bluuebunny/crossref_metadata_2025 huggingface dataset:
A gauge-compatible Hamiltonian splitting algorithm for particle-in-cell simulations using finite element exterior calculus
Authors: Glasser Alexander S. , Qin Hong
Published: May 2022

A particle-in-cell algorithm is derived with a canonical Poisson structure in the formalism of finite element exterior calculus. The resulting method belongs to the class of gauge-compatible splitting algorithms, which exactly preserve gauge symmetries and their associated conservation laws via the momentum map. We numerically demonstrate this time invariance of the momentum map and its usefulness in establishing precise initial conditions with a desired initial electric field and fixed background charge. The restriction of this canonical, finite element Poisson structure to the 1X2P

$1\frac {1}{2}$

-dimensional phase space is also considered and simulated numerically.
Cost-effectiveness analysis of lemborexant for treating insomnia in Japan: a model-based projection, incorporating the risk of falls, motor vehicle collisions, and workplace accidents
Authors: Ikeda Shunya , Azuma Mie Kasai , Fujimoto Kenichi , Shibahara Hidetoshi , Inoue Sachie , Moline Margaret , Ishii Mika , Mishima Kazuo
Published: May 2022

Background

Lemborexant has demonstrated statistically significant improvements in sleep onset and sleep maintenance compared with placebo and zolpidem tartrate extended release, measured both objectively using polysomnography and subjectively using sleep diaries, in the phase 3 clinical trial SUNRISE 1. This study evaluated the cost-effectiveness of lemborexant compared with suvorexant, zolpidem immediate release (IR), and untreated insomnia.

Methods

A decision-tree model was developed for falls, motor vehicle collisions, and workplace accidents associated with insomnia and insomnia treatments from a Japanese healthcare perspective and with a 6-month time horizon. The model extracted subjective sleep onset latency treatment responses and disutility values for non-responders from SUNRISE 1. Cost-effectiveness was assessed using incremental cost per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were conducted to evaluate the impact of parameter uncertainty on the results.

Results

In the base-case analysis, the mean estimated QALYs for lemborexant, suvorexant, zolpidem-IR, and untreated insomnia were 0.4220, 0.4204, 0.4113, and 0.4163, and expected medical costs were JPY 34 034, JPY 38 371, JPY 38 139, and JPY 15 383, respectively. Lemborexant saved JPY 4337 and JPY 4105 compared with suvorexant or zolpidem-IR, respectively, while conferring QALY benefits. The incremental cost-effectiveness ratio (ICER) of lemborexant compared with that of untreated insomnia was JPY 3 220 975 /QALY. Lemborexant was dominant over suvorexant and zolpidem-IR and was cost-effective when compared with untreated insomnia. Sensitivity analyses supported the results' robustness.

Conclusions

In a Japanese clinical practice setting, lemborexant may represent a better investment for treating insomnia in the healthcare system in Japan.
THE FOX AND THE ARMADILLO: AN INQUIRY INTO CLASSIC MAYA “ANIMAL” CATEGORIES
Authors: Newman Sarah E. , Rossi Franco D.
Published: May 2022

This article investigates Classic Maya understandings of two particular animal species: the (gray) fox and the armadillo. We use these species as a point of entry into Classic Maya categorizations of the non-human animal world, examining the salient biological and physical characteristics of those animals that Classic-period artists and scribes chose to highlight. Rather than accepting the creatures depicted on painted pottery or referenced in hieroglyphic texts as generalized examples of particular kinds (i.e., simply “a fox” or “an armadillo”), however, we show how the evidence from ancient art, historical accounts, and contemporary ethnography points to an emphasis onspecificbeings, often named individuals, who engage in particular behaviors and relate to other entities (both human and non-human) in distinctive ways. Although this article focuses exclusively on the fox and the armadillo, those species serve as examples through which we consider the limitations of applying Western taxonomic categories to other systems of knowledge, as well as the possibilities for how we might catch glimpses of radically different ways of organizing the world.
Psychonauts and Seekers: West German Entanglements in the Spiritual Turn of the Global 1960s and 1970s
Authors: Richter Isabel
Published: May 2022

This essay focuses on West Germany as exemplary global-local intersection of the spiritual turn in the long 1960s. It shows how spirituality as practices and beliefs seeking a closer connection with the divine within or outside religious groups experienced a multifaceted renaissance in the countercultures of the long 1960s. In this spiritual quest contemporary explorations in the expansion of consciousness and the increasing interest in meditation were pivotal practices. The essay reflects the international exchange of knowledge about body-mind practices from Amazonia and Mexico to the United States, India and West Germany, showing how actors were influenced by international and national connections. Practitioners found the practices of spirituality neither in Christian contemplative traditions nor in Jewish versions, but in various forms of what seekers received and practised as Hinduism or Buddhism, etc., that gave contemporary followers and seekers a means of connecting to higher truths – to God – without God.
Use of Point-of-Care Ultrasound by Non-Physicians to Assess Respiratory Distress in the Out-of-Hospital Environment: A Scoping Review
Authors: Donovan Jake K. , Burton Samuel O. , Jones Samuel L. , Meadley Benjamin N.
Published: May 2022

Background:

The use of ultrasound in the out-of-hospital environment is increasingly feasible. The potential uses for point-of-care ultrasound (POCUS) by paramedics are many, but have historically been limited to traumatic indications. This study utilized a scoping review methodology to map the evidence for the use of POCUS by paramedics to assess respiratory distress and to gain a broader understanding of the topic.

Methods:

Databases Ovid MEDLINE, EMBASE, CINAHL Plus, and PUBMED were searched from January 1, 1990 through April 14, 2021. Google Scholar was searched, and reference lists of relevant papers were examined to identify additional studies. Articles were included if they reported on out-of-hospital POCUS performed by non-physicians for non-traumatic respiratory distress.

Results:

A total of 591 unique articles were identified, of which seven articles met the inclusion criteria. The articles reported various different scan protocols and, with one exception, suffered from low enrolments and low participation. Most articles reported that non-physician-performed ultrasound was feasible. Articles reported moderate to high levels of agreement between paramedics and expert reviewers for scan interpretation in most studies.

Conclusion:

Paramedics and emergency medical technicians (EMTs) have demonstrated the feasibility of lung ultrasound in the out-of-hospital environment. Further research should investigate the utility of standardized education and scanning protocols in paramedic-performed lung ultrasound for the differentiation of respiratory distress and the implications for patient outcomes.
Modern ornament in fin de siècle Paris: Antonin Raguenet’s Matériaux et documents d’architecture et de sculpture
Authors: He Gary Huafan
Published: May 2022

This article examines the work of Antonin Raguenet (1839–1920), who directed from his studio in Paris between 1872 and 1914 a vast project of architectural taxonomy, the Matériaux et documents d’architecture et de sculpture. Though unique in its vast geographic scope and empiricist approach, Raguenet’s project remains relatively obscure in the current scholarship of art and architectural history. Published monthly in eight-page pamphlets totaling over five hundred serialised issues, the Matériaux et documents ultimately contained over fourteen thousand illustrations of ornaments collected from buildings, plazas, monuments, and cemeteries across the European continent.

Raguenet’s ornamental gaze moves seamlessly from Haussmann-era apartment buildings, to universal expositions in Paris and abroad, to the façades of Lavirotte, Schoellkopf, and Guimard, reflecting the production and reproduction of ornament literature during the period of the Belle Époque. The collecting and cataloguing of architecture elements into categories – windows, cartouche, doors, capitals, balconies, etc. – is aided by the maturation of print media, the passenger railroad industry, and the rise of photographic reproduction in the late nineteenth century. This reading of the Matériaux et documents will introduce its context, contents, and methodology, as well as the role of ornament in imagining and observing the emergence of a new ‘modern style’ at the end of the nineteenth century.
Fluvial Depositional Systems of the African Humid Period: An Analog for an Early, Wet Mars in the Eastern Sahara
Authors: Zaki A. S. , Davis J. M. , Edgett K. S. , Giegengack R. , Roige M. , Conway S. , Schuster M. , Gupta S. , Salese F. , Sangwan K. S. , Fairén A. G. , Hughes C. M. , Pain C. F. , Castelltort S.
Published: May 2022

A widely hypothesized but complex transition from widespread fluvial activity to predominantly aeolian processes is inferred on Mars based on remote sensing data observations of ancient landforms. However, the lack of analysis of in situ martian fluvial deposits hinders our understanding of the flow regime nature and sustainability of the martian fluvial activity and the hunt for ancient life. Studying analogs from arid zones on Earth is fundamental to quantitatively understanding geomorphic processes and climate drivers that might have dominated during early Mars. Here we investigate the formation and preservation of fluvial depositional systems in the eastern Sahara, where the largest arid region on Earth hosts important repositories of past climatic changes. The fluvial systems are composed of well‐preserved single‐thread sinuous to branching ridges and fan‐shaped deposits interpreted as deltas. The systems' configuration and sedimentary content suggest that ephemeral rivers carved these landforms by sequential intermittent episodes of erosion and deposition active for 10–100s years over ∼10,000 years during the late Quaternary. Subsequently, these landforms were sculpted by a marginal role of rainfall and aeolian processes with minimum erosion rates of 1.1 ± 0.2 mm/yr, supplying ∼96 ± 24 × 1010 m3 of disaggregated sediment to adjacent aeolian dunes. Our results imply that similar martian fluvial systems preserving single‐thread, short distance source‐to‐sink courses may have formed due to transient drainage networks active over short durations. Altogether, this study adds to the growing recognition of the complexity of interpreting climate history from orbital images of landforms.
Appreciating GBC Reviewers
Authors: Santos Isaac R. , Fletcher Sara Mikaloff , Houlton Benjamin , Matsumoto Katsumi , Chase Zanna
Published: May 2022

The Editors of the Global Biogeochemical Cycles express their appreciation to those who served as peer reviewers for the journal in 2021.
Greenhouse Gas Mitigation Potential of Alternate Wetting and Drying for Rice Production at National Scale—A Modeling Case Study for the Philippines
Authors: Kraus David , Werner Christian , Janz Baldur , Klatt Steffen , Sander Björn Ole , Wassmann Reiner , Kiese Ralf , Butterbach‐Bahl Klaus
Published: May 2022

Worldwide, rice production contributes about 10% of total greenhouse gas (GHG) emissions from the agricultural sector, mainly due to CH4 emissions from continuously flooded fields. Alternate Wetting and Drying (AWD) is a promising crop technology for mitigating CH4 emissions and reducing the irrigation water currently being applied in many of the world's top rice‐producing countries. However, decreased emissions of CH4 may be partially counterbalanced by increased N2O emissions. In this case study for the Philippines, the national mitigation potential of AWD is explored using the process‐based biogeochemical model LandscapeDNDC. Simulated mean annual CH4 emissions under conventional rice production for the time period 2000–2011 are estimated as 1,180 ± 163 Gg CH4 yr−1. During the cropping season, this is about +16% higher than a former estimate using emission factors. Scenario simulations of nationwide introduction of AWD in irrigated landscapes suggest a considerable decrease in CH4 emissions by −23%, while N2O emissions are only increased by +8%. Irrespective of field management, at national scale, the radiative forcing of irrigated rice production is always dominated by CH4 (>95%). The reduction potential of GHG emissions depends on, for example, number of crops per year, residue management, amount of applied irrigation water, and sand content. Seasonal weather conditions also play an important role since the mitigation potential of AWD is almost double as high in dry as compared to wet seasons. Furthermore, this study demonstrates the importance of temporal continuity, considering off‐season emissions and the long‐term development of GHG emissions across multiple years.
LOEN: Lensless opto-electronic neural network empowered machine vision
Authors: Shi Wanxin , Huang Zheng , Huang Honghao , Hu Chengyang , Chen Minghua , Yang Sigang , Chen Hongwei
Published: May 2022

Machine vision faces bottlenecks in computing power consumption and large amounts of data. Although opto-electronic hybrid neural networks can provide assistance, they usually have complex structures and are highly dependent on a coherent light source; therefore, they are not suitable for natural lighting environment applications. In this paper, we propose a novel lensless opto-electronic neural network architecture for machine vision applications. The architecture optimizes a passive optical mask by means of a task-oriented neural network design, performs the optical convolution calculation operation using the lensless architecture, and reduces the device size and amount of calculation required. We demonstrate the performance of handwritten digit classification tasks with a multiple-kernel mask in which accuracies of as much as 97.21% were achieved. Furthermore, we optimize a large-kernel mask to perform optical encryption for privacy-protecting face recognition, thereby obtaining the same recognition accuracy performance as no-encryption methods. Compared with the random MLS pattern, the recognition accuracy is improved by more than 6%.
Differential expression of gene co-expression networks related to the mTOR signaling pathway in bipolar disorder
Authors: Park Sung Woo , Seo Mi Kyoung , Webster Maree J. , Lee Jung Goo , Kim Sanghyeon
Published: May 2022

Bipolar disorder (BPD) is a severe mental illness characterized by episodes of depression and mania. To investigate the molecular mechanisms underlying the pathophysiology of bipolar disorder, we performed transcriptome studies using RNA-seq data from the prefrontal cortex (PFC) of individuals with BPD and matched controls, as well as data from cell culture and animal model studies. We found 879 differentially expressed genes that were also replicated in an independent cohort of post-mortem samples. Genes involving the mechanistic target of rapamycine (mTOR) pathway were down-regulated, while genes interrelated with the mTOR pathway such as Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway were up-regulated. Gene co-expression network analyses identified a module related to the mTOR pathway that was up-regulated in BPD and also enriched for markers of endothelial cells. We also found a down-regulated co-expression module enriched for genes involved in mTOR signalling and in mTOR related pathways and enriched with neuronal markers. The mTOR related modules were also replicated in the independent cohort of samples. To investigate whether the expression of the modules related to mTOR signalling pathway could be differentially regulated in different cell types we performed comparative network analyses in experimental models. We found both up-regulated modules in the PFC significantly overlapped with an up-regulated module in the brain endothelial cells from mice treated with lipopolysaccharides (LPS) and mTOR related pathways such as JAK-STAT, PI3K-Akt and ribosome were enriched in the common genes. In addition, the down-regulated module in the PFC significantly overlapped with a down-regulated module from neurons treated with the mTOR inhibitor, Torin1 and mTOR signalling, autophagy, and synaptic vesicle cycles were significantly enriched in the common genes. These results suggest that co-expression networks related to mTOR signalling pathways may be up- or down-regulated in different cell types in the PFC of BPD. These results provide novel insights into the molecular mechanisms underlying the pathophysiology of BPD.
The emerging role of ubiquitin-specific protease 20 in tumorigenesis and cancer therapeutics
Authors: Li Qiong , Ye Chanqi , Tian Tian , Jiang Qi , Zhao Peng , Wang Xiaoting , Liu Feiye , Shan Jianzhen , Ruan Jian
Published: May 2022

As a critical member of the ubiquitin-specific proteolytic enzyme family, ubiquitin-specific peptidase 20 (USP20) regulates the stability of proteins via multiple signaling pathways. In addition, USP20 upregulation is associated with various cellular biological processes, such as cell cycle progression, proliferation, migration, and invasion. Emerging studies have revealed the pivotal role of USP20 in the tumorigenesis of various cancer types, such as breast cancer, colon cancer, lung cancer, gastric cancer and adult T cell leukemia. In our review, we highlight the different mechanisms of USP20 in various tumor types and demonstrate that USP20 regulates the stability of multiple proteins. Therefore, regulating the activity of USP20 is a novel tumor treatment. However, the clinical significance of USP20 in cancer treatment merits more evidence. Finally, different prospects exist for the continued research focus of USP20.
Novel roles of RTN4 and CLIMP-63 in regulating mitochondrial structure, bioenergetics and apoptosis
Authors: Carter Rachel J. , Milani Mateus , Beckett Alison J. , Liu Shiyu , Prior Ian A. , Cohen Gerald M. , Varadarajan Shankar
Published: May 2022

The recruitment of DRP1 to mitochondrial membranes prior to fission is facilitated by the wrapping of endoplasmic reticulum (ER) membranes around the mitochondria. To investigate the complex interplay between the ER membranes and DRP1 in the context of mitochondrial structure and function, we downregulate two key ER shaping proteins, RTN4 and CLIMP-63, and demonstrate pronounced mitochondrial hyperfusion and reduced ER-mitochondria contacts, despite their differential regulation of ER architecture. Although mitochondrial recruitment of DRP1 is unaltered in cells lacking RTN4 or CLIMP-63, several aspects of mitochondrial function, such as mtDNA-encoded translation, respiratory capacity and apoptosis are significantly hampered. Further mechanistic studies reveal that CLIMP-63 is required for cristae remodeling (OPA1 proteolysis) and DRP1-mediated mitochondrial fission, whereas both RTN4 and CLIMP-63 regulate the recruitment of BAX to ER and mitochondrial membranes to enable cytochrome c release and apoptosis, thereby performing novel and distinct roles in the regulation of mitochondrial structure and function.
LncRNA LYPLAL1-DT screening from type 2 diabetes with macrovascular complication contributes protective effects on human umbilical vein endothelial cells via regulating the miR-204-5p/SIRT1 axis
Authors: Zhu Xiao , Liu Yihan , Cui Jia , Lv Jianyi , Li Changlong , Lu Jing , Huo Xueyun , Dou Jingtao , Bai Zhigang , Chen Zhenwen , Du Xiaoyan
Published: May 2022

Long noncoding RNAs (lncRNAs) are involved in diabetes related diseases. However, the role of lncRNAs in the pathogenesis of type 2 diabetes with macrovascular complication (DMC) has seldomly been recognized. This study screened lncRNA profiles of leukocytes from DMC patients and explored protective role of lncRNA LYPLAL1-DT in endothelial cells (EC) under high glucose (HG) and inflammatory conditions (IS). Between DMC and healthy controls, 477 differential expression lncRNAs (DE-lncRNAs) were identified. The enrichment and pathway analysis showed that most of the DE-lncRNAs belonged to inflammatory, metabolic, and vascular diseases. A total of 12 lncRNAs was validated as significant DE-lncRNAs in expanding cohorts. Furthermore, these DE-lncRNAs were shown to be significantly related to hypoxia, HG, and IS in EC, especially lncRNA LYPLAL1-DT. LYPLAL1-DT overexpression results in the promotion of the proliferation, and migration of EC, as well as an elevation of autophagy. Overexpressed LYPLAL1-DT reduces the adhesion of monocytes to EC, boosts anti-inflammation, and suppresses inflammatory molecules secreted in the medium. Mechanistically, LYPLAL1-DT acts as competing endogenous RNA (ceRNA) by downregulating miR-204-5p, therefore enhancing SIRT1 and protecting EC autophagy function; thus, alleviating apoptosis. Finally, exosome sequencing revealed LYPLAL1-DT expression was 4 times lower in DMC cells than in healthy samples. In general, we identified LYPLAL1-DT having protective effects on EC as ceRNA mediated through the miR-204-5p/SIRT1 pathway. Therefore, it inhibits the autophagy of EC as well as modulating systemic inflammation. This approach could be regarded as a new potential therapeutic target in DMC.
Derivation of totipotent-like stem cells with blastocyst-like structure forming potential
Authors: Xu Yaxing , Zhao Jingru , Ren Yixuan , Wang Xuyang , Lyu Yulin , Xie Bingqing , Sun Yiming , Yuan Xiandun , Liu Haiyin , Yang Weifeng , Fu Yenan , Yu Yu , Liu Yinan , Mu Rong , Li Cheng , Xu Jun , Deng Hongkui
Published: May 2022

It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble cells from totipotent embryos. Here, we report that a chemical cocktail enables the derivation of totipotent-like stem cells, designated as totipotent potential stem (TPS) cells, from 2-cell mouse embryos and extended pluripotent stem cells, and that these TPS cells can be stably maintained long term in vitro. TPS cells shared features with 2-cell mouse embryos in terms of totipotency markers, transcriptome, chromatin accessibility and DNA methylation patterns. In vivo chimera formation assays show that these cells have embryonic and extraembryonic developmental potentials at the single-cell level. Moreover, TPS cells can be induced into blastocyst-like structures resembling preimplantation mouse blastocysts. Mechanistically, inhibition of HDAC1/2 and DOT1L activity and activation of RARγ signaling are important for inducing and maintaining totipotent features of TPS cells. Our study opens up a new path toward fully capturing totipotent stem cells in vitro.
Fast and accurate population admixture inference from genotype data from a few microsatellites to millions of SNPs
Authors: Wang Jinliang
Published: May 2022

Model-based (likelihood and Bayesian) and non-model-based (PCA andK-means clustering) methods were developed to identify populations and assign individuals to the identified populations using marker genotype data. Model-based methods are favoured because they are based on a probabilistic model of population genetics with biologically meaningful parameters and thus produce results that are easily interpretable and applicable. Furthermore, they often yield more accurate structure inferences than non-model-based methods. However, current model-based methods either are computationally demanding and thus applicable to small problems only or use simplified admixture models that could yield inaccurate results in difficult situations such as unbalanced sampling. In this study, I propose new likelihood methods for fast and accurate population admixture inference using genotype data from a few multiallelic microsatellites to millions of diallelic SNPs. The methods conduct first a clustering analysis of coarse-grained population structure by using the mixture model and the simulated annealing algorithm, and then an admixture analysis of fine-grained population structure by using the clustering results as a starting point in an expectation maximisation algorithm. Extensive analyses of both simulated and empirical data show that the new methods compare favourably with existing methods in both accuracy and running speed. They can analyse small datasets with just a few multiallelic microsatellites but can also handle in parallel terabytes of data with millions of markers and millions of individuals. In difficult situations such as many and/or lowly differentiated populations, unbalanced or very small samples of individuals, the new methods are substantially more accurate than other methods.
Novel NARS2 variant causing leigh syndrome with normal lactate levels
Authors: Tanaka Ryosuke , Takeguchi Ryo , Kuroda Mami , Suzuki Nao , Makita Yoshio , Yanagi Kumiko , Kaname Tadashi , Takahashi Satoru
Published: May 2022

Leigh syndrome is the most genetically heterogenous phenotype of mitochondrial disease. We describe a patient with Leigh syndrome whose diagnosis had not been confirmed because of normal metabolic screening results at the initial presentation. Whole-exome sequencing identified pathogenic variants in NARS2, the gene encoding a mitochondrial asparaginyl-tRNA synthetase. One of the biallelic variants was novel. This highlights the essential role of genetic testing for a definite diagnosis of Leigh syndrome.
Genome and transcriptome mechanisms driving cephalopod evolution
Authors: Albertin Caroline B. , Medina-Ruiz Sofia , Mitros Therese , Schmidbaur Hannah , Sanchez Gustavo , Wang Z. Yan , Grimwood Jane , Rosenthal Joshua J. C. , Ragsdale Clifton W. , Simakov Oleg , Rokhsar Daniel S.
Published: May 2022

Cephalopods are known for their large nervous systems, complex behaviors and morphological innovations. To investigate the genomic underpinnings of these features, we assembled the chromosomes of the Boston market squid, Doryteuthis (Loligo) pealeii, and the California two-spot octopus, Octopus bimaculoides, and compared them with those of the Hawaiian bobtail squid, Euprymna scolopes. The genomes of the soft-bodied (coleoid) cephalopods are highly rearranged relative to other extant molluscs, indicating an intense, early burst of genome restructuring. The coleoid genomes feature multi-megabase, tandem arrays of genes associated with brain development and cephalopod-specific innovations. We find that a known coleoid hallmark, extensive A-to-I mRNA editing, displays two fundamentally distinct patterns: one exclusive to the nervous system and concentrated in genic sequences, the other widespread and directed toward repetitive elements. We conclude that coleoid novelty is mediated in part by substantial genome reorganization, gene family expansion, and tissue-dependent mRNA editing.
Origin of high thermal conductivity in disentangled ultra-high molecular weight polyethylene films: ballistic phonons within enlarged crystals
Authors: Kim Taeyong , Drakopoulos Stavros X. , Ronca Sara , Minnich Austin J.
Published: May 2022

The thermal transport properties of oriented polymers are of fundamental and practical interest. High thermal conductivities ( ≳ 50 Wm−1K−1) have recently been reported in disentangled ultra-high molecular weight polyethylene (UHMWPE) films, considerably exceeding prior reported values for oriented films. However, conflicting explanations have been proposed for the microscopic origin of the high thermal conductivity. Here, we report a characterization of the thermal conductivity and mean free path accumulation function of disentangled UHMWPE films (draw ratio ~200) using cryogenic steady-state thermal conductivity measurements and transient grating spectroscopy. We observe a marked dependence of the thermal conductivity on grating period over temperatures from 30–300 K. Considering this observation, cryogenic bulk thermal conductivity measurements, and analysis using an anisotropic Debye model, we conclude that longitudinal atomic vibrations with mean free paths around 400 nanometers are the primary heat carriers, and that the high thermal conductivity for draw ratio ≳ 150 arises from the enlargement of extended crystals with drawing. The mean free paths appear to remain limited by the extended crystal dimensions, suggesting that the upper limit of thermal conductivity of disentangled UHMWPE films has not yet been realized.
Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages
Authors: Ng Charlotte K. Y. , Dazert Eva , Boldanova Tuyana , Coto-Llerena Mairene , Nuciforo Sandro , Ercan Caner , Suslov Aleksei , Meier Marie-Anne , Bock Thomas , Schmidt Alexander , Ketterer Sylvia , Wang Xueya , Wieland Stefan , Matter Matthias S. , Colombi Marco , Piscuoglio Salvatore , Terracciano Luigi M. , Hall Michael N. , Heim Markus H.
Published: May 2022

Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated HCCs. Here we present an integrated proteogenomic analysis of HCCs across clinical stages and etiologies. Pathways related to cell cycle, transcriptional and translational control, signaling transduction, and metabolism are dysregulated and differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. We describe candidate copy number-driven driver genes involved in epithelial-to-mesenchymal transition, the Wnt-β-catenin, AKT/mTOR and Notch pathways, cell cycle and DNA damage regulation. The targetable aurora kinase A and CDKs are upregulated.CTNNB1andTP53mutations are associated with altered protein phosphorylation related to actin filament organization and lipid metabolism, respectively. Integrative proteogenomic clusters show that HCC constitutes heterogeneous subgroups with distinct regulation of biological processes, metabolic reprogramming and kinase activation. Our study provides a comprehensive overview of the proteomic and phophoproteomic landscapes of HCCs, revealing the major pathways altered in the (phospho)proteome.
Doubly stereoconvergent construction of vicinal all-carbon quaternary and tertiary stereocenters by Cu/Mg-catalyzed propargylic substitution
Authors: Pu Xiang , Dang Qiu-Di , Yang Lei , Zhang Xia , Niu Dawen
Published: May 2022

The construction of vicinal, congested stereocenters with high selectivities is of general utility in chemistry. To build two such stereocenters in one step from readily available starting materials is very desirable, but remains challenging. We report here a doubly stereoconvergent, Cu/Mg-catalyzed asymmetric propargylic substitution reaction to convert simple starting materials to products with vicinal tertiary and all-carbon quaternary stereocenters in high yields and excellent diastereo- and enantioselectivities. Both the nucleophiles and the electrophiles employed in this transformation are racemic. This reaction uses earth abundant metal catalysts, operates under ambient conditions, and demonstrates broad substrate scope. The products of this reaction are functional group rich and synthetically versatile. Key to the success of this development is the devise of a Cu/Mg dual catalytic system and the identification of a bulky tridentate pyridinebisimidazoline (PyBim) ligand.
Superconducting spintronic tunnel diode
Authors: Strambini E. , Spies M. , Ligato N. , Ilić S. , Rouco M. , González-Orellana Carmen , Ilyn Maxim , Rogero Celia , Bergeret F. S. , Moodera J. S. , Virtanen P. , Heikkilä T. T. , Giazotto F.
Published: May 2022

Diodes are key elements for electronics, optics, and detection. Their evolution towards low dissipation electronics has seen the hybridization with superconductors and the realization of supercurrent diodes with zero resistance in only one direction. Here, we present the quasi-particle counterpart, a superconducting tunnel diode with zero conductance in only one direction. The direction-selective propagation of the charge has been obtained through the broken electron-hole symmetry induced by the spin selection of the ferromagnetic tunnel barrier: a EuS thin film separating a superconducting Al and a normal metal Cu layer. The Cu/EuS/Al tunnel junction achieves a large rectification (up to ∼40%) already for a small voltage bias (∼200 μV) thanks to the small energy scale of the system: the Al superconducting gap. With the help of an analytical theoretical model we can link the maximum rectification to the spin polarization (P) of the barrier and describe the quasi-ideal Shockley-diode behavior of the junction. This cryogenic spintronic rectifier is promising for the application in highly-sensitive radiation detection for which two different configurations are evaluated. In addition, the superconducting diode may pave the way for future low-dissipation and fast superconducting electronics.
Transition from predictable to variable motor cortex and striatal ensemble patterning during behavioral exploration
Authors: Kondapavulur Sravani , Lemke Stefan M. , Darevsky David , Guo Ling , Khanna Preeya , Ganguly Karunesh
Published: May 2022

Animals can capitalize on invariance in the environment by learning and automating highly consistent actions; however, they must also remain flexible and adapt to environmental changes. It remains unclear how primary motor cortex (M1) can drive precise movements, yet also support behavioral exploration when faced with consistent errors. Using a reach-to-grasp task in rats, along with simultaneous electrophysiological monitoring in M1 and dorsolateral striatum (DLS), we find that behavioral exploration to overcome consistent task errors is closely associated with tandem increases in M1 and DLS neural variability; subsequently, consistent ensemble patterning returns with convergence to a new successful strategy. We also show that compared to reliably patterned intracranial microstimulation in M1, variable stimulation patterns result in significantly greater movement variability. Our results thus indicate that motor and striatal areas can flexibly transition between two modes, reliable neural pattern generation for automatic and precise movements versus variable neural patterning for behavioral exploration.
Bilayer-folded lamellar mesophase induced by random polymer sequence
Authors: Shin Minjoong , Kim Hayeon , Park Geonhyeong , Park Jongmin , Ahn Hyungju , Yoon Dong Ki , Lee Eunji , Seo Myungeun
Published: May 2022

Randomness is perceived in two different extremes, in macroscopic homogeneity and local heterogeneity, but apparently far away from order. Here we show that a periodic order spontaneously arises from a binary random copolymer when self-assembly occurs in an ensemble containing > 1015 possible chain sequences. A Bernoullian distribution of hydrophilic and hydrophobic side chains grafted onto a linear backbone was constructed by random copolymerization. When the polymer chains associate in water, a sequence matching problem occurs because of the drastic heterogeneity in sequence: this is believed to generate local curvature mismatches which deviate from the ensemble-averaged interfacial curvature. Periodic folding of the self-assembled bilayer stabilizes the curvature instability as recurring hinges. Reminiscent of chain-folded lamellae found in polymer crystallization, this new liquid crystalline mesophase, characterized as bilayer-folded lamellae, manifests itself as an anisotropically alignable birefringent hydrogel with structural hierarchy across multiple length scales.
Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen
Authors: Mac Kain Alice , Maarifi Ghizlane , Aicher Sophie-Marie , Arhel Nathalie , Baidaliuk Artem , Munier Sandie , Donati Flora , Vallet Thomas , Tran Quang Dinh , Hardy Alexandra , Chazal Maxime , Porrot Françoise , OhAinle Molly , Carlson-Stevermer Jared , Oki Jennifer , Holden Kevin , Zimmer Gert , Simon-Lorière Etienne , Bruel Timothée , Schwartz Olivier , van der Werf Sylvie , Jouvenet Nolwenn , Nisole Sébastien , Vignuzzi Marco , Roesch Ferdinand
Published: May 2022

Interferon restricts SARS-CoV-2 replication in cell culture, but only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identify DAXX, a scaffold protein residing in PML nuclear bodies known to limit the replication of DNA viruses and retroviruses, as a potent inhibitor of SARS-CoV-2 and SARS-CoV replication in human cells. Basal expression of DAXX is sufficient to limit the replication of SARS-CoV-2, and DAXX over-expression further restricts infection. DAXX restricts an early, post-entry step of the SARS-CoV-2 life cycle. DAXX-mediated restriction of SARS-CoV-2 is independent of the SUMOylation pathway but dependent on its D/E domain, also necessary for its protein-folding activity. SARS-CoV-2 infection triggers the re-localization of DAXX to cytoplasmic sites and promotes its degradation. Mechanistically, this process is mediated by the viral papain-like protease (PLpro) and the proteasome. Together, these results demonstrate that DAXX restricts SARS-CoV-2, which in turn has evolved a mechanism to counteract its action.
Catalytically efficient Ni-NiOx-Y2O3 interface for medium temperature water-gas shift reaction
Authors: Xu Kai , Ma Chao , Yan Han , Gu Hao , Wang Wei-Wei , Li Shan-Qing , Meng Qing-Lu , Shao Wei-Peng , Ding Guo-Heng , Wang Feng Ryan , Jia Chun-Jiang
Published: May 2022

The metal-support interfaces between metals and oxide supports have long been studied in catalytic applications, thanks to their significance in structural stability and efficient catalytic activity. The metal-rare earth oxide interface is particularly interesting because these early transition cations have high electrophilicity, and therefore good binding strength with Lewis basic molecules, such as H2O. Based on this feature, here we design a highly efficient composite Ni-Y2O3 catalyst, which forms abundant active Ni-NiOx-Y2O3 interfaces under the water-gas shift (WGS) reaction condition, achieving 140.6 μmolCO gcat−1 s−1 rate at 300 °C, which is the highest activity for Ni-based catalysts. A combination of theory and ex/in situ experimental study suggests that Y2O3 helps H2O dissociation at the Ni-NiOx-Y2O3 interfaces, promoting this rate limiting step in the WGS reaction. Construction of such new interfacial structure for molecules activation holds great promise in many catalytic systems.
Modulating Pt-O-Pt atomic clusters with isolated cobalt atoms for enhanced hydrogen evolution catalysis
Authors: Zhao Yufei , Kumar Priyank V. , Tan Xin , Lu Xinxin , Zhu Xiaofeng , Jiang Junjie , Pan Jian , Xi Shibo , Yang Hui Ying , Ma Zhipeng , Wan Tao , Chu Dewei , Jiang Wenjie , Smith Sean C. , Amal Rose , Han Zhaojun , Lu Xunyu
Published: May 2022

Platinum is the most efficient catalyst for hydrogen evolution reaction in acidic conditions, but its widespread use has been impeded by scarcity and high cost. Herein, Pt atomic clusters (Pt ACs) containing Pt-O-Pt units were prepared using Co/N co-doped carbon (CoNC) as support. Pt ACs are anchored to single Co atoms on CoNC by forming strong interactions. Pt-ACs/CoNC exhibits only 24 mV overpotential at 10 mA cm−2 and a high mass activity of 28.6 A mg−1 at 50 mV, which is more than 6 times higher than commercial Pt/C with any Pt loadings. Spectroscopic measurements and computational modeling reveal the enhanced hydrogen generation activity attributes to the charge redistribution between Pt and O atoms in Pt-O-Pt units, making Pt atoms the main active sites and O linkers the assistants, thus optimizing the proton adsorption and hydrogen desorption. This work opens an avenue to fabricate noble-metal-based ACs stabilized by single-atom catalysts with desired properties for electrocatalysis.
Diversity of bacterial small RNAs drives competitive strategies for a mutual chaperone
Authors: Roca Jorjethe , Santiago-Frangos Andrew , Woodson Sarah A.
Published: May 2022

Hundreds of bacterial small RNAs (sRNAs) require the Hfq chaperone to regulate mRNA expression. Hfq is limiting, thus competition among sRNAs for binding to Hfq shapes the proteomes of individual cells. To understand how sRNAs compete for a common partner, we present a single-molecule fluorescence platform to simultaneously visualize binding and release of multiple sRNAs with Hfq. We show that RNA residents rarely dissociate on their own. Instead, clashes between residents and challengers on the same face of Hfq cause rapid exchange, whereas RNAs that recognize different surfaces may cohabit Hfq for several minutes before one RNA departs. The prevalence of these pathways depends on the structure of each RNA and how it interacts with Hfq. We propose that sRNA diversity creates many pairwise interactions with Hfq that allow for distinct biological outcomes: active exchange favors fast regulation whereas co-residence of dissimilar RNAs favors target co-recognition or target exclusion.
Drivers of ecological assembly in the hindgut of Atlantic Cod fed a macroalgal supplemented diet
Authors: Keating C. , Bolton-Warberg M. , Hinchcliffe J. , Davies R. , Whelan S. , Wan A. H. L. , Fitzgerald R. D. , Davies S. J. , Smith C. J. , Ijaz U. Z.
Published: May 2022

It is difficult to disentangle the many variables (e.g. internal or external cues and random events) that shape the microbiota in the gastrointestinal tract of any living species. Ecological assembly processes applied to microbial communities can elucidate these drivers. In our study, farmed Atlantic cod (Gadus morhua) were fed a diet of 10% macroalgae supplement (Ulva rigida [ULVA] or Ascophyllum nodosum [ASCO] or a non-supplemented control diet [CTRL]) over 12 weeks. We determined the influence of ecological assembly processes using a suite of null-modelling tools. We observed dissimilarity in the abundance of common OTUs over time, which was driven by deterministic assembly. The CTRL samples showed selection as a critical assembly process. While dispersal limitation was a driver of the gut microbiome for fish fed the macroalgae supplemented diet at Week 12 (i.e., ASCO and ULVA). Fish from the ASCO grouping diverged into ASCO_N (normal) and ASCO_LG (lower growth), where ASCO_LG individuals found the diet unpalatable. The recruitment of new taxa overtime was altered in the ASCO_LG fish, with the gut microbiome showing phylogenetic underdispersion (nepotistic species recruitment). Finally, the gut microbiome (CTRL and ULVA) showed increasing robustness to taxonomic disturbance over time and lower functional redundancy. This study advances our understanding of the ecological assembly and succession in the hindgut of juvenile Atlantic cod across dietary treatments. Understanding the processes driving ecological assembly in the gut microbiome, in fish research specifically, could allow us to manipulate the microbiome for improved health or resilience to disease for improved aquaculture welfare and production.
Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer
Authors: Yadav Shivangi , Virk Ranya , Chung Carolina H. , Eduardo Mariana Bustamante , VanDerway David , Chen Duojiao , Burdett Kirsten , Gao Hongyu , Zeng Zexian , Ranjan Manish , Cottone Gannon , Xuei Xiaoling , Chandrasekaran Sriram , Backman Vadim , Chatterton Robert , Khan Seema Ahsan , Clare Susan E.
Published: May 2022

Improved understanding of local breast biology that favors the development of estrogen receptor negative (ER−) breast cancer (BC) would foster better prevention strategies. We have previously shown that overexpression of specific lipid metabolism genes is associated with the development of ER− BC. We now report results of exposure of MCF-10A and MCF-12A cells, and mammary organoids to representative medium- and long-chain polyunsaturated fatty acids. This exposure caused a dynamic and profound change in gene expression, accompanied by changes in chromatin packing density, chromatin accessibility, and histone posttranslational modifications (PTMs). We identified 38 metabolic reactions that showed significantly increased activity, including reactions related to one-carbon metabolism. Among these reactions are those that produce S-adenosyl-L-methionine for histone PTMs. Utilizing both an in-vitro model and samples from women at high risk for ER− BC, we show that lipid exposure engenders gene expression, signaling pathway activation, and histone marks associated with the development of ER− BC.
Genetic associations with learning over 100 days of practice
Authors: Youn Cherry , Grotzinger Andrew D. , Lill Christina M. , Bertram Lars , Schmiedek Florian , Lövdén Martin , Lindenberger Ulman , Nivard Michel , Harden K. Paige , Tucker-Drob Elliot M.
Published: May 2022

Cognitive performance is both heritable and sensitive to environmental inputs and sustained practice over time. However, it is currently unclear how genetic effects on cognitive performance change over the course of learning. We examine how polygenic scores (PGS) created from genome-wide association studies of educational attainment and cognitive performance are related to improvements in performance across nine cognitive tests (measuring perceptual speed, working memory, and episodic memory) administered to 131 adults (N = 51, ages = 20–31, andN = 80, ages = 65–80 years) repeatedly across 100 days. We observe that PGS associations with performance on a given task can change over the course of learning, with the specific pattern of change in associations differing across tasks. PGS correlations with pre-test to post-test scores may mask variability in how soon learning occurs over the course of practice. The associations between PGS and learning do not appear to simply reconstitute patterns of association between baseline performance and subsequent learning. Associations involving PGSs, however, were small with large confidence intervals. Intensive longitudinal research such as that described here may be of substantial value for clarifying the genetics of learning when implemented as far larger scale.
MALDI mass spectrometry imaging workflow for the aquatic model organisms Danio rerio and Daphnia magna
Authors: Schirmer Elisabeth , Ritschar Sven , Ochs Matthias , Laforsch Christian , Schuster Stefan , Römpp Andreas
Published: May 2022

Lipids play various essential roles in the physiology of animals. They are also highly dependent on cellular metabolism or status. It is therefore crucial to understand to which extent animals can stabilize their lipid composition in the presence of external stressors, such as chemicals that are released into the environment. We developed a MALDI MS imaging workflow for two important aquatic model organisms, the zebrafish (Danio rerio) and water flea (Daphnia magna). Owing to the heterogeneous structure of these organisms, developing a suitable sample preparation workflow is a highly non-trivial but crucial part of this work and needs to be established first. Relevant parameters and practical considerations in order to preserve tissue structure and composition in tissue sections are discussed for each application. All measurements were based on high mass accuracy enabling reliable identification of imaged compounds. In zebrafish we demonstrate that a detailed mapping between histology and simultaneously determined lipid composition is possible at various scales, from extended structures such as the brain or gills down to subcellular structures such as a single axon in the central nervous system. For D. magna we present for the first time a MALDI MSI workflow, that demonstrably maintains tissue integrity during cryosectioning of non-preserved samples, and allows the mapping of lipids in the entire body and the brood chamber inside the carapace. In conclusion, the lipid signatures that we were able to detect with our method provide an ideal basis to analyze changes caused by pollutants in two key aquatic model organisms.