bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum
Authors: Hayashi Clifford T. H. , Cao Yi , Clark Leor C. , Tripathi Abhai K. , Zavala Fidel , Dwivedi Garima , Knox James , Alameh Mohamad-Gabriel , Lin Paulo J. C. , Tam Ying K. , Weissman Drew , Kumar Nirbhay 
Published: December 2022

AbstractMalaria is a deadly disease responsible for between 550,000 and 627,000 deaths annually. There is a pressing need to develop vaccines focused on malaria elimination. The complex lifecycle of Plasmodium falciparum provides opportunities not only to target the infectious sporozoite stage, introduced by anopheline mosquitoes, but also the sexual stages, which are ingested by mosquitoes during blood feeding, leading to parasite transmission. It is widely recognized that a vaccine targeting multiple stages would induce efficacious transmission reducing immunity. Technological advancements offer new vaccine platforms, such as mRNA-LNPs, which can be used to develop highly effective malarial vaccines. We evaluated the immunogenicity of two leading P. falciparum vaccine candidates, Pfs25 and PfCSP, delivered as mRNA-LNP vaccines. Both vaccines induced extremely potent immune responses when administered alone or in combination, which were superior to Pfs25 and PfCSP DNA vaccine formulations. Purified IgGs from Pfs25 mRNA-LNPs immunized mice were highly potent in reducing malaria transmission to mosquitoes. Additionally, mice after three and four immunizations with PfCSP mRNA-LNP provided evidence for varying degrees of protection against sporozoite challenge. The comparison of immune responses and stage-specific functional activity induced by each mRNA-LNP vaccine, administered alone or in combination, also supports the development of an effective combination vaccine without any risk of immune interference for targeting malaria parasites at various life cycle stages. A combination of vaccines targeting both the infective stage and sexual/midgut stages is expected to interrupt malaria transmission, which is critical for achieving elimination goals.
Dimeric and trimeric catenation of giant chiral [8 + 12] imine cubes driven by weak supramolecular interactions
Authors: Benke Bahiru Punja , Kirschbaum Tobias , Graf Jürgen , Gross Jürgen H. , Mastalerz Michael 
Published: December 2022

AbstractMechanically interlocked structures, such as catenanes and rotaxanes, are fascinating synthetic targets and some are used for molecular switches and machines. Today, the vast majority of catenated structures are built upon macrocycles and only a very few examples of three-dimensional shape-persistent organic cages forming such structures have been reported. However, the catenation in all these cases was based on a thermodynamically favoured π–π-stacking under certain reaction conditions. Here, we show that catenane formation can be induced by adding methoxy or thiomethyl groups to one of the precursors during the synthesis of chiral [8 + 12] imine cubes, giving dimeric and trimeric catenated organic cages. To elucidate the underlying driving forces, we reacted 11 differently 1,4-disubstituted terephthaldehydes with a chiral triamino tribenzotriquinacene under various conditions to study whether monomeric cages or catenated cage dimers are the preferred products. We find that catenation is mainly directed by weak interactions derived from the substituents rather than by π-stacking.
Evidence of an oceanic impact and megatsunami sedimentation in Chryse Planitia, Mars
Authors: Rodriguez J. Alexis P. , Robertson Darrel K. , Kargel Jeffrey S. , Baker Victor R. , Berman Daniel C. , Cohen Jacob , Costard Francois , Komatsu Goro , Lopez Anthony , Miyamoto Hideaki , Zarroca Mario 
Published: December 2022

AbstractIn 1976, NASA's Viking 1 Lander (V1L) was the first spacecraft to operate successfully on the Martian surface. The V1L landed near the terminus of an enormous catastrophic flood channel, Maja Valles. However, instead of the expected megaflood record, its cameras imaged a boulder-strewn surface of elusive origin. We identified a 110-km-diameter impact crater (Pohl) ~ 900 km northeast of the landing site, stratigraphically positioned (a) above catastrophic flood-eroded surfaces formed ~ 3.4 Ga during a period of northern plains oceanic inundation and (b) below the younger of two previously hypothesized megatsunami deposits. These stratigraphic relationships suggest that a marine impact likely formed the crater. Our simulated impact-generated megatsunami run-ups closely match the mapped older megatsunami deposit's margins and predict fronts reaching the V1L site. The site's location along a highland-facing lobe aligned to erosional grooves supports a megatsunami origin. Our mapping also shows that Pohl's knobby rim regionally represents a broader history of megatsunami modification involving circum-oceanic glaciation and sedimentary extrusions extending beyond the recorded megatsunami emplacement in Chryse Planitia. Our findings allow that rocks and soil salts at the landing site are of marine origin, inviting the scientific reconsideration of information gathered from the first in-situ measurements on Mars.
UPRLIMET: UPstream Regional LiDAR Model for Extent of Trout in stream networks
Authors: Penaluna Brooke E. , Burnett Jonathan D. , Christiansen Kelly , Arismendi Ivan , Johnson Sherri L. , Griswold Kitty , Holycross Brett , Kolstoe Sonja H. 
Published: December 2022

AbstractPredicting the edges of species distributions is fundamental for species conservation, ecosystem services, and management decisions. In North America, the location of the upstream limit of fish in forested streams receives special attention, because fish-bearing portions of streams have more protections during forest management activities than fishless portions. We present a novel model development and evaluation framework, wherein we compare 26 models to predict upper distribution limits of trout in streams. The models used machine learning, logistic regression, and a sophisticated nested spatial cross-validation routine to evaluate predictive performance while accounting for spatial autocorrelation. The model resulting in the best predictive performance, termed UPstream Regional LiDAR Model for Extent of Trout (UPRLIMET), is a two-stage model that uses a logistic regression algorithm calibrated to observations of Coastal Cutthroat Trout (Oncorhynchus clarkii clarkii) occurrence and variables representing hydro-topographic characteristics of the landscape. We predict trout presence along reaches throughout a stream network, and include a stopping rule to identify a discrete upper limit point above which all stream reaches are classified as fishless. Although there is no simple explanation for the upper distribution limit identified in UPRLIMET, four factors, including upstream channel length above the point of uppermost fish, drainage area, slope, and elevation, had highest importance. Across our study region of western Oregon, we found that more of the fish-bearing network is on private lands than on state, US Bureau of Land Mangement (BLM), or USDA Forest Service (USFS) lands, highlighting the importance of using spatially consistent maps across a region and working across land ownerships. Our research underscores the value of using occurrence data to develop simple, but powerful, prediction tools to capture complex ecological processes that contribute to distribution limits of species.
Quantifying the benefits of reducing synthetic nitrogen application policy on ecosystem carbon sequestration and biodiversity
Authors: Devaraju N. , Prudhomme Rémi , Lungarska Anna , Wang Xuhui , Yin Zun , de Noblet-Ducoudré Nathalie , Chakir Raja , Jayet Pierre-Alain , Brunelle Thierry , Viovy Nicolas , De Palma Adriana , Gonzalez Ricardo , Ciais Philippe 
Published: December 2022

AbstractSynthetic Nitrogen (N) usage in agriculture has greatly increased food supply over the past century. However, the intensive use of N fertilizer is nevertheless the source of numerous environmental issues and remains a major challenge for policymakers to understand, measure, and quantify the interactions and trade-offs between ecosystem carbon and terrestrial biodiversity loss. In this study, we investigate the impacts of a public policy scenario that aims to halve N fertilizer application across European Union (EU) agriculture on both carbon (C) sequestration and biodiversity changes. We quantify the impacts by integrating two economic models with an agricultural land surface model and a terrestrial biodiversity model (that uses data from a range of taxonomic groups, including plants, fungi, vertebrates and invertebrates). Here, we show that the two economic scenarios lead to different outcomes in terms of C sequestration potential and biodiversity. Land abandonment associated with increased fertilizer price scenario facilitates higher C sequestration in soils (+ 1014 MtC) and similar species richness levels (+ 1.9%) at the EU scale. On the other hand, the more extensive crop production scenario is associated with lower C sequestration potential in soils (− 97 MtC) and similar species richness levels (− 0.4%) because of a lower area of grazing land. Our results therefore highlight the complexity of the environmental consequences of a nitrogen reduction policy, which will depend fundamentally on how the economic models used to project consequences.
Prediction of left lobe hypertrophy after right lobe radioembolization of the liver using a clinical data model with external validation
Authors: Theysohn Jens M. , Demircioglu Aydin , Kleditzsch Malte , Ludwig Johannes M. , Weber Manuel , Umutlu Lale , Li Yan , Kircher Malte , Lapa Constantin , Buck Andreas , Koehler Michael , Wildgruber Moritz , Lange Christian M. , Palard Xavier , Garin Etienne , Herrmann Ken , Forsting Michael , Nensa Felix 
Published: December 2022

AbstractIn cirrhotic patients with hepatocellular carcinoma (HCC), right-sided radioembolization (RE) with Yttrium-90-loaded microspheres is an established palliative therapy and can be considered a “curative intention” treatment when aiming for sequential tumor resection. To become surgical candidate, hypertrophy of the left liver lobe to > 40% (future liver remnant, FLR) is mandatory, which can develop after RE. The amount of radiation-induced shrinkage of the right lobe and compensatory hypertrophy of the left lobe is difficult for clinicians to predict. This study aimed to utilize machine learning to predict left lobe liver hypertrophy in patients with HCC and cirrhosis scheduled for right lobe RE, with external validation. The results revealed that machine learning can accurately predict relative and absolute volume changes of the left liver lobe after right lobe RE. This prediction algorithm could help to estimate the chances of conversion from palliative RE to curative major hepatectomy following significant FLR hypertrophy.
Utilizing AI to unveil the nonlinear interplay of convection, drift, and diffusion on galactic cosmic ray modulation in the inner heliosphere
Authors: Inceoglu Fadil , Pacini Alessandra Abe , Loto’aniu Paul T. M. 
Published: December 2022

AbstractGalactic Cosmic Rays (GCRs) are charged particles, originating from galactic and/or extra-galactic Supernova Remnants (SNR), that continuously permeate the Heliosphere. The GCRs are modulated in the heliosphere by convection by solar wind (SW), drift via gradients and curvatures in the Heliospheric Magnetic Field (HMF), diffusion from fluctuations in the HMF, and adiabatic cooling in the expanding SW. An improved understanding of their modulation is imperative as studies on the variations in solar activity levels and solar eruptions in the past rely heavily on the relationship between their modulation and formation of the secondary particles in the Earth’s atmosphere. Here, for the first time, we utilize an AI method, Light Gradient Boosting Machines (LightGBM), to investigate the nonlinear interplay among the modulation processes in different timescales. Our study indicates that the nonlinear interplay among the mechanisms responsible for the GCR modulation in the inner heliosphere are not limited to the scenario of “drift-dominated solar minimum” versus “diffusion-dominated solar maximum”, instead they have dynamic behavior displaying variations in time and in timescales. This study also demonstrates the value of using AI methods to investigate non-linear physical processes in Space Physics in the era of big data.
Pan-cancer landscape of AID-related mutations, composite mutations, and their potential role in the ICI response
Authors: Hernández-Verdin Isaias , Akdemir Kadir C. , Ramazzotti Daniele , Caravagna Giulio , Labreche Karim , Mokhtari Karima , Hoang-Xuan Khê , Peyre Matthieu , Bielle Franck , Touat Mehdi , Idbaih Ahmed , Duval Alex , Sanson Marc , Alentorn Agustí 
Published: December 2022

AbstractActivation-induced cytidine deaminase, AICDA or AID, is a driver of somatic hypermutation and class-switch recombination in immunoglobulins. In addition, this deaminase belonging to the APOBEC family may have off-target effects genome-wide, but its effects at pan-cancer level are not well elucidated. Here, we used different pan-cancer datasets, totaling more than 50,000 samples analyzed by whole-genome, whole-exome, or targeted sequencing. AID mutations are present at pan-cancer level with higher frequency in hematological cancers and higher presence at transcriptionally active TAD domains. AID synergizes initial hotspot mutations by a second composite mutation. AID mutational load was found to be independently associated with a favorable outcome in immune-checkpoint inhibitors (ICI) treated patients across cancers after analyzing 2000 samples. Finally, we found that AID-related neoepitopes, resulting from mutations at more frequent hotspots if compared to other mutational signatures, enhance CXCL13/CCR5 expression, immunogenicity, and T-cell exhaustion, which may increase ICI sensitivity.
Mycobacterium tuberculosis senses host Interferon-γ via the membrane protein MmpL10
Authors: Ahmed Mohamed , Mackenzie Jared , Tezera Liku , Krause Robert , Truebody Barry , Garay-Baquero Diana , Vallejo Andres , Govender Katya , Adamson John , Fisher Hayden , Essex Jonathan W. , Mansour Salah , Elkington Paul , Steyn Adrie J. C. , Leslie Alasdair 
Published: December 2022

AbstractMycobacterium tuberculosis (Mtb) is one of the most successful human pathogens. Several cytokines are known to increase virulence of bacterial pathogens, leading us to investigate whether Interferon-γ (IFN-γ), a central regulator of the immune defense against Mtb, has a direct effect on the bacteria. We found that recombinant and T-cell derived IFN-γ rapidly induced a dose-dependent increase in the oxygen consumption rate (OCR) of Mtb, consistent with increased bacterial respiration. This was not observed in attenuated Bacillus Calmette–Guérin (BCG), and did not occur for other cytokines tested, including TNF-α. IFN-γ binds to the cell surface of intact Mtb, but not BCG. Mass spectrometry identified mycobacterial membrane protein large 10 (MmpL10) as the transmembrane binding partner of IFN-γ, supported by molecular modelling studies. IFN-γ binding and the OCR response was absent in Mtb Δmmpl10 strain and restored by complementation with wildtype mmpl10. RNA-sequencing and RT-PCR of Mtb exposed to IFN-γ revealed a distinct transcriptional profile, including genes involved in virulence. In a 3D granuloma model, IFN-γ promoted Mtb growth, which was lost in the Mtb Δmmpl10 strain and restored by complementation, supporting the involvement of MmpL10 in the response to IFN-γ. Finally, IFN-γ addition resulted in sterilization of Mtb cultures treated with isoniazid, indicating clearance of phenotypically resistant bacteria that persist in the presence of drug alone. Together our data are the first description of a mechanism allowing Mtb to respond to host immune activation that may be important in the immunopathogenesis of TB and have use in novel eradication strategies.
DNA methylation and hydroxymethylation characterize the identity of D1 and D2 striatal projection neurons
Authors: Marion-Poll Lucile , Roussarie Jean-Pierre , Taing Lieng , Dard-Dascot Cloelia , Servant Nicolas , Jaszczyszyn Yan , Jordi Emmanuelle , Mulugeta Eskeatnaf , Hervé Denis , Bourc’his Déborah , Greengard Paul , Thermes Claude , Girault Jean-Antoine 
Published: December 2022

AbstractNeuronal DNA modifications differ from those in other cells, including methylation outside CpG context and abundant 5-hydroxymethylation whose relevance for neuronal identities are unclear. Striatal projection neurons expressing D1 or D2 dopamine receptors allow addressing this question, as they share many characteristics but differ in their gene expression profiles, connections, and functional roles. We compare translating mRNAs and DNA modifications in these two populations. DNA methylation differences occur predominantly in large genomic clusters including differentially expressed genes, potentially important for D1 and D2 neurons. Decreased gene body methylation is associated with higher gene expression. Hydroxymethylation differences are more scattered and affect transcription factor binding sites, which can influence gene expression. We also find a strong genome-wide hydroxymethylation asymmetry between the two DNA strands, particularly pronounced at expressed genes and retrotransposons. These results identify novel properties of neuronal DNA modifications and unveil epigenetic characteristics of striatal projection neurons heterogeneity.
Cr2+ solid solution in UO2 evidenced by advanced spectroscopy
Authors: Smith Hannah , Townsend Luke T. , Mohun Ritesh , Cordara Théo , Stennett Martin C. , Mosselmans J. Frederick W. , Kvashnina Kristina , Corkhill Claire L. 
Published: December 2022

AbstractAdvanced Cr-doped UO2 fuels are essential for driving safe and efficient generation of nuclear energy. Although widely deployed, little is known about their fundamental chemistry, which is a critical gap for development of new fuel materials and radioactive waste management strategies. Utilising an original approach, we directly evidence the chemistry of Cr(3+)2O3–doped U(4+)O2. Advanced high-flux, high-spectral purity X-ray absorption spectroscopy (XAS), corroborated by diffraction, Raman spectroscopy and high energy resolved fluorescence detection-XAS, is used to establish that Cr2+ directly substitutes for U4+, accompanied by U5+ and oxygen vacancy charge compensation. Extension of the analysis to heat-treated simulant nuclear fuel reveals a mixed Cr2+/3+ oxidation state, with Cr in more than one physical form, explaining the substantial discrepancies that exist in the literature. Successful demonstration of this analytical advance, and the scientific underpinning it provides, opens opportunities for an expansion in the range of dopants utilised in advanced UO2 fuels.
Elongated skyrmion as spin torque nano-oscillator and magnonic waveguide
Authors: Liang Xue , Shen Laichuan , Xing Xiangjun , Zhou Yan 
Published: December 2022

AbstractSpin torque nano-oscillator has been extensively studied both theoretically and experimentally in recent decades due to its potential applications in future microwave communication technology and neuromorphic computing. In this work, we present a skyrmion-based spin torque nano-oscillator driven by a spatially uniform direct current, where an elongated skyrmion is confined by two pinning sites. Different from other skyrmion-based oscillators that arise from the circular motion or the breathing mode of a skyrmion, the steady-state oscillatory motion is produced by the periodic deformation of the elongated skyrmion, which originates from the oscillation of its partial domain walls under the joint action of spin torques, the damping and the boundary effect. Micromagnetic simulations are performed to demonstrate the dependence of the oscillation frequency on the driving current, the damping constant, the magnetic parameters as well as the characteristics of pinning sites. This nonlinear response to a direct current turns out to be universal and can also appear in the case of elongated antiskyrmions, skyrmioniums and domain walls. Furthermore, the elongated skyrmion possesses a rectangle-like domain wall, which could also serve as a magnonic waveguide. These findings will enrich the design options for future skyrmion-based devices in the information technology.
Effects of Unilateral Hearing Loss on Speech-Evoked Auditory Brainstem Responses and Reading: A Preliminary Study
Authors: Johnstone Patti , Marston Rachel , Bickley Natalie , Rishiq Dania , Harkrider Ashley , Plyler Erin , Hedrick Mark 
Published: December 2022

Purpose:
The purpose of this study was to determine whether the speech-evoked auditory brainstem responses (sABRs) obtained by stimulating the ear with normal sensitivity in children with unilateral hearing loss (UHL) were different from that of children with normal hearing (NH), and to explore correlations between the sABR findings and measures of reading.

Method:
Eleven children with UHL and 11 children with NH were tested via the BioMARK sABR protocol using the syllable /da/; latency and amplitudes of Waves V, A, C, D, E, F, and O were measured. Participants also were tested on the Phonemic Synthesis Test (PST) and the Woodcock Reading Mastery Test–Revised (WRMT-R), particularly the Reading Readiness, Basic Skills, and Comprehension subtests.

Results:
Multivariate analysis of variance testing showed a significantly higher amplitude for Wave A for the NH group as compared to the UHL group. Separate ANOVAs also found significantly lower scores for the UHL group compared to the NH group on Basic Skills and Comprehension subtests of the Woodcock. Significant positive Spearman rho correlations were found for the UHL group between wave amplitudes for V, A, and O and the Reading Readiness score, and between wave amplitudes for V, A, D, and O and the Reading Comprehension score. A significant correlation also was found between the Total Reading score and wave amplitudes for V and A. No such correlations were found between wave amplitude and Woodcock scores for the NH group. Further testing of the UHL data found significant relationships between the pure-tone average of the hearing loss ear and the Basic Skills, Comprehension, and Total Reading scores from the WRMT-R. There was also a significant correlation between the PST score and Wave C amplitude.

Conclusion:
There may be a connection between speech encoding and measures of reading in children with UHL.
Performance analysis of dual stator six‐phase embedded‐pole permanent magnet synchronous motor for electric vehicle application
Authors: Kumar Raja Ram , Devi Priyanka , Chetri Chandan , Kumari Ankita , Saikia Papu Moni , Saket Ram Khelawan , Kumar Kundan , Khan Baseem 
Published: December 2022

AbstractThe motive of this study is to analyse the characteristics of a novel dual‐stator embedded‐pole six‐phase permanent magnet synchronous motor for the application of electric vehicles. A comparative analysis of two separate motor topologies, namely, dual stator embedded‐pole six‐phase permanent magnet synchronous motor and single stator single rotor surface‐mounted permanent magnet synchronous motor, is accomplished to illustrate the performance superiority of the proposed motor. Furthermore, for optimal designing of the proposed motor, a design methodology has also been presented. For the above application, the motor should retain high torque density (HTD) and high reliability. In this regard, a novel H‐Shaped flux barrier is introduced in the rotor portion, which fulfils the requirement of HTD. Moreover, the availability of two sets of the stator winding enhances the performance efficiency and ensures the proposed motor's more significant fault‐tolerating ability of the motor. For performance evaluation, the Finite Element Method analysis is chosen, as it gives appropriate and precise results. From the above analysis, it is concluded that the HTD and the proposed motor's dynamic performance are better than the above‐mentioned conventional motor.