bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theorizing about faith and faithfulness with Jonathan Kvanvig
Authors: McKaughan Daniel J. , Howard-Snyder Daniel 
Published: July 2021

AbstractWhat are faith and faithfulness, and how are they related? We consider two views that express very different answers to these questions. On our view, faith and faithfulness are distinct and yet complement each other. Faith is resilient reliance and faithfulness is resilient reliability, both of which involve conative and/or affective elements. In contrast, while Jonathan Kvanvig also holds that faith involves conative and/or affective elements, he identifies faith with a disposition to act in service of an ideal in the face of difficulty. However, this view of faith leads to some puzzling claims about how faith relates to faithfulness. We evaluate several claims suggested by what Kvanvig says, arguing both that his view loses sight of the distinctness of faith and faithfulness and that the inferences he wants to draw from faithfulness or faithful behaviour to faith are unjustified. Instead, we aim to show how the insights he calls to our attention can be better accommodated and explained by a more comprehensive, unified theory of faith and faithfulness and their relations.
Continuity and catastrophic risk
Authors: Stefánsson H. Orri 
Published: July 2021

AbstractSuppose that a decision-maker’s aim, under certainty, is to maximize some continuous value, such as lifetime income or continuous social welfare. Can such a decision-maker rationally satisfy what has been called ‘continuity for easy cases’ while at the same time satisfying what seems to be a widespread intuition against the full-blown continuity axiom of expected utility theory? In this note I argue that the answer is ‘no’: given transitivity and a weak trade-off principle, continuity for easy cases violates the anti-continuity intuition. I end the note by exploring an even weaker continuity condition that is consistent with the aforementioned intuition.
Random fractals and their intersection with winning sets
Authors: DAYAN YIFTACH 
Published: July 2021

AbstractWe show that fractal percolation sets in $\mathbb{R}^{d}$ almost surely intersect every hyperplane absolutely winning (HAW) set with full Hausdorff dimension. In particular, if $E\subset\mathbb{R}^{d}$ is a realisation of a fractal percolation process, then almost surely (conditioned on $E\neq\emptyset$), for every countable collection $\left(f_{i}\right)_{i\in\mathbb{N}}$ of $C^{1}$ diffeomorphisms of $\mathbb{R}^{d}$, $\dim_{H}\left(E\cap\left(\bigcap_{i\in\mathbb{N}}f_{i}\left(\text{BA}_{d}\right)\right)\right)=\dim_{H}\left(E\right)$, where $\text{BA}_{d}$ is the set of badly approximable vectors in $\mathbb{R}^{d}$. We show this by proving that E almost surely contains hyperplane diffuse subsets which are Ahlfors-regular with dimensions arbitrarily close to $\dim_{H}\left(E\right)$.We achieve this by analysing Galton–Watson trees and showing that they almost surely contain appropriate subtrees whose projections to $\mathbb{R}^{d}$ yield the aforementioned subsets of E. This method allows us to obtain a more general result by projecting the Galton–Watson trees against any similarity IFS whose attractor is not contained in a single affine hyperplane. Thus our general result relates to a broader class of random fractals than fractal percolation.
How China's Wildlife Trade Legislation Permits Commercial Trade in Protected Wild Animal Species
Authors: White Aron 
Published: July 2021

AbstractWildlife trade policies in China and elsewhere have come under increased scrutiny following suggestions that the emergence of the coronavirus SARS-CoV-2 may have been linked to trade in wild animals. The breeding of and trade in most terrestrial wild animal species for consumption as food were prohibited in China in February 2020, but trade for non-food purposes such as ornamental items or traditional medicine continues to be covered by provisions in the Wildlife Protection Law (WPL). While a superficial reading of the WPL could lead to the conclusion that commercial trade in nationally protected species is generally prohibited, in practice key language is interpreted to permit commercial trade in the parts and derivatives of protected wild animal species, including those subject to the most stringent protection within China and internationally, such as leopards and pangolins.
Different Spatiotemporal Patterns in Global Human Population and Built‐Up Land
Authors: Gao Jing , O'Neill Brian 
Published: July 2021

AbstractPopulation concentration and built‐up land expansion are two prominent features of contemporary urbanization. Existing literature on the population aspect of urbanization has mostly focused on national and regional aggregates, and literature on the land development aspect has often relied on spatial case studies of individual cities or their meta‐analyses. Using newly‐available data, here we conduct the first global‐coverage, spatial analysis of the relationship between (changes in) population and built‐up land at multiple spatial scales, and compare to existing common beliefs about urbanization based on individual city studies. We find that population and built‐up land show distinctly different spatial and temporal patterns (with a global correlation coefficient around 0.6). Contrary to common impressions, our results show that during recent decades, developed and developing regions across the world experienced comparable amounts of built‐up land expansion. While meta‐analyses have reported that built‐up land in urban areas expands globally on average twice as fast as population grows, our results show the global change rates of built‐up land and population are similar. Also, most global population, including what national statistics agencies call urban population, reside in areas with low land development levels (which are frequently less than 5% built up). These changes in perspective suggest that urbanization's potential large‐scale impacts may need to be re‐evaluated, and lead to best‐practice recommendations for urbanization modeling and analysis. Especially, the common practice in large‐scale earth system modeling of assuming demographically‐defined urban population resides in areas with medium to high built‐up land development levels should change.
What Controls the Probability Distribution of Local Wave Activity in the Midlatitudes?
Authors: Valva Claire , Nakamura Noboru 
Published: July 2021

AbstractThis paper examines probability distributions of local wave activity (LWA), a measure of the jet stream's meander, and factors that control them. The observed column‐mean LWA distributions exhibit significant seasonal, interhemispheric, and regional variations but are always positively skewed in the extratropics, and their tail often involves disruptions of the jet stream. A previously derived one‐dimensional (1D) traffic flow model driven by observed spectra of transient eddy forcing qualitatively reproduces the shape of the observed LWA distribution. It is shown that the skewed distribution emerges from nonlinearity in the zonal advection of LWA even though the eddy forcing is symmetrically distributed. A slower jet and stronger transient and stationary eddy forcings, when introduced independently, all broaden the LWA distribution and increase the probability of spontaneous jet disruption. A quasigeostrophic two‐layer model also simulates skewed LWA distributions in the upper layer. However, in the two‐layer model both transient eddy forcing and the jet speed increase with an increasing shear (meridional temperature gradient), and their opposing influence leaves the frequency of jet disruptions insensitive to the vertical shear. When the model's nonlinearity in the zonal flux of potential vorticity is artificially suppressed, it hinders wave‐flow interaction and virtually eliminates reversal of the upper‐layer zonal wind. The study underscores the importance of nonlinearity in the zonal transmission of Rossby waves to the frequency of jet disruptions and associated weather anomalies.
Calbindin regulates Kv4.1 trafficking and excitability in dentate granule cells via CaMKII-dependent phosphorylation
Authors: Kim Kyung-Ran , Jeong Hyeon-Ju , Kim Yoonsub , Lee Seung Yeon , Kim Yujin , Kim Hyun-Ji , Lee Suk-Ho , Cho Hana , Kang Jong-Sun , Ho Won-Kyung 
Published: July 2021

AbstractCalbindin, a major Ca2+ buffer in dentate granule cells (GCs), plays a critical role in shaping Ca2+ signals, yet how it regulates neuronal function remains largely unknown. Here, we found that calbindin knockout (CBKO) mice exhibited dentate GC hyperexcitability and impaired pattern separation, which co-occurred with reduced K+ current due to downregulated surface expression of Kv4.1. Relatedly, manipulation of calbindin expression in HT22 cells led to changes in CaMKII activation and the level of surface localization of Kv4.1 through phosphorylation at serine 555, confirming the mechanism underlying neuronal hyperexcitability in CBKO mice. We also discovered that Ca2+ buffering capacity was significantly reduced in the GCs of Tg2576 mice to the level of CBKO GCs, and this reduction was restored to normal levels by antioxidants, suggesting that calbindin is a target of oxidative stress. Our data suggest that the regulation of CaMKII signaling by Ca2+ buffering is crucial for neuronal excitability regulation.
Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank
Authors: Wainberg Michael , Kloiber Stefan , Diniz Breno , McIntyre Roger S. , Felsky Daniel , Tripathy Shreejoy J. 
Published: July 2021

AbstractPrevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.
A novel and effective approach to generate germline-like monoclonal antibodies by integration of phage and mammalian cell display platforms
Authors: Jin Yu-jia , Yu Diao , Tian Xiao-long , Li Hui-xian , Zhou Xiao-chao , Kong Yu , Zhang Wei , Zhang Lu , Lei Cheng , Yang Zhen-lin , Tu Chao , Wu Yan-ling , Ying Tian-lei 
Published: July 2021

AbstractPhage display technology allows for rapid selection of antibodies from the large repertoire of human antibody fragments displayed on phages. However, antibody fragments should be converted to IgG for biological characterizations and affinity of antibodies obtained from phage display library is frequently not sufficient for efficient use in clinical settings. Here, we describe a new approach that combines phage and mammalian cell display, enabling simultaneous affinity screening of full-length IgG antibodies. Using this strategy, we successfully obtained a novel germline-like anti-TIM-3 monoclonal antibody named m101, which was revealed to be a potent anti-TIM-3 therapeutic monoclonal antibody via in vitro and in vivo experiments, indicating its effectiveness and power. Thus, this platform can help develop new monoclonal antibody therapeutics with high affinity and low immunogenicity.
Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice
Authors: Beaulac Holly J. , Gilels Felicia , Zhang Jingyuan , Jeoung Sarah , White Patricia M. 
Published: July 2021

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/−), and Foxo3 knock-out (Foxo3−/−) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and caspase-independent apoptosis. Lower immunoreactivity of the calcium buffer Oncomodulin in Foxo3−/− OHCs correlated with cell loss beginning 4 h post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3−/− mice that may contribute to OHC noise susceptibility. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise-exposed Foxo3−/− mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.
Intestinal Klebsiella pneumoniae infection enhances susceptibility to epileptic seizure which can be reduced by microglia activation
Authors: Lin Peijia , Lin Aolei , Tao Kaiyan , Yang Min , Ye Qinglin , Chen Hongnian , Chen Yuanyuan , Ma Yuanlin , Lin Zijun , He Miaoqing , Wang Xuefeng , Tian Xin 
Published: July 2021

AbstractEpilepsy is a common nervous system disease, and the existing theory does not fully clarify its pathogenesis. Recent research suggests that intestinal microbes may be involved in the development of epilepsy, but which microbe is involved remains unclear. We used 16s rRNA sequencing to identify the most relevant gut microbe. To determine the relationship between this microbe and epilepsy, we used an animal model. In addition, western blotting and immunofluorescence, as well as inhibitor studies, were used to evaluate and confirm the role of microglia in this process. In this study, we first report an increase in gut Klebsiella pneumoniae in patients with epilepsy. Subsequently, animal studies revealed that Klebsiella pneumoniae in the intestinal tract affects seizure susceptibility and activates microglial cells to release inflammatory factors. Furthermore, the inflammatory response of microglial cells plays a protective role in the seizure susceptibility caused by an increased abundance of Klebsiella pneumoniae. Our results suggest that gut disruption may be involved in seizure regulation and microglia protect the brain against seizure under this condition. These findings provide a new perspective for research on the pathogenesis and prevention of epilepsy.
Ferromagnetism and giant magnetoresistance in zinc-blende FeAs monolayers embedded in semiconductor structures
Authors: Anh Le Duc , Hayakawa Taiki , Nakagawa Yuji , Shinya Hikari , Fukushima Tetsuya , Kobayashi Masaki , Katayama-Yoshida Hiroshi , Iwasa Yoshihiro , Tanaka Masaaki 
Published: July 2021

AbstractMaterial structures containing tetrahedral FeAs bonds, depending on their density and geometrical distribution, can host several competing quantum ground states ranging from superconductivity to ferromagnetism. Here we examine structures of quasi two-dimensional (2D) layers of tetrahedral Fe-As bonds embedded with a regular interval in a semiconductor InAs matrix, which resembles the crystal structure of Fe-based superconductors. Contrary to the case of Fe-based pnictides, these FeAs/InAs superlattices (SLs) exhibit ferromagnetism, whose Curie temperature (TC) increases rapidly with decreasing the InAs interval thickness tInAs (TC ∝ tInAs−3), and an extremely large magnetoresistance up to 500% that is tunable by a gate voltage. Our first principles calculations reveal the important role of disordered positions of Fe atoms in the establishment of ferromagnetism in these quasi-2D FeAs-based SLs. These unique features mark the FeAs/InAs SLs as promising structures for spintronic applications.
Hexosamine biosynthetic pathway and O-GlcNAc-processing enzymes regulate daily rhythms in protein O-GlcNAcylation
Authors: Liu Xianhui , Blaženović Ivana , Contreras Adam J. , Pham Thu M. , Tabuloc Christine A. , Li Ying H. , Ji Jian , Fiehn Oliver , Chiu Joanna C. 
Published: July 2021

AbstractThe integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. Using Drosophila as an animal model, we show that cellular protein O-GlcNAcylation exhibits robust 24-hour rhythm and represents a key post-translational mechanism that regulates circadian physiology. We observe strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms are severely dampened when we subject flies to time-restricted feeding at unnatural feeding time. This suggests the presence of clock-regulated buffering mechanisms that prevent excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We show that this buffering mechanism is mediated by the expression and activity of GFAT, OGT, and OGA, which are regulated through integration of circadian and metabolic signals. Finally, we generate a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.
Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women
Authors: Adedokun Babatunde , Du Zhaohui , Gao Guimin , Ahearn Thomas U. , Lunetta Kathryn L. , Zirpoli Gary , Figueroa Jonine , John Esther M. , Bernstein Leslie , Zheng Wei , Hu Jennifer J. , Ziegler Regina G. , Nyante Sarah , Bandera Elisa V. , Ingles Sue A. , Press Michael F. , Deming-Halverson Sandra L. , Rodriguez-Gil Jorge L. , Yao Song , Ogundiran Temidayo O. , Ojengbede Oladosu , Blot William , Troester Melissa A. , Nathanson Katherine L. , Hennis Anselm , Nemesure Barbara , Ambs Stefan , Fiorica Peter N. , Sucheston-Campbell Lara E. , Bensen Jeannette T. , Kushi Lawrence H. , Torres-Mejia Gabriela , Hu Donglei , Fejerman Laura , Bolla Manjeet K. , Dennis Joe , Dunning Alison M. , Easton Douglas F. , Michailidou Kyriaki , Pharoah Paul D. P. , Wang Qin , Sandler Dale P. , Taylor Jack A. , O’Brien Katie M. , Kitahara Cari M. , Falusi Adeyinka G. , Babalola Chinedum , Yarney Joel , Awuah Baffour , Addai-Wiafe Beatrice ,   The GBHS Study Team, Chanock Stephen J. , Olshan Andrew F. , Ambrosone Christine B. , Conti David V. , Ziv Elad , Olopade Olufunmilayo I. , Garcia-Closas Montserrat , Palmer Julie R. , Haiman Christopher A. , Huo Dezheng 
Published: July 2021

AbstractOur study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
Mariana-type ophiolites constrain the establishment of modern plate tectonic regime during Gondwana assembly
Authors: Yao Jinlong , Cawood Peter A. , Zhao Guochun , Han Yigui , Xia Xiaoping , Liu Qian , Wang Peng 
Published: July 2021

AbstractInitiation of Mariana-type oceanic subduction zones requires rheologically strong oceanic lithosphere, which developed through secular cooling of Earth’s mantle. Here, we report a 518 Ma Mariana-type subduction initiation ophiolite from northern Tibet, which, along with compilation of similar ophiolites through Earth history, argues for the establishment of the modern plate tectonic regime by the early Cambrian. The ophiolite was formed during the subduction initiation of the Proto-Tethys Ocean that coincided with slab roll-back along the southern and western Gondwana margins at ca. 530-520 Ma. This global tectonic re-organization and the establishment of modern plate tectonic regime was likely controlled by secular cooling of the Earth, and facilitated by enhanced lubrication of subduction zones by sediments derived from widespread surface erosion of the extensive mountain ranges formed during Gondwana assembly. This time also corresponds to extreme events recorded in climate and surface proxies that herald formation of the contemporary Earth.