bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction
Authors: Danaj Ermira
Published: March 2022

International and internal migration have characterised Albania since 1990, when the communist regime established in the aftermath of the Second World War was on its last legs. While the number of studies on Albanian migration, both national and transnational, has grown, only a few adopt the perspective of gender. Employing a gender perspective on migration is not only about using sex-disaggregated statistics but also explaining the processes and discourses in migration involving women and men, their relations to each other (Erel et al., 2003) and among women themselves (Parreñas, 2009)
Theoretical Framework
Authors: Danaj Ermira
Published: March 2022

This chapter sets out the epistemological lenses and the central theoretical concepts guiding this research. Given the many theories and models regarding the intersection of gender and migration, it is important to highlight those that inspire this research and help to investigate and better understand how gender affects migration processes and, vice versa, how migration impacts gender relations. The first section of this chapter presents the main perspectives adopted here: feminist and constructivist epistemology. The next section discusses patterns of various migration trajectories. The third section gives a brief historical overview of the debate on gender in migration studies and clarifies the theorisation of gender and migration in this book. The analytical Chaps.4,5,6and7include other essential concepts and findings.
Conclusions
Authors: Danaj Ermira
Published: March 2022

I began my research by asking, ‘How can we understand the interrelation between gender and migration in Albania?’. As my research progressed, three other questions emerged, which necessitated, first, investigating the tactics migrant women used during migration; second, identifying their migratory trajectories; and finally, understanding their experiences in the city of Tirana. To answer these questions, I conducted interviews with thirty-two migrant women involved in internal or multiple migratory trajectories who were all living in Tirana at the time when I conducted my fieldwork.
Information structure and OV word order in Old and Middle English: a phase-based approach
Authors: Struik Tara , van Kemenade Ans
Published: March 2022

This article re-examines the evidence for OV and VO variation and the loss of OV order in historical English, and presents a novel and unified analysis of Old and Middle English word order based on a uniform VO grammar, with leftward scrambling of specific types of objects. This analysis provides an insightful framework for a precise analysis of how OV word orders differ from VO word orders. We show in detail that OV with referential objects involves discourse-given objects. We then present a phase-based analysis from a VO base in which objects undergo feature-driven movement to spec,vP triggered by the information structure of the object. We propose that this analysis also yields a syntactic framework for analysing the derivation of preverbal quantified and negated objects, as well as a natural explanation for the stepwise loss of OV word order.
Sequential generalized Riemann–Liouville derivatives based on distributional convolution
Authors: Kleiner Tillmann , Hilfer Rudolf
Published: March 2022

Sequential generalized fractional Riemann–Liouville derivatives are introduced as composites of distributional derivatives on the right half axis and partially defined operators, called Dirac-function removers, that remove the component of singleton support at the origin of distributions that are of order zero on a neighborhood of the origin. The concept of Dirac-function removers allows to formulate generalized initial value problems with less restrictions on the orders and types than previous approaches to sequential fractional derivatives. The well-posedness of these initial value problems and the structure of their solutions are studied.
Combining shallow-water and analytical wake models for tidal array micro-siting
Authors: Jordan Connor , Dundovic Davor , Fragkou Anastasia K. , Deskos Georgios , Coles Daniel S. , Piggott Matthew D. , Angeloudis Athanasios
Published: March 2022

For tidal-stream energy to become a competitive renewable energy source, clustering multiple turbines into arrays is paramount. Array optimisation is thus critical for achieving maximum power performance and reducing cost of energy. However, ascertaining an optimal array layout is a complex problem, subject to specific site hydrodynamics and multiple inter-disciplinary constraints. In this work, we present a novel optimisation approach that combines an analytical-based wake model, FLORIS, with an ocean model, Thetis. The approach is demonstrated through applications of increasing complexity. By utilising the method of analytical wake superposition, the addition or alteration of turbine position does not require re-calculation of the entire flow field, thus allowing the use of simple heuristic techniques to perform optimisation at a fraction of the computational cost of more sophisticated methods. Using a custom condition-based placement algorithm, this methodology is applied to the Pentland Firth for arrays with turbines of $$3.05\,\hbox {m}/\hbox {s}$$

3.05

m
/
s

rated speed, demonstrating practical implications whilst considering the temporal variability of the tide. For a 24-turbine array case, micro-siting using this technique delivered an array 15.8% more productive on average than a staggered layout, despite flow speeds regularly exceeding the rated value. Performance was evaluated through assessment of the optimised layout within the ocean model that treats turbines through a discrete turbine representation. Used iteratively, this methodology could deliver improved array configurations in a manner that accounts for local hydrodynamic effects.
Survey of Open Data Concepts Within Fundamental Physics: An Initiative of the PUNCH4NFDI Consortium
Authors: Enke Harry , Haungs Andreas , Schörner-Sadenius Thomas , Schwarz Kilian , Demleitner Markus , Geiser Achim , Heinrich Lukas , Kramer Michael , Maier Gernot , Schwarz Dominik , Seitz-Moskaliuk Hendrik , Simma Hubert , Sterzik Michael , Typel Stefan
Published: March 2022

PUNCH4NFDI (Particles, Universe, NuClei and Hadrons for the NFDI) aims at developing concepts and tools for the efficient management of digital research products in fundamental physics research. At the heart of the research products are scientific data sets that should be made interoperable and available to a broad scientific community and the public for a sustainable usage (“open data”). The first PUNCH4NFDI “Open Data Workshop” gave the opportunity for an initial survey of existing and planned open data initiatives within the PUNCH science field. The paper addresses the conceptual differences and commonalities of the participating communities presented in the workshop. Existing open data collections were presented and discussed. This is an inquiry into the community’s requirements for a better use of open data and in this context also of “Open Science”.
Investigation on shock-induced separation loss mitigation method considering radial equilibrium in a transonic compressor rotor
Authors: Liu Y. , Zhao Q. , Zhao W. , Zhou Q. , Xu J.
Published: March 2022

A shock-induced separation loss reduction method, using local blade suction surface shape modification (smooth ramp structure) with constant adverse pressure gradient with the consideration of radial equilibrium effect to split a single shock foot into multiple weaker shock wave configuration, is investigated on the NASA Rotor 37 for promoting aerodynamic performance of a transonic compressor rotor. Numerical investigation on baseline blade and improved one with blade modification on suction side has been conducted employing the Reynolds-averaged Navier–Stokes method to reveal flow physics of ramp structure. The results indicate that the passage shock foot of baseline is replaced with a family of compression waves and a weaker shock foot generating moderate adverse pressure gradient on ramp profile, which is beneficial for mitigating the shock foot and shrinking flow separation region as well. In addition, the radial secondary flow of low-momentum fluids within boundary layer is decreased significantly in the region of passage shock-wave/boundary-layer interaction on blade suction side, which mitigates the mass flow and mixing intensity of tip leakage flow. With the reduction of flow separation loss induced by passage shock, the adiabatic efficiency and total pressure ratio of improved rotor are superior to baseline model. This study herein implies a potential application of ramp profile in design method of transonic and supersonic compressors.
The Prevention of the Sixth Mass Extinction: Socio-Legal Responses to Mitigate the Anthropogenic Crises in Asia and Beyond
Authors: Fukurai Hiroshi
Published: March 2022

This Special Issue highlights the most recent socio-legal research related to the mitigation, if not the elimination, of the threat of anthropogenic disasters in Asia and beyond. The drafts of these papers were originally presented at the Presidential Session on “The Anthropocene and the Law in Asia” at the Fourth Asian Law and Society Association (ALSA) Conference held in the vibrant city of Osaka, Japan in December 2019. The timing of this particular session, the first of its kind to be held at an ALSA Conference, turned out to be somewhat prophetic, in that two anthropogenic catastrophes—the historic zoonotic pandemic and the cataclysmic wild bushfires—had just begun to strike in December in Wuhan, China and in New South Wales, Australia, respectively. The novel coronavirus pandemic would kill more than 1 million people in the following months, after infecting more than 40 million across the globe. The Australian wild bushfires killed and displaced more than 3 billion animals, becoming the worst wildfire ever recorded in the world. Since that last ALSA Conference in December 2019, multiple anthropogenic disasters have hit various regions in Asia and across the world. The papers in this Special Issue examine various impacts of anthropogenic disasters and propose innovative socio-legal strategies to mitigate them. Included are arguments for the proposal of new legal education curricula and innovative pedagogy on environmental law and the exploration of an international multidisciplinary teaching framework in reconsidering and reshaping human-centric legal education. Also proposed is the development of a robust Earth Jurisprudence based on the adoption of the Rights of Nature principles, while moving away from the Euro-American exploitive view of nature as commodified properties. Additionally proposed is the establishment of a land-based, topological jurisprudence that incorporates the nuanced narratives of indigenous voices in dealing with the threat of human-induced ecological and environmental disasters in the years ahead.
Fanon, Hegel, and the Problem of Reciprocity
Authors: Badenhorst Daniel
Published: March 2022

In this article I put forward an interpretation of what is at stake in Frantz Fanon's claim that there is a reciprocity at the basis of G. W. F Hegel's master-servant dialectic. I do this by staging a critique of the ‘shared-humanity’ interpretation of Fanon's claim. Fanon's problem, as this interpretation understands it, is that the master-servant dialectic describes a situation in which two human beings knowingly confront one another as such. Such a situation—because human-to-human confrontation is assumed—does not adequately describe a racially divided situation because of racism's dehumanizing force. Fanon's problem would thus be that Hegel assumed shared humanity. I contest this reading by claiming that Fanon's issue is not reciprocal humanity but reciprocal struggle. To get to this point requires demonstrating that the shared-humanity reading is implausible on a variety of grounds. Thanks to the work of Philippe Van Haute it can already be said that in Hegel's text no shared humanity takes place. But Van Haute nevertheless claims that the shared-humanity problem is present in Kojève. Thus, it first needs to be shown that Kojève's text disallows such a reading. With this result in hand, I move to show the textually unsupportable nature of a subset of the shared-humanity reading—the ‘ontological reading’—whose strategy of reading Fanon's Black Skin, White Masks obscures the Sartrean-Beauvoirian commitments which would in fact allow a more accurate reading of Fanon's claims about reciprocity in Hegel to be made. I then seek to show—with reference to these commitments and a broadly Kojèvean emphasis on the centrality of struggle in human subject-formation—that Fanon's comments about reciprocity take aim at the question of mutual struggle in Hegel and Kojève. ‘The French Negro’, Fanon argues, did not get to experience the cost and value of freedom, unlike Hegel's servant.
Two-dimensional response of a floating ice plate to a line load moving at variable speed
Authors: Hosking Roger J. , Milinazzo Fausto
Published: March 2022

We significantly extend the results of Miles & Sneyd (J. Fluid Mech., vol. 497, 2003, pp. 435–439) for an accelerating line load on a floating ice plate in their simple linear mathematical model by proceeding to numerical calculations for the response due to a decelerating load. Our results show: (i) how the deflections produced by an impulsively started steadily moving line load begin to develop and eventually approach the well-known steady load-speed-dependent quasi-static and wave-like forms, including above the shallow water gravity wave speed where the shadow zone evolves; (ii) the singularity in the deflection predicted in the simple linear model when the load moves steadily is indeed avoided by a uniformly accelerating load, where the magnitude of the deflection continually increases and its maximum lags a little further behind as the load moves through the critical speed and beyond; (iii) there is also no singularity in the deflection due to a uniformly decelerating load, but whereas the response from a subcritical starting speed is preserved and travels with the load, the magnitude of the deflection may become quite large near a load starting from supercritical speed and approaching rest, which is attributed to constructive interference (reinforcement) as erstwhile trailing, predominantly gravity, waves catch up with the load. While this reinforcement poses no risk to Hercules transport aircraft landing on the thick sea ice at McMurdo Sound, it can account for the reported rapid sinking of the detached cockpit shortly after it came to rest in the 1974 Lockheed Electra aircraft crash in the Canadian Arctic.
Histories of Hearing
Authors: BIJSTERVELD KARIN
Published: March 2022

In January 2019, the Centre de Recherches sur les Arts et le Langage (CRAL) at L’École des Hautes Études en Sciences Sociales (EHESS) in Paris presented the conference Sound and Music in the Prism of Sound Studies.1 A spectacular video announces the event: a heavy-metal band screams about the conference’s themes and cries out each speaker’s name, which is in turn spelt out on screen in gothic-bloody font. The band’s song lyrics note that the focus of sound studies is on topics such as soundscape, noise, silence, recording techniques and listening. Most critically, the band shouts: ‘These are issues that musicology has been dealing with for a long time. What is then the place of musicology in the wake of sound studies?’
Off the COVID-19 Epicentre: The Impact of Quarantine Controls on Employment, Education and Health in China's Rural Communities
Authors: Wang Huan , Dill Sarah-Eve , Zhou Huan , Ma Yue , Xue Hao , Loyalka Prashant , Sylvia Sean , Boswell Matthew , Lin Jason , Rozelle Scott
Published: March 2022

This study documents the COVID-19 disease-control measures enacted in rural China and examines the economic and social impacts of these measures. We conducted two rounds of surveys with 726 randomly selected village informants across seven provinces. Strict disease-control measures have been universally enforced and appear to have been successful in limiting disease transmission in rural communities. The infection rate in our sample was 0.001 per cent, a rate that is near the national average outside of Hubei province. None of the villages reported any COVID-19-related deaths. For a full month during the quarantine, the rate of employment of rural workers was essentially zero. Even after the quarantine measures were lifted, nearly 70 per cent of the villagers still were unable to work owing to workplace closures. Although action has been taken to mitigate the potential negative effects, these disease-control measures might have accelerated the inequality between rural and urban households in China.
Dietary diversity indices v. dietary guideline-based indices and their associations with non-communicable diseases, overweight and energy intake: evidence from China
Authors: Zhou Jiajun , Leepromrath Sirimaporn , Zhou De
Published: March 2022

Objectives:

To evaluate various diet quality indices and to estimate their associations with major non-communicable diseases (NCD) (i.e. diabetes mellitus (DM) and myocardial infarction (MI)) and risk for overweight (OW).

Design:

Four dietary diversity indices (namely, count index (Count), dietary diversity score index, berry index (BI) and entropy index (EI)) and three Chinese dietary guideline-based indices (namely, China healthy diet index, Chinese food pagoda score and diet quality divergence index) were employed to evaluate Chinese diet quality. DM, MI and OW were used as diet-related health indicators. Logit regressions were employed to unveil the associations between diet quality indices and NCD and risk for OW. The relationships between diet quality indices and daily energy intakes were checked with ordinary least squares linear regressions.

Setting:

Four recent waves (2004, 2006, 2009, 2011) of longitudinal individual data from China Health and Nutrition Survey.

Participants:

Chinese adults (aged 18–64 years) from twelve provinces were included in the analysis (n 30 350).

Results:

Count, BI, and EI were positively associated with higher OW risk and daily energy intakes. As dietary guideline-based indices got better, people were exposed to lower DM and OW risks and got lower daily energy intakes. Finally, dietary guideline-based indices properly revealed the expected relationships that high-quality diets would reduce NCD and risk for OW, while high diversity indices were usually correlated with over-nutrition and high risks.

Conclusions:

Increasing diversity of the diet does not necessarily improve the nutrition and health. Dietary guideline-based indices are more robust than dietary diversity indices; thus, they should be highly recommended when evaluating diet quality.
Disentangling Emotions during the Coronavirus Outbreak in Spain: Inner Emotions, Descriptive Feeling Rules and Socioemotional Conventions
Authors: Caballero Amparo , Villar Sergio , Fernández Itziar , Sevillano Verónica , Gavilán Pablo , Carrera Pilar
Published: March 2022

For constructionism, language is the link among different levels of analysis of emotional events, from individual to interpersonal and macrosocial. The interaction among these emotional levels allows us to construe an emotional episode and label it with an emotion word, coordinate with the emotions perceived in others, and represent events as a society. Across two studies, we found similarities and differences among inner emotions experienced (individual level), emotions perceived in others (descriptive feeling rules, interpersonal level) and emotions shared on the internet (socioemotional conventions, macrosocial level), with all these emotional targets focused on the COVID–19 outbreak. The results indicate a similarity between the emotional meaning of COVID–19 in society and the descriptive feeling rules, whereas the reported inner emotions were clearly distinct: Joy was irrelevant at the interpersonal and macrosocial levels but clearly important at the individual level. A mismatch also appeared for fear and hope. While fear was the most predominant emotion at the interpersonal and macrosocial levels during most of the phases, it was moderately predominant at the individual level. Hope followed the opposite pattern, being the most relevant emotion at the individual level but less relevant at the interpersonal and macrosocial levels. Each level might have different consequences: Mixed emotions at the individual level might promote resilience; fear perceived in other people might motivate protective behaviors; and sadness socially shared during Christmas might generate greater empathy. These results support the complexity of emotional concepts and the suitability of exploring them at different levels of analysis.
Leader Extraversion as a Boundary Condition in the Relationship between Transformational Leadership, Vitality, and Job Improvement
Authors: Lajoie Denis , Rousseau Vincent , Boudrias Jean-Sébastien
Published: March 2022

We examine the relationship between transformational leadership and job improvement behaviors by considering the moderating effect of leader extraversion and the mediating role of employee vitality. Multi-level path analysis on data from 101 leaders and 619 subordinates provided support to the moderating effect of leader extraversion, such that the relationship between transformational leadership and employee vitality is stronger when the level of leader extraversion is high. Moreover, a moderated mediation procedure showed that the indirect effect of transformational leadership on job improvement via employee vitality was conditional to the level of leader extraversion. We highlight the original contributions of these findings by discussing the moderating role of leader extraversion as an understudied theoretical alternative to its already well-explored role as an antecedent to leadership behaviors. On a practical level, our results indicate that organizations should consider not only what leaders do (transformational leadership behaviors) but also how these behaviors are contextualized by leaders’ typical approach (extraversion) to instill a maximum of positive emotion such as vitality in employees.
Cross‐Shore Distribution of the Wave‐Induced Circulation Over a Dissipative Beach Under Storm Wave Conditions
Authors: Pezerat Marc , Bertin Xavier , Martins Kévin , Lavaud Laura
Published: March 2022

This study explores the spatial distribution and the driving mechanisms of the wave‐induced cross‐shore flow within the shoreface and surf zone of a dissipative beach. Unpublished results from a field campaign carried out in early 2021 under storm wave conditions are presented and compared with the predictions from a state‐of‐the‐art phase‐averaged three‐dimensional circulation modeling system based on the vortex force formalism. Under storm wave conditions, the cross‐shore flow is dominated by a strong seaward‐directed current in the lower part of the water column. The largest current velocities of this return current are located in the surf zone, where the dissipation by depth‐induced breaking is most intense, but offshore‐directed velocities up to 0.25 m/s are observed as far as 4 km from the shoreline (≃12 m‐depth). Numerical experiments further highlight the key control exerted by non‐conservative wave forces and wave‐enhanced mixing on the cross‐shore flow across a transition zone, where depth‐induced breaking, whitecapping, and bottom friction all significantly contribute to the wave energy dissipation. Under storm conditions, this transition zone extended almost 6 km offshore and the cross‐shore Lagrangian circulation shows a strong seaward‐directed jet in the lower part of the water column, whose intensity progressively decreases offshore. In contrast, the surf zone edge appears clearly delimited under fair weather conditions and the seaward‐directed current is weakened by a near bottom shoreward‐directed current associated with wave bottom streaming in the shoaling region, such that the clockwise Lagrangian overturning circulation is constrained by an additional anti‐clockwise overturning cell at the surf zone edge.
Characterization of a small-molecule inhibitor targeting NEMO/IKKβ to suppress colorectal cancer growth
Authors: Yu Zhenlong , Gao Jian , Zhang Xiaolei , Peng Yulin , Wei Wenlong , Xu Jianrong , Li Zhenwei , Wang Chao , Zhou Meirong , Tian Xiangge , Feng Lei , Huo Xiaokui , Liu Min , Ye Mingliang , Guo De-an , Ma Xiaochi
Published: March 2022

NEMO/IKKβ complex is a central regulator of NF-κB signaling pathway, its dissociation has been considered to be an attractive therapeutic target. Herein, using a combined strategy of molecular pharmacological phenotyping, proteomics and bioinformatics analysis, Shikonin (SHK) is identified as a potential inhibitor of the IKKβ/NEMO complex. It destabilizes IKKβ/NEMO complex with IC50 of 174 nM, thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in vivo. In addition, we also elucidated the potential target sites of SHK in the NEMO/IKKβ complex. Our study provides some new insights for the development of potent small-molecule PPI inhibitors.
secDrug: a pipeline to discover novel drug combinations to kill drug-resistant multiple myeloma cells using a greedy set cover algorithm and single-cell multi-omics
Authors: Kumar Harish , Mazumder Suman , Chakravarti Sayak , Sharma Neeraj , Mukherjee Ujjal Kumar , Kumar Shaji , Baughn Linda B , Van Ness Brian G , Mitra Amit Kumar
Published: March 2022

Multiple myeloma, the second-most common hematopoietic malignancy in the United States, still remains an incurable disease with dose-limiting toxicities and resistance to primary drugs like proteasome inhibitors (PIs) and Immunomodulatory drugs (IMiDs).

We have created a computational pipeline that uses pharmacogenomics data-driven optimization-regularization/greedy algorithm to predict novel drugs (“secDrugs”) against drug-resistant myeloma. Next, we used single-cell RNA sequencing (scRNAseq) as a screening tool to predict top combination candidates based on the enrichment of target genes. For in vitro validation of secDrugs, we used a panel of human myeloma cell lines representing drug-sensitive, innate/refractory, and acquired/relapsed PI- and IMiD resistance. Next, we performed single-cell proteomics (CyTOF or Cytometry time of flight) in patient-derived bone marrow cells (ex vivo), genome-wide transcriptome analysis (bulk RNA sequencing), and functional assays like CRISPR-based gene editing to explore molecular pathways underlying secDrug efficacy and drug synergy. Finally, we developed a universally applicable R-software package for predicting novel secondary therapies in chemotherapy-resistant cancers that outputs a list of the top drug combination candidates with rank and confidence scores.

Thus, using 17AAG (HSP90 inhibitor) + FK866 (NAMPT inhibitor) as proof of principle secDrugs, we established a novel pipeline to introduce several new therapeutic options for the management of PI and IMiD-resistant myeloma.
Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis
Authors: Yang Yiqi , Lin Yixuan , Wang Minqi , Yuan Kai , Wang Qishan , Mu Pei , Du Jingke , Yu Zhifeng , Yang Shengbing , Huang Kai , Wang Yugang , Li Hanjun , Tang Tingting
Published: March 2022

Diabetic osteoporosis (DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1 (HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment.
PGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis
Authors: Jiang Wenhao , Jin Yunyun , Zhang Shiwei , Ding Yi , Huo Konglin , Yang Junjie , Zhao Lei , Nian Baoning , Zhong Tao P. , Lu Weiqiang , Zhang Hankun , Cao Xu , Shah Karan Mehul , Wang Ning , Liu Mingyao , Luo Jian
Published: March 2022

Prostaglandin E2 (PGE2), a major cyclooxygenase-2 (COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis (OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts (EP4LysM) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in theEP4LysMmice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of platelet-derived growth factor-BB (PDGF-BB) was also lower in theEP4LysMmice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in theEP4LysMmice. Finally, we showed that the Gαs/PI3K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.
Atomic structure of a seed-sized gold nanoprism
Authors: Song Yongbo , Li Yingwei , Zhou Meng , Li Hao , Xu Tingting , Zhou Chuanjun , Ke Feng , Huo Dayujia , Wan Yan , Jie Jialong , Xu Wen Wu , Zhu Manzhou , Jin Rongchao
Published: March 2022

The growth of nanoparticles along one or two directions leads to anisotropic nanoparticles, but the nucleation (i.e., the formation of small seeds of specific shape) has long been elusive. Here, we show the total structure of a seed-sized Au56 nanoprism, in which the side Au{100} facets are surrounded by bridging thiolates, whereas the top/bottom {111} facets are capped by phosphine ligands at the corners and Br− at the center. The bromide has been proved to be the key to effectively stabilize the Au{111} to fulfill a complete face-centered-cubic core. In femtosecond electron dynamics analysis, the non-evolution of transient absorption spectra of Au56 is similar to that of larger-sized gold nanoclusters (n > 100), which is ascribed to the completeness of the prismatic Au56 core and an effective electron relaxation pathway created by the stronger Au-Au bonds inside. This work provides some insights for the understanding of plasmonic nanoprism formation.
Synthesis of a magnetic π-extended carbon nanosolenoid with Riemann surfaces
Authors: Wang Jinyi , Zhu Yihan , Zhuang Guilin , Wu Yayu , Wang Shengda , Huang Pingsen , Sheng Guan , Chen Muqing , Yang Shangfeng , Greber Thomas , Du Pingwu
Published: March 2022

Riemann surfaces are deformed versions of the complex plane in mathematics. Locally they look like patches of the complex plane, but globally, the topology may deviate from a plane. Nanostructured graphitic carbon materials resembling a Riemann surface with helicoid topology are predicted to have interesting electronic and photonic properties. However, fabrication of such processable and large π-extended nanographene systems has remained a major challenge. Here, we report a bottom-up synthesis of a metal-free carbon nanosolenoid (CNS) material with a low optical bandgap of 1.97 eV. The synthesis procedure is rapid and possible on the gram scale. The helical molecular structure of CNS can be observed by direct low-dose high-resolution imaging, using integrated differential phase contrast scanning transmission electron microscopy. Magnetic susceptibility measurements show paramagnetism with a high spin density for CNS. Such a π-conjugated CNS allows for the detailed study of its physical properties and may form the base of the development of electronic and spintronic devices containing CNS species.
Multiscale simulation approach to investigate the binder distribution in catalyst layers of high-temperature polymer electrolyte membrane fuel cells
Authors: Kwon Sung Hyun , Lee So Young , Kim Hyoung-Juhn , Yim Sung-Dae , Sohn Young-Jun , Lee Seung Geol
Published: March 2022

A multiscale approach involving both density functional theory (DFT) and molecular dynamics (MD) simulations was used to deduce an appropriate binder for Pt/C in the catalyst layers of high-temperature polymer electrolyte membrane fuel cells. The DFT calculations showed that the sulfonic acid (SO3−) group has higher adsorption energy than the other functional groups of the binders, as indicated by its normalized adsorption area on Pt (− 0.1078 eV/Å2) and carbon (− 0.0608 eV/Å2) surfaces. Consequently, MD simulations were performed with Nafion binders as well as polytetrafluoroethylene (PTFE) binders at binder contents ranging from 14.2 to 25.0 wt% on a Pt/C model with H3PO4 at room temperature (298.15 K) and operating temperature (433.15 K). The pair correlation function analysis showed that the intensity of phosphorus atoms in phosphoric acid around Pt ($${\rho }_{\mathrm{P}}{g}_{\mathrm{Pt}-\mathrm{P}}\left(r\right)$$

ρ
P

g

Pt
-
P

r

) increased with increasing temperature because of the greater mobility and miscibility of H3PO4 at 433.15 K than at 298.15 K. The coordination numbers (CNs) of Pt–P(H3PO4) gradually decreased with increasing ratio of the Nafion binders until the Nafion binder ratio reached 50%, indicating that the adsorption of H3PO4 onto the Pt surface decreased because of the high adsorption energy of SO3− groups with Pt. However, the CNs of Pt–P(H3PO4) gradually increased when the Nafion binder ratio was greater than 50% because excess Nafion binder agglomerated with itself via its SO3− groups. Surface coverage analysis showed that the carbon surface coverage by H3PO4 decreased as the overall binder content was increased to 20.0 wt% at both 298.15 and 433.15 K. The Pt surface coverage by H3PO4 at 433.15 K reached its lowest value when the PTFE and Nafion binders were present in equal ratios and at an overall binder content of 25.0 wt%. At the Pt (lower part) surface covered by H3PO4 at 433.15 K, an overall binder content of at least 20.0 wt% and equal proportions of PTFE and Nafion binder are needed to minimize H3PO4 contact with the Pt.
Quantitative proteomic analysis of the lysine acetylome reveals diverse SIRT2 substrates
Authors: Zhang Hui , Dammer Eric B. , Duong Duc M. , Danelia Diana , Seyfried Nicholas T. , Yu David S.
Published: March 2022

Sirtuin 2 (SIRT2) is a NAD+-dependent deacetylase, which regulates multiple biological processes, including genome maintenance, aging, tumor suppression, and metabolism. While a number of substrates involved in these processes have been identified, the global landscape of the SIRT2 acetylome remains unclear. Using a label-free quantitative proteomic approach following enrichment for acetylated peptides from SIRT2-depleted and SIRT2-overexpressing HCT116 human colorectal cancer cells, we identified a total of 2,846 unique acetylation sites from 1414 proteins. 896 sites from 610 proteins showed a > 1.5-fold increase in acetylation with SIRT2 knockdown, and 509 sites from 361 proteins showed a > 1.5-fold decrease in acetylation with SIRT2 overexpression, with 184 proteins meeting both criteria. Sequence motif analyses identified several site-specific consensus sequence motifs preferentially recognized by SIRT2, most commonly KxxxxK(ac). Gene Ontology, KEGG, and MetaCore pathway analyses identified SIRT2 substrates involved in diverse pathways, including carbon metabolism, glycolysis, spliceosome, RNA transport, RNA binding, transcription, DNA damage response, the cell cycle, and colorectal cancer. Collectively, our findings expand on the number of known acetylation sites, substrates, and cellular pathways targeted by SIRT2, providing support for SIRT2 in regulating networks of proteins in diverse pathways and opening new avenues of investigation into SIRT2 function.
PET in vivo generators 134Ce and 140Nd on an internalizing monoclonal antibody probe
Authors: Severin G. W. , Fonslet J. , Kristensen L. K. , Nielsen C. H. , Jensen A. I. , Kjær A. , Mazar A. P. , Johnston K. , Köster U.
Published: March 2022

The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes. Ante-mortem and post-mortem PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides 134La and 140Pr from tumor tissue (p > 0.5). The lack of redistribution indicates that the parent radionuclides 134Ce and 140Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like 177Lu, 161Tb and 225Ac when internalizing bioconjugates are employed.
Evaluation of auto-planning in VMAT for locally advanced nasopharyngeal carcinoma
Authors: Jihong Chen , Kaiqiang Chen , Yitao Dai , Xiuchun Zhang , Yanyu Chen , Penggang Bai
Published: March 2022

The aim of this study is to demonstrate the feasibility of a commercially available Auto-Planning module for the radiation therapy treatment planning for locally advanced nasopharyngeal carcinoma (NPC). 22 patients with locally advanced NPC were included in this study. For each patient, volumetric modulated arc therapy (VMAT) plans were generated both manually by an experienced physicist and automatically by the Auto-Planning module. The dose distribution, dosimetric parameters, monitor units and planning time were compared between automatic plans (APs) and manual plans (MPs). Meanwhile, the overall stage of disease was factored into the evaluation. The target dose coverage of APs was comparable to that of MPs. For the organs at risk (OARs) except spinal cord, the dose parameters of APs were superior to that of MPs. The Dmax and V50 of brainstem were statistically lower by 1.0 Gy and 1.32% respectively, while the Dmax of optic nerves and chiasm were also lower in the APs (p < 0.05). The APs provided a similar or superior quality to MPs in most cases, except for several patients with stage IV disease. The dose differences for most OARs were similar between the two types of plans regardless of stage while the APs provided better brainstem sparing for patients with stage III and improved the sparing of the parotid glands for stage IV patients. The total monitor units and planning time were significantly reduced in the APs. Auto-Planning is feasible for the VMAT treatment planning for locally advanced NPC.
Prevalence of mild cognitive impairment and its association with handgrip strength in patients on hemodialysis
Authors: Hidaka Sumi , Nishimiura Akinori , Hirata Masahiro , Ishioka Kunihiro , Ohtake Takayasu , Oka Machiko , Tamura Teiichi , Shibata Kazuhiko , Nishihara Masahiro , Kuji Tadashi , Oshikawa Jin , Satta Hidehisa , Imoto Kiyotaka , Kunieda Takehiko , Ozawa Kiyoshi , Kobayashi Shuzo
Published: March 2022

Dementia is associated with a high risk of death and hospitalization among patients on hemodialysis (HD). We retrospectively evaluated the prevalence of mild cognitive impairment (MCI) in 421 patients on maintenance HD across nine facilities and investigated whether decreased handgrip strength was associated with decreased cognitive function. The Montreal Cognitive Assessment-Japan (MoCA-J) score and handgrip strength were measured. The mean age was 69.8 ± 11.2 years, and the median dialysis vintage 74.5 (IQR 30–150) months. The median MoCA-J score was 25 (IQR 21–27), and MCI was confirmed in 245 (58.2%) patients. Both the MoCA-J score and MoCA-J executive score were associated with age, history of cerebrovascular disease (CVA), and handgrip strength after adjustments. We found, among patients on HD aged under 70 years with a history of CVA, a handgrip strength < 90% (25.2 kg in males and 16.2 kg in females) correlated with significantly lower MoCA-J scores. A high prevalence of MCI and decreased handgrip strength were observed in patients on HD. Handgrip strength may be useful for the easy detection of MCI. A decrease in handgrip strength would allow for the early detection of MCI, especially among patients on HD aged under 70 years with a history of CVA.
Collective effects of human genomic variation on microbiome function
Authors: New Felicia N. , Baer Benjamin R. , Clark Andrew G. , Wells Martin T. , Brito Ilana L.
Published: March 2022

Studies of the impact of host genetics on gut microbiome composition have mainly focused on the impact of individual single nucleotide polymorphisms (SNPs) on gut microbiome composition, without considering their collective impact or the specific functions of the microbiome. To assess the aggregate role of human genetics on the gut microbiome composition and function, we apply sparse canonical correlation analysis (sCCA), a flexible, multivariate data integration method. A critical attribute of metagenome data is its sparsity, and here we propose application of a Tweedie distribution to accommodate this. We use the TwinsUK cohort to analyze the gut microbiomes and human variants of 250 individuals. Sparse CCA, or sCCA, identified SNPs in microbiome-associated metabolic traits (BMI, blood pressure) and microbiome-associated disorders (type 2 diabetes, some neurological disorders) and certain cancers. Both common and rare microbial functions such as secretion system proteins or antibiotic resistance were found to be associated with host genetics. sCCA applied to microbial species abundances found known associations such asBifidobacteriaspecies, as well as novel associations. Despite our small sample size, our method can identify not only previously known associations, but novel ones as well. Overall, we present a new and flexible framework for examining host-microbiome genetic interactions, and we provide a new dimension to the current debate around the role of human genetics on the gut microbiome.
Crucial role of oxygen on the bulk and surface electronic properties of stable β phase of tungsten
Authors: Chattaraj Ananya , Joulie Sebastien , Serin Virginie , Claverie Alain , Kumar Vijay , Kanjilal Aloke
Published: March 2022

The A15 β phase of tungsten has recently attracted great interest for spintronic applications due to the finding of giant spin-Hall effect. As β phase is stabilized by oxygen, we have studied the electronic structure of O-doped β-W from first principles calculations. It is found that 20 at.% O-doping makes β phase lower in energy than α-W. These results are in good agreement with energy dispersive X-ray spectroscopy which also shows ~ 16.84 at.% O in 60 nm thick W films. The latter has predominantly β phase as confirmed by grazing incidence X-ray diffraction (XRD). The simulated XRD of bulk β having 15.79 at.% O also agrees with XRD results. Oxygen binds strongly on the surface and affects the Dirac fermion behavior in pure β-W. There is structural disorder, O-inhomogeneity, and higher density-of-states in O-doped β-W at EF compared with pure α. These results are promising to understand the properties of β-W.
Shared barriers and facilitators to enrollment of adolescents and young adults on cancer clinical trials
Authors: Mittal Nupur , Saha Aniket , Avutu Viswatej , Monga Varun , Freyer David R. , Roth Michael
Published: March 2022

Adolescent and young adult (AYA) enrollment in cancer clinical trials (CCT) is suboptimal. Few studies have explored site level barriers and facilitators to AYA enrollment on CCTs and the efficacy of interventions to enhance enrollment. A cross sectional survey was developed by the COG AYA Oncology Discipline Committee Responsible Investigator (RI) Network to identify perceived barriers and facilitators to enrollment, as well as opportunities to improve enrollment. Associations of barriers and facilitators to enrollment with program demographics were assessed. The survey was sent to all AYA RI Network members (n = 143) and quantitative and thematic analyses were conducted. The overall response rate was 42% (n = 60/143). Participants represented diverse institutions based on size, presence or absence of dedicated AYA programs, and proximity and relationship between pediatric and medical oncology practices within the institution. The most frequently cited barriers to enrolling AYAs in CCTs were administrative logistical issues (45%), disparate enrollment practices (42%) and communication issues (27%) between pediatric and medical oncology and perceived limited trial availability (27%). The most frequently reported facilitators to enrollment included having strong communication between pediatric and medical oncology (48%), having a supportive research infrastructure (35%) and the presence of AYA champions (33%). Many barriers and facilitators were similar across institutions and AYA program types. Shared barriers and facilitators to AYA CCT enrollment exist across the landscape of cancer care settings. Interventions aimed at increasing coordination between pediatric and medical oncology clinical trials offices and providers have high potential to improve site-level AYA enrollment.
A comprehensive systematic review and network meta-analysis: the role of anti-angiogenic agents in advanced epithelial ovarian cancer
Authors: Helali Aya El , Wong Charlene H. L. , Choi Horace C. W. , Chan Wendy W. L. , Dickson Naomi , Siu Steven W. K. , Chan Karen K. , Ngan Hextan Y. S. , Ngan Roger K. C. , Kennedy Richard D.
Published: March 2022

The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. Therefore, we conducted a systematic review and network meta-analysis (NMA) to synthesize evidence of their comparative effectiveness for improving overall survival (OS) among EOC patients. We searched six databases for randomized controlled trials (RCTs) from their inception to February 2021. We performed an NMA with hazard ratios (HRs) and 95%-confidence intervals (CIs) to evaluate comparative effectiveness among different AAAs in chemotherapy-naïve and recurrent EOC. P-score was used to provide an effectiveness hierarchy ranking. Sensitivity NMA was carried out by focusing on studies that reported high-risk chemotherapy-naïve, platinum-resistant, and platinum-sensitive EOC. The primary outcome was OS. We identified 23 RCTs that assessed the effectiveness of AAAs. In recurrent EOC, concurrent use of trebananib (10 mg/kg) with chemotherapy was likely to be the best option (P-score: 0.88, HR 1.67, 95% CI 0.94; 2.94). The NMA indicated that bevacizumab plus chemotherapy followed by maintenance bevacizumab (P-score: 0.99) and pazopanib combined with chemotherapy (P-score: 0.79) both had the highest probability of being the best intervention for improving OS in high-risk chemotherapy-naïve and platinum-resistant EOC, respectively. AAAs may not play a significant clinical role in non-high-risk chemotherapy-naïve and platinum-sensitive EOC.