bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding Chinese Bilateral Investment Treaties
Authors: Wei Shen
Published: August 2021

This is a major work investigating China's bilateral investment treaties (BITs) regime through various approaches including textual analysis, case study, comparative study and empirical study. This book tries to unveil some of the puzzles in Chinese BITs. The general consensus is that the evolution of China's BIT regime has its underlying logic, which follows an investment liberalization trend and fits China's changing role from a key capital-importing state to a major capital-exporting state. A similar trend is evident in Chinese BIT-making and BIT policy. This book investigates these theoretical assumptions and looks into some of the loopholes in Chinese BITs.
Americium Inhalational Exposure with Successful Chelation Therapy
Authors: Keenan Michael , Behrens Torsten , Bravenec Stan , Davis Jason , Bowen Angie , Goans Ronald , Iddins Carol
Published: August 2021

Americium is a man-made metal produced in very small quantities in nuclear reactors. Americium-241 is one of the radioactive isotopes of americium and has commercial applications, including use in smoke detectors. This is a case report of an occupational inhalation of americium-241, treated with both effective external decontamination and the use of diethylenetriamine pentaacetate to promote decorporation. This experience is significant because of the potential for americium or similar radionuclides to be used in “dirty” bombs or other radiological dispersion devices to cause large-scale radioactive contamination.
Scholarship, trade and politics: Andalusian contribution to the Mediterranean standing of Tripoli (3rd/9th–5th/11th centuries)
Authors: Montel Aurélien
Published: August 2021

Given the lack of local sources, the history of Tripoli as a global Mediterranean city remains unclear until the Ottoman conquest of the 16th century. Given that documentary record, the exploration of the rich Arabic tradition written in al-Andalus provides a fresh insight into how Tripoli constructed its Mediterranean stature prior to the 11th century. First, the systematic analysis of Islamic biographical literature (ṭabaqāt) shows Tripoli was one of the most visited cities by the Andalusian scholars across the Islamic world. It also reveals they were in close contact with the Tripolitanian Mālikī networks. Eventually, The Tripolitanian elites took advantage, of that specific Andalusian connection, and using the rivalry between the caliphal powers at the dawn of the 11th century they assured the independence of the city for the first time while rejecting the Fatimid-Zirid power and recognizing the sovereignty of the Spanish Umayyads.
Adaptive celestial positioning for the stationary Mars rover based on a self-calibration model for the star sensor
Authors: Zhan Yinhu , Chen Shaojie , Zhang Xu
Published: August 2021

This paper proposes a method for self-calibrating the star sensor on the Mars rover considering several years of exploration on the surface of Mars. The natural stars in the night sky are considered the control points, and a self-calibration model is deduced in detail according to an imaging model. An adaptive celestial positioning (ACP) algorithm is then introduced, and the calculation procedure is presented in detail to realise self-adjustment based on the self-calibration of the star sensor. Three field tests were conducted on Earth, the results of which show good self-calibration and celestial positioning performances. The positioning results indicate an obvious accuracy improvement using the ACP algorithm compared with that without calibration. Multiple positionings in one night can improve the celestial positioning accuracy to approximately 15 m. For future studies, this self-calibration model will be useful not only for star sensors but also for other optical sensors, such as sun sensors and binocular or stereo-vision cameras.
Medical Coordination Rescue Members’ and Ambulance Nurses’ Perspectives on a New Model for Mass Casualty and Disaster Management and a Novel Terror Attack Mitigation Approach in the Netherlands: A Qualitative Study
Authors: Berben Sivera A.A. , Vloet Lilian C.M. , Lischer Frans , Pieters Moniek , de Cock Johan
Published: August 2021

Introduction:

Mass-casualty incidents (MCIs), specifically incidents with chemical, biological, radiological, and nuclear agents (CBRN) or terrorist attacks, challenge medical coordination, rescue, availability, and adequate provision of prehospital and hospital-based emergency care. In the Netherlands, a new model for Mass Casualty and Disaster Management (MCDM) along with a Terror Attack Mitigation Approach (TAMA) was introduced in 2016.

Study Objective:

The objective of this study was to provide insight in the first experiences of health policy advisors and managers with a medical rescue coordinator and ambulance nursing background regarding the new MCDM and TAMA in order to identify strengths and pitfalls in emergency preparedness and to provide recommendations for improvement.

Methods:

The study had a qualitative design and was performed from January 2017 through June 2018. Purposeful sampling was used and the inclusion comprehended health policy advisors and managers with a medical rescue coordinator and ambulance nursing background involved in emergency preparedness. The respondents were interviewed semi-structured and the researchers used a topic list that was based on the literature and content of the newly introduced model and approach. All interviews were typed out verbatim and qualitative content analyzing was used in order to identify relevant themes.

Results:

Respondents based their perceptions on large-scale training exercises, as MCDM and TAMA were not yet used during MCIs. Perceived issues of MCDM were the two-tiered triage system, the change in focus from “stay and play” towards “scoop and run,” difficulties with new tasks and roles of professionals, and improvement in material provision. Regarding TAMA, all respondents supported the principles (do the most for the most; scoop and run; acceptable personal risk; never walk alone; and standard operational procedure); however, the definitions were lacking clarity while the awareness of optimal personal safety of professionals was absent.

As there are currently regional differences in the level of implementation of MCDM and TAMA, this may pose a risk for an optimal inter-regional collaboration.

Conclusion:

The conclusions refer to experiences of professionals in the Netherlands. Elements of the MCDM and TAMA were highly appreciated and seemed to improve emergency preparedness, while other aspects needed further attention, training, and integration in daily routine. The Netherlands’ MCDM model and TAMA will need continuous systematic evaluation based on (inter)national performance criteria in order to underpin the useful and effective elements and to improve the observed pitfalls in emergency preparedness.
Exploring the food–energy–water nexus approach to enhance coastal community resilience research and planning
Authors: Raub Kristin B. , Stepenuck Kristine F. , Panikkar Bindu
Published: August 2021

Non-technical summary

Coastal communities face environmental challenges that put food, energy, and water systems at risk. Although highly interdependent, it is unknown the extent to which coastal resilience research has considered interactions among food–energy–water systems. Twenty peer-reviewed articles were identified that focused on these systems and coastal resilience. Although a nexus approach was not employed universally, these studies most commonly addressed interactions among these systems related to acute hazards. They consistently acknowledged the influence of energy and transportation systems upon the others. As such, planners should incorporate linkages across all three systems during coastal resilience planning especially in relation to acute hazards.

Technical summary

Coastal communities strive for resilience in the face of an ever-growing suite of threats by planning and preparing for numerous uncertain futures. Food, energy, and water systems are highly interconnected and essential to the well-being of coastal communities. However, it is unknown the extent to which coastal resilience research has included food–energy–water nexus considerations. This study used a systematic literature review of peer-reviewed research articles and identified 20 studies that focused on food, energy, and water systems as related to coastal resilience. Results revealed four main findings: (1) the food–energy–water nexus approach was most commonly applied to coastal resilience in the study of US locations and in the context of acute hazards, (2) a direct food–energy–water or other nexus approach was directly employed by only half of the studies, however, all highlighted the relevance of systems interconnections in the context of coastal resilience, (3) the energy system was shown to impact every system to which it was connected, and (4) the transportation system was also shown to impact every system to which it was connected, which suggests that the food–energy–water nexus should be expanded to include transportation systems.

Social media summary

Coastal resilience and food–energy–water nexus literature synthesis finds interconnected systems considerations relevant to resilience.
Experimental Constraints on Solid Nitride Phases in Rocky Mantles of Reduced Planets and Implications for Observable Atmosphere Compositions
Authors: Daviau Kierstin , Lee Kanani K. M.
Published: August 2021

Astronomical surveys have discovered thousands of transiting exoplanets, revealing that rocky planets are common in the galaxy. A planet's interior chemistry is frequently inferred by average density, described by mass‐radius (M‐R) relationships. However, M‐R relationships give rise to non‐unique interpretations of a planet's interior composition, an issue that limits our ability to characterize far‐away worlds. We present experimental and density functional theoretical results addressing the influence of an ultra‐reducing (oxygen‐poor) interior chemistry on rocky mantle phases and discuss the possible implications for atmospheric observables. We show that silicon carbide (SiC) and molecular nitrogen (N2) react to form solid silicon nitride (γ‐Si3N4) at high pressures and high temperatures in a laser‐heated diamond‐anvil cell, consistent with ab initio computations. Si3N4 remains stable under extreme conditions and when quenched to ambient conditions. As SiC is a common compound found under very reducing conditions, these results indicate that nitrogen may form solid phases in an oxygen‐poor rocky planet. If, by sequestering nitrogen in a planet's mantle, the distribution of nitrogen between a planet's interior and atmosphere is altered (i.e., a nitrogen‐rich mantle and nitrogen‐poor atmosphere), these results indicate that there may be atmospheric observables connected to the mantle‐redox state of a rocky planet besides the oxygen‐containing phases ubiquitous in exoplanet literature.
Postseismic Deformation of the 2008 Wenchuan Earthquake Illuminates Lithospheric Rheological Structure and Dynamics of Eastern Tibet
Authors: Wang Min , Shen Zheng‐Kang , Wang Yan‐Zhao , Bürgmann Roland , Wang Fan , Zhang Pei‐Zhen , Liao Hua , Zhang Rui , Wang Qi , Jiang Zai‐Sen , Chen Wei‐Tao , Hao Ming , Li Yu , Gu Tie , Tao Wei , Wang Kang , Xue Lian
Published: August 2021

Tectonic research of the Tibetan Plateau has long focused on its deformation style and mechanisms. The 2008 Mw7.9 Wenchuan earthquake ruptured the Longmen Shan fault located at the eastern rim of the plateau and excited a viscoelastic response of the lithosphere. We infer a three‐dimensional (3D) rheological structure of eastern Tibet from modeling nine years of postseismic displacements observed by GPS. Our solution provides tight constraints on the lower‐crustal and upper‐mantle steady‐state viscosities of the Songpan‐Ganzi Terrane as (5.0 ± 0.7) × 1018 and (1.3 ± 0.3) × 1019 Pa s, respectively, consistent with a “jelly sandwich” model of Tibet, but not with some crustal channel flow models featuring much lower viscosities. The inferred lower‐crustal and upper‐mantle transient viscosities are (5.0 ± 1.3) × 1017 and (5.0 ± 1.5) × 1018 Pa s, respectively, suggesting nonlinear deformation mechanisms. The adjacent West Qinling and Sichuan blocks feature an order‐of‐magnitude higher rheological strength, which is consistent with the changes in the crustal material properties and interseismic deformation style across the East Kunlun‐Tazang and Longmen Shan faults. Our results enable us to propose a conceptual 3D tectonic deformation model, in which the eastward extrusion of Tibet is absorbed in the Songpan‐Ganzi crust mainly by E‐W shortening and N‐S extension, accommodated through faulting of conjugate strike‐slip faults in the upper crust and distributed shear in the lower crust.
The Ecology of River Ice
Authors: Thellman Audrey , Jankowski Kathi Jo , Hayden Brian , Yang Xiao , Dolan Wayana , Smits Adrianne P. , O'Sullivan Antóin M.
Published: August 2021

Many of the world's rivers are ice‐covered during winter months but increasing evidence indicates that the extent of river ice will shift substantially as winters warm. However, our knowledge of rivers during winter lags far behind that of the growing season, limiting our understanding of how ice loss will affect rivers. Physical, chemical, and biological processes change from headwaters to large rivers; thus, we expect ice processes and resulting effects on the ecology of rivers could also vary with river size, as a result of the associated changes in geomorphology, temperature regimes, and connectivity. To conceptualize these relationships, we review typically disparate literature on ice processes and winter ecology and compare what is known in the smallest and largest rivers. In doing so, we show that our ability to link ice with ecology across river networks is made difficult by a primary focus on ice processes in larger rivers and a lack of study of ecosystem processes during winter. To address some of these gaps, we provide new scenarios of river ice loss and analyses of how the annual importance of winter gross primary productivity (GPP) varies with river size. We show projected ice loss varied with large‐scale watershed characteristics such as north‐south orientation and that the importance of winter to annual GPP was greatest in the smallest rivers. Finally, we highlight information needed to fill knowledge gaps on winter across river networks and improve our understanding of how rivers may change as climate and ice regimes shift.
Incorporating Fish Tolerance to Supersaturated Total Dissolved Gas for Generating Flood Pulse Discharge Patterns Based on a Simulation‐Optimization Approach
Authors: Wan Hang , Tan Qian , Li Ran , Cai Yanpeng , Shen Xiaomei , Yang Zhifeng , Shen Xia
Published: August 2021

Supersaturated total dissolved gas (STDG) caused by the flood discharge can result in bubble disease and even fish death, posing potential risks to aquatic ecosystems. In order to reduce the impacts of STDG on such ecosystem, a dynamic multi‐objective STDG management model (DMO‐STDGM) with the flood pulse discharge pattern is developed based on the prototype observation and laboratory test analysis, which consists of STDG prediction, fish safety assessment, multi‐objective optimization and 2‐D STDG transport diffusion simulation modules. The proposed model can support generation of flood pulse discharge patterns to reduce the level of STDG and minimize the maximum residence time of STDG water. The developed model is applied to optimize the discharge pattern of Xiluodu project to reduce the effects of STDG on fish. Simulation results of the worst scenario with the flood pulse discharge pattern show that the maximum residence time of STDG for T120%, T125%, T130%, and T140% are 12, 9, 4, 3 and 1 h, which are less than the corresponding LT50s (Mean Lethal Time). It means that the physiological function of fish can recover from the affect of STDG, thus fish can survive in the worst scenario. The established model can also be employed for increasing power generation. Simulation results indicate that the flood pulse discharge pattern with equal weight of ecology and power generation can ensure full load operation of hydropower station with 12,600 MW. The established model is widely applicable and can provide an important theoretical and technical support for water quality and ecosystem management under multiple complexities.
Modeling and Experimental Study of the Effect of Pore Water Velocity on the Spectral Induced Polarization Signature in Porous Media
Authors: Tsukanov K. , Assa I. , Schwartz N.
Published: August 2021

Induced polarization (IP) is increasingly applied for hydrological, environmental and agricultural purposes. Interpretation of IP data is based on understanding the relationship between the IP signature and the porous media property of interest. Mechanistic models on the IP phenomenon rely on the Poisson‐Nernst‐Plank equations, where diffusion and electromigration fluxes are the driving forces of charge transport and are directly related to IP. However, to our knowledge, the impact of advection flux on IP was not investigated experimentally and was not considered in any IP model. In this work, we measured the spectral IP (SIP) signature of porous media under varying flow conditions, in addition to developing and solving a model for SIP signature of porous media, which takes flow into consideration. The experimental and the model results demonstrate that as bulk velocity increases, polarization and relaxation time decrease. Using a numerical model, we established that fluid flow near the particle deforms the electrical double layer (EDL) structure, accounting for the observed reduction in polarization. We found a qualitative agreement between the model and the measurements. Still, the model overestimates the impact of flow rate on SIP signature, which we explain in terms of the flow boundary conditions. Overall, our results demonstrate the sensitivity of the SIP signature to fluid flow, highlighting the need to consider fluid velocity in the interpretation of the SIP signature of porous media, and opening an exciting new direction for noninvasive measurements of fluid flow at the EDL scale.
Homeostasis and food craving in obesity: a functional MRI study
Authors: Stopyra M. A. , Friederich H.-C. , Lavandier N. , Mönning E. , Bendszus M. , Herzog W. , Simon J. J.
Published: August 2021

Objectives

Food intake in obesity has been found to be reward-based and less contingent on homeostatic needs. Accordingly, previous studies investigating neural processing of food cues observed aberrant processing in reward- and control-related brain regions in obesity. To further investigate the relation between homeostasis and food intake, this study investigated the influence of glucose metabolism on the neuronal response during the regulation of food craving in participants with obesity.

Methods

Twenty-five normal-weight and 25 women with obesity were examined on two occasions after receiving either water or glucose directly into the stomach using a nasogastric tube. Participants were blinded to the type of infusion and were required to refrain from eating for 16 h before each visit. An event-related fMRI paradigm was used to investigate the effect of intestinal glucose load on the neuronal response during the regulation of food craving.

Results

A 2 × 2 mixed-model ANOVA revealed that craving regulation was associated with increased activation in fronto-parietal regions in participants with obesity when compared to healthy controls. However, this effect was observed independently from homeostatic satiety. A regression analysis revealed that the reduction of food craving was related to increased activation in the lingual gyrus in individuals with obesity following the infusion of water.

Conclusions

In participants with obesity, the neuronal response during the regulation of food craving is associated with increased neural cognitive top-down control and increased visual food processing. Since this observation was independent from satiety status, our results indicate a reduced influence of homeostasis on neural processing during food craving in obesity. This study was registered on clinicaltrials.org: NCT03075371.
Lysosome purinergic receptor P2X4 regulates neoangiogenesis induced by microvesicles from sarcoma patients
Authors: Palinski Wulf , Monti Maria , Camerlingo Rosa , Iacobucci Ilaria , Bocella Serena , Pinto Federica , Iannuzzi Clara , Mansueto Gelsomina , Pignatiello Sara , Fazioli Flavio , Gallo Michele , Marra Laura , Cozzolino Flora , De Chiara Annarosaria , Pucci Piero , Bilancio Antonio , de Nigris Filomena
Published: August 2021

The tumor microenvironment modulates cancer growth. Extracellular vesicles (EVs) have been identified as key mediators of intercellular communication, but their role in tumor growth is largely unexplored. Here, we demonstrate that EVs from sarcoma patients promote neoangiogenesis via a purinergic X receptor 4 (P2XR4) -dependent mechanism in vitro and in vivo. Using a proteomic approach, we analyzed the protein content of plasma EVs and identified critical activated pathways in human umbilical vein endothelial cells (HUVECs) and human progenitor hematopoietic cells (CD34+). We then showed that vessel formation was due to rapid mitochondrial activation, intracellular Ca2+ mobilization, increased extracellular ATP, and trafficking of the lysosomal P2XR4 to the cell membrane, which is required for cell motility and formation of stable branching vascular networks. Cell membrane translocation of P2XR4 was induced by proteins and chemokines contained in EVs (e.g. Del-1 and SDF-1). Del-1 was found expressed in many EVs from sarcoma tumors and several tumor types. P2XR4 blockade reduced EVs-induced vessels in angioreactors, as well as intratumor vascularization in mouse xenografts. Together, these findings identify P2XR4 as a key mediator of EVs-induced tumor angiogenesis via a signaling mediated by mitochondria-lysosome-sensing response in endothelial cells, and indicate a novel target for therapeutic interventions.
Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes
Authors: Tan Joel M. J. , Garner Monica E. , Regeimbal James M. , Greene Catherine J. , Márquez Jorge D. Rojas , Ammendolia Dustin A. , McCluggage Adam R. R. , Li Taoyingnan , Wu Katherine J. , Cemma Marija , Ostrowski Philip P. , Raught Brian , Diamond Michael S. , Grinstein Sergio , Yates Robin M. , Higgins Darren E. , Brumell John H.
Published: August 2021

The type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3−/− mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.
The physiological basis for contrast opponency in motion computation in Drosophila
Authors: Ramos-Traslosheros Giordano , Silies Marion
Published: August 2021

In Drosophila, direction-selective neurons implement a mechanism of motion computation similar to cortical neurons, using contrast-opponent receptive fields with ON and OFF subfields. It is not clear how the presynaptic circuitry of direction-selective neurons in the OFF pathway supports this computation if all major inputs are OFF-rectified neurons. Here, we reveal the biological substrate for motion computation in the OFF pathway. Three interneurons, Tm2, Tm9 and CT1, provide information about ON stimuli to the OFF direction-selective neuron T5 across its receptive field, supporting a contrast-opponent receptive field organization. Consistent with its prominent role in motion detection, variability in Tm9 receptive field properties transfers to T5, and calcium decrements in Tm9 in response to ON stimuli persist across behavioral states, while spatial tuning is sharpened by active behavior. Together, our work shows how a key neuronal computation is implemented by its constituent neuronal circuit elements to ensure direction selectivity.
Electrocatalytic upcycling of polyethylene terephthalate to commodity chemicals and H2 fuel
Authors: Zhou Hua , Ren Yue , Li Zhenhua , Xu Ming , Wang Ye , Ge Ruixiang , Kong Xianggui , Zheng Lirong , Duan Haohong
Published: August 2021

Plastic wastes represent a largely untapped resource for manufacturing chemicals and fuels, particularly considering their environmental and biological threats. Here we report electrocatalytic upcycling of polyethylene terephthalate (PET) plastic to valuable commodity chemicals (potassium diformate and terephthalic acid) and H2 fuel. Preliminary techno-economic analysis suggests the profitability of this process when the ethylene glycol (EG) component of PET is selectively electrooxidized to formate (>80% selectivity) at high current density (>100 mA cm−2). A nickel-modified cobalt phosphide (CoNi0.25P) electrocatalyst is developed to achieve a current density of 500 mA cm−2 at 1.8 V in a membrane-electrode assembly reactor with >80% of Faradaic efficiency and selectivity to formate. Detailed characterizations reveal the in-situ evolution of CoNi0.25P catalyst into a low-crystalline metal oxy(hydroxide) as an active state during EG oxidation, which might be responsible for its advantageous performances. This work demonstrates a sustainable way to implement waste PET upcycling to value-added products.
Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis
Authors: Bao Bokan , Kellman Benjamin P. , Chiang Austin W. T. , Zhang Yujie , Sorrentino James T. , York Austin K. , Mohammad Mahmoud A. , Haymond Morey W. , Bode Lars , Lewis Nathan E.
Published: August 2021

Glycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the essential roles of glycans. Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps. Furthermore, the overlap of measured glycans can be low across samples. We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power. Using GlyCompare, we study diverse N-glycan profiles from glycoengineered erythropoietin. We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures. We further analyze human milk oligosaccharide profiles and find mother’s fucosyltransferase-dependent secretor-status indirectly impact the sialylation. Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations. Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
ELMO1 signaling is a promoter of osteoclast function and bone loss
Authors: Arandjelovic Sanja , Perry Justin S. A. , Zhou Ming , Ceroi Adam , Smirnov Igor , Walk Scott F. , Shankman Laura S. , Cambré Isabelle , Onengut-Gumuscu Suna , Elewaut Dirk , Conrads Thomas P. , Ravichandran Kodi S.
Published: August 2021

Osteoporosis affects millions worldwide and is often caused by osteoclast induced bone loss. Here, we identify the cytoplasmic protein ELMO1 as an important ‘signaling node’ in osteoclasts. We note that ELMO1 SNPs associate with bone abnormalities in humans, and that ELMO1 deletion in mice reduces bone loss in four in vivo models: osteoprotegerin deficiency, ovariectomy, and two types of inflammatory arthritis. Our transcriptomic analyses coupled with CRISPR/Cas9 genetic deletion identify Elmo1 associated regulators of osteoclast function, including cathepsin G and myeloperoxidase. Further, we define the ‘ELMO1 interactome’ in osteoclasts via proteomics and reveal proteins required for bone degradation. ELMO1 also contributes to osteoclast sealing zone on bone-like surfaces and distribution of osteoclast-specific proteases. Finally, a 3D structure-based ELMO1 inhibitory peptide reduces bone resorption in wild type osteoclasts. Collectively, we identify ELMO1 as a signaling hub that regulates osteoclast function and bone loss, with relevance to osteoporosis and arthritis.
Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis
Authors: Wu Xunyao , Liu Yi , Jin Shanzhao , Wang Min , Jiao Yuhao , Yang Bo , Lu Xin , Ji Xin , Fei Yunyun , Yang Huaxia , Zhao Lidan , Chen Hua , Zhang Yaran , Li Hao , Lipsky Peter E. , Tsokos George C. , Bai Fan , Zhang Xuan
Published: August 2021

The presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease heterogeneity with unknown diverse immunopathological mechanisms. Here we profile CD45+ hematopoietic cells from peripheral blood or synovial tissues from both ACPA+ and ACPA- RA patients by single-cell RNA sequencing and identify subsets of immune cells that contribute to the pathogenesis of RA subtypes. We find several synovial immune cell abnormalities, including up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the HLA-DR15 haplotype (DRB1/DRB5) conveys an increased risk of developing active disease in ACPA+ RA in a large cohort of patients with treatment-naive RA. Immunohistochemical staining shows increased infiltration of CCL13 and CCL18-expressing immune cells in synovial tissues of ACPA- RA. Collectively, our data provide evidence of the differential involvement of cellular and molecular pathways involved in the pathogenesis of seropositive and seronegative RA subtypes and reveal the importance of precision therapy based on ACPA status.
Spatiotemporally-resolved mapping of RNA binding proteins via functional proximity labeling reveals a mitochondrial mRNA anchor promoting stress recovery
Authors: Qin Wei , Myers Samuel A. , Carey Dominique K. , Carr Steven A. , Ting Alice Y.
Published: August 2021

Proximity labeling (PL) with genetically-targeted promiscuous enzymes has emerged as a powerful tool for unbiased proteome discovery. By combining the spatiotemporal specificity of PL with methods for functional protein enrichment, we show that it is possible to map specific protein subclasses within distinct compartments of living cells. In particular, we develop a method to enrich subcompartment-specific RNA binding proteins (RBPs) by combining peroxidase-catalyzed PL with organic-aqueous phase separation of crosslinked protein-RNA complexes (“APEX-PS”). We use APEX-PS to generate datasets of nuclear, nucleolar, and outer mitochondrial membrane (OMM) RBPs, which can be mined for novel functions. For example, we find that the OMM RBP SYNJ2BP retains specific nuclear-encoded mitochondrial mRNAs at the OMM during translation stress, facilitating their local translation and import of protein products into the mitochondrion during stress recovery. Functional PL in general, and APEX-PS in particular, represent versatile approaches for the discovery of proteins with novel function in specific subcellular compartments.
In situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion systems
Authors: Mageswaran Shrawan Kumar , Guérin Amandine , Theveny Liam M. , Chen William David , Martinez Matthew , Lebrun Maryse , Striepen Boris , Chang Yi-Wei
Published: August 2021

Parasites of the phylum Apicomplexa cause important diseases including malaria, cryptosporidiosis and toxoplasmosis. These intracellular pathogens inject the contents of an essential organelle, the rhoptry, into host cells to facilitate invasion and infection. However, the structure and mechanism of this eukaryotic secretion system remain elusive. Here, using cryo-electron tomography and subtomogram averaging, we report the conserved architecture of the rhoptry secretion system in the invasive stages of two evolutionarily distant apicomplexans, Cryptosporidium parvum and Toxoplasma gondii. In both species, we identify helical filaments, which appear to shape and compartmentalize the rhoptries, and an apical vesicle (AV), which facilitates docking of the rhoptry tip at the parasite’s apical region with the help of an elaborate ultrastructure named the rhoptry secretory apparatus (RSA); the RSA anchors the AV at the parasite plasma membrane. Depletion of T. gondii Nd9, a protein required for rhoptry secretion, disrupts the RSA ultrastructure and AV-anchoring. Moreover, T. gondii contains a line of AV-like vesicles, which interact with a pair of microtubules and accumulate towards the AV, leading to a working model for AV-reloading and discharging of multiple rhoptries. Together, our analyses provide an ultrastructural framework to understand how these important parasites deliver effectors into host cells.
A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants
Authors: Du Yanyun , Shi Rui , Zhang Ying , Duan Xiaomin , Li Li , Zhang Jing , Wang Fengze , Zhang Ruixue , Shen Hao , Wang Yue , Wu Zheng , Peng Qianwen , Pan Ting , Sun Wanwei , Huang Weijin , Feng Yue , Feng Hui , Xiao Junyu , Tan Wenjie , Wang Youchun , Wang Chenhui , Yan Jinghua
Published: August 2021

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.
Deep forest model for diagnosing COVID-19 from routine blood tests
Authors: AlJame Maryam , Imtiaz Ayyub , Ahmad Imtiaz , Mohammed Ameer
Published: August 2021

The Coronavirus Disease 2019 (COVID-19) global pandemic has threatened the lives of people worldwide and posed considerable challenges. Early and accurate screening of infected people is vital for combating the disease. To help with the limited quantity of swab tests, we propose a machine learning prediction model to accurately diagnose COVID-19 from clinical and/or routine laboratory data. The model exploits a new ensemble-based method called the deep forest (DF), where multiple classifiers in multiple layers are used to encourage diversity and improve performance. The cascade level employs the layer-by-layer processing and is constructed from three different classifiers: extra trees, XGBoost, and LightGBM. The prediction model was trained and evaluated on two publicly available datasets. Experimental results show that the proposed DF model has an accuracy of 99.5%, sensitivity of 95.28%, and specificity of 99.96%. These performance metrics are comparable to other well-established machine learning techniques, and hence DF model can serve as a fast screening tool for COVID-19 patients at places where testing is scarce.
Predicting the development of normal tension glaucoma and related risk factors in normal tension glaucoma suspects
Authors: Park Hae-Young Lopilly , Shin Da Young , Jeon Soo Ji , Kim Yong-Chan , Jung Younhea , Kim Eun Kyoung , Shin Hye-Young , Jung Kyoung In , Choi Jin A. , Lee Na Young , Hong Seung Woo , Park Chan Kee
Published: August 2021

This study investigated the predicted risk factors for the development of normal-tension glaucoma (NTG) in NTG suspects. A total of 684 eyes of 379 NTG suspects who were followed-up for at least 5 years were included in the study. NTG suspects were those having (1) intraocular pressure within normal range, (2) suspicious optic disc (neuroretinal rim thinning) or enlarged cup-to-disc ratio (≥ 0.6), but without definite localized retinal nerve fiber layer (RNFL) defects on red-free disc/fundus photographs, and (3) normal visual field (VF). Demographic, systemic, and ocular characteristics were determined at the time of the first visit via detailed history-taking and examination of past medical records. Various ocular parameters were assess using spectral-domain optical coherence tomography and Heidelberg retinal tomography. Conversion to NTG was defined either by the presence of a new localized RNFL defect at the superotemporal or inferotemporal region on disc/fundus red-free photographs, or presence of a glaucomatous VF defect on pattern standard deviation plots on two consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. In total, 86 (12.6%) of the 684 NTG suspects converted to NTG during the follow-up period of 69.39 ± 7.77 months. Significant (P < 0.05, Cox regression) risk factors included medication for systemic hypertension, longer axial length, worse baseline VF parameters, thinner baseline peripapillary RNFL, greater disc torsion, and lamina cribrosa (LC) thickness < 180.5 μm (using a cut-off value obtained by regression analysis). Significant (P < 0.05, Cox regression) risk factors in the non-myopic NTG suspects included medication for systemic hypertension and a LC thinner than the cut-off value. Significant (P < 0.05, Cox regression) risk factors in the myopic NTG suspects included greater disc torsion. The results indicated that 12.6% of NTG suspects converted to NTG during the 5–6-year follow-up period. NTG suspects taking medication for systemic hypertension, disc torsion of the optic disc in the inferotemporal direction, and thinner LC of the optic nerve head at baseline were at greater risk of NTG conversion. Related baseline risk factors were different between myopic and non-myopic NTG suspects.
Choosing a treatment method for post-catheterization pseudoaneurysms guided by the late to early velocity index
Authors: Kurzawski Jacek , Zandecki Lukasz , Janion-Sadowska Agnieszka , Piatek Lukasz , Jaroszynska Anna , Domagala Szymon , Sadowski Marcin , Baranska Edyta
Published: August 2021

Ultrasound-guided thrombin injection (UGTI) is often the first-line treatment for iatrogenic post-catheterization pseudoaneurysms (psA). There are also first reports of the use of biologically derived tissue glues (TG) instead of sole thrombin especially when UGTI was unsuccessful or in case of psA recurrence. Previously, we have established that a late to early velocity index (LEVI) < 0.2 could be a predictor of an increased risk of psA recurrence after standard UGTI. In this paper, we report our first experiences when the choice of the first-line treatment method was based on LEVI assessment. From May 2017 till January 2020 we included 36 patients with psA. Of them, 10 had LEVI < 0.2 and they underwent ultrasound-guided tissue glue injection (UGTGI) with biological TG and 26 had LEVI > 0.2 and they underwent UGTI. The injection set containing human thrombin and fibrinogen was used for UGTGI. Bovine thrombin was used for UGTI. The success rate was 100% and no psA recurrence was detected during a 2-week follow-up. It was significantly better when compared to the expected recurrence rates based on our previous 14 years of experience (0% vs. 13%, p = 0.01). All complications (10% in the UGTGI group and 15% in the UGTI group) were mild and transient and included clinical symptoms of paresthesia, numbness, tingling, or pain. Their rates were comparable to the rates we previously reported. No significant differences in other characteristics were observed. The approach to choose the first-line treatment method for iatrogenic psA based on LEVI is encouraging. It may increase the success rate and avoid unnecessary repetition of the procedure, without increasing complication rate while keeping costs of the procedure reasonable.
Impact of anthropogenic activities on morphological and deposition flux changes in the Pearl River Estuary, China
Authors: Wei Xing , Cai Shuqun , Zhan Weikang
Published: August 2021

The evolution of the Pearl River Estuary (PRE), China in recent decades has been dominated by human activities. Historical admiralty charts and remote sensing images indicated that from 1936 to 2017, the tidal flat area and water area decreased by 23.6 × 107 m2 and 60.7 × 107 m2, respectively. The average advancing rate of the coastline of the PRE to the sea from 1972 to 2017 reached approximately 64.8 m/year, which is several times or even dozens of times that since the mid-Holocene. Land reclamation was the main reason for the dramatic changes in the water area and coastline. Although the water volume of the PRE showed a decreasing trend from 1936 to 2017, the water volume reduction rates for 1996–2005 and 2005–2017 were only 29% (1.27 × 107 m3/year) and 12% (0.53 × 107 m3/year), respectively, of that for 1936–1972. The combined influences of channel dredging, sand mining, and sediment load reduction caused by dam construction have contributed to this change. From the perspective of the filling up of the estuary, channel dredging, sand mining, and dam construction in the river basin are beneficial for prolonging the life of the estuary.
Exploration of bioconvection flow of MHD thixotropic nanofluid past a vertical surface coexisting with both nanoparticles and gyrotactic microorganisms
Authors: Koriko Olubode Kolade , Shah Nehad Ali , Saleem S. , Chung Jae Dong , Omowaye Adeola John , Oreyeni Tosin
Published: August 2021

This communication presents analysis of gravity-driven flow of a thixotropic fluid containing both nanoparticles and gyrotactic microorganisms along a vertical surface. To further describe the transport phenomenon, special cases of active and passive controls of nanoparticles are investigated. The governing partial differential equations of momentum, energy, nanoparticles concentration, and density of gyrotactic microorganisms equations are converted and parameterized into system of ordinary differential equations and the series solutions are obtained through Optimal Homotopy Analysis Method (OHAM). The related important parameters are tested and shown on the velocity, temperature, concentration and density of motile microorganisms profiles. It is observed that for both cases of active and passive control of nanoparticles, incremental values of thermophoretic parameters corresponds to decrease in the velocity distributions and augment the temperature distributions.
Supramolecular self-assembly of a nitro-incorporating quinoxaline framework: insights into the origin of fluorescence turn-on response towards the benzene group of VOCs
Authors: Basak Megha , Das Gopal
Published: August 2021

A nitro incorporating quinoxaline based probe displays remarkable selectivity and sensitivity towards mesitylene amidst all VOCs in aqueous medium along with morphological evolution to higher order stone-shaped aggregates.
Precise and convenient size barcode on microfluidic chip for multiplex biomarker detection
Authors: Tang Man , Chen Jinyao , Lei Jia , Ai Zhao , Liu Feng , Hong Shao-Li , Liu Kan
Published: August 2021

A size barcode method is presented based on a wedge-shaped microfluidic chip. This method is simple, precise, and capable of simultaneous detection multiplex biomarkers, demonstrating significant potential in point-of-care tests.
Synthesis and evaluation of “Ama-Flash”, a photocaged amatoxin prodrug for light-activated RNA Pol II inhibition and cell death
Authors: Matinkhoo Kaveh , Pryyma Alla , Wong Antonio A. W. L. , Perrin David M.
Published: August 2021

It's now a matter of light and death. A non-toxic photoactivatable amatoxin, Ama-Flash is synthesized and evaluated on cells wherein it remains non-toxic until photoactivation.
An analyte-triggered artificial peroxidase system based on dimanganese complex for a versatile enzyme assay
Authors: Lee Suji , Han Min Su
Published: August 2021

We report the design and evaluation of an analyte-activatable artificial peroxidase system that allows the expansion of the applicability of the peroxidase activity-based sensing platform for the detection of a wide range of analytes.
Molecular dynamics simulation of extension-induced crystallization of branched bimodal HDPE: Unraveling the effects of short-chain branches
Authors: Cao Yiran , Zhao Li , Wang Jieqi , Shao Yunqi , He Xuelian
Published: August 2021

Bimodal HDPE models were designed for extension-induced crystallization imitating the architecture of industrial bimodal HDPE copolymerized with ethylene and 1-butene, 1-hexene, or 1-octene.
Theoretical investigation of the enhancement of positron affinity by the vibration and dimerization of non-polar carbon disulfide
Authors: Furushima Miku , Yoshida Daisuke , Kita Yukiumi , Shimazaki Tomomi , Tachikawa Masanori
Published: August 2021

We found that CS2 obtains positron binding ability by dimerization with vibrational Feshbach resonance.
31P nuclear spin singlet lifetimes in a system with switchable magnetic inequivalence: experiment and simulation
Authors: Korenchan David E. , Lu Jiaqi , Levitt Malcolm H. , Jerschow Alexej
Published: August 2021

31P NMR nuclear spin singlet order is reported for the first time. Experiments and molecular dynamics simulations indicate that the singlet order relaxes primarily via chemical shift anisotropy at high magnetic field strengths.
Towards the development of the emerging process of CO2heterogenous hydrogenation into high-value unsaturated heavy hydrocarbons
Authors: Wei Jian , Yao Ruwei , Han Yu , Ge Qingjie , Sun Jian
Published: August 2021

This review covers recent developments in the synthesis of α-olefins and aromatics from CO2hydrogenationviadirect and indirect routes.
Boosting NH3production from nitrate electroreductionviaelectronic structure engineering of Fe3C nanoflakes
Authors: Wang Yuanyuan , Zhang Linlin , Niu Yongjian , Fang Dong , Wang Jiao , Su Qingxiao , Wang Cheng
Published: August 2021

Optimized electronic structures of Fe3C/NC boosted NH3production from nitrate electroreduction, which proceededviaa stepwise NO3−–NO2−–NH3pathway.
Magnetic behavior of polymorph composite nickel titanate nanofibers
Authors: Sachin Kumar B. , Dhanasekhar C. , Anandhan S. , Kalpathy Sreeram K.
Published: August 2021

Synergetic effect of nickel ion-rich spinel phase and morphology of nickel titanate (NTO) nanofiber on magnetic properties.