bluuebunny/crossref_metadata_2025_split huggingface dataset:
A great convergence: The American frontier and the origins of Japanese migration to Brazil
Authors: Lu Sidney Xu 
Published: June 2021

AbstractThis article explains how the US westward expansion influenced and stimulated Japanese migration to Brazil. Emerging in the nineteenth century as expanding powers in East Asia and Latin America, respectively, both Meiji Japan and post-independence Brazil looked to the US westward expansion as a central reference for their own processes of settler colonialism. The convergence of Japan and Brazil in their imitation of US settler colonialism eventually brought the two sides together at the turn of the twentieth century to negotiate for the start of Japanese migration to Brazil. This article challenges the current understanding of Japanese migration to Brazil, conventionally regarded as a topic of Latin American ethnic studies, by placing it in the context of settler colonialism in both Japanese and Brazilian histories. The study also explores the shared experiences of East Asia and Latin America as they felt the global impact of the American westward expansion.
An Integrated Framework to Streamline Resilience in the Context of Urban Climate Risk Assessment
Authors: Urquiza A. , Amigo C. , Billi M. , Calvo R. , Gallardo L. , Neira C. I. , Rojas M. 
Published: June 2021

AbstractCities are increasingly acknowledged as crucial when facing climate change—and the environmental crisis more in general—, offering challenges and opportunities in terms of both mitigation and adaptation. Climate change‐sensitive urban governance requires proactive, integrated, and contextualized approaches, making room for the complex, multilayered, multiscalar, and dynamic processes constituting a city. The notion of “resilience” has been acquiring growing recognition as a flexible and powerful concept to respond to these challenges. Resilience itself, however, is also a polysemic notion, often treated as little more than a catchword or a wishful aim or superimposed with other climate‐related terms, such as risk, vulnerability, or adaptation. To promote a stronger integration among different problem‐settings and epistemic communities, this paper advances six analytical distinctions aiming to provide structure and articulation to existing definitions of the concept of “resilience.” Likewise, it offers an integrated analytical framework and methodological pipeline to streamline resilience analysis in the context of urban climate risk assessment. The framework is specially defined to link up with the definition of climate risk provided by the Intergovernmental Panel on Climate Change (IPCC) latest Assessment Reports and is illustrated through examples derived from the recent experience of the Chilean Climate Risk Atlas.
An Early Garnet Redox‐Filter as an Additive Oxidizer in Lower Continental Arc Crust Traced Through Fe Isotopes
Authors: Li Qi‐Wei , Nebel‐Jacobsen Yona , Zhao Jun‐Hong , Nebel Oliver , Richter Marianne , Cawood Peter A. , Wang Qiang 
Published: June 2021

AbstractThe magmatic differentiation of cooling arc lavas on their way to the surface is dominated by fractional crystallization, which predominantly occurs at lower crustal arc levels (25–40 km) at continental margins. The magmatic storage in the deep crust is complex and remote, and rarely studied compared to shallow magma fractionation, but carries key information for the formation and evolution of the lower continental crust. At convergent continental margins, mantle‐derived melts must pass through a complex system of rocks in the lower arc crust. In particular, melts inevitably transition through deep “hot” (melt‐rich) or “cold” (i.e., water‐rich) zones, collectively termed here lower crustal arc zones (LoCAZ) to account for both scenarios. Their role in driving melt modification, including formation and oxidation of calc‐alkaline suites, remains unclear. Here we report stable Fe isotope compositions of 40 well‐characterized Neoproterozoic mafic dikes from the northwestern margin of the Yangtze Block, representing three stages of continental arc evolution. Rocks from the Tongde dikes display strong correlations between δ57Fe values and trace element indices of garnet fractionation (e.g., high La/Yb and depleted heavy REE patterns). An increase in heavy Fe isotopes with garnet fractionation indicates a redox‐filtering of melts through LoCAZ. We thus propose that retention of Fe2+ in deep crustal garnet is one driver for elevated fO2 and the calc‐alkaline trend in continental margin rocks. With continental arc rocks being on average more oxidized than intra‐oceanic arc lavas, garnet redox‐filtering may be an additive oxidizer in thicker arc crust. The Tongde dike swarms may represent a rare, volumetrically small, direct example of melts ejected out of the lower arc crust. The complex mixing and mingling of melts reported for most arcs and their plutons may obscure this redox process contributing to continental crust growth.
Estimation of Macrodispersivity in Bounded Formations by Circulant Embedding and Analysis of Variance
Authors: Liao Qinzhuo , Lei Gang , Zhang Dongxiao , Patil Shirish 
Published: June 2021

AbstractWe present a new method to estimate the displacement covariance and macrodispersivity for solute transport in bounded formations. Here we use circulant embedding, which is based on fast Fourier transform and is much more efficient than eigen‐decomposition, for the factorization of random spatial fields. We compute the displacement covariances by the analysis of variance approach, and introduce an interpolation process to significantly reduce the number of forward simulations. Once the effect of each eigenvector on the displacement covariance is obtained, it is unnecessary to rerun the simulator for different spatial covariance functions or anisotropy ratios, which saves a large amount of computational effort. The proposed method is validated in various tests in two‐dimensional and three‐dimensional examples and accurately matches the results from the Monte Carlo simulation. It is found that the longitudinal dispersivity is less sensitive to the impervious boundaries, while the transverse and vertical dispersivities are greatly affected. The method is applied to the Borden site and provides a better explanation of the observed data after considering the effect of vertical boundaries. These results show that our method could serve as a promising tool for studying and predicting the characteristics of solute transport in heterogeneous media.
Lactate dehydrogenases amplify reactive oxygen species in cancer cells in response to oxidative stimuli
Authors: Wu Hao , Wang Yuqi , Ying Minfeng , Jin Chengmeng , Li Jiangtao , Hu Xun 
Published: June 2021

AbstractPrevious studies demonstrated that superoxide could initiate and amplify LDH-catalyzed hydrogen peroxide production in aqueous phase, but its physiological relevance is unknown. Here we showed that LDHA and LDHB both exhibited hydrogen peroxide-producing activity, which was significantly enhanced by the superoxide generated from the isolated mitochondria from HeLa cells and patients’ cholangiocarcinoma specimen. After LDHA or LDHB were knocked out, hydrogen peroxide produced by Hela or 4T1 cancer cells were significantly reduced. Re-expression of LDHA in LDHA-knockout HeLa cells partially restored hydrogen peroxide production. In HeLa and 4T1 cells, LDHA or LDHB knockout or LDH inhibitor FX11 significantly decreased ROS induction by modulators of the mitochondrial electron transfer chain (antimycin, oligomycin, rotenone), hypoxia, and pharmacological ROS inducers piperlogumine (PL) and phenethyl isothiocyanate (PEITC). Moreover, the tumors formed by LDHA or LDHB knockout HeLa or 4T1 cells exhibited a significantly less oxidative state than those formed by control cells. Collectively, we provide a mechanistic understanding of a link between LDH and cellular hydrogen peroxide production or oxidative stress in cancer cells in vitro and in vivo.
U2AF1 mutation promotes tumorigenicity through facilitating autophagy flux mediated by FOXO3a activation in myelodysplastic syndromes
Authors: Zhu Yuqian , Song Dandan , Guo Juan , Jin Jiacheng , Tao Ying , Zhang Zheng , Xu Feng , He Qi , Li Xiao , Chang Chunkang , Wu Lingyun 
Published: June 2021

AbstractMutations in the U2 small nuclear RNA auxiliary factor 1 (U2AF1) gene are the common feature of a major subset in myelodysplastic syndromes (MDS). However, the genetic landscape and molecular pathogenesis of oncogenic U2AF1S34F mutation in MDS are not totally understood. We performed comprehensive analysis for prognostic significance of U2AF1 mutations in acute myeloid leukemia (AML) cohort based on The Cancer Genome Atlas (TCGA) database. Functional analysis of U2AF1S34F mutation was performed in vitro. Differentially expressed genes (DEGs) and significantly enriched pathways were identified by RNA sequencing. The forkhead box protein O3a (FOXO3a) was investigated to mediate the function of U2AF1S34F mutation in cell models using lentivirus. Chromatin immunoprecipitation, immunoblotting analyses, and immunofluorescence assays were also conducted. U2AF1 mutations were associated with poor prognosis in MDS and AML samples, which significantly inhibited cell proliferation and induced cellular apoptosis in cell models. Our data identified that U2AF1-mutant cell lines undergo FOXO3a-dependent apoptosis and NLRP3 inflammasome activation, which induces pyroptotic cell death. Particularly, an increase in the level of FOXO3a promoted the progression of MDS in association with restored autophagy program leading to NLRP3 inflammasome activation in response to U2AF1S34F mutation. Based on the result that U2AF1S34F mutation promoted the transcriptional activity of Bim through upregulating FOXO3a with transactivation of cell cycle regulators p21Cip1 and p27Kip1, FOXO3a, a potentially cancer-associated transcription factor, was identified as the key molecule on which these pathways converge. Overall, our studies provide new insights that U2AF1S34F mutation functions the crucial roles in mediating MDS disease progression via FOXO3a activation, and demonstrate novel targets of U2AF1 mutations to the pathogenesis of MDS.
Endoplasmic reticulum−mitochondria coupling increases during doxycycline-induced mitochondrial stress in HeLa cells
Authors: Lopez-Crisosto Camila , Díaz-Vegas Alexis , Castro Pablo F. , Rothermel Beverly A. , Bravo-Sagua Roberto , Lavandero Sergio 
Published: June 2021

AbstractSubcellular organelles communicate with each other to regulate function and coordinate responses to changing cellular conditions. The physical-functional coupling of the endoplasmic reticulum (ER) with mitochondria allows for the direct transfer of Ca2+ between organelles and is an important avenue for rapidly increasing mitochondrial metabolic activity. As such, increasing ER−mitochondrial coupling can boost the generation of ATP that is needed to restore homeostasis in the face of cellular stress. The mitochondrial unfolded protein response (mtUPR) is activated by the accumulation of unfolded proteins in mitochondria. Retrograde signaling from mitochondria to the nucleus promotes mtUPR transcriptional responses aimed at restoring protein homeostasis. It is currently unknown whether the changes in mitochondrial−ER coupling also play a role during mtUPR stress. We hypothesized that mitochondrial stress favors an expansion of functional contacts between mitochondria and ER, thereby increasing mitochondrial metabolism as part of a protective response. Hela cells were treated with doxycycline, an antibiotic that inhibits the translation of mitochondrial-encoded proteins to create protein disequilibrium. Treatment with doxycycline decreased the abundance of mitochondrial encoded proteins while increasing expression of CHOP, C/EBPβ, ClpP, and mtHsp60, markers of the mtUPR. There was no change in either mitophagic activity or cell viability. Furthermore, ER UPR was not activated, suggesting focused activation of the mtUPR. Within 2 h of doxycycline treatment, there was a significant increase in physical contacts between mitochondria and ER that was distributed throughout the cell, along with an increase in the kinetics of mitochondrial Ca2+ uptake. This was followed by the rise in the rate of oxygen consumption at 4 h, indicating a boost in mitochondrial metabolic activity. In conclusion, an early phase of the response to doxycycline-induced mitochondrial stress is an increase in mitochondrial−ER coupling that potentiates mitochondrial metabolic activity as a means to support subsequent steps in the mtUPR pathway and sustain cellular adaptation.
Teprotumumab for thyroid eye disease: early response is not required for benefit
Authors: Ugradar Shoaib , Wang Yao , Mester Tunde , Kahaly George J. , Douglas Raymond S. 
Published: June 2021

Abstract
Purpose
In recent trials, 50% of patients treated with teprotumumab for thyroid eye disease had significant improvements in proptosis at 6 weeks. However, a small subgroup of patients did not have a significant response by week 12. We examine the outcomes at week 24 in patients from both trials who had little or no proptosis response at week 12.

Design
In this post hoc analysis, data from teprotumumab-treated patients in the placebo-controlled randomized phases 2 and 3 trials were reviewed.

Methods
Patients treated with teprotumumab or placebo with a ≤2 mm reduction from baseline in proptosis at week 12 and completed assessments at both the weeks 12 and 24 visits were included. The main outcome measures were a change in proptosis, clinical activity score (CAS) and diplopia in response to teprotumumab therapy at baseline and weeks 6, 12, 18, and 24.

Results
From the phases 2 and 3 studies, 24 patients from the treated and placebo groups were included for analysis (48 total). In the teprotumumab group, of the 24 who had no improvement in proptosis (≥2 mm from baseline) at 12 weeks, 15 (63%) demonstrated a clinically significant improvement at week 24. No patients from the 24 placebo patients had a clinically significant improvement in proptosis at 12 weeks, and 24 weeks. At week 12, 22 patients (92%) in the teprotumumab group had a significant reduction in the CAS (≥2 points) and at 24 weeks all patients achieved this reduction. At week 12, 11 (46%) patients from the placebo group had a significant improvement, while 10 (42%) had a significant improvement at 24 weeks. 22 of the 24 patients (92%) in the teprotumumab group had a diplopia grade > 0 at baseline. At week 12, 12 of the 22 (55%) had improvement in diplopia ≥ 1 grade. By week 24, 16 patients (73%) had an improvement in diplopia ≥ 1 grade. In the placebo group, 15 (63%) had significant diplopia. At week 12, 3 (20%) from this group had improvement in diplopia ≥ 1 grade, while at 24 weeks this number rose to 4 (27%).

Conclusions
There is variability in the time taken to manifest a clinically significant response to teprotumumab, some patients my need a longer time to respond.
The Great Oxygenation Event as a consequence of ecological dynamics modulated by planetary change
Authors: Olejarz Jason , Iwasa Yoh , Knoll Andrew H. , Nowak Martin A. 
Published: June 2021

AbstractThe Great Oxygenation Event (GOE), ca. 2.4 billion years ago, transformed life and environments on Earth. Its causes, however, are debated. We mathematically analyze the GOE in terms of ecological dynamics coupled with a changing Earth. Anoxygenic photosynthetic bacteria initially dominate over cyanobacteria, but their success depends on the availability of suitable electron donors that are vulnerable to oxidation. The GOE is triggered when the difference between the influxes of relevant reductants and phosphate falls below a critical value that is an increasing function of the reproductive rate of cyanobacteria. The transition can be either gradual and reversible or sudden and irreversible, depending on sources and sinks of oxygen. Increasing sources and decreasing sinks of oxygen can also trigger the GOE, but this possibility depends strongly on migration of cyanobacteria from privileged sites. Our model links ecological dynamics to planetary change, with geophysical evolution determining the relevant time scales.
Emergence of local and global synaptic organization on cortical dendrites
Authors: Kirchner Jan H. , Gjorgjieva Julijana 
Published: June 2021

AbstractSynaptic inputs on cortical dendrites are organized with remarkable subcellular precision at the micron level. This organization emerges during early postnatal development through patterned spontaneous activity and manifests both locally where nearby synapses are significantly correlated, and globally with distance to the soma. We propose a biophysically motivated synaptic plasticity model to dissect the mechanistic origins of this organization during development and elucidate synaptic clustering of different stimulus features in the adult. Our model captures local clustering of orientation in ferret and receptive field overlap in mouse visual cortex based on the receptive field diameter and the cortical magnification of visual space. Including action potential back-propagation explains branch clustering heterogeneity in the ferret and produces a global retinotopy gradient from soma to dendrite in the mouse. Therefore, by combining activity-dependent synaptic competition and species-specific receptive fields, our framework explains different aspects of synaptic organization regarding stimulus features and spatial scales.
Type II alveolar cell MHCII improves respiratory viral disease outcomes while exhibiting limited antigen presentation
Authors: Toulmin Sushila A. , Bhadiadra Chaitali , Paris Andrew J. , Lin Jeffrey H. , Katzen Jeremy , Basil Maria C. , Morrisey Edward E. , Worthen G. Scott , Eisenlohr Laurence C. 
Published: June 2021

AbstractType II alveolar cells (AT2s) are critical for basic respiratory homeostasis and tissue repair after lung injury. Prior studies indicate that AT2s also express major histocompatibility complex class II (MHCII) molecules, but how MHCII expression by AT2s is regulated and how it contributes to host defense remain unclear. Here we show that AT2s express high levels of MHCII independent of conventional inflammatory stimuli, and that selective loss of MHCII from AT2s in mice results in modest worsening of respiratory virus disease following influenza and Sendai virus infections. We also find that AT2s exhibit MHCII presentation capacity that is substantially limited compared to professional antigen presenting cells. The combination of constitutive MHCII expression and restrained antigen presentation may position AT2s to contribute to lung adaptive immune responses in a measured fashion, without over-amplifying damaging inflammation.
Tuning of lattice oxygen reactivity and scaling relation to construct better oxygen evolution electrocatalyst
Authors: Huang Zhen-Feng , Xi Shibo , Song Jiajia , Dou Shuo , Li Xiaogang , Du Yonghua , Diao Caozheng , Xu Zhichuan J. , Wang Xin 
Published: June 2021

AbstractDeveloping efficient and low-cost electrocatalysts for oxygen evolution reaction is crucial in realizing practical energy systems for sustainable fuel production and energy storage from renewable energy sources. However, the inherent linear scaling relation for most catalytic materials imposes a theoretical overpotential ceiling, limiting the development of efficient electrocatalysts. Herein, using modeled NaxMn3O7 materials, we report an effective strategy to construct better oxygen evolution electrocatalyst through tuning both lattice oxygen reactivity and scaling relation via alkali metal ion mediation. Specifically, the number of Na+ is linked with lattice oxygen reactivity, which is determined by the number of oxygen hole in oxygen lone-pair states formed by native Mn vacancies, governing the barrier symmetry between O–H bond cleavage and O–O bond formation. On the other hand, the presence of Na+ could have specific noncovalent interaction with pendant oxygen in *OOH to overcome the limitation from linear scaling relation, reducing the overpotential ceiling. Combining in situ spectroscopy-based characterization with first-principles calculations, we demonstrate that an intermediate level of Na+ mediation (NaMn3O7) exhibits the optimum oxygen evolution activity. This work provides a new rational recipe to develop highly efficient catalyst towards water oxidation or other oxidative reactions through tuning lattice oxygen reactivity and scaling relation.
Restoration of the molecular clock is tumor suppressive in neuroblastoma
Authors: Moreno-Smith Myrthala , Milazzo Giorgio , Tao Ling , Fekry Baharan , Zhu Bokai , Mohammad Mahmoud A. , Di Giacomo Simone , Borkar Roshan , Reddy Karthik Reddy Kami , Capasso Mario , Vasudevan Sanjeev A. , Sumazin Pavel , Hicks John , Putluri Nagireddy , Perini Giovanni , Eckel-Mahan Kristin , Burris Thomas P. , Barbieri Eveline 
Published: June 2021

AbstractMYCN activation is a hallmark of advanced neuroblastoma (NB) and a known master regulator of metabolic reprogramming, favoring NB adaptation to its microenvironment. We found that the expression of the main regulators of the molecular clock loops is profoundly disrupted in MYCN-amplified NB patients, and this disruption independently predicts poor clinical outcome. MYCN induces the expression of clock repressors and downregulates the one of clock activators by directly binding to their promoters. Ultimately, MYCN attenuates the molecular clock by suppressing BMAL1 expression and oscillation, thereby promoting cell survival. Reestablishment of the activity of the clock activator RORα via its genetic overexpression and its stimulation through the agonist SR1078, restores BMAL1 expression and oscillation, effectively blocks MYCN-mediated tumor growth and de novo lipogenesis, and sensitizes NB tumors to conventional chemotherapy. In conclusion, reactivation of RORα could serve as a therapeutic strategy for MYCN-amplified NBs by blocking the dysregulation of molecular clock and cell metabolism mediated by MYCN.
A universal Urbach rule for disordered organic semiconductors
Authors: Kaiser Christina , Sandberg Oskar J. , Zarrabi Nasim , Li Wei , Meredith Paul , Armin Ardalan 
Published: June 2021

AbstractIn crystalline semiconductors, absorption onset sharpness is characterized by temperature-dependent Urbach energies. These energies quantify the static, structural disorder causing localized exponential-tail states, and dynamic disorder from electron-phonon scattering. Applicability of this exponential-tail model to disordered solids has been long debated. Nonetheless, exponential fittings are routinely applied to sub-gap absorption analysis of organic semiconductors. Herein, we elucidate the sub-gap spectral line-shapes of organic semiconductors and their blends by temperature-dependent quantum efficiency measurements. We find that sub-gap absorption due to singlet excitons is universally dominated by thermal broadening at low photon energies and the associated Urbach energy equals the thermal energy, regardless of static disorder. This is consistent with absorptions obtained from a convolution of Gaussian density of excitonic states weighted by Boltzmann-like thermally activated optical transitions. A simple model is presented that explains absorption line-shapes of disordered systems, and we also provide a strategy to determine the excitonic disorder energy. Our findings elaborate the meaning of the Urbach energy in molecular solids and relate the photo-physics to static disorder, crucial for optimizing organic solar cells for which we present a revisited radiative open-circuit voltage limit.