bluuebunny/crossref_metadata_2025 huggingface dataset:
Earth Science, Art and Coastal Engineering at the Seaside: Envisioning an Open Exploratorium or Geo-Promenade at Weston-super-Mare, Somerset, United Kingdom
Authors: Whalley W. Brian
Published: October 2022

The paper outlines how an outdoor ‘exploratorium’ can be curated to place field observations, together with some knowledge of the local environment, in a manner that relates to geology, geomorphology and artistic aesthetics. The exploratorium can also be used to help explain what is seen, touched or felt as part of ‘sensory geology’. The locations used are on an accessible walk, a geo-promenade, along the sea front of a coastal town, Weston-super-Mare, England. Sites, such as a sea wall and recent engineering structures, are linked to flood prevention measures and sculpture and stone promenade furniture relate to various aspects of geoheritage. Notions of consilience and decision-making in the behavioural environment are introduced, together with ways in which perceptions of the landscape can be shared with visually impaired visitors. Notes are provided to illustrate the additional information (metadata) that might be supplied in constructing a geo-promenade. The use of mobile technologies for recording observations, providing locations (using decimal Latitude Longitude designations) and general information is also discussed with respect to accessible visits. Attention is also given to cognition and educational models of experiential discussion and knowledge sharing that can be used in exploratoria and geoheritage in general.
Special solutions to the space fractional diffusion problem
Authors: Namba Tokinaga , Rybka Piotr , Sato Shoichi
Published: October 2022

We derive a fundamental solution $${{\mathscr {E}}}$$
E
to a space-fractional diffusion problem on the half-line. The equation involves the Caputo derivative. We establish properties of $${{\mathscr {E}}}$$
E
as well as formulas for solutions to the Dirichlet and fixed slope problems in terms of convolution of $${{\mathscr {E}}}$$
E
with data. We also study integrability of derivatives of solutions given in this way. We present conditions, which are sufficient for uniqueness of solutions. Finally, we show the infinite speed of signal propagation.
Assessing the feasibility of deep-seabed mining of polymetallic nodules in the Area of seabed and ocean floor beyond the limits of national jurisdiction, as a method of alleviating supply-side issues for cobalt to US markets
Authors: Cunningham Alexander
Published: October 2022

The growing importance of cobalt to the US economy has led to its categorisation as a critical mineral. Cobalt demand is increasing due to its requirement in lithium-ion batteries, which will significantly contribute to the energy transition. Supply is threatened for various reasons, primarily regarding supply chain concentrations, with the majority of the world’s cobalt originating in terrestrial deposits in the Democratic Republic of the Congo, and being refined in China. There remain environmental and ethical concerns over the present supply chain. Previous discussions around reducing cobalt’s criticality have suggested diversifying processing locations to reduce geographical and jurisdictional reliance where possible. This study assesses the viability of extracting cobalt from polymetallic nodules (PMNs) located on the deep-seabed in the Area, as an alternative strategy to reduce cobalt’s criticality. Assessments are made of the viability of PMN extraction considering ongoing barriers to introduction, contrasted with current arguments supporting PMN extraction. PMN mining offers a more stable and decentralised alternative to current cobalt supply. There exist impediments to its introduction, notably potential environmental impacts, which remain poorly understood. Technical and political restrictions must also be overcome. It is argued that the wider environmental benefits of increased cobalt supply from PMN mining may offset its detrimental environmental impacts. It is suggested that PMN mining be used in a wider strategy to improve supply security of cobalt to US markets.
Numerical Simulations of Fuel Shape Change and Swirling Flows in Paraffin/Oxygen Hybrid Rocket Engines
Authors: Fabiani Marco , Gubernari Giorgio , Migliorino Mario Tindaro , Bianchi Daniele , Nasuti Francesco
Published: October 2022

The objective of this work is to describe and validate a numerical axisymmetric approach for the simulation of hybrid rocket engines (HREs), based on Reynolds-averaged Navier–Stokes simulations, with sub-models for fluid–surface interaction, radiation, chemistry, and turbulence. Fuel grain consumption is considered on both radial and axial directions and both axial and swirl injection of the oxidizer are simulated. Firing tests of two different paraffin–oxygen hybrid rockets are considered. First, a numerical rebuilding of fuel grain profile, regression rate and pressure for axial-injected HREs is performed, yielding a reasonable agreement with the available experimental data. Then, the same numerical model is applied to swirl-injected HREs and employed to analyze both the flowfield and the regression rate variation with swirl intensity. A validation of the model through the rebuilding of small-scale firing tests is also performed.
Advancing equity and justice through community science programming in design, construction, and research of a nature-based solution: the Duwamish Floating Wetlands Project
Authors: Andrews Leann , Mocorro Powell Ashley D. , Rottle Nancy , Engelke Jennifer
Published: October 2022

Dxwdəw refers to the Black-Green Rivers confluences that made the Duwamish River in Seattle, Washington, USA, prior to the 1910s. Significant industrial activity and human-made diversions to these rivers caused heavy pollution and eliminated 97% of historic wetlands, forever altering the historic river systems, salmon runs and human and aquatic health. Today the Green-Duwamish River and Duwamish Estuary are an industrial and commercial corridor, albeit also a site of cultural significance and fishing rights for urban Indigenous and Coast Salish tribes, and home and workplace to diverse urban populations of sustenance fishers, immigrants and refugees, communities of color, and low-income neighborhoods. Using a socio-ecological and environmental justice perspective within a nature-based solution, the Duwamish Floating Wetlands Project designed and piloted four constructed floating wetland structures for two years on the Duwamish River and researched their feasibility to provide habitat for out-migrating juvenile salmon. A multi-pronged community team (community leaders, liaisons, stewards and scientists) worked alongside academics and professionals. This paper showcases the formulation and adaptation of a two-year citizen/community science program integrated into the project. We outline the frameworks, approach, outcomes, and lessons-learned of the community science and outreach program, and compiled these in a list of guidelines to provide practitioner, researcher and community insight into the value and necessity of prioritizing environmental justice, racial equity, and ecosystem needs in nature-based solutions.
Communal breeding by women is associated with lower investment from husbands
Authors: He Qiao-Qiao , Rui Jun-Wen , Zhang Li , Tao Yi , Wu Jia-Jia , Mace Ruth , Ji Ting
Published: October 2022

According to Hamilton's rule, matrilineal-biased investment restrains men in matrilineal societies from maximising their inclusive fitness (the ‘matrilineal puzzle'). A recent hypothesis argues that when women breed communally and share household resources, a man should help his sisters' household, rather than his wife's household, as investment to the later but not the former would be diluted by other unrelated members (Wu et al., 2013). According to this hypothesis, a man is less likely to help on his wife's farm when there are more women reproducing in the wife's household, because on average he would be less related to his wife's household. We used a farm-work observational dataset, that we collected in the matrilineal Mosuo in southwest China, to test this hypothesis. As predicted, high levels of communal breeding by women in his wife's households do predict less effort spent by men on their wife's farm, and communal breeding in men's natal households do not affect whether men help on their natal farms. Thus, communal breeding by women dilutes the inclusive fitness benefits men receive from investment to their wife and children, and may drive the evolution of matrilineal-biased investment by men. These results can help solve the ‘matrilineal puzzle'.
Introducing ‘Business Plus Education Ecosystem’ as a Commentary to Fey (2022)
Authors: Wei Jiang , Zhang Zhongyuan
Published: October 2022

In a recent paper, Carl Fey (2022) ponders the future development of Chinese business schools. He observes that the American model of business education – the target of emulation for most Chinese business schools up to this point – shows signs of serious inadequacy. It is high time, Fey argues, that Chinese business schools come up with ‘indigenous’ models of business education that better serve the needs of China's social and economical development. The paper then sketches a framework featuring some fundamental aspects of such indigenous models. We find Fey's central argument and framework both timely and inspiring. In what follows, we draw on what is happening at the School of Management of Zhejiang University (‘the School’) to respond to, and dialogue with, some of Fey's ideas.
Flocking of autonomous unmanned air vehicles
Authors: Crowther B.
Published: October 2022

The use of large numbers of unmanned air vehicles in a given air space presents a challenge for conventional air traffic control methods. Flocking (or schooling, swarming or herding) in nature arises when mobile organisms find benefit in living at high densities. The present paper applies rules of flocking (cohesion, alignment, separation, and migration) to the problem of managing the flight of a number of autonomous unmanned air vehicles. A six-degree of freedom aerodynamic model of an existing UAV is used to simulate the flocking flight vehicles. It is found that application of the cohesion and alignment rules is sufficient to generate true flocking behaviour in that the flight vehicle density is increased and the flock members converge on a common heading. Increasing rule strength reduces the time taken to achieve flocking behaviour. However increasing rule strength too far leads to oscillatory or unstable flight paths. It is found that flock behaviour can be adequately described using the time histories of two statistical parameters: the mean radius between flock members and the standard deviation of the flock members’ heading angles.
Towards meeting VLTA challenges for evacuation slides and slide-rafts
Authors: Gosling P. D. , Riches C. G.
Published: October 2022

The intrinsic dependence on the necessary minimum structural performance of inflatable aircraft evacuation slides and slide-rafts in the event of and emergency or precautionary aircraft evacuation is described in the context of the certification of both new (or modified) aircraft and slide designs. The concepts of the pneumatic structure with analytical and numerical methodologies are briefly reviewed. Fundamental principles of inflatable evacuation slide performance and assessment are presented, while the characteristics of typical structural responses are identified for single deck aircraft. The implications of evacuation from an upper deck of a VLTA are identified in the interpretation of two new commercial inflatable evacuation slide designs. Alternative meso and macro pneumatic structural forms are proposed as evolutions of the conventional inflated tube. Outline details of a simple mixed finite element and vector-based simulation algorithm for the analysis of pneumatic structures precede examples verifying the numerical formulation and demonstrating the potential of multi-cell beam (meso) and “semi-pneumatic shell membrane” (macro) pneumatic concepts. Recommendations for future research conclude the paper.
The role of infinitival clauses in the dialogues of German-speaking children and adults
Authors: SZAGUN Gisela , STUMPER Barbara
Published: October 2022

The present study aims at analysing the role of infinitival clauses (INFCs) in German child-adult dialogue. In German subject-less INFCs are a grammatical sentence pattern. Extensive corpora of spontaneous speech between 6 children aged 1;5 to 2;10 and adults were analysed applying structural and contextual analyses. We extended Freudenthal, Pine and Gobet’s (2010) model of lexically specific learning to include INFCs in adult input. Results show that frequencies of adult INFC and MOD+INF clauses are related to child INFCs. We interpret these results as reflecting shared verb vocabulary and, regarding INFCs, as an adaptation of adult CDS to child grammatical structure. While most child INFCs have modal meaning, some occur in non-modal contexts. The majority of child INFCs are subject-less clauses with final infinitives and therefore grammatical. Results are discussed in terms of the pragmatic function of child and adult INFCs and the role of adult INFCs in German CDS.
Words on Trial: Morality and Legality in Frida Vigdorova's Journalism
Authors: Reich Rebecca
Published: October 2022

During the Khrushchev period, the journalist Frida Vigdorova charged Soviet society with a moral indifference that expressed itself through evasive language. Such language, she argued, claimed to exercise moral judgment, while in fact enabling both individuals and institutions to sidestep their responsibilities. As the state enacted reforms aimed at raising society's moral consciousness, Vigdorova applied this critique of language to the Soviet justice system. This study traces the evolution of that critique across her published and unpublished writings about legal and paralegal rituals of justice from 1955 to 1963. For Vigdorova, these rituals offered object lessons in society's failure to combat indifference: evidence that linguistic evasion plagued those very institutions charged with adjudicating morality. By cultivating a transcriptive style, Vigdorova situated herself and her readers as witnesses to that language: a community of listeners gathered in space and time. In doing so, she presented journalism as a higher court that could call society to account.
The Islamic Framing of the Economic Activities of Salafi-oriented Muslims in Dagestan, North Caucasus: An Anthropological Approach
Authors: Kaliszewska Iwona , Schmidt Jagoda , Kaleta Marek
Published: October 2022

In this paper, we explore the entanglement of spiritual and economic life through the example of Dagestani, Salafi-oriented entrepreneurs who try to live out their religious ideals in moral economic practices. We ask how living a religious life shapes economic behavior and its moral dimensions, and how the gradual acquisition of the norms of an Islamic economy influences the everyday economic practices of Salafi-oriented Muslims in Dagestan. Drawing on Stephen Gudeman's market-community framework, and offering our research as a corrective, we show how an Islamic framing of everyday economic activities and the gradual acquisition of the norms of the Islamic economy allows Salafi-oriented Muslims to escape traditional obligations, and to some extent, “the state,” while at the same time bestowing meaning on “cold” market relations. As a result, instead of escaping the market-society script (that they criticize), they reinforce it. Our analysis is based on the results of ethnographic fieldwork conducted in Dagestan between 2014 and 2018.
Following the Path of Least Resistance
Authors: Mitchell Donald G.
Published: October 2022

The reason a path may be the path of least resistance is because it may be the path for which you are most suited. For you it may look like a stroll in the park; for someone else, it may look like climbing Everest. Or vice versa. Taking the “easy” route is not copping out; it is a form of playing to your strength. Here I detail my professional path from digging holes for antennas in graduate school to designer and builder of energetic neutral atom imagers that have flown and continue to fly throughout the heliosphere.
Professional Development, Mentoring, and Outreach in Scientific Research
Authors: Smith Charles W.
Published: October 2022

The following contains opinions drawn from four decades of employment in scientific research in the field of space plasma physics that followed the customary two decades of formal education. For the most part, the opinions that follow address the role of mentors in scientific education and professional development with a few words of candid advice for the young professional. They are only my opinions.
Observations of Night‐Time Equatorial Ionosphere Structure With the FPMU on Board the International Space Station
Authors: Newheart Anastasia M. , Sazykin Stanislav , Coffey Victoria N. , Chandler Michael O. , Coster Anthea J. , Fejer Bela G. , Minow Joseph I. , Swenson Charles M.
Published: October 2022

Electron density measurements from the Floating Potential Measurement Unit (FPMU) onboard the International Space Station allow us to observe the structure of the equatorial ionosphere. During two geomagnetically quiet time periods, we examined the equatorial F‐region structure at night using FPMU electron density measurements along with Swarm spacecraft electron density measurements and Total Electron Content from ground‐based Global Navigation Satellite System receivers for comparison. During these time periods, the equatorial ionization anomaly (EIA) extended to local times late as post‐midnight in some cases. The EIA occurrences at night showed a longitudinal dependence. The mean density of the EIA peaks exhibited a 3‐wave pattern in longitude likely due to lower atmospheric planetary wave activity, similar to the longitudinal dependence previously observed in the EIA.
Strengthened Impacts of Indian Ocean Dipole on the Yangtze Precipitation Contribute to the Extreme Rainfall of 2020 Meiyu Season
Authors: Wang YanXin , Wang Shanshan , Luo Fu , Wang Hao
Published: October 2022

In June‐July 2020, the Middle and Lower Yangtze River Region (MLYR) encountered the most severe precipitation event over the past 60 years. The Indian Ocean Dipole (IOD) in the previous autumn of the unusual precipitation event was the main contributing factor. Nonetheless, not every strong IOD event could bring anomalously high precipitation in the MLYR. This study showed significantly enhanced influence of IOD on East Asia climate since 2000. The IOD's effect on MLYR summer precipitation has strengthened significantly with the correlation coefficient up to 0.55 during 2000–2020. The northward movement of East Asia–Pacific pattern associated with IOD since 2000 (as compared with before) was primarily responsible for the enhanced effect. Since 2000, the MLYR has been controlled by a deep baroclinic instability system with anomalous low pressure in the lower troposphere and anomalous high pressure (completely different from before). Furthermore, the western Pacific subtropical high shifted northward and westerly jets were significantly enhanced with eastward expansion. All of these patterns contributed to the water vapor convergence and precipitation generation in the MLYR, which was not the case in the past. The record‐breaking IOD in 2019 autumn and the enhanced IOD's climatic effect in 2000–2020 contribute to the extreme Meiyu in 2020 jointly. The significant change in the influence of IOD and the enhanced climate effect of IOD highlight exciting new avenues for improving climate predictions in the MLYR.
Analysis of Gravity‐Driven Infiltration With the Development of a Saturated Region
Authors: Shadab Mohammad Afzal , Hesse Marc Andre
Published: October 2022

Understanding the controls on the infiltration of precipitation into soil is an important problem in hydrology and its representation in heterogeneous media is still challenging. Here we investigate the reduction of gravity‐driven infiltration by the development of a saturated region due to the downward decrease in porosity and/or hydraulic conductivity. The formation of a saturated region chokes the flow and leads to a rising perched water table that causes ponding even when rainfall intensity is lower than the surface infiltration capacity. Mathematically this problem is interesting, because its governing partial differential equation switches from hyperbolic in the unsaturated region to elliptic in the saturated region. To analyze this coupled unsaturated‐saturated flow we develop an extended kinematic wave analysis in the limit of no capillary forces. This theory provides a general framework to solve gravity‐dominated infiltration problems for arbitrary downward decrease in porosity and/or conductivity. We apply the framework to three soil profiles (two‐layer, exponential and power‐law decay with depth) and develop (semi‐) analytic solutions for evolution of the water saturation. For the case of a two‐layer soil the saturated flux, and therefore the front speeds, are constant which allows explicit analytic solutions that agree well with Hydrus‐1D. All solutions show excellent agreement with our numerical solutions of the governing equations in the limit of no capillary forces. Similarly, our solutions compare well with experimental data for infiltration into a multi‐layer soil with declining hydraulic conductivity.
Hyperdiploidy: the longest known, most prevalent, and most enigmatic form of acute lymphoblastic leukemia in children
Authors: Haas Oskar A. , Borkhardt Arndt
Published: October 2022

Hyperdiploidy is the largest genetic entity B-cell precursor acute lymphoblastic leukemia in children. The diagnostic hallmark of its two variants that will be discussed in detail herein is a chromosome count between 52 and 67, respectively. The classical HD form consists of heterozygous di-, tri-, and tetrasomies, whereas the nonclassical one (usually viewed as “duplicated hyperhaploid”) contains only disomies and tetrasomies. Despite their apparently different clinical behavior, we show that these two sub-forms can in principle be produced by the same chromosomal maldistribution mechanism. Moreover, their respective array, gene expression, and mutation patterns also indicate that they are biologically more similar than hitherto appreciated. Even though in-depth analyses of the genomic intricacies of classical HD leukemias are indispensable for the elucidation of the disease process, the ensuing results play at present surprisingly little role in treatment stratification, a fact that can be attributed to the overall good prognoses and low relapse rates of the concerned patients and, consequently, their excellent treatment outcome. Irrespective of this underutilization, however, the detailed genetic characterization of HD leukemias may, especially in planned treatment reduction trials, eventually become important for further treatment stratification, patient management, and the clinical elucidation of outcome data. It should therefore become an integral part of all upcoming treatment studies.
OTUB1 suppresses Hippo signaling via modulating YAP protein in gastric cancer
Authors: Yan Cheng , Yang Huijie , Su Peng , Li Xin , Li Zhongbo , Wang Dehai , Zang Yifeng , Wang Tianshi , Liu Ziping , Bao Zhuocong , Dong Shuxiao , Zhuang Ting , Zhu Jian , Ding Yinlu
Published: October 2022

Gastric cancer is one of the most lethal human malignancies in the world. Although great efforts are put in developing novel therapeutic targets, the effective targeting drugs are still limited. Recent studies reveal the abnormality of Hippo/YAP axis play critical role in the oncogenic process of gastric cancer. It is of great importance to demonstrate the regulation of Hippo signaling activity and YAP protein turnover in gastric cancer. Besides, the phosphorylation cascade on YAP function, which has been thoroughly investigated, the ubiquitination of YAP is also important in Hippo signaling status. Here, We utilized the DUB (Deubiquitinase) siRNA library to identify critical DUB for Hippo signaling. We discovered OTUB1 as a critical factor to facilitate gastric cancer cell stemness and progression, which deubiquitinated and stabilized YAP protein. The clinical data analysis implicated OTUB1 was higher expressed in gastric cancer, which correlated with YAP activity and poor survival. OUTB1 interacted with YAP protein via its OTU domain (Ovarian tumor domain) and deubiquitinated YAP at several lysine sites (K90, K280, K343, K494 and K497), which subsequently inhibited YAP degradation. Our study revealed a novel deubiquitinase of Hippo/YAP axis and one possible therapeutic target for YAP-driven gastric cancer.
Non-enzymatic role of SOD1 in intestinal stem cell growth
Authors: Wang Ying-Chao , Leng Xiao-Xu , Zhou Cheng-Bei , Lu Shi-Yuan , Tsang Chi Kwan , Xu Jie , Zhang Ming-Ming , Chen Hui-Min , Fang Jing-Yuan
Published: October 2022

Superoxide dismutase 1 (SOD1) modulates intestinal barrier integrity and intestinal homeostasis as an antioxidant enzyme. Intestinal homeostasis is maintained by the intestinal stem cells (ISCs). However, whether and how SOD1 regulates ISCs is unknown. In this study, we established intestinal organoids from tamoxifen–inducible intestinal epithelial cell–specific Sod1 knockout (Sod1f/f; Vil-creERT2) mice. We found that loss of Sod1 in organoids suppressed the proliferation and survival of cells and Lgr5 gene expression. SOD1 is known for nearly half a century for its canonical role as an antioxidant enzyme. We identified its enzyme-independent function in ISC: inhibition of SOD1 enzymatic activity had no impact on organoid growth, and enzymatically inactive Sod1 mutants could completely rescue the growth defects of Sod1 deficient organoids, suggesting that SOD1-mediated ISC growth is independent of its enzymatic activity. Moreover, Sod1 deficiency did not affect the ROS levels of the organoid, but induced the elevated WNT signaling and excessive Paneth cell differentiation, which mediates the occurrence of growth defects in Sod1 deficient organoids. In vivo, epithelial Sod1 loss induced a higher incidence of apoptosis in the stem cell regions and increased Paneth cell numbers, accompanied by enhanced expression of EGFR ligand Epiregulin (EREG) in the stromal tissue, which may compensate for Sod1 loss and maintain intestinal structure in vivo. Totally, our results show a novel enzyme-independent function of SOD1 in ISC growth under homeostasis.
An unconstrained approach to systematic structural and energetic screening of materials interfaces
Authors: Di Liberto Giovanni , Morales-García Ángel , Bromley Stefan T.
Published: October 2022

From grain boundaries and heterojunctions to manipulating 2D materials, solid-solid interfaces play a key role in many technological applications. Understanding and predicting properties of these complex systems present an ongoing and increasingly important challenge. Over the last few decades computer simulation of interfaces has become vastly more powerful and sophisticated. However, theoretical interface screening remains based on largely heuristic methods and is strongly biased to systems that are amenable to modelling within constrained periodic cell approaches. Here we present an unconstrained and generally applicable non-periodic screening approach for systematic exploration of material’s interfaces based on extracting and aligning disks from periodic reference slabs. Our disk interface method directly and accurately describes how interface structure and energetic stability depends on arbitrary relative displacements and twist angles of two interacting surfaces. The resultant detailed and comprehensive energetic stability maps provide a global perspective for understanding and designing interfaces. We confirm the power and utility of our method with respect to the catalytically important TiO2 anatase (101)/(001) and TiO2 anatase (101)/rutile (110) interfaces.
NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart
Authors: Müller Marion , Eghbalian Rose , Boeckel Jes-Niels , Frese Karen S. , Haas Jan , Kayvanpour Elham , Sedaghat-Hamedani Farbod , Lackner Maximilian K. , Tugrul Oguz F. , Ruppert Thomas , Tappu Rewati , Martins Bordalo Diana , Kneuer Jasmin M. , Piekarek Annika , Herch Sabine , Schudy Sarah , Keller Andreas , Grammes Nadja , Bischof Cornelius , Klinke Anna , Cardoso-Moreira Margarida , Kaessmann Henrik , Katus Hugo A. , Frey Norbert , Steinmetz Lars M. , Meder Benjamin
Published: October 2022

To adapt to changing hemodynamic demands, regulatory mechanisms modulate actin-myosin-kinetics by calcium-dependent and -independent mechanisms. We investigate the posttranslational modification of human essential myosin light chain (ELC) and identify NIMA-related kinase 9 (NEK9) to interact with ELC. NEK9 is highly expressed in the heart and the interaction with ELC is calcium-dependent. Silencing of NEK9 results in blunting of calcium-dependent ELC-phosphorylation. CRISPR/Cas9-mediated disruption of NEK9 leads to cardiomyopathy in zebrafish. Binding to ELC is mediated via the protein kinase domain of NEK9. A causal relationship between NEK9 activity and ELC-phosphorylation is demonstrated by genetic sensitizing in-vivo. Finally, we observe significantly upregulated ELC-phosphorylation in dilated cardiomyopathy patients and provide a unique map of human ELC-phosphorylation-sites. In summary, NEK9-mediated ELC-phosphorylation is a calcium-dependent regulatory system mediating cardiac contraction and inotropy.
Tuning the many-body interactions in a helical Luttinger liquid
Authors: Jia Junxiang , Marcellina Elizabeth , Das Anirban , Lodge Michael S. , Wang BaoKai , Ho Duc-Quan , Biswas Riddhi , Pham Tuan Anh , Tao Wei , Huang Cheng-Yi , Lin Hsin , Bansil Arun , Mukherjee Shantanu , Weber Bent
Published: October 2022

In one-dimensional (1D) systems, electronic interactions lead to a breakdown of Fermi liquid theory and the formation of a Tomonaga-Luttinger Liquid (TLL). The strength of its many-body correlations can be quantified by a single dimensionless parameter, the Luttinger parameter K, characterising the competition between the electrons’ kinetic and electrostatic energies. Recently, signatures of a TLL have been reported for the topological edge states of quantum spin Hall (QSH) insulators, strictly 1D electronic structures with linear (Dirac) dispersion and spin-momentum locking. Here we show that the many-body interactions in such helical Luttinger Liquid can be effectively controlled by the edge state’s dielectric environment. This is reflected in a tunability of the Luttinger parameter K, distinct on different edges of the crystal, and extracted to high accuracy from the statistics of tunnelling spectra at tens of tunnelling points. The interplay of topology and many-body correlations in 1D helical systems has been suggested as a potential avenue towards realising non-Abelian parafermions.
A BDNF-TrkB autocrine loop enhances senescent cell viability
Authors: Anerillas Carlos , Herman Allison B. , Munk Rachel , Garrido Amanda , Lam Kwan-Wood Gabriel , Payea Matthew J. , Rossi Martina , Tsitsipatis Dimitrios , Martindale Jennifer L. , Piao Yulan , Mazan-Mamczarz Krystyna , Fan Jinshui , Cui Chang-Yi , De Supriyo , Abdelmohsen Kotb , de Cabo Rafael , Gorospe Myriam
Published: October 2022

Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP) whereby cells secrete pro-inflammatory and tissue-remodeling factors. Given that the SASP exacerbates age-associated pathologies, some aging interventions aim at selectively eliminating senescent cells. In this study, a drug library screen uncovered TrkB (NTRK2) inhibitors capable of triggering apoptosis of several senescent, but not proliferating, human cells. Senescent cells expressed high levels of TrkB, which supported senescent cell viability, and secreted the TrkB ligand BDNF. The reduced viability of senescent cells after ablating BDNF signaling suggested an autocrine function for TrkB and BDNF, which activated ERK5 and elevated BCL2L2 levels, favoring senescent cell survival. Treatment with TrkB inhibitors reduced the accumulation of senescent cells in aged mouse organs. We propose that the activation of TrkB by SASP factor BDNF promotes cell survival and could be exploited therapeutically to reduce the senescent-cell burden.
Direct observation of photoinduced carrier blocking in mixed-dimensional 2D/3D perovskites and the origin
Authors: Yu Dejian , Cao Fei , Liao Jinfeng , Wang Bingzhe , Su Chenliang , Xing Guichuan
Published: October 2022

Mixed-dimensional 2D/3D halide perovskite solar cells promise high stability but practically deliver poor power conversion efficiency, and the 2D HP component has been held as the culprit because its intrinsic downsides (ill charge conductivity, wider bandgap, and strong exciton binding) were intuitively deemed to hinder carrier transport. Herein, we show that the 2D HP fragments, in fact, allow free migration of carriers in darkness but only block the carrier transport under illumination. While surely limiting the photovoltaic performance, such photoinduced carrier blocking effect is unexplainable by the traditional understanding above but is found to stem from the trap-filling-enhanced built-in potential of the 2D/3D HP interface. By parsing the depth-profile nanoscopic phase arrangement of the mixed-dimensional 2D/3D HP film for solar cells and revealing a photoinduced potential barrier up to several hundred meV, we further elucidate how the photoinduced carrier blocking mechanism jeopardizes the short-circuit current and fill factor.
Exhumation and tectonic history of inaccessible subglacial interior East Antarctica from thermochronology on glacial erratics
Authors: Fitzgerald Paul G. , Goodge John W.
Published: October 2022

The geology, tectonic history and landscape evolution of ice-covered East Antarctica are the least known of any continent. Lithic boulders eroded from the continental interior and deposited in glacial moraines flanking the Transantarctic Mountains provide rare constraints on the geological history of central interior East Antarctica. Crystallization ages and ice velocities indicate these glacial erratics are not sourced locally from the Transantarctic Mountains but rather originate from the continental interior, possibly as far inland as the enigmatic Gamburtsev Subglacial Mountains. We apply low-temperature thermochronology to these boulders, including multi-kinetic inverse thermal modeling, to constrain a multi-stage episodic exhumation history. Cambro-Ordovician and Jurassic rapid-cooling episodes correlate with significant exhumation events accompanying Pan-African convergence and Gondwanan supercontinent rifting, respectively. Here we show that while Cretaceous rapid cooling overlaps temporally with Transantarctic Mountains formation, a lack of discrete younger rapid-cooling pulses precludes significant Cenozoic tectonic or glacial exhumation of central interior East Antarctica.
Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy
Authors: He Gang , Li Yashi , Younis Muhammad Rizwan , Fu Lian-Hua , He Ting , Lei Shan , Lin Jing , Huang Peng
Published: October 2022

5-Aminolevulinic acid-based photodynamic therapy heavily depends on the biological transformation efficiency of 5-aminolevulinic acid to protoporphyrin IX, while the lack of an effective delivery system and imaging navigation are major hurdles in improving the accumulation of protoporphyrin IX and optimizing therapeutic parameters. Herein, we leverage a synthetic biology approach to construct a transdermal theranostic microneedle patch integrated with 5-aminolevulinic acid and catalase co-loaded tumor acidity-responsive copper-doped calcium phosphate nanoparticles for efficient 5-aminolevulinic acid-based photodynamic therapy by maximizing the enrichment of intratumoral protoporphyrin IX. We show that continuous oxygen generation by catalase in vivo reverses tumor hypoxia, enhances protoporphyrin IX accumulation by blocking protoporphyrin IX efflux (downregulating hypoxia-inducible factor-1α and ferrochelatase) and upregulates protoporphyrin IX biosynthesis (providing exogenous 5-aminolevulinic acid and upregulating ALA-synthetase). In vivo fluorescence/photoacoustic duplex imaging can monitor intratumoral oxygen saturation and protoporphyrin IX metabolic kinetics simultaneously. This approach thus facilitates the optimization of therapeutic parameters for different cancers to realize Ca2+/Cu2+-interferences-enhanced repeatable photodynamic therapy, making this theranostic patch promising for clinical practice.
Structural insight into the ligand binding mechanism of aryl hydrocarbon receptor
Authors: Dai Shuyan , Qu Lingzhi , Li Jun , Zhang Ye , Jiang Longying , Wei Hudie , Guo Ming , Chen Xiaojuan , Chen Yongheng
Published: October 2022

The aryl hydrocarbon receptor (AHR), a member of the basic helix–loop–helix (bHLH) Per–Arnt–Sim (PAS) family of transcription factors, plays important roles in regulating xenobiotic metabolism, cellular differentiation, stem cell maintenance, as well as immunity. More recently, AHR has gained significant interest as a drug target for the development of novel cancer immunotherapy drugs. Detailed understanding of AHR-ligand binding has been hampered for decades by the lack of a three-dimensional structure of the AHR PAS-B domain. Here, we present multiple crystal structures of the Drosophila AHR PAS-B domain, including its apo, ligand-bound, and AHR nuclear translocator (ARNT) PAS-B-bound forms. Together with biochemical and cellular assays, our data reveal structural features of the AHR PAS-B domain, provide insights into the mechanism of AHR ligand binding, and provide the structural basis for the future development of AHR-targeted therapeutics.
Flexible learning of quantum states with generative query neural networks
Authors: Zhu Yan , Wu Ya-Dong , Bai Ge , Wang Dong-Sheng , Wang Yuexuan , Chiribella Giulio
Published: October 2022

Deep neural networks are a powerful tool for characterizing quantum states. Existing networks are typically trained with experimental data gathered from the quantum state that needs to be characterized. But is it possible to train a neural network offline, on a different set of states? Here we introduce a network that can be trained with classically simulated data from a fiducial set of states and measurements, and can later be used to characterize quantum states that share structural similarities with the fiducial states. With little guidance of quantum physics, the network builds its own data-driven representation of a quantum state, and then uses it to predict the outcome statistics of quantum measurements that have not been performed yet. The state representations produced by the network can also be used for tasks beyond the prediction of outcome statistics, including clustering of quantum states and identification of different phases of matter.
Central role of Prominin-1 in lipid rafts during liver regeneration
Authors: Bahn Myeong-Suk , Yu Dong-Min , Lee Myoungwoo , Jo Sung-Je , Lee Ji-Won , Kim Ho-Chul , Lee Hyun , Kim Hong Lim , Kim Arum , Hong Jeong-Ho , Kim Jun Seok , Koo Seung-Hoi , Lee Jae-Seon , Ko Young-Gyu
Published: October 2022

Prominin-1, a lipid raft protein, is required for maintaining cancer stem cell properties in hepatocarcinoma cell lines, but its physiological roles in the liver have not been well studied. Here, we investigate the role of Prominin-1 in lipid rafts during liver regeneration and show that expression of Prominin-1 increases after 2/3 partial hepatectomy or CCl4 injection. Hepatocyte proliferation and liver regeneration are attenuated in liver-specific Prominin-1 knockout mice compared to wild-type mice. Detailed mechanistic studies reveal that Prominin-1 interacts with the interleukin-6 signal transducer glycoprotein 130, confining it to lipid rafts so that STAT3 signaling by IL-6 is effectively activated. The overexpression of the glycosylphosphatidylinsositol-anchored first extracellular domain of Prominin-1, which is the domain that binds to GP130, rescued the proliferation of hepatocytes and liver regeneration in liver-specific Prominin-1 knockout mice. In summary, Prominin-1 is upregulated in hepatocytes during liver regeneration where it recruits GP130 into lipid rafts and activates the IL6-GP130-STAT3 axis, suggesting that Prominin-1 might be a promising target for therapeutic applications in liver transplantation.
Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility
Authors: Futamata Haon , Fukuda Masahiro , Umeda Rie , Yamashita Keitaro , Tomita Atsuhiro , Takahashi Satoe , Shikakura Takafumi , Hayashi Shigehiko , Kusakizako Tsukasa , Nishizawa Tomohiro , Homma Kazuaki , Nureki Osamu
Published: October 2022

Outer hair cell elecromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, we report the cryo-EM structures of thermostabilized prestin (PresTS), complexed with chloride, sulfate, or salicylate at 3.52-3.63 Å resolutions. The central positively-charged cavity allows flexible binding of various anion species, which likely accounts for the known distinct modulations of nonlinear capacitance (NLC) by different anions. Comparisons of these PresTS structures with recent prestin structures suggest rigid-body movement between the core and gate domains, and provide mechanistic insights into prestin inhibition by salicylate. Mutations at the dimeric interface severely diminished NLC, suggesting that stabilization of the gate domain facilitates core domain movement, thereby contributing to the expression of NLC. These findings advance our understanding of the molecular mechanism underlying mammalian cochlear amplification.
Force-triggered rapid microstructure growth on hydrogel surface for on-demand functions
Authors: Mu Qifeng , Cui Kunpeng , Wang Zhi Jian , Matsuda Takahiro , Cui Wei , Kato Hinako , Namiki Shotaro , Yamazaki Tomoko , Frauenlob Martin , Nonoyama Takayuki , Tsuda Masumi , Tanaka Shinya , Nakajima Tasuku , Gong Jian Ping
Published: October 2022

Living organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions. We demonstrate the oriented growth of cells and directional transportation of water droplets on the engineered hydrogel surfaces. This force-triggered method to chemically engineer the hydrogel surfaces provides a new tool in addition to the conventional methods using light or heat, and will promote the wide application of hydrogels in various fields.
Myogenic tissue nanotransfection improves muscle torque recovery following volumetric muscle loss
Authors: Clark Andrew , Ghatak Subhadip , Guda Poornachander Reddy , El Masry Mohamed S. , Xuan Yi , Sato Amy Y. , Bellido Teresita , Sen Chandan K.
Published: October 2022

This work rests on our non-viral tissue nanotransfection (TNT) platform to deliver MyoD (TNTMyoD) to injured tissue in vivo. TNTMyoD was performed on skin and successfully induced expression of myogenic factors. TNTMyoD was then used as a therapy 7 days following volumetric muscle loss (VML) of rat tibialis anterior and rescued muscle function. TNTMyoD is promising as VML intervention.
CCRT and aerobic exercise: a randomised controlled study of processing speed, cognitive flexibility, and serum BDNF expression in schizophrenia
Authors: Dai Yuanyuan , Ding Hongyan , Lu Xiaozi , Wu Xiumei , Xu Chunhua , Jiang Tingting , Ming Liang , Xia Zhong , Song Chuanfu , Shen Hongxian , Hao Wei , Huang Shucai
Published: October 2022

Computerised cognitive remediation therapy (CCRT) and aerobic exercise are often used to rehabilitate social functioning in patients with schizophrenia. However, there is limited knowledge regarding the effects of CCRT combined with aerobic exercise on cognitive function and brain-derived neurotrophic factor (BDNF) levels in patients with schizophrenia and cognitive impairment. Ninety-six patients with schizophrenia and cognitive impairment were included in this study and randomly divided into control, aerobic exercise (AE), and CCRT combined with aerobic exercise (CAE) groups. Changes in processing speed and cognitive flexibility at week 8 were evaluated as primary and secondary cognitive outcomes using the Trail Making Test: Part A, the Brief Assessment of Cognition in Schizophrenia: Symbol Coding Test, and the Stroop Colour-Word Test. Positive and Negative Syndrome Scale (PANSS) scores and serum BDNF expression were determined as other secondary outcomes. The CAE group showed significantly better performance in terms of changes in processing speed and cognitive flexibility than the control and AE groups at week 8 (p < 0.05); however, no significant improvements in processing speed and cognitive flexibility were found between the control and AE groups. The CAE group showed significant improvements in the PANSS negative symptoms than the control group at week 8 (p < 0.05), but the AE group showed no significant difference in the changes of PANSS negative symptoms when compared with the other two groups. The CAE group and AE group showed a greater increase in serum BDNF levels than the control group (p < 0.01), but there was no significant difference in serum BDNF expression between the CAE group and AE group. In conclusion, 8-week CCRT combined with aerobic exercise may improve some cognitive performance and negative symptoms in patients with schizophrenia. Aerobic exercise may have an immediate effect on serum BDNF levels rather than cognitive function.
IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation
Authors: Ni Xinhui , Xu Yi , Wang Wang , Kong Baida , Ouyang Jian , Chen Jiwei , Yan Man , Wu Yawei , Chen Qi , Wang Xinxin , Li Hongquan , Gao Xiaoguang , Guo Hongquan , Cui Lian , Chen Zeyu , Shi Yuling , Zhu Ronghui , Li Wei , Shi Tieliu , Wang Lin-Fa , Huang Jinling , Dong Chen , Lai Yuping
Published: October 2022

Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesions in patients with atopic dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of Ddx5 (Ddx5∆KC) were more susceptible to cutaneous inflammation. Inhibition of DDX5 expression in keratinocytes was induced by the cytokine interleukin (IL)-17D through activation of the CD93–p38 MAPK–AKT–SMAD2/3 signaling pathway and led to pre-messenger RNA splicing events that favored the production of membrane-bound, intact IL-36 receptor (IL-36R) at the expense of soluble IL-36R (sIL-36R) and to the selective amplification of IL-36R-mediated inflammatory responses and cutaneous inflammation. Restoration of sIL-36R in Ddx5∆KC mice with experimental atopic dermatitis or psoriasis suppressed skin inflammation and alleviated the disease phenotypes. These findings indicate that IL-17D modulation of DDX5 expression controls inflammation in keratinocytes during inflammatory skin diseases.