bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turn-key constrained parameter space exploration for particle accelerators using Bayesian active learning
Authors: Roussel Ryan , Gonzalez-Aguilera Juan Pablo , Kim Young-Kee , Wisniewski Eric , Liu Wanming , Piot Philippe , Power John , Hanuka Adi , Edelen Auralee 
Published: September 2021

AbstractParticle accelerators are invaluable discovery engines in the chemical, biological and physical sciences. Characterization of the accelerated beam response to accelerator input parameters is often the first step when conducting accelerator-based experiments. Currently used techniques for characterization, such as grid-like parameter sampling scans, become impractical when extended to higher dimensional input spaces, when complicated measurement constraints are present, or prior information known about the beam response is scarce. Here in this work, we describe an adaptation of the popular Bayesian optimization algorithm, which enables a turn-key exploration of input parameter spaces. Our algorithm replaces the need for parameter scans while minimizing prior information needed about the measurement’s behavior and associated measurement constraints. We experimentally demonstrate that our algorithm autonomously conducts an adaptive, multi-parameter exploration of input parameter space, potentially orders of magnitude faster than conventional grid-like parameter scans, while making highly constrained, single-shot beam phase-space measurements and accounts for costs associated with changing input parameters. In addition to applications in accelerator-based scientific experiments, this algorithm addresses challenges shared by many scientific disciplines, and is thus applicable to autonomously conducting experiments over a broad range of research topics.
Collaborative management of the Grand Ethiopian Renaissance Dam increases economic benefits and resilience
Authors: Basheer Mohammed , Nechifor Victor , Calzadilla Alvaro , Siddig Khalid , Etichia Mikiyas , Whittington Dale , Hulme David , Harou Julien J. 
Published: September 2021

AbstractThe landscape of water infrastructure in the Nile Basin is changing with the construction of the Grand Ethiopian Renaissance Dam. Although this dam could improve electricity supply in Ethiopia and its neighbors, there is a lack of consensus between Ethiopia, Sudan, and Egypt on the dam operation. We introduce a new modeling framework that simulates the Nile River System and Egypt’s macroeconomy, with dynamic feedbacks between the river system and the macroeconomy. Because the two systems “coevolve” throughout multi-year simulations, we term this a “coevolutionary” modeling framework. The framework is used to demonstrate that a coordinated operating strategy could allow the Grand Ethiopian Renaissance Dam to help meet water demands in Egypt during periods of water scarcity and increase hydropower generation and storage in Ethiopia during high flows. Here we show the hydrological and macroeconomic performance of this coordinated strategy compared to a strategy that resembles a recent draft proposal for the operation of the dam discussed in Washington DC.
Peering into lunar permanently shadowed regions with deep learning
Authors: Bickel V. T. , Moseley B. , Lopez-Francos I. , Shirley M. 
Published: September 2021

AbstractThe lunar permanently shadowed regions (PSRs) are expected to host large quantities of water-ice, which are key for sustainable exploration of the Moon and beyond. In the near future, NASA and other entities plan to send rovers and humans to characterize water-ice within PSRs. However, there exists only limited information about the small-scale geomorphology and distribution of ice within PSRs because the orbital imagery captured to date lacks sufficient resolution and/or signal. In this paper, we develop and validate a new method of post-processing LRO NAC images of PSRs. We show that our method is able to reveal previously unseen geomorphological features such as boulders and craters down to 3 meters in size, whilst not finding evidence for surface frost or near-surface ice. Our post-processed images significantly facilitate the exploration of PSRs by reducing the uncertainty of target selection and traverse/mission planning.
9p21 loss confers a cold tumor immune microenvironment and primary resistance to immune checkpoint therapy
Authors: Han Guangchun , Yang Guoliang , Hao Dapeng , Lu Yang , Thein Kyaw , Simpson Benjamin S. , Chen Jianfeng , Sun Ryan , Alhalabi Omar , Wang Ruiping , Dang Minghao , Dai Enyu , Zhang Shaojun , Nie Fengqi , Zhao Shuangtao , Guo Charles , Hamza Ameer , Czerniak Bogdan , Cheng Chao , Siefker-Radtke Arlene , Bhat Krishna , Futreal Andrew , Peng Guang , Wargo Jennifer , Peng Weiyi , Kadara Humam , Ajani Jaffer , Swanton Charles , Litchfield Kevin , Ahnert Jordi Rodon , Gao Jianjun , Wang Linghua 
Published: September 2021

AbstractImmune checkpoint therapy (ICT) provides substantial clinical benefits to cancer patients, but a large proportion of cancers do not respond to ICT. To date, the genomic underpinnings of primary resistance to ICT remain elusive. Here, we performed immunogenomic analysis of data from TCGA and clinical trials of anti-PD-1/PD-L1 therapy, with a particular focus on homozygous deletion of 9p21.3 (9p21 loss), one of the most frequent genomic defects occurring in ~13% of all cancers. We demonstrate that 9p21 loss confers “cold” tumor-immune phenotypes, characterized by reduced abundance of tumor-infiltrating leukocytes (TILs), particularly, T/B/NK cells, altered spatial TILs patterns, diminished immune cell trafficking/activation, decreased rate of PD-L1 positivity, along with activation of immunosuppressive signaling. Notably, patients with 9p21 loss exhibited significantly lower response rates to ICT and worse outcomes, which were corroborated in eight ICT trials of >1,000 patients. Further, 9p21 loss synergizes with PD-L1/TMB for patient stratification. A “response score” was derived by incorporating 9p21 loss, PD-L1 expression and TMB levels in pre-treatment tumors, which outperforms PD-L1, TMB, and their combination in identifying patients with high likelihood of achieving sustained response from otherwise non-responders. Moreover, we describe potential druggable targets in 9p21-loss tumors, which could be exploited to design rational therapeutic interventions.
Direct photoresponsive inhibition of a p53-like transcription activation domain in PIF3 by Arabidopsis phytochrome B
Authors: Yoo Chan Yul , He Jiangman , Sang Qing , Qiu Yongjian , Long Lingyun , Kim Ruth Jean-Ae , Chong Emily G. , Hahm Joseph , Morffy Nicholas , Zhou Pei , Strader Lucia C. , Nagatani Akira , Mo Beixin , Chen Xuemei , Chen Meng 
Published: September 2021

AbstractPhotoactivated phytochrome B (PHYB) binds to antagonistically acting PHYTOCHROME-INTERACTING transcription FACTORs (PIFs) to regulate hundreds of light responsive genes in Arabidopsis by promoting PIF degradation. However, whether PHYB directly controls the transactivation activity of PIFs remains ambiguous. Here we show that the prototypic PIF, PIF3, possesses a p53-like transcription activation domain (AD) consisting of a hydrophobic activator motif flanked by acidic residues. A PIF3mAD mutant, in which the activator motif is replaced with alanines, fails to activate PIF3 target genes in Arabidopsis, validating the functions of the PIF3 AD in vivo. Intriguingly, the N-terminal photosensory module of PHYB binds immediately adjacent to the PIF3 AD to repress PIF3’s transactivation activity, demonstrating a novel PHYB signaling mechanism through direct interference of the transactivation activity of PIF3. Our findings indicate that PHYB, likely also PHYA, controls the stability and activity of PIFs via structurally separable dual signaling mechanisms.
Lattice reconstruction induced multiple ultra-flat bands in twisted bilayer WSe2
Authors: Li En , Hu Jin-Xin , Feng Xuemeng , Zhou Zishu , An Liheng , Law Kam Tuen , Wang Ning , Lin Nian 
Published: September 2021

AbstractMoiré superlattices in van der Waals heterostructures provide a tunable platform to study emergent properties that are absent in the natural crystal form. Twisted bilayer transition metal dichalcogenides (TB-TMDs) can host moiré flat bands over a wide range of twist angles. For twist angle close to 60°, it was predicted that TB-TMDs undergo a lattice reconstruction which causes the formation of ultra-flat bands. Here, by using scanning tunneling microscopy and spectroscopy, we show the emergence of multiple ultra-flat bands in twisted bilayer WSe2 when the twist angle is within 3° of 60°. The ultra-flat bands are manifested as narrow tunneling conductance peaks with estimated bandwidth less than 10 meV, which is only a fraction of the estimated on-site Coulomb repulsion energy. The number of these ultra-flat bands and spatial distribution of the wavefunctions match well with the theoretical predictions, strongly evidencing that the observed ultra-flat bands are induced by lattice reconstruction. Our work provides a foundation for further study of the exotic correlated phases in TB-TMDs.
SARS-CoV-2 mucosal antibody development and persistence and their relation to viral load and COVID-19 symptoms
Authors: Fröberg Janeri , Gillard Joshua , Philipsen Ria , Lanke Kjerstin , Rust Joyce , van Tuijl Diana , Teelen Karina , Bousema Teun , Simonetti Elles , van der Gaast-de Jongh Christa E. , Bos Mariska , van Kuppeveld Frank J. , Bosch Berend-Jan , Nabuurs-Franssen Marrigje , van der Geest-Blankert Nannet , van Daal Charlotte , Huynen Martijn A. , de Jonge Marien I. , Diavatopoulos Dimitri A. 
Published: September 2021

AbstractAlthough serological studies have shown that antibodies against SARS-CoV-2 play an important role in protection against (re)infection, the dynamics of mucosal antibodies during primary infection and their potential impact on viral load and the resolution of disease symptoms remain unclear. During the first pandemic wave, we assessed the longitudinal nasal antibody response in index cases with mild COVID-19 and their household contacts. Nasal and serum antibody responses were analysed for up to nine months. Higher nasal receptor binding domain and spike protein-specific antibody levels at study inclusion were associated with lower viral load. Older age was correlated with more frequent COVID-19 related symptoms. Receptor binding domain and spike protein-specific mucosal antibodies were associated with the resolution of systemic, but not respiratory symptoms. Finally, receptor binding domain and spike protein-specific mucosal antibodies remained elevated up to nine months after symptom onset.
Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions
Authors: Gómez Xavier , Sanon Serena , Zambrano Kevin , Asquel Samira , Bassantes Mariuxi , Morales Julián E. , Otáñez Gabriela , Pomaquero Core , Villarroel Sarah , Zurita Alejandro , Calvache Carlos , Celi Kathlyn , Contreras Terry , Corrales Dylan , Naciph María Belén , Peña José , Caicedo Andrés 
Published: September 2021

AbstractExposure to microgravity and ionizing radiation during spaceflight missions causes excessive reactive oxygen species (ROS) production that contributes to cellular stress and damage in astronauts. Average spaceflight mission time is expected to lengthen as humanity aims to visit other planets. However, longer missions or spaceflights will undoubtedly lead to an increment in microgravity, ionizing radiation and ROS production. Strategies to minimize ROS damage are necessary to maintain the health of astronauts, future space colonists, and tourists during and after spaceflight missions. An antioxidant cocktail formulated to prevent or mitigate ROS damage during space exploration could help maintain the health of space explorers. We propose key points to consider when developing an antioxidant cocktail. We discuss how ROS damages our body and organs, the genetic predisposition of astronauts to its damage, characteristics and evidence of the effectiveness of antioxidants to combat excess ROS, differences in drug metabolism when on Earth and in space that could modify antioxidant effects, and the characteristics and efficacy of common antioxidants. Based on this information we propose a workflow for assessing astronaut resistance to ROS damage, infight monitoring of ROS production, and an antioxidant cocktail. Developing an antioxidant cocktail represents a big challenge to translate current medical practices from an Earth setting to space. The key points presented in this review could promote the development of different antioxidant formulations to maintain space explorers’ health in the future.
Quantifying the optimal strategy of population control of quorum sensing network in Escherichia coli
Authors: Li Xiang , Jin Jun , Zhang Xiaocui , Xu Fei , Zhong Jinjin , Yin Zhiyong , Qi Hong , Wang Zhaoshou , Shuai Jianwei 
Published: September 2021

AbstractBiological functions of bacteria can be regulated by monitoring their own population density induced by the quorum sensing system. However, quantitative insight into the system’s dynamics and regulatory mechanism remain challenging. Here, we construct a comprehensive mathematical model of the synthetic quorum sensing circuit that controls population density in Escherichia coli. Simulations agree well with experimental results obtained under different ribosome-binding site (RBS) efficiencies. We present a quantitative description of the component dynamics and show how the components respond to isopropyl-β-D-1-thiogalactopyranoside (IPTG) induction. The optimal IPTG-induction range for efficiently controlling population density is quantified. The controllable area of population density by acyl-homoserine lactone (AHL) permeability is quantified as well, indicating that high AHL permeability should be treated with a high dose of IPTG, while low AHL permeability should be induced with low dose for efficiently controlling. Unexpectedly, an oscillatory behavior of the growth curve is observed with proper RBS-binding strengths and the oscillation is greatly restricted by the bacterial death induced by toxic metabolic by-products. Moreover, we identify that the mechanism underlying the emergence of oscillation is determined by the negative feedback loop structure within the signaling. Bifurcation analysis and landscape theory are further employed to study the stochastic dynamic and global stability of the system, revealing two faces of toxic metabolic by-products in controlling oscillatory behavior. Overall, our study presents a quantitative basis for understanding and new insights into the control mechanism of quorum sensing system, providing possible clues to guide the development of more rational control strategy.
Mass measurements of 99–101In challenge ab initio nuclear theory of the nuclide 100Sn
Authors: Mougeot M. , Atanasov D. , Karthein J. , Wolf R. N. , Ascher P. , Blaum K. , Chrysalidis K. , Hagen G. , Holt J. D. , Huang W. J. , Jansen G. R. , Kulikov I. , Litvinov Yu. A. , Lunney D. , Manea V. , Miyagi T. , Papenbrock T. , Schweikhard L. , Schwenk A. , Steinsberger T. , Stroberg S. R. , Sun Z. H. , Welker A. , Wienholtz F. , Wilkins S. G. , Zuber K. 
Published: September 2021

AbstractThe tin isotope 100Sn is of singular interest for nuclear structure due to its closed-shell proton and neutron configurations. It is also the heaviest nucleus comprising protons and neutrons in equal numbers—a feature that enhances the contribution of the short-range proton–neutron pairing interaction and strongly influences its decay via the weak interaction. Decay studies in the region of 100Sn have attempted to prove its doubly magic character1 but few have studied it from an ab initio theoretical perspective2,3, and none of these has addressed the odd-proton neighbours, which are inherently more difficult to describe but crucial for a complete test of nuclear forces. Here we present direct mass measurements of the exotic odd-proton nuclide 100In, the beta-decay daughter of 100Sn, and of 99In, with one proton less than 100Sn. We use advanced mass spectrometry techniques to measure 99In, which is produced at a rate of only a few ions per second, and to resolve the ground and isomeric states in 101In. The experimental results are compared with ab initio many-body calculations. The 100-fold improvement in precision of the 100In mass value highlights a discrepancy in the atomic-mass values of 100Sn deduced from recent beta-decay results4,5.
Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor
Authors: Liu Qiufeng , Yang Dehua , Zhuang Youwen , Croll Tristan I. , Cai Xiaoqing , Dai Antao , He Xinheng , Duan Jia , Yin Wanchao , Ye Chenyu , Zhou Fulai , Wu Beili , Zhao Qiang , Xu H. Eric , Wang Ming-Wei , Jiang Yi 
Published: September 2021

AbstractCholecystokinin A receptor (CCKAR) belongs to family A G-protein-coupled receptors and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKAR is its ability to interact with a sulfated ligand and to couple with divergent G-protein subtypes, including Gs, Giand Gq. However, the basis for G-protein coupling promiscuity and ligand recognition by CCKAR remains unknown. Here, we present three cryo-electron microscopy structures of sulfated CCK-8-activated CCKAR in complex with Gs, Giand Gqheterotrimers, respectively. CCKAR presents a similar conformation in the three structures, whereas conformational differences in the ‘wavy hook’ of the Gα subunits and ICL3 of the receptor serve as determinants in G-protein coupling selectivity. Our findings provide a framework for understanding G-protein coupling promiscuity by CCKAR and uncover the mechanism of receptor recognition by sulfated CCK-8.
Light intensity and spectral composition drive reproductive success in the marine benthic diatom Seminavis robusta
Authors: Bilcke Gust , Van Craenenbroeck Lore , Castagna Alexandre , Osuna-Cruz Cristina Maria , Vandepoele Klaas , Sabbe Koen , De Veylder Lieven , Vyverman Wim 
Published: September 2021

AbstractThe properties of incident light play a crucial role in the mating process of diatoms, a group of ecologically important microalgae. While species-specific requirements for light intensity and photoperiod have been observed in several diatom species, little is known about the light spectrum that allows sexual reproduction. Here, we study the effects of spectral properties and light intensity on the initiation and progression of sexual reproduction in the model benthic diatom Seminavis robusta. We found that distinct stages of the mating process have different requirements for light. Vigorous mating pair formation occurred under a broad range of light intensities, ranging from 10 to 81 µE m−2 s−1, while gametogenesis and subsequent stages were strongly affected by moderate light intensities of 27 µE m−2 s−1 and up. In addition, light of blue or blue–green wavelengths was required for the formation of mating pairs. Combining flow cytometric analysis with expression profiling of the diatom-specific cyclin dsCyc2 suggests that progression through a blue light-dependent checkpoint in the G1 cell cycle phase is essential for induction of sexual reproduction. Taken together, we expand the current model of mating in benthic pennate diatoms, which relies on the interplay between light, cell cycle and sex pheromone signaling.
Transcriptional expression of ZICs as an independent indicator of survival in gliomas
Authors: Han Zhaocheng , Jia Jingnan , Lv Yangting , Wang Rongyanqi , Cao Kegang 
Published: September 2021

AbstractThe functional significance of the zinc-finger of the cerebellum (ZIC) gene family in gliomas remains to be elucidated. Clinical data from patients with gliomas, containing expression levels of ZIC genes, were extracted from CCLE, GEPIA2 and The Human Protein Atlas (HPA). Univariate survival analysis adjusted by Cox regression via OncoLnc was used to determine the prognostic significance of ZIC expression. We used cBioPortal to explore the correlation between gene mutations and overall survival (OS). ZIC expression was found to be related to immune cell infiltration in gliomas via TIMER analysis. GO term and KEGG pathway enrichment analyzes were performed with Metascape. PPI networks were constructed using STRING. The expression levels of ZIC1/3/4/5 in gliomas were significantly different from those in normal samples. High expression levels of ZIC1/5 were associated with poor OS in brain low-grade glioma (LGG) patients, while low ZIC3 expression combined was related to favorable OS in glioblastoma multiforme (GBM). ZIC alterations were associated with poor prognosis in LGG patients and related to favorable prognosis in GBM patients. We observed that the expression of ZICs was related to immune cell infiltration in glioma patients. ZICs were enriched in several pathways and biological processes involving Neuroactive ligand-receptor interaction (hsa04080). The PPI network revealed that some proteins coexpressed with ZICs played a role in the pathogenesis of gliomas. Differences in the expression levels of ZIC genes could provide a significant marker for predicting prognosis in gliomas.
Trends and age-period-cohort effects on hypertension mortality rates from 1998 to 2018 in Mexico
Authors: Castro-Porras Lilia V. , Rojas-Martínez Rosalba , Aguilar-Salinas Carlos A. , Bello-Chavolla Omar Yaxmehen , Becerril-Gutierrez Carlos , Escamilla-Nuñez Consuelo 
Published: September 2021

AbstractArterial hypertension is a major global health problem. It is the main risk factor for preventable death and the leading cause of premature death in the world. This study aims to describe the changes in hypertension-related mortality in Mexico between 1998 and 2018. Using death certificates and national population public data sets, a total of 335,863 deaths due to hypertension were found in Mexico, disaggregated by sex and age, during the time period covered in this study. An age-period-cohort analysis was conducted to show trends in hypertension mortality rates. Mortality due to hypertension in Mexico affects more women than men. In the most recent cohorts, the risk of dying from hypertension is two times higher in men compared to women. Hypertensive kidney disease is found to be the main underlying cause, with an average increase throughout the period studied. Our results indicate that mortality rates due to hypertension continue to grow and point to an alarming trend of mortality shifting towards younger ages, with sex-based disparities in absolute numbers and in changing trends.