration varies widely between species. Mammals have a limited regenerative capacity whilst lower vertebrates such as the zebrafish (Danio rerio), a freshwater teleost, can robustly regenerate a range of tissues, including the spinal cord, heart, and fin. The molecular and cellular basis of this altered response is one of intense investigation. In this review, we summarise the current understanding of the association between zebrafish regeneration and Hippo pathway function, a phosphorylation cascade that regulates cell proliferation, mechanotransduction, stem cell fate, and tumorigenesis, amongst others. We also compare this function to Hippo pathway activity in the regenerative response of other species. We find that the Hippo pathway effectors Yap/Taz facilitate zebrafish regeneration and that this appears to be latent in mammals, suggesting that therapeutically promoting precise and temporal YAP/TAZ signalling in humans may enhance regeneration and hence reduce morbidity.
High-throughput platform for yeast morphological profiling predicts the targets of bioactive compounds
Authors: Ohnuki Shinsuke , Ogawa Itsuki , Itto-Nakama Kaori , Lu Fachuang , Ranjan Ashish , Kabbage Mehdi , Gebre Abraham Abera , Yamashita Masao , Li Sheena C. , Yashiroda Yoko , Yoshida Satoshi , Usui Takeo , Piotrowski Jeff S. , Andrews Brenda J. , Boone Charles , Brown Grant W. , Ralph John , Ohya Yoshikazu
Published: January 2022

Morphological profiling is an omics-based approach for predicting intracellular targets of chemical compounds in which the dose-dependent morphological changes induced by the compound are systematically compared to the morphological changes in gene-deleted cells. In this study, we developed a reliable high-throughput (HT) platform for yeast morphological profiling using drug-hypersensitive strains to minimize compound use, HT microscopy to speed up data generation and analysis, and a generalized linear model to predict targets with high reliability. We first conducted a proof-of-concept study using six compounds with known targets: bortezomib, hydroxyurea, methyl methanesulfonate, benomyl, tunicamycin, and echinocandin B. Then we applied our platform to predict the mechanism of action of a novel diferulate-derived compound, poacidiene. Morphological profiling of poacidiene implied that it affects the DNA damage response, which genetic analysis confirmed. Furthermore, we found that poacidiene inhibits the growth of phytopathogenic fungi, implying applications as an effective antifungal agent. Thus, our platform is a new whole-cell target prediction tool for drug discovery.
Immune persistence and response to booster dose of Vi-DT vaccine at 27.5 months post-first dose
Authors: Capeding Maria Rosario , Tadesse Birkneh Tilahun , Sil Arijit , Alberto Edison , Kim Deok Ryun , Park Eun Lyeong , Park Ju Yeon , Yang Jae Seung , Eluru Jagadeesh Reddy , Jo Sue-Kyoung , Kim Hun , Yang Seon-Young , Ryu Ji Hwa , Park Hokeun , Shin Jong Hoon , Lee Yoonyeong , Kim Jerome H. , Mojares Zenaida Reynoso , Wartel T. Anh , Sahastrabuddhe Sushant
Published: January 2022

Vaccination with typhoid conjugate vaccines (TCV) is a major part of typhoid prevention. However, little is known about long-term immune persistence following vaccination with TCVs. In this phase-2, randomized double-blind trial (NCT03527355), 285 children aged 6–23 months were randomized to one of three groups: (1) the group that received a first dose of Vi polysaccharide conjugated to diphtheria-toxoid (Vi-DT) vaccine followed by an “early booster” at 24 weeks, (2) the group that which received a first dose of Vi-DT followed by a “late booster” at 96 or 110 weeks, and (3) comparator group. Safety and immunogenicity of anti-Vi IgG GMTs were assessed at weeks 0, 4, 24, 28, 60, 96, 110, and 114 since the first dose. Here, we describe persistence of immune responses at weeks 60, 96, 110, and 114 post first dose. The anti-Vi IgG seroconversion rate after 27.5 months of follow-up was 88.16% (95% CI: 79.00, 93.64) in late-booster and 94.76% (95% CI: 86.91, 97.88) in early booster Vi-DT groups (p = 0.081). Whereas anti-Vi IgG GMTs were significantly higher in the early booster group (11.95 [95% CI: 9.65, 14.81]) than prebooster GMTs in the late booster group (5.50 [95% CI: 4.44, 6.80], p < 0.0001). GMT in the late booster group significantly increased to 351.76 (95% CI: 265.01, 466.93) (p < 0.0001) when measured 4 weeks after they received their “late-booster” shot. In conclusion, late booster dosing with Vi-DT at 27.5 months post first dose was safe and elicited robust anti-Vi IgG immune responses. Anti-Vi IgG seroconversion rates were persistently comparable in early and late-booster Vi-DT groups.
Pre-existing antibodies directed against a tetramerizing domain enhance the immune response against artificially stabilized soluble tetrameric influenza neuraminidase
Authors: Catani João Paulo Portela , Job Emma R. , Ysenbaert Tine , Smet Anouk , Ray Satyajit , LaRue Lauren , Stegalkina Svetlana , Barro Mario , Vogel Thorsten U. , Saelens Xavier
Published: January 2022

The neuraminidase (NA) is an abundant antigen at the surface of influenza virions. Recent studies have highlighted the immune-protective potential of NA against influenza and defined anti-NA antibodies as an independent correlate of protection. Even though NA head domain changes at a slightly slower pace than hemagglutinin (HA), NA is still subject to antigenic drift, and therefore an NA-based influenza vaccine antigen may have to be updated regularly and thus repeatedly administered. NA is a tetrameric type II membrane protein, which readily dissociates into dimers and monomers when expressed in a soluble form. By using a tetramerizing zipper, such as the tetrabrachion (TB) fromStaphylothermus marinus, it is possible to stabilize soluble NA in its active tetrameric conformation, an imperative for the optimal induction of protective NA inhibitory antibodies. The impact of repetitive immunizations with TB-stabilized antigens on the immunogenicity of soluble TB-stabilized NA is unknown. We demonstrate that TB is immunogenic in mice. Interestingly, preexisting anti-TB antibodies enhance the anti-NA antibody response induced by immunization with TB-stabilized NA. This immune-enhancing effect was transferable by serum and operated independently of activating Fcγ receptors. We also demonstrate that priming with TB-stabilized NA antigens, enhances the NA inhibitory antibody responses against a heterosubtypic TB-stabilized NA. These findings have implications for the clinical development of oligomeric vaccine antigens that are stabilized by a heterologous oligomerizing domain.
Multi-kingdom microbiota analyses identify
bacterial–fungal interactions and biomarkers of colorectal cancer across
cohorts
Authors: Liu Ning-Ning , Jiao Na , Tan Jing-Cong , Wang Ziliang , Wu Dingfeng , Wang An-Jun , Chen Jie , Tao Liwen , Zhou Chenfen , Fang Wenjie , Cheong Io Hong , Pan Weihua , Liao Wanqing , Kozlakidis Zisis , Heeschen Christopher , Moore Geromy G. , Zhu Lixin , Chen Xingdong , Zhang Guoqing , Zhu Ruixin , Wang Hui
Published: January 2022

Despite recent progress in our understanding of the association between
the gut microbiome and colorectal cancer (CRC), multi-kingdom gut microbiome
dysbiosis in CRC across cohorts is unexplored. We investigated four-kingdom
microbiota alterations using CRC metagenomic datasets of 1,368 samples from 8
distinct geographical cohorts. Integrated analysis identified 20 archaeal, 27
bacterial, 20 fungal and 21 viral species for each single-kingdom diagnostic model.
However, our data revealed superior diagnostic accuracy for models constructed with
multi-kingdom markers, in particular the addition of fungal species. Specifically,
16 multi-kingdom markers including 11 bacterial, 4 fungal and 1 archaeal feature,
achieved good performance in diagnosing patients with CRC (area under the receiver
operating characteristic curve (AUROC) = 0.83) and maintained
accuracy across 3 independent cohorts. Coabundance analysis of the ecological
network revealed associations between bacterial and fungal species, such as
Talaromyces islandicus and Clostridium saccharobutylicum. Using metagenome shotgun
sequencing data, the predictive power of the microbial functional potential was
explored and elevated D-amino acid metabolism and butanoate metabolism were observed
in CRC. Interestingly, the diagnostic model based on functional EggNOG genes
achieved high accuracy (AUROC = 0.86). Collectively, our findings
uncovered CRC-associated microbiota common across cohorts and demonstrate the
applicability of multi-kingdom and functional markers as CRC diagnostic tools and,
potentially, as therapeutic targets for the treatment of CRC.
p3k14c, a synthetic global database of archaeological radiocarbon dates
Authors: Bird Darcy , Miranda Lux , Vander Linden Marc , Robinson Erick , Bocinsky R. Kyle , Nicholson Chris , Capriles José M. , Finley Judson Byrd , Gayo Eugenia M. , Gil Adolfo , d’Alpoim Guedes Jade , Hoggarth Julie A. , Kay Andrea , Loftus Emma , Lombardo Umberto , Mackie Madeline , Palmisano Alessio , Solheim Steinar , Kelly Robert L. , Freeman Jacob
Published: January 2022

Archaeologists increasingly use large radiocarbon databases to model prehistoric human demography (also termed paleo-demography). Numerous independent projects, funded over the past decade, have assembled such databases from multiple regions of the world. These data provide unprecedented potential for comparative research on human population ecology and the evolution of social-ecological systems across the Earth. However, these databases have been developed using different sample selection criteria, which has resulted in interoperability issues for global-scale, comparative paleo-demographic research and integration with paleoclimate and paleoenvironmental data. We present a synthetic, global-scale archaeological radiocarbon database composed of 180,070 radiocarbon dates that have been cleaned according to a standardized sample selection criteria. This database increases the reusability of archaeological radiocarbon data and streamlines quality control assessments for various types of paleo-demographic research. As part of an assessment of data quality, we conduct two analyses of sampling bias in the global database at multiple scales. This database is ideal for paleo-demographic research focused on dates-as-data, bayesian modeling, or summed probability distribution methodologies.
Asymmetry between right and left fundus images identified using convolutional neural networks
Authors: Kang Tae Seen , Kim Bum Jun , Nam Ki Yup , Lee Seongjin , Kim Kyonghoon , Lee Woong-sub , Kim Jinhyun , Han Yong Seop
Published: January 2022

We analyzed fundus images to identify whether convolutional neural networks (CNNs) can discriminate between right and left fundus images. We gathered 98,038 fundus photographs from the Gyeongsang National University Changwon Hospital, South Korea, and augmented these with the Ocular Disease Intelligent Recognition dataset. We created eight combinations of image sets to train CNNs. Class activation mapping was used to identify the discriminative image regions used by the CNNs. CNNs identified right and left fundus images with high accuracy (more than 99.3% in the Gyeongsang National University Changwon Hospital dataset and 91.1% in the Ocular Disease Intelligent Recognition dataset) regardless of whether the images were flipped horizontally. The depth and complexity of the CNN affected the accuracy (DenseNet121: 99.91%, ResNet50: 99.86%, and VGG19: 99.37%). DenseNet121 did not discriminate images composed of only left eyes (55.1%, p = 0.548). Class activation mapping identified the macula as the discriminative region used by the CNNs. Several previous studies used the flipping method to augment data in fundus photographs. However, such photographs are distinct from non-flipped images. This asymmetry could result in undesired bias in machine learning. Therefore, when developing a CNN with fundus photographs, care should be taken when applying data augmentation with flipping.
Programmable wavelength filter with double ring loaded MZI
Authors: Wang Mi , Chen Xiangfeng , Khan Umar , Bogaerts Wim
Published: January 2022

We propose a novel filter circuit that incorporates a double ring resonator with a balanced Mach–Zehnder interferometer (MZI). The circuit has a response equivalent to a conventional ring loaded MZI filter, but with added flexibility in terms of configurability. The second-order filter can also be cascaded to realize higher-order filters. The circuit incorporates a two-stage input and output coupler to further reduce the effect of dispersion. A combination of local and global optimization strategies to program the filter, using tailored objective functions, have been tested in simulation and experiments. To our best knowledge, this is the first time a global optimization strategy is directly used in ARMA filter synthesis and simulation without any additional requirement. We further extend the optimization strategy into experiments and demonstrated its use in practical case for programmable filter circuits.