bluuebunny/crossref_metadata_2025_split huggingface dataset:
Permissive Laws and Teleology in Kant’s Juridical and Political Philosophy
Authors: Klein Joel T. 
Published: January 2022

AbstractIn this article I argue that the current readings of permissive law fall into hermeneutical difficulties and do not completely explain Kant’s complex use of the concept. I argue that the shortcomings of these interpretations can only be overcome by relating permissive law to practical teleology. That teleological thinking has a role in Kant’s moral thought by way of history is not new. Here, however, I argue that the system of rights itself is in some manner teleologically situated. This interpretation allows us to understand that Kant’s Doctrine of Right plays the role of a realist utopia.
Melt Migration and Chemical Differentiation by Reactive Porosity Waves
Authors: Bessat Annelore , Pilet Sébastien , Podladchikov Yuri Y. , Schmalholz Stefan M. 
Published: January 2022

AbstractMelt transport across the ductile mantle is essential for oceanic crust formation or intraplate volcanism. However, mechanisms of melt migration and associated chemical interaction between melt and solid mantle remain unclear. Here, we present a thermo‐hydro‐mechanical‐chemical (THMC) model for melt migration coupled to chemical differentiation. We consider melt migration by porosity waves and a chemical system of forsterite‐fayalite‐silica. We solve the one‐dimensional (1D) THMC model numerically using the finite difference method. Variables, such as solid and melt densities or MgO and SiO2 mass concentrations, are functions of pressure (P), temperature (T), and total silica mass fraction (). These variables are pre‐computed with Gibbs energy minimization and their variations with evolving P, T, and are implemented in the THMC model. We consider P and T conditions relevant around the lithosphere‐asthenosphere boundary. Systematic 1D simulations quantify the impact of initial distributions of porosity and on the melt velocity. Larger perturbations of cause larger melt velocities. An adiabatic or conductive geotherm cause fundamentally different vertical variations of densities and concentrations, and an adiabatic geotherm generates higher melt velocities. We quantify differences between melt transport (considering incompatible tracers), major element transport and porosity evolution. Melt transport is significant in the models. We also quantify the relative importance of four porosity variation mechanisms: (a) mechanical compaction and decompaction, (b) density variation, (c) compositional variation, and (d) solid‐melt mass exchange. In the models, (de)compaction dominates the porosity variation. We further discuss preliminary results of 2D THMC simulations showing blob‐like and channel‐like porosity waves.
Effects of EMIC Wave‐Driven Proton Precipitation on the Ionosphere
Authors: Tian Xingbin , Yu Yiqun , Zhu Minghui , Ma Longxing , Cao Jinbin , PR Shreedevi , Jordanova Vania K. , Solomon Stanley C. 
Published: January 2022

AbstractWe investigate the proton precipitation caused by electromagnetic ion cyclotron (EMIC) waves and its impact on the ionosphere with the self‐consistent ring current‐atmosphere interactions model (RAM‐SCBE) coupled with an ionospheric particle transport model Global Airglow (GLOW). The EMIC wave diffusion process causes significant precipitation of tens of keV protons, particularly in the afternoon to midnight sector. These precipitating energetic protons further impact the ionosphere‐thermosphere and contribute to the ionization in the E/F regions. The integrated auroral conductance is significantly enhanced in the dusk‐to‐midnight sector. Although the EMIC waves do not directly interact with the ring current electrons, after the EMIC wave scattering included in the model, remarkable changes are found in the global distribution of precipitating electron flux. This means that the addition of proton precipitation driven by EMIC waves results in feedback effects on the ring current electron dynamics through the circulation system. Validation is also conducted by comparing the simulated precipitation flux and ionospheric electron density with observations.
Australian Black Summer Smoke Observed by Lidar at the French Antarctic Station Dumont d’Urville
Authors: Tencé Florent , Jumelet Julien , Bekki Slimane , Khaykin Sergey , Sarkissian Alain , Keckhut Philippe 
Published: January 2022

AbstractIn the follow‐up of the Australian ”Black Summer” event that persisted from August 2019 to March 2020, we present the optical properties of the stratospheric aerosols injected into the atmosphere by these wildfires. The outbreak of pyrocumulonimbus (PyroCb) activity triggered between 2019/12/29 and 2020/01/04 has raised the stratospheric aerosol load of the Southern Hemisphere to unprecedented levels. Long‐range transport brought some of the plumes down to the Antarctic region, where general circulation patterns kept them circling around the continent. The 532 nm Rayleigh/Mie/Raman ground‐based lidar of the French Antarctic station Dumont d’Urville (66.6°S–140°E) acquired unprecedented time series of these carbonaceous aerosols starting approximately 20 days after the injection and up to the most recent measurements in October 2019 where local radiosonde reported anomalous ozone depletion as compared to the decadal average. The lidar provides a first and unique time series at high vertical and temporal resolution, complemented by satellite measurements from Ozone Monitoring Instrument, Ozone Mapping and Profiler Suite, and Microwave Limb Sounder. Aerosol backscatter ratio decreases from 1.9 to 1.2 between January and June 2020. Aerosol origin and persistence are characterized, as well as their optical properties and vertical distribution over several months.
The Origin of Tree‐Ring Reconstructed Summer Cooling in Northern Europe During the 18th Century Eruption of Laki
Authors: Edwards Julie , Anchukaitis Kevin J. , Gunnarson Björn E. , Pearson Charlotte , Seftigen Kristina , von Arx Georg , Linderholm Hans W. 
Published: January 2022

AbstractBasaltic fissure eruptions, which are characteristic of Icelandic volcanism, are extremely hazardous due to the large quantities of gases and aerosols they release into the atmosphere. The 1783–1784 CE Laki eruption was one of the most significant high‐latitude eruptions in the last millennium and had substantial environmental and climatic impacts. Contemporary observations recorded the presence of a sulfuric haze over Iceland and Europe, which caused famine from vegetation damage and resulted in a high occurrence of respiratory illnesses and related mortality. Historical records in northern Europe show that the summer of 1783 was anomalously warm, but regional tree‐ring maximum latewood density (MXD) data from that year are low and lead to erroneously colder reconstructed summer temperatures. Here, we measure wood anatomical characteristics of Scots pine (Pinus sylvestris) from Jämtland, Sweden in order to identify the cause of this discrepancy. We show that the presence of intraannual density fluctuations in the majority of 1783 growth rings, a sudden reduction in lumen and cell wall area, and the measurement resolution of traditional X‐ray densitometry led to the observed reduced annual MXD value. Multiple independent lines of evidence suggest these anatomical anomalies were most likely the result of direct acidic damage to trees in Northern Europe and that the normal relationship between summer temperature and MXD can be disrupted by this damage. Our study also demonstrates that quantitative wood anatomy offers a high‐resolution approach to identifying anomalous years and extreme events in the tree‐ring record.
Ethical Quandaries at End of Life: Navigating Real-World Case Examples as a Pediatric Psychologist
Authors: Schneider Nicole M. , Steinberg Dara M. , Pahl Daniel A. , Steffin David H. M. , Gangopadhyay Maalobeeka 
Published: January 2022

Objective: The aim of this article is to illustrate and discuss ethical dilemmas that might occur in the context of pediatric end-of-life care using case examples. The cases highlight ethical principles and are distilled by a multidisciplinary group of pediatric providers (i.e., psychologists, medical student, psychiatrist, bone marrow transplant physician), offering a unique perspective and insight. Familiarity with the principles discussed is important for pediatric psychologists working in medical settings, who might be uniquely suited to help patients, families, and medical teams navigate these challenges. Method: Two composite case examples are presented that focus on commonly encountered ethical dilemmas including: disclosing poor prognoses to patients; disagreements between families and medical teams; differing opinions on plans of care between medical team members. Important cultural considerations are also highlighted. Core ethical dilemmas are discussed and potential ways in which pediatric psychologists can offer expertise and intervention. Results: Recognition and collaboration around ethical dilemmas is essential to managing complex situations in pediatric palliative care. Moreover, it is imperative to consider the cultural factors of a family, which could provide additional insight into their preferences and values. Conclusions: Ethical challenges are prevalent in the field of pediatric palliative care. As the medical field continues to advance, pediatric psychologists are likely to encounter a range of clinical dilemmas. They should be prepared to consider the complex systemic, interpersonal, family, and cultural factors that might arise in their work. Implications for Impact Statement This article discusses ethical challenges pediatric psychologists might encounter when treating patients at the end of life. It is written by a group of multidisciplinary providers, thus offering a unique perspective. Two composite case examples are presented which demonstrate the complex ethical dilemmas that often arise when working with critically ill youth, including those with poor prognosis. Pediatric psychologists involved in pediatric palliative care might benefit from being familiar with ethical principles in order to navigate challenging and complex situations.
Parents’ perceptions of their child’s weight among children in their first year of primary school: a mixed-methods analysis of an Australian cross-sectional (complete enumeration) study
Authors: O’Brien Kathleen , Agostino Jason , Ciszek Karen , Douglas Kirsty A. 
Published: January 2022

Abstract
Background/Objectives
To describe trends in overweight/obesity in early childhood for all children and those whose parents are concerned about their weight. To describe parents’ perceptions of their child’s weight and differences by their child’s anthropometric and sociodemographic factors.

Subjects/Methods
Analysis of the Kindergarten Health Check, a survey of all children enrolled in their first year of primary education in the Australian Capital Territory. Analysis of detailed data for 2014–2017, including qualitative analysis of parents’ comments on weight, and trends for 2001–2017.

Results
71,963 children participated in the survey between 2001 and 2017 (20,427 between 2014 and 2017). The average age of children (2001–2017) was 5 years and 9.6 months at the time of their physical health check. 2377 children (3.5%) were classified as obese based on measured body mass index (BMI) between 2001 and 2017, and a further 7766 (11.6%) overweight. Similar proportions were seen for 2014–2017. Among children with overweight/obesity in 2014–2017, 86.4% of parents (2479/2868) described their children’s weight as healthy and 13.3% (382/2868) as overweight/obese. Just 11.5% (339/2946) of parents whose children were later measured with overweight/obesity identified having a concern about their child’s weight.
Parental comments varied widely and were often incongruent with the known health risks associated with their child’s measured BMI. Comments from parents whose children were measured as obese often were normalising e.g., “born big, always big. Definitely NOT overweight, just bigger all over”, whilst parents of children in the healthy range expressed concerns about underweight.

Conclusion
Parents do not accurately perceive their child’s weight and few document concerns, even among children measuring in the obese BMI category. This lack of concern makes early interventions challenging as parents are in the “pre-contemplative” stage of behaviour change and may see public health campaigns or clinicians’ attempts to address their child’s weight as irrelevant or unhelpful.
Immunomodulatory effects and mechanisms of distraction osteogenesis
Authors: Yang Shude , Wang Ning , Ma Yutong , Guo Shuaichen , Guo Shu , Sun Hongchen 
Published: January 2022

AbstractDistraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.
Canonical TGFβ signaling induces collective invasion in colorectal carcinogenesis through a Snail1- and Zeb1-independent partial EMT
Authors: Flum Marion , Dicks Severin , Teng Yu-Hsiang , Schrempp Monika , Nyström Alexander , Boerries Melanie , Hecht Andreas 
Published: January 2022

AbstractLocal invasion is the initial step towards metastasis, the main cause of cancer mortality. In human colorectal cancer (CRC), malignant cells predominantly invade as cohesive collectives and may undergo partial epithelial-mesenchymal transition (pEMT) at the invasive front. How this particular mode of stromal infiltration is generated is unknown. Here we investigated the impact of oncogenic transformation and the microenvironment on tumor cell invasion using genetically engineered organoids as CRC models. We found that inactivation of the Apc tumor suppressor combined with expression of oncogenic KrasG12D and dominant-negative Trp53R172H did not cell-autonomously induce invasion in vitro. However, oncogenic transformation primed organoids for activation of a collective invasion program upon exposure to the prototypical microenvironmental factor TGFβ1. Execution of this program co-depended on a permissive extracellular matrix which was further actively remodeled by invading organoids. Although organoids shed some epithelial properties particularly at the invasive edge, TGFβ1-stimulated organoids largely maintained epithelial gene expression while additionally implementing a mesenchymal transcription pattern, resulting in a pEMT phenotype that did not progress to a fully mesenchymal state. Notably, while TGFβ1 induced pEMT and promoted collective invasion, it abrogated self-renewal capacity of TKA organoids which correlated with the downregulation of intestinal stem cell (ISC) marker genes. Mechanistically, induction of the non-progressive pEMT required canonical TGFβ signaling mediated by Smad transcription factors (TFs), whereas the EMT master regulators Snail1 and Zeb1 were dispensable. Gene expression profiling provided further evidence for pEMT of TGFβ1-treated organoids and showed that their transcriptomes resemble those of human poor prognosis CMS4 cancers which likewise exhibit pEMT features. We propose that collective invasion in colorectal carcinogenesis is triggered by microenvironmental stimuli through activation of a novel, transcription-mediated form of non-progressive pEMT independently of classical EMT regulators.
Glucose-regulated protein 78 modulates cell growth, epithelial–mesenchymal transition, and oxidative stress in the hyperplastic prostate
Authors: Fu Xun , Liu Jianmin , Liu Daoquan , Zhou Yongying , Guo Yuhang , Wang Zhen , Yang Shu , He Weixiang , Chen Ping , Wang Xinghuan , DiSanto Michael E. , Zhang Xinhua 
Published: January 2022

AbstractBenign prostatic hyperplasia (BPH) is a chronic condition which mainly affects elderly males. Existing scientific evidences have not completely revealed the pathogenesis of BPH. Glucose-regulated protein 78 (GRP78) is a member of the heat shock protein 70 superfamily, which serves as an important regulator in many diseases. This study aims at elucidating the role of GRP78 in the BPH process. Human prostate tissues, cultured human prostate cell lines (BPH-1 and WPMY-1) and clinical data from BPH patients were utilized. The expression and localization of GRP78 were determined with quantitative real time PCR (qRT-PCR), Western blotting and immunofluorescence staining. GRP78 knockdown and overexpression cell models were created with GRP78 siRNA and GRP78 plasmid transfection. With these models, cell viability, apoptosis rate, as well as marker levels for epithelial-mesenchymal transition (EMT) and oxidative stress (OS) were detected by CCK8 assay, flow cytometry analysis and Western blotting respectively. AKT/mTOR and MAPK/ERK pathways were also evaluated. Results showed GRP78 was localized in the epithelium and stroma of the prostate, with higher expression in BPH tissues. There was no significant difference in GRP78 expression between BPH-1 and WPMY-1 cell lines. In addition, GRP78 knockdown (KD) slowed cell growth and induced apoptosis, without effects on the cell cycle stage of both cell lines. Lack of GRP78 affected expression levels of markers for EMT and OS. Consistently, overexpression of GRP78 completely reversed all effects of knocking down GRP78. We further found that GRP78 modulated cell growth and OS via AKT/mTOR signaling, rather than the MAPK/ERK pathway. Overall, our novel data demonstrates that GRP78 plays a significant role in the development of BPH and suggests that GRP78 might be rediscovered as a new target for treatment of BPH.
Targeting ADRB2 enhances sensitivity of non-small cell lung cancer to VEGFR2 tyrosine kinase inhibitors
Authors: Xu Yingzhuo , Wang Jian , Wang Xu , Zhou Xiaoshu , Tang Jing , Jie Xiaohua , Yang Xijie , Rao Xinrui , Xu Yunhong , Xing Biyuan , Li Zhenyu , Wu Gang 
Published: January 2022

AbstractVascular Endothelial Growth Factor Receptor 2 (VEGFR2) tyrosine kinase inhibitors (TKIs) have achieved remarkable clinical progress in the treatment of non-small-cell lung cancer; however, resistance has limited their therapeutic efficacy. Therefore, understanding the mechanisms of VEGF-TKI and ICI resistance will help to develop effective treatment strategies for patients with advanced NSCLC. Our results suggested that treatment with VEGFR2-TKIs upregulated ADRB2 expression in NSCLC cells. Propranolol, a common ADRB2 antagonist, significantly enhanced the therapeutic effect of VEGFR2-TKIs by inhibiting the ADRB2 signaling pathway in NSCLC cells in vitro and in vivo. Mechanically, the treatment-induced ADRB2 upregulation and the enhancement of ADRB2/VEGFR2 interaction caused resistance to VEGFR2-TKIs in NSCLC. And the inhibition of the ADRB2/CREB/PSAT1 signaling pathway sensitized cells to VEGFR2-TKIs. We demonstrated that ADRB2 signaling is crucial in mediating resistance to VEGFR2-TKIs and provided a novel promising combinatory approach to enhance the antitumor effect of VEGFR2-TKIs in NSCLC combining with propranolol.
ER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cells
Authors: Hagenlocher Cathrin , Siebert Robin , Taschke Bruno , Wieske Senait , Hausser Angelika , Rehm Markus 
Published: January 2022

AbstractProlonged ER stress and the associated unfolded protein response (UPR) can trigger programmed cell death. Studies in cancer cell lines demonstrated that the intracellular accumulation of TRAIL receptor-2 (TRAIL-R2) and the subsequent activation of caspase-8 contribute significantly to apoptosis induction upon ER stress. While this might motivate therapeutic strategies that promote cancer cell death through ER stress-induced caspase-8 activation, it could also support the unwanted demise of non-cancer cells. Here, we therefore investigated if TRAIL-R2 dependent signaling towards apoptosis can be induced in pancreatic β cells, whose loss by prolonged ER stress is associated with the onset of diabetes. Interestingly, we found that elevated ER stress in these cells does not result in TRAIL-R2 transcriptional induction or elevated protein levels, and that the barely detectable expression of TRAIL-R2 is insufficient to allow TRAIL-induced apoptosis to proceed. Overall, this indicates that apoptotic cell death upon ER stress most likely proceeds independent of TRAIL-R2 in pancreatic β cells. Our findings therefore point to differences in ER stress response and death decision-making between cancer cells and pancreatic β cells and also have implications for future targeted treatment strategies that need to differentiate between ER stress susceptibility of cancer cells and pancreatic β cells.
Integration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development
Authors: Magaletta Margaret E. , Lobo Macrina , Kernfeld Eric M. , Aliee Hananeh , Huey Jack D. , Parsons Teagan J. , Theis Fabian J. , Maehr René 
Published: January 2022

AbstractMaldevelopment of the pharyngeal endoderm, an embryonic tissue critical for patterning of the pharyngeal region and ensuing organogenesis, ultimately contributes to several classes of human developmental syndromes and disorders. Such syndromes are characterized by a spectrum of phenotypes that currently cannot be fully explained by known mutations or genetic variants due to gaps in characterization of critical drivers of normal and dysfunctional development. Despite the disease-relevance of pharyngeal endoderm, we still lack a comprehensive and integrative view of the molecular basis and gene regulatory networks driving pharyngeal endoderm development. To close this gap, we apply transcriptomic and chromatin accessibility single-cell sequencing technologies to generate a multi-omic developmental resource spanning pharyngeal endoderm patterning to the emergence of organ-specific epithelia in the developing mouse embryo. We identify cell-type specific gene regulation, distill GRN models that define developing organ domains, and characterize the role of an immunodeficiency-associated forkhead box transcription factor.
Significance of gene variants for the functional biogeography of the near-surface Atlantic Ocean microbiome
Authors: Dlugosch Leon , Poehlein Anja , Wemheuer Bernd , Pfeiffer Birgit , Badewien Thomas H. , Daniel Rolf , Simon Meinhard 
Published: January 2022

AbstractMicrobial communities are major drivers of global elemental cycles in the oceans due to their high abundance and enormous taxonomic and functional diversity. Recent studies assessed microbial taxonomic and functional biogeography in global oceans but microbial functional biogeography remains poorly studied. Here we show that in the near-surface Atlantic and Southern Ocean between 62°S and 47°N microbial communities exhibit distinct taxonomic and functional adaptations to regional environmental conditions. Richness and diversity showed maxima around 40° latitude and intermediate temperatures, especially in functional genes (KEGG-orthologues, KOs) and gene profiles. A cluster analysis yielded three clusters of KOs but five clusters of genes differing in the abundance of genes involved in nutrient and energy acquisition. Gene profiles showed much higher distance-decay rates than KO and taxonomic profiles. Biotic factors were identified as highly influential in explaining the observed patterns in the functional profiles, whereas temperature and biogeographic province mainly explained the observed taxonomic patterns. Our results thus indicate fine-tuned genetic adaptions of microbial communities to regional biotic and environmental conditions in the Atlantic and Southern Ocean.