bluuebunny/crossref_metadata_2025 huggingface dataset:
Can We Detect Urban‐Scale CO2 Emission Changes Within Medium‐Sized Cities?
Authors: Mallia Derek V. , Mitchell Logan E. , Gonzalez Vidal Andres Eduardo , Wu Dien , Kunik Lewis , Lin John C.
Published: May 2023

The COVID‐19 pandemic resulted in a widespread lockdown during the spring of 2020. Measurements collected on a light rail system in the Salt Lake Valley (SLV), combined with observations from the Utah Urban Carbon Dioxide Network observed a notable decrease in urban CO2 concentrations during the spring of 2020 relative to previous years. These decreases coincided with a ∼30% reduction in average traffic volume. CO2 measurements across the SLV were used within a Bayesian inverse model to spatially allocate anthropogenic emission reductions for the first COVID‐19 lockdown. The inverse model was first used to constrain anthropogenic emissions for the previous year (2019) to provide the best possible estimate of emissions for 2020, before accounting for emission reductions observed during the COVID‐19 lockdown. The posterior emissions for 2019 were then used as the prior emission estimate for the 2020 COVID‐19 lockdown analysis. Results from the inverse analysis suggest that the SLV observed a 20% decrease in afternoon CO2 emissions from March to April 2020 (−90.5 tC hr−1). The largest reductions in CO2 emissions were centered over the northern part of the valley (downtown Salt Lake City), near major roadways, and potentially at industrial point sources. These results demonstrate that CO2 monitoring networks can track reductions in CO2 emissions even in medium‐sized cities like Salt Lake City.
Representing Eddy Diffusion in the Surface Boundary Layer of Ocean Models With General Vertical Coordinates
Authors: Marques Gustavo M. , Shao Andrew E. , Bachman Scott D. , Danabasoglu Gokhan , Bryan Frank O.
Published: May 2023

The mixing of tracers by mesoscale eddies, parameterized in many ocean general circulation models (OGCMs) as a diffusive‐advective process, contributes significantly to the distribution of tracers in the ocean. In the ocean interior, diffusive contribution occurs mostly along the direction parallel to local neutral density surfaces. However, near the surface of the ocean, small‐scale turbulence and the presence of the boundary itself break this constraint and the mesoscale transport occurs mostly along a plane parallel to the ocean surface (horizontal). Although this process is easily represented in OGCMs with geopotential vertical coordinates, the representation is more challenging in OGCMs that use a general vertical coordinate, where surfaces can be tilted with respect to the horizontal. We propose a method for representing the diffusive horizontal mesoscale fluxes within the surface boundary layer of general vertical coordinate OGCMs. The method relies on regridding/remapping techniques to represent tracers in a geopotential grid. Horizontal fluxes are calculated on this grid and then remapped back to the native grid, where fluxes are applied. The algorithm is implemented in an ocean model and tested in idealized and realistic settings. Horizontal diffusion can account for up to 10% of the total northward heat transport in the Southern Ocean and Western boundary current regions of the Northern Hemisphere. It also reduces the vertical stratification of the upper ocean, which results in an overall deepening of the surface boundary layer depth. Finally, enabling horizontal diffusion leads to meaningful reductions in the near‐surface global bias of potential temperature and salinity.
Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies
Authors: Wu Xiumei , Xu Mengyun , Geng Mengya , Chen Shuo , Little Peter J. , Xu Suowen , Weng Jianping
Published: May 2023

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. The most common form of NCD is metabolic diseases, which affect people of all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding of the pathobiology of metabolic diseases will generate novel targets for improved therapies across the common metabolic spectrum. Protein posttranslational modification (PTM) is an important term that refers to biochemical modification of specific amino acid residues in target proteins, which immensely increases the functional diversity of the proteome. The range of PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, and several novel PTMs. Here, we offer a comprehensive review of PTMs and their roles in common metabolic diseases and pathological consequences, including diabetes, obesity, fatty liver diseases, hyperlipidemia, and atherosclerosis. Building upon this framework, we afford a through description of proteins and pathways involved in metabolic diseases by focusing on PTM-based protein modifications, showcase the pharmaceutical intervention of PTMs in preclinical studies and clinical trials, and offer future perspectives. Fundamental research defining the mechanisms whereby PTMs of proteins regulate metabolic diseases will open new avenues for therapeutic intervention.
Hematopoietic reconstitution dynamics of mobilized- and bone marrow-derived human hematopoietic stem cells after gene therapy
Authors: Scala Serena , Ferrua Francesca , Basso-Ricci Luca , Dionisio Francesca , Omrani Maryam , Quaranta Pamela , Jofra Hernandez Raisa , Del Core Luca , Benedicenti Fabrizio , Monti Ilaria , Giannelli Stefania , Fraschetta Federico , Darin Silvia , Albertazzi Elena , Galimberti Stefania , Montini Eugenio , Calabria Andrea , Cicalese Maria Pia , Aiuti Alessandro
Published: May 2023

Mobilized peripheral blood is increasingly used instead of bone marrow as a source of autologous hematopoietic stem/progenitor cells for ex vivo gene therapy. Here, we present an unplanned exploratory analysis evaluating the hematopoietic reconstitution kinetics, engraftment and clonality in 13 pediatric Wiskott-Aldrich syndrome patients treated with autologous lentiviral-vector transduced hematopoietic stem/progenitor cells derived from mobilized peripheral blood (n = 7), bone marrow (n = 5) or the combination of the two sources (n = 1). 8 out of 13 gene therapy patients were enrolled in an open-label, non-randomized, phase 1/2 clinical study (NCT01515462) and the remaining 5 patients were treated under expanded access programs. Although mobilized peripheral blood- and bone marrow- hematopoietic stem/progenitor cells display similar capability of being gene-corrected, maintaining the engineered grafts up to 3 years after gene therapy, mobilized peripheral blood-gene therapy group shows faster neutrophil and platelet recovery, higher number of engrafted clones and increased gene correction in the myeloid lineage which correlate with higher amount of primitive and myeloid progenitors contained in hematopoietic stem/progenitor cells derived from mobilized peripheral blood. In vitro differentiation and transplantation studies in mice confirm that primitive hematopoietic stem/progenitor cells from both sources have comparable engraftment and multilineage differentiation potential. Altogether, our analyses reveal that the differential behavior after gene therapy of hematopoietic stem/progenitor cells derived from either bone marrow or mobilized peripheral blood is mainly due to the distinct cell composition rather than functional differences of the infused cell products, providing new frames of references for clinical interpretation of hematopoietic stem/progenitor cell transplantation outcome.
Enabling selective zinc-ion intercalation by a eutectic electrolyte for practical anodeless zinc batteries
Authors: Li Chang , Kingsbury Ryan , Thind Arashdeep Singh , Shyamsunder Abhinandan , Fister Timothy T. , Klie Robert F. , Persson Kristin A. , Nazar Linda F.
Published: May 2023

Two major challenges hinder the advance of aqueous zinc metal batteries for sustainable stationary storage: (1) achieving predominant Zn-ion (de)intercalation at the oxide cathode by suppressing adventitious proton co-intercalation and dissolution, and (2) simultaneously overcoming Zn dendrite growth at the anode that triggers parasitic electrolyte reactions. Here, we reveal the competition between Zn2+vsproton intercalation chemistry of a typical oxide cathode using ex-situ/operandotechniques, and alleviate side reactions by developing a cost-effective and non-flammable hybrid eutectic electrolyte. A fully hydrated Zn2+solvation structure facilitates fast charge transfer at the solid/electrolyte interface, enabling dendrite-free Zn plating/stripping with a remarkably high average coulombic efficiency of 99.8% at commercially relevant areal capacities of 4 mAh cm−2and function up to 1600 h at 8 mAh cm−2. By concurrently stabilizing Zn redox at both electrodes, we achieve a new benchmark in Zn-ion battery performance of 4 mAh cm−2anode-free cells that retain 85% capacity over 100 cycles at 25 °C. Using this eutectic-design electrolyte, Zn | |Iodine full cells are further realized with 86% capacity retention over 2500 cycles. The approach represents a new avenue for long-duration energy storage.
Incoherent nonadiabatic to coherent adiabatic transition of electron transfer in colloidal quantum dot molecules
Authors: Hou Bokang , Thoss Michael , Banin Uri , Rabani Eran
Published: May 2023

Electron transfer is a fundamental process in chemistry, biology, and physics. One of the most intriguing questions concerns the realization of the transitions between nonadiabatic and adiabatic regimes of electron transfer. Using colloidal quantum dot molecules, we computationally demonstrate how the hybridization energy (electronic coupling) can be tuned by changing the neck dimensions and/or the quantum dot sizes. This provides a handle to tune the electron transfer from the incoherent nonadiabatic regime to the coherent adiabatic regime in a single system. We develop an atomistic model to account for several states and couplings to the lattice vibrations and utilize the mean-field mixed quantum-classical method to describe the charge transfer dynamics. Here, we show that charge transfer rates increase by several orders of magnitude as the system is driven to the coherent, adiabatic limit, even at elevated temperatures, and delineate the inter-dot and torsional acoustic modes that couple most strongly to the charge transfer dynamics.
Inference of cell type-specific gene regulatory networks on cell lineages from single cell omic datasets
Authors: Zhang Shilu , Pyne Saptarshi , Pietrzak Stefan , Halberg Spencer , McCalla Sunnie Grace , Siahpirani Alireza Fotuhi , Sridharan Rupa , Roy Sushmita
Published: May 2023

Cell type-specific gene expression patterns are outputs of transcriptional gene regulatory networks (GRNs) that connect transcription factors and signaling proteins to target genes. Single-cell technologies such as single cell RNA-sequencing (scRNA-seq) and single cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), can examine cell-type specific gene regulation at unprecedented detail. However, current approaches to infer cell type-specific GRNs are limited in their ability to integrate scRNA-seq and scATAC-seq measurements and to model network dynamics on a cell lineage. To address this challenge, we have developed single-cell Multi-Task Network Inference (scMTNI), a multi-task learning framework to infer the GRN for each cell type on a lineage from scRNA-seq and scATAC-seq data. Using simulated and real datasets, we show that scMTNI is a broadly applicable framework for linear and branching lineages that accurately infers GRN dynamics and identifies key regulators of fate transitions for diverse processes such as cellular reprogramming and differentiation.
Directionality of developing skeletal muscles is set by mechanical forces
Authors: Sunadome Kazunori , Erickson Alek G. , Kah Delf , Fabry Ben , Adori Csaba , Kameneva Polina , Faure Louis , Kanatani Shigeaki , Kaucka Marketa , Dehnisch Ellström Ivar , Tesarova Marketa , Zikmund Tomas , Kaiser Jozef , Edwards Steven , Maki Koichiro , Adachi Taiji , Yamamoto Takuya , Fried Kaj , Adameyko Igor
Published: May 2023

Formation of oriented myofibrils is a key event in musculoskeletal development. However, the mechanisms that drive myocyte orientation and fusion to control muscle directionality in adults remain enigmatic. Here, we demonstrate that the developing skeleton instructs the directional outgrowth of skeletal muscle and other soft tissues during limb and facial morphogenesis in zebrafish and mouse. Time-lapse live imaging reveals that during early craniofacial development, myoblasts condense into round clusters corresponding to future muscle groups. These clusters undergo oriented stretch and alignment during embryonic growth. Genetic perturbation of cartilage patterning or size disrupts the directionality and number of myofibrils in vivo. Laser ablation of musculoskeletal attachment points reveals tension imposed by cartilage expansion on the forming myofibers. Application of continuous tension using artificial attachment points, or stretchable membrane substrates, is sufficient to drive polarization of myocyte populations in vitro. Overall, this work outlines a biomechanical guidance mechanism that is potentially useful for engineering functional skeletal muscle.
Multi-neuron connection using multi-terminal floating–gate memristor for unsupervised learning
Authors: Won Ui Yeon , An Vu Quoc , Park Sung Bum , Park Mi Hyang , Dam Do Van , Park Hyun Jun , Yang Heejun , Lee Young Hee , Yu Woo Jong
Published: May 2023

Multi-terminal memristor and memtransistor (MT-MEMs) has successfully performed complex functions of heterosynaptic plasticity in synapse. However, theses MT-MEMs lack the ability to emulate membrane potential of neuron in multiple neuronal connections. Here, we demonstrate multi-neuron connection using a multi-terminal floating-gate memristor (MT-FGMEM). The variable Fermi level (EF) in graphene allows charging and discharging of MT-FGMEM using horizontally distant multiple electrodes. Our MT-FGMEM demonstrates high on/off ratio over 105 at 1000 s retention about ~10,000 times higher than other MT-MEMs. The linear behavior between current (ID) and floating gate potential (VFG) in triode region of MT-FGMEM allows for accurate spike integration at the neuron membrane. The MT-FGMEM fully mimics the temporal and spatial summation of multi-neuron connections based on leaky-integrate-and-fire (LIF) functionality. Our artificial neuron (150 pJ) significantly reduces the energy consumption by 100,000 times compared to conventional neurons based on silicon integrated circuits (11.7 μJ). By integrating neurons and synapses using MT-FGMEMs, a spiking neurosynaptic training and classification of directional lines functioned in visual area one (V1) is successfully emulated based on neuron’s LIF and synapse’s spike-timing-dependent plasticity (STDP) functions. Simulation of unsupervised learning based on our artificial neuron and synapse achieves a learning accuracy of 83.08% on the unlabeled MNIST handwritten dataset.
Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex
Authors: Patel Avinash B. , Qing Jinkang , Tam Kelly H. , Zaman Sara , Luiso Maria , Radhakrishnan Ishwar , He Yuan
Published: May 2023

The Rpd3L histone deacetylase (HDAC) complex is an ancient 12-subunit complex conserved in a broad range of eukaryotes that performs localized deacetylation at or near sites of recruitment by DNA-bound factors. Here we describe the cryo-EM structure of this prototypical HDAC complex that is characterized by as many as seven subunits performing scaffolding roles for the tight integration of the only catalytic subunit, Rpd3. The principal scaffolding protein, Sin3, along with Rpd3 and the histone chaperone, Ume1, are present in two copies, with each copy organized into separate lobes of an asymmetric dimeric molecular assembly. The active site of one Rpd3 is completely occluded by a leucine side chain of Rxt2, while the tips of the two lobes and the more peripherally associated subunits exhibit varying levels of flexibility and positional disorder. The structure reveals unexpected structural homology/analogy between unrelated subunits in the fungal and mammalian complexes and provides a foundation for deeper interrogations of structure, biology, and mechanism of these complexes, as well as for the discovery of HDAC complex-specific inhibitors.
Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum
Authors: Kümpornsin Krittikorn , Kochakarn Theerarat , Yeo Tomas , Okombo John , Luth Madeline R. , Hoshizaki Johanna , Rawat Mukul , Pearson Richard D. , Schindler Kyra A. , Mok Sachel , Park Heekuk , Uhlemann Anne-Catrin , Jana Gouranga P. , Maity Bikash C. , Laleu Benoît , Chenu Elodie , Duffy James , Moliner Cubel Sonia , Franco Virginia , Gomez-Lorenzo Maria G. , Gamo Francisco Javier , Winzeler Elizabeth A. , Fidock David A. , Chookajorn Thanat , Lee Marcus C. S.
Published: May 2023

In vitro evolution of drug resistance is a powerful approach for identifying antimalarial targets, however, key obstacles to eliciting resistance are the parasite inoculum size and mutation rate. Here we sought to increase parasite genetic diversity to potentiate resistance selections by editing catalytic residues of Plasmodium falciparum DNA polymerase δ. Mutation accumulation assays reveal a ~5–8 fold elevation in the mutation rate, with an increase of 13–28 fold in drug-pressured lines. Upon challenge with the spiroindolone PfATP4-inhibitor KAE609, high-level resistance is obtained more rapidly and at lower inocula than wild-type parasites. Selections also yield mutants with resistance to an “irresistible” compound, MMV665794 that failed to yield resistance with other strains. We validate mutations in a previously uncharacterised gene, PF3D7_1359900, which we term quinoxaline resistance protein (QRP1), as causal for resistance to MMV665794 and a panel of quinoxaline analogues. The increased genetic repertoire available to this “mutator” parasite can be leveraged to drive P. falciparum resistome discovery.
Overestimated nitrogen loss from denitrification for natural terrestrial ecosystems in CMIP6 Earth System Models
Authors: Feng Maoyuan , Peng Shushi , Wang Yilong , Ciais Philippe , Goll Daniel S. , Chang Jinfeng , Fang Yunting , Houlton Benjamin Z. , Liu Gang , Sun Yan , Xi Yi
Published: May 2023

Denitrification and leaching nitrogen (N) losses are poorly constrained in Earth System Models (ESMs). Here, we produce a global map of natural soil15N abundance and quantify soil denitrification N loss for global natural ecosystems using an isotope-benchmarking method. We show an overestimation of denitrification by almost two times in the 13 ESMs of the Sixth Phase Coupled Model Intercomparison Project (CMIP6, 73 ± 31 Tg N yr−1), compared with our estimate of 38 ± 11 Tg N yr−1, which is rooted in isotope mass balance. Moreover, we find a negative correlation between the sensitivity of plant production to rising carbon dioxide (CO2) concentration and denitrification in boreal regions, revealing that overestimated denitrification in ESMs would translate to an exaggeration of N limitation on the responses of plant growth to elevated CO2. Our study highlights the need of improving the representation of the denitrification in ESMs and better assessing the effects of terrestrial ecosystems on CO2mitigation.
Photoinhibiting via simultaneous photoabsorption and free-radical reaction for high-fidelity light-based bioprinting
Authors: He Ning , Wang Xiaonan , Shi Liyang , Li Jing , Mo Lan , Chen Feng , Huang Yuting , Liu Hairong , Zhu Xiaolong , Zhu Wei , Mao Yiqi , Han Xiaoxiao
Published: May 2023

Light-based 3D bioprinting is now employed widely to fabricate geometrically complex constructs for various biomedical applications. However, the inherent light scattering defect creates significant challenges in patterning dilute hydrogels to form high-fidelity structures with fine-scale features. Herein, we introduce a photoinhibiting approach that can effectively suppress the light scattering effect via a mechanism of simultaneous photoabsorption and free-radical reaction. This biocompatible approach significantly improves the printing resolution (~1.2 - ~2.1 pixels depending on swelling) and shape fidelity (geometric error less than 5%), while minimising the costly trial-and-error procedures. The capability in patterning 3D complex constructs using different hydrogels is demonstrated by manufacturing various scaffolds featuring intricate multi-sized channels and thin-walled networks. Importantly, cellularised gyroid scaffolds (HepG2) are fabricated successfully, exhibiting high cell proliferation and functionality. The strategy established in this study promotes the printability and operability of light-based 3D bioprinting systems, allowing numerous new applications for tissue engineering.
Deep learning enables satellite-based monitoring of large populations of terrestrial mammals across heterogeneous landscape
Authors: Wu Zijing , Zhang Ce , Gu Xiaowei , Duporge Isla , Hughey Lacey F. , Stabach Jared A. , Skidmore Andrew K. , Hopcraft J. Grant C. , Lee Stephen J. , Atkinson Peter M. , McCauley Douglas J. , Lamprey Richard , Ngene Shadrack , Wang Tiejun
Published: May 2023

New satellite remote sensing and machine learning techniques offer untapped possibilities to monitor global biodiversity with unprecedented speed and precision. These efficiencies promise to reveal novel ecological insights at spatial scales which are germane to the management of populations and entire ecosystems. Here, we present a robust transferable deep learning pipeline to automatically locate and count large herds of migratory ungulates (wildebeest and zebra) in the Serengeti-Mara ecosystem using fine-resolution (38-50 cm) satellite imagery. The results achieve accurate detection of nearly 500,000 individuals across thousands of square kilometers and multiple habitat types, with an overall F1-score of 84.75% (Precision: 87.85%, Recall: 81.86%). This research demonstrates the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of terrestrial mammals across a highly heterogeneous landscape. We also discuss the potential for satellite-derived species detections to advance basic understanding of animal behavior and ecology.
macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma
Authors: Nikolic Ana , Maule Francesca , Bobyn Anna , Ellestad Katrina , Paik Seungil , Marhon Sajid A. , Mehdipour Parinaz , Lun Xueqing , Chen Huey-Miin , Mallard Claire , Hay Alexander J. , Johnston Michael J. , Gafuik Christopher J. , Zemp Franz J. , Shen Yaoqing , Ninkovic Nicoletta , Osz Katalin , Labit Elodie , Berger N. Daniel , Brownsey Duncan K. , Kelly John J. , Biernaskie Jeff , Dirks Peter B. , Derksen Darren J. , Jones Steven J. M. , Senger Donna L. , Chan Jennifer A. , Mahoney Douglas J. , De Carvalho Daniel D. , Gallo Marco
Published: May 2023

Self-renewal is a crucial property of glioblastoma cells that is enabled by the choreographed functions of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could therefore represent an important step toward developing effective treatments for this universally lethal cancer. Here we uncover an epigenetic axis of self-renewal mediated by the histone variant macroH2A2. With omics and functional assays deploying patient-derived in vitro and in vivo models, we show that macroH2A2 shapes chromatin accessibility at enhancer elements to antagonize transcriptional programs of self-renewal. macroH2A2 also sensitizes cells to small molecule-mediated cell death via activation of a viral mimicry response. Consistent with these results, our analyses of clinical cohorts indicate that high transcriptional levels of this histone variant are associated with better prognosis of high-grade glioma patients. Our results reveal a targetable epigenetic mechanism of self-renewal controlled by macroH2A2 and suggest additional treatment approaches for glioblastoma patients.
Controllable degradation behavior of Mg-Sr-Y alloys for the bio-applications
Authors: Li Yingying , Yuan Yuan , Wang Jun , Wu Liang , Cao Fuyong , Zhang Ligang , Pan Fusheng
Published: May 2023

The biodegradation behavior and mechanical properties of Mg-Sr-Y alloys were systematically investigated for the medical application. The alloy (Mg-0.3Sr-0.5Y) exhibits a comparable UTS as 111.53 MPa and shows a general uniform degradation behavior with low corrosion rate as only 0.823 mm y−1 in Hanks’ solution. The simultaneous solid solution of Y in α-Mg phase and in Mg17Sr2 phase reduces the micro-galvanic corrosion. Additionally, the formation of a compact composite film of Mg(OH)2, Y2O3 and Sr-substituted phosphate (Sr-HA) delivers the protection for the matrix. Low corrosion rate, fine precipitates and dispersed Y rich-zones, which hinder the corrosion propagation, further guarantees a uniform degradation behavior. While, with increasing Sr content, the corrosion resistance is deteriorated because of the formed continuous distribution of Mg17Sr2 along grain boundaries. By tailoring composition and structure, Mg-Sr-Y alloys with balanced mechanical and bio-degradation properties can be promising for the bio-applications.
DNA based neoepitope vaccination induces tumor control in syngeneic mouse models
Authors: Viborg Nadia , Pavlidis Michail Angelos , Barrio-Calvo Marina , Friis Stine , Trolle Thomas , Sørensen Anders Bundgaard , Thygesen Christian Bahne , Kofoed Søren Vester , Kleine-Kohlbrecher Daniela , Hadrup Sine Reker , Rønø Birgitte
Published: May 2023

Recent findings have positioned tumor mutation-derived neoepitopes as attractive targets for cancer immunotherapy. Cancer vaccines that deliver neoepitopes via various vaccine formulations have demonstrated promising preliminary results in patients and animal models. In the presented work, we assessed the ability of plasmid DNA to confer neoepitope immunogenicity and anti-tumor effect in two murine syngeneic cancer models. We demonstrated that neoepitope DNA vaccination led to anti-tumor immunity in the CT26 and B16F10 tumor models, with the long-lasting presence of neoepitope-specific T-cell responses in blood, spleen, and tumors after immunization. We further observed that engagement of both the CD4+ and CD8+ T cell compartments was essential to hamper tumor growth. Additionally, combination therapy with immune checkpoint inhibition provided an additive effect, superior to either monotherapy. DNA vaccination offers a versatile platform that allows the encoding of multiple neoepitopes in a single formulation and is thus a feasible strategy for personalized immunotherapy via neoepitope vaccination.
Full-Stokes polarization multispectral images of various stereoscopic objects
Authors: Fan Axin , Xu Tingfa , Teng Geer , Wang Xi , Zhang Yuhan , Xu Chang , Xu Xin , Li Jianan
Published: May 2023

Polarization multispectral imaging (PMI) has been applied widely with the ability of characterizing physicochemical properties of objects. However, traditional PMI relies on scanning each domain, which is time-consuming and occupies vast storage resources. Therefore, it is imperative to develop advanced PMI methods to facilitate real-time and cost-effective applications. In addition, PMI development is inseparable from preliminary simulations based on full-Stokes polarization multispectral images (FSPMI). Whereas, FSPMI measurements are always necessary due to the lack of relevant databases, which is extremely complex and severely limits PMI development. In this paper, we therefore publicize abundant FSPMI with 512 × 512 spatial pixels measured by an established system for 67 stereoscopic objects. In the system, a quarter-wave plate and a linear polarizer are rotated to modulate polarization information, while bandpass filters are switched to modulate spectral information. The required FSPMI are finally calculated from designed 5 polarization modulation and 18 spectral modulation. The publicly available FSPMI database may have the potential to greatly promote PMI development and application.
Measuring Subnational Trade Competitiveness
Authors: Huber Robert A. , Stiller Yannick , Dür Andreas
Published: May 2023

Much research has tried to measure the competitiveness of territorial units such as countries and subnational regions. We propose new measures of subnational trade competitiveness that reflect the economic focus of regions on their country’s comparative advantage. Our approach starts with data on the revealed comparative advantage of countries at the industry level. We then combine these measures with data on the employment structure of subnational regions to arrive at measures of subnational trade competitiveness. In total, we offer data for 6,475 regions across 63 countries and over a time period of 21 years. In this article, we introduce our measures and provide descriptive evidence, include two case studies for Bolivia and South Korea, that shows the plausibility of these measures. These data are relevant for many areas of research, including on the competitiveness of territorial units, the economic and political impact of trade on importing countries, and the economic and political consequences of globalization.
Memory, perceptual, and motor costs affect the strength of categorical encoding during motor learning of object properties
Authors: Cesanek Evan , Flanagan J. Randall , Wolpert Daniel M.
Published: May 2023

Nearly all tasks of daily life involve skilled object manipulation, and successful manipulation requires knowledge of object dynamics. We recently developed a motor learning paradigm that reveals the categorical organization of motor memories of object dynamics. When participants repeatedly lift a constant-density “family” of cylindrical objects that vary in size, and then an outlier object with a greater density is interleaved into the sequence of lifts, they often fail to learn the weight of the outlier, persistently treating it as a family member despite repeated errors. Here we examine eight factors (Similarity, Cardinality, Frequency, History, Structure, Stochasticity, Persistence, and Time Pressure) that could influence the formation and retrieval of category representations in the outlier paradigm. In our web-based task, participants (N = 240) anticipated object weights by stretching a virtual spring attached to the top of each object. Using Bayesiant-tests, we analyze the relative impact of each manipulated factor on categorical encoding (strengthen, weaken, or no effect). Our results suggest that category representations of object weight are automatic, rigid, and linear and, as a consequence, the key determinant of whether an outlier is encoded as a member of the family is its discriminability from the family members.
Hormonal control of promoter activities of Cannabis sativa prenyltransferase 1 and 4 and salicylic acid mediated regulation of cannabinoid biosynthesis
Authors: Sands Lauren B. , Haiden Samuel R. , Ma Yi , Berkowitz Gerald A.
Published: May 2023

Cannabissativa aromatic prenyltransferase 4 (CsPT4) and 1 (CsPT1) have been shown to catalyze cannabigerolic acid (CBGA) biosynthesis, a step that rate-limits the cannabinoid biosynthetic pathway; both genes are highly expressed in flowers. CsPT4 and CsPT1 promoter driven β-glucuronidase (GUS) activities were detected in leaves of cannabis seedlings, and strong CsPT4 promoter activities were associated with glandular trichomes. Hormonal regulation of cannabinoid biosynthetic genes is poorly understood. An in silico analysis of the promoters identified putative hormone responsive elements. Our work examines hormone-responsive elements in the promoters of CsPT4 and CsPT1 in the context of physiological responses of the pathway to the hormone in planta. Dual luciferase assays confirmed the regulation of promoter activities by the hormones. Further studies with salicylic acid (SA) demonstrated that SA pretreatment increased the expression of genes located downstream of the cannabinoid biosynthetic pathway. The results from all aspects of this study demonstrated an interaction between certain hormones and cannabinoid synthesis. The work provides information relevant to plant biology, as we present evidence demonstrating correlations between molecular mechanisms that regulate gene expression and influence plant chemotypes.
Acute aerobic exercise benefits allocation of neural resources related to selective attention
Authors: Ligeza Tomasz S. , Vens Marie Julie , Bluemer Thea , Junghofer Markus
Published: May 2023

A single session of aerobic exercise has been shown to potentially benefit subsequent performance in a wide range of cognitive tasks, but the underlying mechanisms are still not fully understood. In this study, we investigated the effects of exercise on selective attention, a cognitive process that involves prioritized processing of a subset of available inputs over others. Twenty-four healthy participants (12 women) underwent two experimental interventions in a random, crossover, and counterbalanced design: a vigorous-intensity exercise (60–65% HRR) and a seated rest (control) condition. Before and after each protocol, participants performed a modified selective attention task that demanded attending stimuli of different spatial frequencies. Event-related magnetic fields were concurrently recorded using magnetoencephalography. The results showed that exercise, relative to the seated rest condition, reduced neural processing of unattended stimuli and increased processing of attended stimuli. The findings suggest that changes in neural processing related to selective attention may be one of the mechanisms underlying exercise-induced improvements in cognition.
Karst-bauxite formation during the Great Oxidation Event indicated by dating of authigenic rutile and its thorium content
Authors: Cabral Alexandre Raphael , Zeh Armin
Published: May 2023

Aluminium (Al)-rich palaeosols—i.e., palaeobauxite deposits—should have formed in karst depressions in carbonate sequences as a result of acidic solutions from oxidative weathering of sulfide minerals during the Great Oxidation Event (GOE), but no GOE-related karst-palaeobauxite deposits have so far been recorded. Here, we report results of in situ uranium–lead (U–Pb) dating of detrital zircon and spatially associated rutile from a metamorphosed Al-rich rock within a dolomite sequence in the Quadrilátero Ferrífero (QF) of Minas Gerais, Brazil, known as the Gandarela Formation. Rutile grains are highly enriched in thorium (Th = 3–46 ppm; Th/U ratio = 0.3–3.7) and yielded an isochron, lower-intercept age of ca. 2.12 Ga, which coincides with the final phase of the GOE—i.e., the Lomagundi event. The rutile age represents either authigenic growth of TiO2 enriched in Th, U and Pb during bauxite formation, or subsequent rutile crystallisation during metamorphic overprint. Both cases require an authigenic origin for the rutile. Its high Th contents can be used as a palaeoenvironmental indicator for decreased soil pH during the GOE. Our results also have implications for iron (Fe)-ore genesis in the QF. This study demonstrates that in situ U–Th–Pb-isotope analyses of rutile can place tight constraints on the age and nature of palaeosols.
Panoptic quality should be avoided as a metric for assessing cell nuclei segmentation and classification in digital pathology
Authors: Foucart Adrien , Debeir Olivier , Decaestecker Christine
Published: May 2023

Panoptic Quality (PQ), designed for the task of “Panoptic Segmentation” (PS), has been used in several digital pathology challenges and publications on cell nucleus instance segmentation and classification (ISC) since its introduction in 2019. Its purpose is to encompass the detection and the segmentation aspects of the task in a single measure, so that algorithms can be ranked according to their overall performance. A careful analysis of the properties of the metric, its application to ISC and the characteristics of nucleus ISC datasets, shows that is not suitable for this purpose and should be avoided. Through a theoretical analysis we demonstrate that PS and ISC, despite their similarities, have some fundamental differences that make PQ unsuitable. We also show that the use of the Intersection over Union as a matching rule and as a segmentation quality measure within PQ is not adapted for such small objects as nuclei. We illustrate these findings with examples taken from the NuCLS and MoNuSAC datasets. The code for replicating our results is available on GitHub (https://github.com/adfoucart/panoptic-quality-suppl).
Reducing CNOT count in quantum Fourier transform for the linear nearest-neighbor architecture
Authors: Park Byeongyong , Ahn Doyeol
Published: May 2023

Physical limitations of quantum hardware often necessitate nearest-neighbor (NN) architecture. When synthesizing quantum circuits using the basic gate library, which consists of CNOT and single-qubit gates, CNOT gates are required to convert a quantum circuit into one suitable for an NN architecture. In the basic gate library, CNOT gates are considered the primary cost of quantum circuits due to their higher error rates and longer execution times compared to single-qubit gates. In this paper, we propose a new linear NN (LNN) circuit design for quantum Fourier transform (QFT), one of the most versatile subroutines in quantum algorithms. Our LNN QFT circuit has only about 40% of the number of CNOT gates compared to previously known LNN QFT circuits. Subsequently, we input both our QFT circuits and conventional QFT circuits into the Qiskit transpiler to construct QFTs on IBM quantum computers, which necessitate NN architectures. Consequently, our QFT circuits demonstrate a substantial advantage over conventional QFT circuits in terms of the number of CNOT gates. This outcome implies that the proposed LNN QFT circuit design could serve as a novel foundation for developing QFT circuits implemented in quantum hardware that demands NN architecture.
NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc
Authors: Meng Sibo , Xia Yuan , Li Mingying , Wu Yuyan , Wang Dongmei , Zhou Ying , Ma Daoxin , Ye Jingjing , Sun Tao , Ji Chunyan
Published: May 2023

Diffuse large B-cell lymphoma (DLBCL) is malignant hyperplasia of B lymphocytes and standard care cannot satisfactorily meet clinical needs. Potential diagnostic and prognostic DLBCL biomarkers are needed. NCBP1 could bind to the 5ʹ-end cap of pre-mRNAs to participate in RNA processing, transcript nuclear export and translation. Aberrant NCBP1 expression is involved in the pathogenesis of cancers, but little is known about NCBP1 in DLBCL. We proved that NCBP1 is significantly elevated in DLBCL patients and is associated with their poor prognosis. Then, we found that NCBP1 is important for the proliferation of DLBCL cells. Moreover, we verified that NCBP1 enhances the proliferation of DLBCL cells in a METTL3-dependent manner and found that NCBP1 enhances the m6A catalytic function of METTL3 by maintaining METTL3 mRNA stabilization. Mechanistically, the expression of c-MYC is regulated by NCBP1-enhanced METTL3, and the NCBP1/METTL3/m6A/c-MYC axis is important for DLBCL progression. We identified a new pathway for DLBCL progression and suggest innovative ideas for molecular targeted therapy of DLBCL.
Performance evaluation of DEWMA3 in phase-II for capturing changes in simple linear profiles based on run rule mechanism
Authors: Sherwani Rehan Ahmad Khan , Qasim Humaira , Abbas Shumaila , Abbas Tahir , Aslam Muhammad
Published: May 2023

In Statistical Process Control, many techniques exist for monitoring the stability of a process over time. In this work, we study the relationship of the response variable with explanatory variables in the form of linear profiles for detecting changes in slope and intercept of the linear quality profiles. We used the transformation of explanatory variables approach used for make the regression estimates independent of each other to have zero average. A comparative study of three phase-II methods using DEWMA statistics in monitoring and capturing undesirable deviations in the slope, intercept, and variability is also studied by applying different proposed run rules schemes i.e., R1/1, R2/3, R3/3. Monte Carlo simulations were carried out on R-Software for finding the results of proposed schemes by taking various levels of shifts for intercept, slope, and standard deviation in identifying the false alarm rate of a process. The simulation results based on the average run length criterion show that the proposed run rule schemes improve the detection ability of the control structure. Among all the proposed schemes R2/3 is found to be the best one because of its quick detection ability of false alarm rate. The proposed scheme also shows superiority in comparison to other schemes. The simulation results are further justified with a real data application.
Eribulin inhibits growth of cutaneous squamous cell carcinoma cell lines and a novel patient-derived xenograft
Authors: Hsu Che-Yuan , Yanagi Teruki , Maeda Takuya , Nishihara Hiroshi , Miyamoto Kodai , Kitamura Shinya , Tokuchi Keiko , Ujiie Hideyuki
Published: May 2023

Advanced cutaneous squamous cell carcinoma (cSCC) is treated with chemotherapy and/or radiotherapy, but these typically fail to achieve satisfactory clinical outcomes. There have been no preclinical studies to evaluate the effectiveness of eribulin against cSCC. Here, we examine the effects of eribulin using cSCC cell lines and a novel cSCC patient-derived xenograft (PDX) model. In the cSCC cell lines (A431 and DJM-1 cells), eribulin was found to inhibit tumor cell proliferation in vitro as assessed by cell ATP levels. DNA content analysis by fluorescence-activated cell sorting (FACS) showed that eribulin induced G2/M cell cycle arrest and apoptosis. In xenograft models of cSCC cell lines, the administration of eribulin suppressed tumor growth in vivo. We also developed a cSCC patient-derived xenograft (PDX) which reproduces the histological and genetic characteristics of a primary tumor. Pathogenic mutations in TP53 and ARID2 were detected in the patient’s metastatic tumor and in the PDX tumor. The cSCC-PDX responded well to the administration of eribulin and cisplatin. In conclusion, the present study shows the promising antineoplastic effects of eribulin in cSCC. Also, we established a novel cSCC-PDX model that preserves the patient’s tumor. This PDX could assist researchers who are exploring innovative therapies for cSCC.
An exploratory study of dynamic foot shape measurements with 4D scanning system
Authors: Zhang Li-ying , Yick Kit-lun , Yue Mei-jun , Yip Joanne , Ng Sun-pui
Published: May 2023

Accurate and reliable foot measurements at different stances offer comprehensive geometrical information on foot, thus enabling a more comfortable insole/footwear for practical use and daily activities. However, there lacks investigations on continuous deformation of foot shape during the roll-over process. This study analyses the foot deformation of 19 female diabetic patients during half weight bearing standing and self-selected walking speed by using a novel 4D foot scanning system. The scanning system has good repeatability and accuracy in both static and dynamic scanning situations. Point cloud registration for scanned image reorientation and algorithms to automatically extract foot measurements is developed. During the foot roll-over process, maximum deformation of length and girth dimensions are found at first toe contact. Width dimensions have maximum deformation at heel take off. The findings provide a new understanding of foot shape changes in dynamic situations, thus providing an optimal solution for foot comfort, function and protection.
Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer
Authors: Medler Terry R. , Blair Tiffany C. , Alice Alejandro F. , Dowdell Alexa K. , Piening Brian D. , Crittenden Marka R. , Gough Michael J.
Published: May 2023

Radiation therapy induces immunogenic cell death in cancer cells, whereby released endogenous adjuvants are sensed by immune cells to direct adaptive immune responses. TLRs expressed on several immune subtypes recognize innate adjuvants to direct downstream inflammatory responses in part via the adapter protein MyD88. We generated Myd88 conditional knockout mice to interrogate its contribution to the immune response to radiation therapy in distinct immune populations in pancreatic cancer. Surprisingly, Myd88 deletion in Itgax (CD11c)-expressing dendritic cells had little discernable effects on response to RT in pancreatic cancer and elicited normal T cell responses using a prime/boost vaccination strategy. Myd88 deletion in Lck-expressing T cells resulted in similar or worsened responses to radiation therapy compared to wild-type mice and lacked antigen-specific CD8+ T cell responses from vaccination, similar to observations in Myd88−/− mice. Lyz2-specific loss of Myd88 in myeloid populations rendered tumors more susceptible to radiation therapy and elicited normal CD8+ T cell responses to vaccination. scRNAseq in Lyz2-Cre/Myd88fl/fl mice revealed gene signatures in macrophages and monocytes indicative of enhanced type I and II interferon responses, and improved responses to RT were dependent on CD8+ T cells and IFNAR1. Together, these data implicate MyD88 signaling in myeloid cells as a critical source of immunosuppression that hinders adaptive immune tumor control following radiation therapy.
Circulating miRNA expression in long-standing type 1 diabetes mellitus
Authors: Morales-Sánchez Paula , Lambert Carmen , Ares-Blanco Jessica , Suárez-Gutiérrez Lorena , Villa-Fernández Elsa , Garcia Ana Victoria , García-Villarino Miguel , Tejedor Juan Ramón , Fraga Mario F. , Torre Edelmiro Menéndez , Pujante Pedro , Delgado Elías
Published: May 2023

Type 1 diabetes is a chronic autoimmune disease which results in inefficient regulation of glucose homeostasis and can lead to different vascular comorbidities through life. In this study we aimed to analyse the circulating miRNA expression profile of patients with type 1 diabetes, and with no other associated pathology. For this, fasting plasma was obtained from 85 subjects. Next generation sequencing analysis was firstly performed to identify miRNAs that were differentially expressed between groups (20 patients vs. 10 controls). hsa-miR-1-3p, hsa-miR-200b-3p, hsa-miR-9-5p, and hsa-miR-1200 expression was also measured by Taqman RT-PCR to validate the observed changes (34 patients vs. 21 controls). Finally, through a bioinformatic approach, the main pathways affected by the target genes of these miRNAs were studied. Among the studied miRNAs, hsa-miR-1-3p expression was found significantly increased in patients with type 1 diabetes compared to controls, and positively correlated with glycated haemoglobin levels. Additionally, by using a bioinformatic approach, we could observe that changes in hsa-miR-1-3p directly affect genes involved in vascular development and cardiovascular pathologies. Our results suggest that, circulating hsa-miR-1-3p in plasma, together with glycaemic control, could be used as prognostic biomarkers in type 1 diabetes, helping to prevent the development of vascular complications in these patients.