bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Each According to Their Ability? An Analysis of Endowment Taxation and Potential Earnings
Authors: Sam Erick J. 
Published: February 2022

AbstractThis Article examines ability taxation, which is a tax on a person’s earning ability or potential earnings, rather than earned income. Despite this regime’s longstanding favor as a theoretical ideal for fair and efficient taxation among public finance economists, certain political philosophers, and tax law scholars, insufficient effort has been made to provide an analysis of what ‘potential earnings’ means. This Article explores competing understandings of this notion, and situates them within a multipart taxonomy. In so doing, it unearths a tension at the core of the ability tax program involving a fundamental misalignment between the metaphysics (or correct conceptual analysis) of potential earnings and the economics of its taxation. It concludes that once we correctly understand its requirements, we should reject ability taxation as the first-best normative ideal it has been held out to be on the grounds that it is overly burdensome and unfair to certain individuals.
Sensitivity of musculoskeletal models to variation in muscle architecture parameters
Authors: Kramer Patricia Ann , Feuerriegel Elen M. , Lautzenheiser Steven G. , Sylvester Adam D. 
Published: February 2022

Abstract
Musculoskeletal models, like all theoretical models of physical processes, depend on the assumptions needed to construct the model. For musculoskeletal models, these assumptions include, among other things, the kinematic data, the kinetic data and the muscle parameters. The former (dynamic) data can be acquired relatively easily from living subjects, but the latter are usually based on limited information, frequently determined from cadaver studies performed on elderly individuals. Previously, we determined the sensitivity of forces to dynamic differences among 10 humans walking on a straight path. Here, we assess the sensitivity of the muscle and joint reaction forces developed in human walking to variable muscle parameters obtained from 10 living adults, whose data were recently reported, and compared the results with the values from a standard model that depends on cadaveric data. We found that, while the force patterns across the stance cycle were similar among muscle parameter models, differences of as much as 15% in the force magnitude were produced. Whether or not the variation between the standard model and other muscle parameters is important depends on why the forces are required.
Power/resistance: External actors, local agency, and the Burundian peacebuilding project
Authors: Féron Elise , Krause Keith 
Published: February 2022

AbstractPeacebuilding policies and practices represent strong attempts by external actors to exercise power in postconflict settings. Yet the extensive theoretical treatments of power in International Relations remain somewhat disconnected from empirical analyses of peacebuilding, and how external actors exercise power is under-conceptualised in the literature. Likewise, the literature on forms of resistance by local actors is seldom examined as an exercise of power in itself, and as part of a multidimensional relationship of power/resistance between external and local actors. This article thus theorises the different dimensions of power/resistance, with a detailed focus on an exemplary case – international efforts at peacebuilding in Burundi – that spans more than twenty years. It deploys a tripartite conception of both to analyse the ways in which different forms of power and resistance can be uncovered in peacebuilding practices, We demonstrate this via an analysis of postconflict peacebuilding in Burundi, and in particular the longer-term efforts of local actors to overtly and covertly bend and fuse peacebuilding practices to their own ends.
Quantitative modelling of fine-scale variations in the Arabidopsis thaliana crossover landscape
Authors: Hsu Yu-Ming , Falque Matthieu , Martin Olivier C. 
Published: February 2022

Abstract
In, essentially, all species where meiotic crossovers (COs) have been studied, they occur preferentially in open chromatin, typically near gene promoters and to a lesser extent, at the end of genes. Here, in the case of Arabidopsis thaliana, we unveil further trends arising when one considers contextual information, namely summarised epigenetic status, gene or intergenic region size, and degree of divergence between homologs. For instance, we find that intergenic recombination rate is reduced if those regions are less than 1.5 kb in size. Furthermore, we propose that the presence of single nucleotide polymorphisms enhances the rate of CO formation compared to when homologous sequences are identical, in agreement with previous works comparing rates in adjacent homozygous and heterozygous blocks. Lastly, by integrating these different effects, we produce a quantitative and predictive model of the recombination landscape that reproduces much of the experimental variation.
Dynamic apico-basal enrichment of the F-actin during cytokinesis in Arabidopsis cells embedded in their tissues
Authors: Lebecq Alexis , Fangain Aurélie , Boussaroque Alice , Caillaud Marie-Cécile 
Published: February 2022

Abstract
Cell division is a tightly regulated mechanism, notably in tissues where malfunctions can lead to tumour formation or developmental defects. This is particularly true in land plants, where cells cannot relocate and therefore cytokinesis determines tissue topology. In plants, cell division is executed in radically different manners than in animals, with the appearance of new structures and the disappearance of ancestral mechanisms. Whilst F-actin and microtubules closely co-exist, recent studies mainly focused on the involvement of microtubules in this key process. Here, we used a root tracking system to image the spatio-temporal dynamics of both F-actin reporters and cell division markers in dividing cells embedded in their tissues. In addition to the F-actin accumulation at the phragmoplast, we observed and quantified a dynamic apico-basal enrichment of F-actin from the prophase/metaphase transition until the end of the cytokinesis.
Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis
Authors: Koh Jung Hee , Yoon Sang Jun , Kim Mina , Cho Seonghun , Lim Johan , Park Youngjae , Kim Hyun-Sook , Kwon Sung Won , Kim Wan-Uk 
Published: February 2022

AbstractLipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes.
A mouse model of gestational diabetes shows dysregulated lipid metabolism post-weaning, after return to euglycaemia
Authors: Furse Samuel , Fernandez-Twinn Denise S. , Beeson Jessica H. , Chiarugi Davide , Ozanne Susan E. , Koulman Albert 
Published: February 2022

Abstract
Background
Gestational diabetes is associated with increased risk of type 2 diabetes mellitus and cardiovascular disease for the mother in the decade after delivery. However, the molecular mechanisms that drive these effects are unknown. Recent studies in humans have shown that lipid metabolism is dysregulated before diagnosis of and during gestational diabetes and we have shown previously that lipid metabolism is also altered in obese female mice before, during and after pregnancy. These observations led us to the hypothesis that this persistent dysregulation reflects an altered control of lipid distribution throughout the organism.

Methods
We tested this in post-weaning (PW) dams using our established mouse model of obese GDM (high fat, high sugar, obesogenic diet) and an updated purpose-built computational tool for plotting the distribution of lipid variables throughout the maternal system (Lipid Traffic Analysis v2.3).

Results
This network analysis showed that unlike hyperglycaemia, lipid distribution and traffic do not return to normal after pregnancy in obese mouse dams. A greater range of phosphatidylcholines was found throughout the lean compared to obese post-weaning dams. A range of triglycerides that were found in the hearts of lean post-weaning dams were only found in the livers of obese post-weaning dams and the abundance of odd-chain FA-containing lipids differed locally in the two groups. We have therefore shown that the control of lipid distribution changed for several metabolic pathways, with evidence for changes to the regulation of phospholipid biosynthesis and FA distribution, in a number of tissues.

Conclusions
We conclude that the control of lipid metabolism is altered following an obese pregnancy. These results support the hypothesis that obese dams that developed GDM maintain dysregulated lipid metabolism after pregnancy even when glycaemia returned to normal, and that these alterations could contribute to the increased risk of later type 2 diabetes and cardiovascular disease.
On the horizon: Hedgehog signaling to heal broken bones
Authors: Kuwahara Stephanie T. , Liu Shuwan , Chareunsouk Andrew , Serowoky Maxwell , Mariani Francesca V. 
Published: February 2022

AbstractUncovering the molecular pathways that drive skeletal repair has been an ongoing challenge. Initial efforts have relied on in vitro assays to identify the key signaling pathways that drive cartilage and bone differentiation. While these assays can provide some clues, assessing specific pathways in animal models is critical. Furthermore, definitive proof that a pathway is required for skeletal repair is best provided using genetic tests. Stimulating the Hh (Hedgehog) pathway can promote cartilage and bone differentiation in cell culture assays. In addition, the application of HH protein or various pathway agonists in vivo has a positive influence on bone healing. Until recently, however, genetic proof that the Hh pathway is involved in bone repair has been lacking. Here, we consider both in vitro and in vivo studies that examine the role of Hh in repair and discuss some of the challenges inherent in their interpretation. We also identify needed areas of study considering a new appreciation for the role of cartilage during repair, the variety of cell types that may have differing roles in repair, and the recent availability of powerful lineage tracing techniques. We are optimistic that emerging genetic tools will make it possible to precisely define when and in which cells promoting Hh signaling can best promote skeletal repair, and thus, the clinical potential for targeting the Hh pathway can be realized.
Induction of senescence-associated secretory phenotype underlies the therapeutic efficacy of PRC2 inhibition in cancer
Authors: Chu Liping , Qu Yuxiu , An Yang , Hou Linjun , Li Juewan , Li Weijia , Fan Gaofeng , Song Bao-Liang , Li En , Zhang Liye , Qi Wei 
Published: February 2022

AbstractThe methyltransferase Polycomb Repressive Complex 2 (PRC2), composed of EZH2, SUZ12, and EED subunits, is associated with transcriptional repression via tri-methylation of histone H3 on lysine 27 residue (H3K27me3). PRC2 is a valid drug target, as the EZH2 gain-of-function mutations identified in patient samples drive tumorigenesis. PRC2 inhibitors have been discovered and demonstrated anti-cancer efficacy in clinic. However, their pharmacological mechanisms are poorly understood. MAK683 is a potent EED inhibitor in clinical development. Focusing on MAK683-sensitive tumors with SMARCB1 or ARID1A loss, we identified a group of PRC2 target genes with high H3K27me3 signal through epigenomic and transcriptomic analysis. Multiple senescence-associated secretory phenotype (SASP) genes, such as GATA4, MMP2/10, ITGA2 and GBP1, are in this group besides previously identified CDKN2A/p16. Upon PRC2 inhibition, the de-repression of SASP genes is detected in multiple sensitive models and contributes to decreased Ki67+, extracellular matrix (ECM) reorganization, senescence associated inflammation and tumor regression even in CDKN2A/p16 knockout tumor. And the combination of PRC2 inhibitor and CDK4/6 inhibitor leads to better effect. The genes potential regulated by PRC2 in neuroblastoma samples exhibited significant enrichment of ECM and senescence associated inflammation, supporting the clinical relevance of our results. Altogether, our results unravel the pharmacological mechanism of PRC2 inhibitors and propose a combination strategy for MAK683 and other PRC2 drugs.
E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2
Authors: Langel Stephanie N. , Kelly Francine L. , Brass David M. , Nagler Andrew E. , Carmack Dylan , Tu Joshua J. , Travieso Tatianna , Goswami Ria , Permar Sallie R. , Blasi Maria , Palmer Scott M. 
Published: February 2022

SummaryDiacetyl (DA) is an α-diketone that is used to flavor microwave popcorn, coffee, and e-cigarettes. Occupational exposure to high levels of DA causes impaired lung function and obstructive airway disease. Additionally, lower levels of DA exposure dampen host defenses in vitro. Understanding DA’s impact on lung epithelium is important for delineating exposure risk on lung health. In this study, we assessed the impact of DA on normal human bronchial epithelial cell (NHBEC) morphology, transcriptional profiles, and susceptibility to SARS-CoV-2 infection. Transcriptomic analysis demonstrated cilia dysregulation, an increase in hypoxia and sterile inflammation associated pathways, and decreased expression of interferon-stimulated genes after DA exposure. Additionally, DA exposure resulted in cilia loss and increased hyaluronan production. After SARS-CoV-2 infection, both genomic and subgenomic SARS-CoV-2 RNA were increased in DA vapor- compared to vehicle-exposed NHBECs. This work suggests that transcriptomic and physiologic changes induced by DA vapor exposure damage cilia and increase host susceptibility to SARS-CoV-2.
Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2
Authors: Liang Yu , Zhang Jing , Yuan Run Yu , Wang Mei Yu , He Peng , Su Ji Guo , Han Zi Bo , Jin Yu Qin , Hou Jun Wei , Zhang Hao , Zhang Xue Feng , Shao Shuai , Hou Ya Nan , Liu Zhao Ming , Du Li Fang , Shen Fu Jie , Zhou Wei Min , Xu Ke , Gao Ru Qin , Tang Fang , Lei Ze Hua , Liu Shuo , Zhen Wei , Wu Jin Juan , Zheng Xiang , Liu Ning , Chen Shi , Ma Zhi Jing , Zheng Fan , Ren Si Yu , Hu Zhong Yu , Huang Wei Jin , Wu Gui Zhen , Ke Chang Wen , Li Qi Ming 
Published: February 2022

AbstractThe continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.
Organic anion transporter 1 is an HDAC4-regulated mediator of nociceptive hypersensitivity in mice
Authors: Litke Christian , Hagenston Anna M. , Kenkel Ann-Kristin , Paldy Eszter , Lu Jianning , Kuner Rohini , Mauceri Daniela 
Published: February 2022

AbstractPersistent pain is sustained by maladaptive changes in gene transcription resulting in altered function of the relevant circuits; therapies are still unsatisfactory. The epigenetic mechanisms and affected genes linking nociceptive activity to transcriptional changes and pathological sensitivity are unclear. Here, we found that, among several histone deacetylases (HDACs), synaptic activity specifically affects HDAC4 in murine spinal cord dorsal horn neurons. Noxious stimuli that induce long-lasting inflammatory hypersensitivity cause nuclear export and inactivation of HDAC4. The development of inflammation-associated mechanical hypersensitivity, but neither acute nor basal sensitivity, is impaired by the expression of a constitutively nuclear localized HDAC4 mutant. Next generation RNA-sequencing revealed an HDAC4-regulated gene program comprising mediators of sensitization including the organic anion transporter OAT1, known for its renal transport function. Using pharmacological and molecular tools to modulate OAT1 activity or expression, we causally link OAT1 to persistent inflammatory hypersensitivity in mice. Thus, HDAC4 is a key epigenetic regulator that translates nociceptive activity into sensitization by regulating OAT1, which is a potential target for pain-relieving therapies.
Cell specific peripheral immune responses predict survival in critical COVID-19 patients
Authors: Amrute Junedh M. , Perry Alexandra M. , Anand Gautam , Cruchaga Carlos , Hock Karl G. , Farnsworth Christopher W. , Randolph Gwendalyn J. , Lavine Kory J. , Steed Ashley L. 
Published: February 2022

AbstractSARS-CoV-2 triggers a complex systemic immune response in circulating blood mononuclear cells. The relationship between immune cell activation of the peripheral compartment and survival in critical COVID-19 remains to be established. Here we use single-cell RNA sequencing and Cellular Indexing of Transcriptomes and Epitomes by sequence mapping to elucidate cell type specific transcriptional signatures that associate with and predict survival in critical COVID-19. Patients who survive infection display activation of antibody processing, early activation response, and cell cycle regulation pathways most prominent within B-, T-, and NK-cell subsets. We further leverage cell specific differential gene expression and machine learning to predict mortality using single cell transcriptomes. We identify interferon signaling and antigen presentation pathways within cDC2 cells, CD14 monocytes, and CD16 monocytes as predictors of mortality with 90% accuracy. Finally, we validate our findings in an independent transcriptomics dataset and provide a framework to elucidate mechanisms that promote survival in critically ill COVID-19 patients. Identifying prognostic indicators among critical COVID-19 patients holds tremendous value in risk stratification and clinical management.
TLR4 is a regulator of trained immunity in a murine model of Duchenne muscular dystrophy
Authors: Bhattarai Salyan , Li Qian , Ding Jun , Liang Feng , Gusev Ekaterina , Lapohos Orsolya , Fonseca Gregory J. , Kaufmann Eva , Divangahi Maziar , Petrof Basil J. 
Published: February 2022

AbstractDysregulation of the balance between pro-inflammatory and anti-inflammatory macrophages has a key function in the pathogenesis of Duchenne muscular dystrophy (DMD), a fatal genetic disease. We postulate that an evolutionarily ancient protective mechanism against infection, known as trained immunity, drives pathological inflammation in DMD. Here we show that bone marrow-derived macrophages from a murine model of DMD (mdx) exhibit cardinal features of trained immunity, consisting of transcriptional hyperresponsiveness associated with metabolic and epigenetic remodeling. The hyperresponsive phenotype is transmissible by bone marrow transplantation to previously healthy mice and persists for up to 11 weeks post-transplant. Mechanistically, training is induced by muscle extract in vitro. The functional and epigenetic changes in bone marrow-derived macrophages from dystrophic mice are TLR4-dependent. Adoptive transfer experiments further support the TLR4-dependence of trained macrophages homing to damaged muscles from the bone marrow. Collectively, this suggests that a TLR4-regulated, memory-like capacity of innate immunity induced at the level of the bone marrow promotes dysregulated inflammation in DMD.
Manipulating the carrier concentration and phase transition via Nb content in SrTiO3
Authors: Zhang Zhe , Qian Peihua , Yang Xingming , Wu Baixi , Cai H. L. , Zhang F. M. , Wu X. S. 
Published: February 2022

AbstractSrTiO3is a model of the perovskite-like compounds for structural transition which inducing the intriguing physical properties around the critical phase transition temperature TAFD(antiferrodistortive, abbrev. as AFD). Here we report that the electrical transport behavior is a new way to quantify Nb concentration for Nb-doped SrTiO3. The lattice parameter (c), phase transition temperature (TAFD), and the carrier concentration (n) of SrTiO3may be manipulated by niobium doping. TAFDincreases with increasing the niobium content in a rate of about 30 K per (wt%, i.e. niobium element’s weight verses total weight) niobium and n in a rate of about 2.5$$\times$$×1020/cm3per (wt%) niobium.
Semi-classical Monte Carlo algorithm for the simulation of X-ray grating interferometry
Authors: Tessarini Stefan , Fix Michael Karl , Manser Peter , Volken Werner , Frei Daniel , Mercolli Lorenzo , Stampanoni Marco 
Published: February 2022

AbstractTraditional simulation techniques such as wave optics methods and Monte Carlo (MC) particle transport cannot model both interference and inelastic scattering phenomena within one framework. Based on the rules of quantum mechanics to calculate probabilities, we propose a new semi-classical MC algorithm for efficient and simultaneous modeling of scattering and interference processes. The similarities to MC particle transport allow the implementation as a flexible c++ object oriented extension of EGSnrc—a well-established MC toolkit. In addition to previously proposed Huygens principle based transport through optics components, new variance reduction techniques for the transport through gratings are presented as transport options to achieve the required improvement in speed and memory costs necessary for an efficient exploration (system design—dose estimations) of the medical implementation of X-ray grating interferometry (GI), an emerging imaging technique currently subject of tremendous efforts towards clinical translation. The feasibility of simulation of interference effects is confirmed in four academic cases and an experimental table-top GI setup. Comparison with conventional MC transport show that deposited energy features of EGSnrc are conserved.