bluuebunny/crossref_metadata_2025 huggingface dataset:
Does a Scale‐Aware Convective Parameterization Scheme Improve the Simulation of Heavy Rainfall Events?
Authors: Park Haerin , Hwang Jiwon , Cha Dong‐Hyun , Lee Myong‐In , Song Chang‐Keun , Kim Joowan , Park Sang‐Hun , Lee Dong‐Kyou
Published: April 2024

Precipitation predictability using the non‐scale‐aware and scale‐aware convective parameterization schemes (CPSs) was investigated to assess the necessity of the CPSs within the gray‐zone. This study evaluates the performance of the Weather Research and Forecasting (WRF) model's CPS for 135 heavy rainfall events (HREs) over the Korean Peninsula for 10 years (i.e., 2011–2020). We tested the Kain–Fritsch (KF) scheme (non‐scale‐aware) and Multi‐scale Kain–Fritsch (MSKF) scheme (scale‐aware) in the WRF model. The MSKF scheme shows an overall improved performance of precipitation simulation compared to the KF scheme, but the precipitation forecast performance of CPS depends on the characteristics of HREs. When the HREs are characterized by synoptic‐scale atmospheric conditions with strong winds and large‐scale water vapor transport, the forecast performance of both CPSs is similar because a cloud microphysics scheme can explicitly resolve most of the precipitation. However, in the case of HREs with weak synoptic forcing conditions (e.g., moisture transport and winds) related to the localized and meso‐scale HREs, the MSKF scheme can improve overall simulated precipitation by increasing grid‐scale precipitation and reducing the overestimation of subgrid‐scale precipitation simulated in the KF scheme. Therefore, using the scale‐aware CPS in the gray‐zone can provide more accurate precipitation forecasts regardless of the environmental condition of the HREs.
Where in the World Are Vegetation Patterns Controlled by Hillslope Water Dynamics?
Authors: Li Shuping , Yamazaki Dai , Zhou Xudong , Zhao Gang
Published: April 2024

Some recent land surface models can explicitly represent land surface process and focus more on sub‐grid terrestrial features. Many studies have involved the analysis of how hillslope water dynamics determine vegetation patterns and shape ecologically and hydrologically important landscapes, such as desert riparian and waterlogged areas. However, the global locations and abundance of hillslope‐dominated landscapes remain unclear. To address this knowledge gap, we propose a globally applicable method that employs high‐resolution elevation, hydrography, and land cover data to concisely resolve explicit land cover heterogeneity for the mapping of hillslope‐dominated landscapes. First, we aggregate pixels into unit catchments to represent topography‐based hydrological units, and then vertically discretize them into height bands to approximate the hillslope profile. The dominant land cover type in each height band is determined, and the uphill land cover transition is analyzed to identify hillslope‐dominated landscapes. The results indicate that hillslope‐dominated landscapes are distributed extensively worldwide in diverse climate zones. Notably, some landscapes, including gallery forests in northeastern Russia and desert riparian in the Horn of Africa, are newly revealed. Furthermore, the proposed strategy enables more accurate representation of explicit land cover heterogeneity than does the simple downscaling of a rectangular grid from larger to smaller units, revealing its capability to concisely resolve land cover heterogeneity in land surface modeling with relatively high accuracy. Overall, we present the extensive global distribution of landscapes shaped by hillslope water dynamics, underscoring the importance of the explicit resolution of heterogeneity in land surface modeling.
Spatiotemporal Variation of the Cretaceous‐Eocene Arc Magmatism in Lhasa‐Tengchong Terrane
Authors: Liu Yongmin , Fan Weiming , Peng Touping , Shi Rendeng , Chen Shengsheng , Huangfu Pengpeng
Published: April 2024

It was recognized that two magmatic belts in the Lhasa‐Tengchong terrane formed due to the Mesozoic‐Cenozoic Tethyan evolution. Still, their spatiotemporal variations of magmatic flare‐ups/lulls are rarely discussed. Here we use the new U‐Pb and Lu‐Hf isotopic data of captured zircons and a comprehensive data set to show that the flare‐up of northern magmatic belt has peak ages of 110 Ma in central and northern Lhasa and 120 Ma in eastern Tengchong, possibly related to the tectonic transition from Meso‐ and Neo‐Tethyan double subduction to Neo‐Tethyan single subduction. For the southern magmatic belt, the flare‐ups at 100–85 Ma and 65–45 Ma in eastern southern Lhasa indicate obvious juvenile crustal growth, while flare‐ups at 75–45 Ma in western southern Lhasa and Tengchong record ancient crustal reworking. Such flare‐up variations in the southern magmatic belt possibly resulted from asynchronous changes in the Neo‐Tethyan slab dip.
Using the benefit-harm trade-off method to determine the smallest worthwhile effect of intensive motor training on strength for people with spinal cord injury
Authors: Tranter Keira E. , Glinsky Joanne V. , Ben Marsha , Patterson Helen , Blecher Lynn , Chu Jackie , Harvey Lisa A.
Published: April 2024

Study design

Interviews using the benefit-harm trade-off method and an online survey.

Objectives

To determine the smallest worthwhile effect (SWE) of motor training on strength for people with spinal cord injury (SCI).

Setting

SCI units, Australia.

Methods

Forty people with recent SCI who had participated in motor training as part of their rehabilitation program (patient participants) and 37 physiotherapists (physiotherapist participants) working in SCI were recruited. The patient participants underwent an iterative process using the benefit-harm trade-off method to determine the SWE of motor training on strength. The physiotherapist participants were given an online survey to determine the SWE for five different scenarios. Both groups considered the SWE of a physiotherapy intervention involving an additional 12 h of motor training for 10 weeks on top of usual care. They were required to estimate the smallest improvement in strength (points on the Total Motor Score of the International Standards for Neurological Classification of SCI) to justify the effort and associated costs, risks or inconveniences of the motor training.

Results

The median (interquartile range) smallest improvement in strength that patient and physiotherapist participants deemed worth the effort and associated costs, risks or inconveniences of the motor training was 3 (1–5) points, and 9 (7–13) points, respectively.

Conclusions

People with recent SCI are willing to devote 12 h a week for 10 weeks to motor training in addition to their usual care to gain small changes in strength. Physiotherapists wanted to see greater improvements to justify the intervention.
Behaviour-correlated profiles of cerebellar-cerebral functional connectivity observed in independent neurodevelopmental disorder cohorts
Authors: Morgado Felipe , Vandewouw Marlee M. , Hammill Christopher , Kelley Elizabeth , Crosbie Jennifer , Schachar Russell , Ayub Muhammad , Nicolson Robert , Georgiades Stelios , Arnold Paul , Iaboni Alana , Kushki Azadeh , Taylor Margot J. , Anagnostou Evdokia , Lerch Jason P.
Published: April 2024

The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist – Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, rPOND-HBN = −0.97; FC feature vectors, rPOND-HBN = −0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, rPOND-HBN = −0.99; FC feature vectors, rPOND-HBN = −0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.
Heat flows enrich prebiotic building blocks and enhance their reactivity
Authors: Matreux Thomas , Aikkila Paula , Scheu Bettina , Braun Dieter , Mast Christof B.
Published: April 2024

The emergence of biopolymer building blocks is a crucial step during the origins of life1–6. However, all known formation pathways rely on rare pure feedstocks and demand successive purification and mixing steps to suppress unwanted side reactions and enable high product yields. Here we show that heat flows through thin, crack-like geo-compartments could have provided a widely available yet selective mechanism that separates more than 50 prebiotically relevant building blocks from complex mixtures of amino acids, nucleobases, nucleotides, polyphosphates and 2-aminoazoles. Using measured thermophoretic properties7,8, we numerically model and experimentally prove the advantageous effect of geological networks of interconnected cracks9,10 that purify the previously mixed compounds, boosting their concentration ratios by up to three orders of magnitude. The importance for prebiotic chemistry is shown by the dimerization of glycine11,12, in which the selective purification of trimetaphosphate (TMP)13,14 increased reaction yields by five orders of magnitude. The observed effect is robust under various crack sizes, pH values, solvents and temperatures. Our results demonstrate how geologically driven non-equilibria could have explored highly parallelized reaction conditions to foster prebiotic chemistry.
Molecular insights into capsular polysaccharide secretion
Authors: Kuklewicz Jeremi , Zimmer Jochen
Published: April 2024

Capsular polysaccharides (CPSs) fortify the cell boundaries of many commensal and pathogenic bacteria1. Through the ABC-transporter-dependent biosynthesis pathway, CPSs are synthesized intracellularly on a lipid anchor and secreted across the cell envelope by the KpsMT ABC transporter associated with the KpsE and KpsD subunits1,2. Here we use structural and functional studies to uncover crucial steps of CPS secretion in Gram-negative bacteria. We show that KpsMT has broad substrate specificity and is sufficient for the translocation of CPSs across the inner bacterial membrane, and we determine the cell surface organization and localization of CPSs using super-resolution fluorescence microscopy. Cryo-electron microscopy analyses of the KpsMT–KpsE complex in six different states reveal a KpsE-encaged ABC transporter, rigid-body conformational rearrangements of KpsMT during ATP hydrolysis and recognition of a glycolipid inside a membrane-exposed electropositive canyon. In vivo CPS secretion assays underscore the functional importance of canyon-lining basic residues. Combined, our analyses suggest a molecular model of CPS secretion by ABC transporters.
Immune microniches shape intestinal Treg function
Authors: Gu Yisu , Bartolomé-Casado Raquel , Xu Chuan , Bertocchi Alice , Janney Alina , Heuberger Cornelia , Pearson Claire F. , Teichmann Sarah A. , Thornton Emily E. , Powrie Fiona
Published: April 2024

The intestinal immune system is highly adapted to maintaining tolerance to the commensal microbiota and self-antigens while defending against invading pathogens1,2. Recognizing how the diverse network of local cells establish homeostasis and maintains it in the complex immune environment of the gut is critical to understanding how tolerance can be re-established following dysfunction, such as in inflammatory disorders. Although cell and molecular interactions that control T regulatory (Treg) cell development and function have been identified3,4, less is known about the cellular neighbourhoods and spatial compartmentalization that shapes microorganism-reactive Treg cell function. Here we used in vivo live imaging, photo-activation-guided single-cell RNA sequencing5–7 and spatial transcriptomics to follow the natural history of T cells that are reactive towards Helicobacter hepaticus through space and time in the settings of tolerance and inflammation. Although antigen stimulation can occur anywhere in the tissue, the lamina propria—but not embedded lymphoid aggregates—is the key microniche that supports effector Treg (eTreg) cell function. eTreg cells are stable once their niche is established; however, unleashing inflammation breaks down compartmentalization, leading to dominance of CD103+SIRPα+ dendritic cells in the lamina propria. We identify and validate the putative tolerogenic interaction between CD206+ macrophages and eTreg cells in the lamina propria and identify receptor–ligand pairs that are likely to govern the interaction. Our results reveal a spatial mechanism of tolerance in the lamina propria and demonstrate how knowledge of local interactions may contribute to the next generation of tolerance-inducing therapies.
Ancestral allele of DNA polymerase gamma modifies antiviral tolerance
Authors: Kang Yilin , Hepojoki Jussi , Maldonado Rocio Sartori , Mito Takayuki , Terzioglu Mügen , Manninen Tuula , Kant Ravi , Singh Sachin , Othman Alaa , Verma Rohit , Uusimaa Johanna , Wartiovaara Kirmo , Kareinen Lauri , Zamboni Nicola , Nyman Tuula Anneli , Paetau Anders , Kipar Anja , Vapalahti Olli , Suomalainen Anu
Published: April 2024

Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response1–4. The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1)5. Patients homozygous for the MIRAS variant p.W748S show exceptionally variable ages of onset and symptoms5, indicating that unknown modifying factors contribute to disease manifestation. We report that the mtDNA replicase POLG1 has a role in antiviral defence mechanisms to double-stranded DNA and positive-strand RNA virus infections (HSV-1, TBEV and SARS-CoV-2), and its p.W748S variant dampens innate immune responses. Our patient and knock-in mouse data show that p.W748S compromises mtDNA replisome stability, causing mtDNA depletion, aggravated by virus infection. Low mtDNA and mtRNA release into the cytoplasm and a slow IFN response in MIRAS offer viruses an early replicative advantage, leading to an augmented pro-inflammatory response, a subacute loss of GABAergic neurons and liver inflammation and necrosis. A population databank of around 300,000 Finnish individuals6demonstrates enrichment of immunodeficient traits in carriers of thePOLG1p.W748S mutation. Our evidence suggests that POLG1 defects compromise antiviral tolerance, triggering epilepsy and liver disease. The finding has important implications for the mitochondrial disease spectrum, including epilepsy, ataxia and parkinsonism.
Interim analyses of a first-in-human phase 1/2 mRNA trial for propionic acidaemia
Authors: Koeberl Dwight , Schulze Andreas , Sondheimer Neal , Lipshutz Gerald S. , Geberhiwot Tarekegn , Li Lerong , Saini Rajnish , Luo Junxiang , Sikirica Vanja , Jin Ling , Liang Min , Leuchars Mary , Grunewald Stephanie
Published: April 2024

Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or β (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.
Structural basis of Integrator-dependent RNA polymerase II termination
Authors: Fianu Isaac , Ochmann Moritz , Walshe James L. , Dybkov Olexandr , Cruz Joseph Neos , Urlaub Henning , Cramer Patrick
Published: April 2024

The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript1, but has not explained how Integrator removes Pol II from the DNA template. Here we present three cryo-electron microscopy structures of the complete Integrator–PP2A complex in different functional states. The structure of the pre-termination complex reveals a previously unresolved, scorpion-tail-shaped INTS10–INTS13–INTS14–INTS15 module that may use its ‘sting’ to open the DSIF DNA clamp and facilitate termination. The structure of the post-termination complex shows that the previously unresolved subunit INTS3 and associated sensor of single-stranded DNA complex (SOSS) factors prevent Pol II rebinding to Integrator after termination. The structure of the free Integrator–PP2A complex in an inactive closed conformation2 reveals that INTS6 blocks the PP2A phosphatase active site. These results lead to a model for how Integrator terminates Pol II transcription in three steps that involve major rearrangements.
Mapping Road Surface Type of Kenya Using OpenStreetMap and High-resolution Google Satellite Imagery
Authors: Zhou Qi , Liu Zixian , Huang Zesheng
Published: April 2024

Identifying road surface types (paved or unpaved) can ensure road vehicle safety, reduce energy consumption, and promote economic development. Existing studies identified road surface types by using sensors mounted on mobile devices and high-resolution satellite images that are not openly accessible, which makes it difficult to apply them to large-scale (e.g., national or regional) study areas. Addressing this issue, this study developed a dataset of road surface types (paved and unpaved) for the national road network of Kenya, containing 1,267,818 road segments classified as paved or unpaved. To accomplish this, this study proposes a method that integrates crowdsourced geographic data (OpenStreetMap) and Google satellite imagery to identify road surface types. The accuracy, recall, and F1 score of the method were all above 0.94, validating the effectiveness of the method. The data sources of the method are freely available, and the method may be applied to other countries and regions. The dataset developed based on the method can provide data support and decision support for local governments to improve road infrastructure.
Strain-dependent grain boundary properties of n-type germanium layers
Authors: Igura Kota , Nozawa Koki , Ishiyama Takamitsu , Suemasu Takashi , Toko Kaoru
Published: April 2024

Polycrystalline Ge thin films have attracted considerable attention as potential materials for use in various electronic and optical devices. We recently developed a low-temperature solid-phase crystallization technology for a doped Ge layer and achieved the highest electron mobility in a polycrystalline Ge thin film. In this study, we investigated the effects of strain on the crystalline and electrical properties of n-type polycrystalline Ge layers. By inserting a GeOx interlayer directly under Ge and selecting substrates with different coefficients of thermal expansion, we modulated the strain in the polycrystalline Ge layer, ranging from approximately 0.6% (tensile) to − 0.8% (compressive). Compressive strain enlarged the grain size to 12 µm, but decreased the electron mobility. The temperature dependence of the electron mobility clarified that changes in the potential barrier height of the grain boundary caused this behavior. Furthermore, we revealed that the behavior of the grain boundary barrier height with respect to strain is opposite for the n- and p-types. This result strongly suggests that this phenomenon is due to the piezoelectric effect. These discoveries will provide guidelines for improving the performance of Ge devices and useful physical knowledge of various polycrystalline semiconductor thin films.
Investigating the phase diagram-ionic conductivity isotherm relationship in aqueous solutions of common acids: hydrochloric, nitric, sulfuric and phosphoric acid
Authors: Al-Salih Hilal , Abu-Lebdeh Yaser
Published: April 2024

The relationship between phase diagram features around the solid–liquid equilibrium region and ionic conductivity in aqueous solutions is not well understood over the whole concentration range as is the case for acidic aqueous solutions. In this work, we have studied the ionic conductivity (κ) as a function of molar fraction (x) and temperature (T) for four acid/water solutions namely, monoprotic hydrochloric acid (HCl) and nitric acid (HNO3), diprotic sulfuric acid (H2SO4) and triprotic phosphoric acid (H3PO4) along with their binary phase diagrams. The connection between the main features of the phase diagrams and the trends in the ionic conductivity isotherms is established with a new insight on the two pertinent dominant conductivity mechanisms (hopping and vehicular). Ionic conductivity at different temperatures were collected from literature and fitted to reported isothermal (κ vs. x) and iso-compositional (κ vs. T) equations along with a novel semi-empirical equation (κ = f (x, T)) for diprotic and triprotic acids. This equation not only has the best fit for acids with different valency; but also contains four parameters, less than any other similar equation in literature. This work is one of few that advances the understanding of the intricate relationship between structure and ionic transport in various acidic aqueous solutions.
Design of a broadband circularly polarised uniplanar crossed-dipole antenna
Authors: Wang Heesu , Park Yong Bae , Park Ikmo
Published: April 2024

This study presents the design of a uniplanar crossed-dipole antenna with broadband characteristics. The antenna comprises a pair of identical crossed-dipole arms printed on the same plane of a dielectric substrate. The crossed-dipole arms are corner-cut fat dipoles that are perpendicular to each other and connected with a bent stripline to generate circularly polarised (CP) radiations. A wide dipole arm was used to improve impedance matching and widen the axial ratio (AR) bandwidth. Additionally, the corner of each dipole arm was cut into a triangular shape to broaden the impedance and AR bandwidths further. The antenna in free space is excited via a wideband microstrip-to-parallel stripline tapered balun to reduce the effect of leakage current on the coaxial cable. Experiments and full-wave electromagnetic simulations were employed to design, verify, and validate the antenna design. The antenna, having an overall size of 45 × 45 × 0.508 mm3 (0.4 × 0.4 × 0.0045 λL3 where λL is the lowest frequency in the 3-dB AR bandwidth), demonstrates the following measured performances: an |S11|< − 10 dB impedance bandwidth of 2.53–9.14 GHz (113.3%), a 3 dB AR bandwidth of 2.65–7.75 GHz (98.1%), and peak gain of 3.7 dBic at 6.6 GHz.
Real-time monitoring of CdTe quantum dots growth in aqueous solution
Authors: da Costa P. F. G. M. , Merízio L. G. , Wolff N. , Terraschke H. , de Camargo A. S. S.
Published: April 2024

Quantum dots (QDs) are remarkable semiconductor nanoparticles, whose optical properties are strongly size-dependent. Therefore, the real-time monitoring of crystal growth pathway during synthesis gives an excellent opportunity to a smart design of the QDs luminescence. In this work, we present a new approach for monitoring the formation of QDs in aqueous solution up to 90 °C, through in situ luminescence analysis, using CdTe as a model system. This technique allows a detailed examination of the evolution of their light emission. In contrast to in situ absorbance analysis, the in situ luminescence measurements in reflection geometry are particularly advantageous once they are not hindered by the concentration increase of the colloidal suspension. The synthesized particles were additionally characterized using X-ray diffraction analysis, transition electron microscopy, UV-Vis absorption and infrared spectroscopy. The infrared spectra showed that 3-mercaptopropionic acid (MPA)-based thiols are covalently bound on the surface of QDs and microscopy revealed the formation of CdS. Setting a total of 3 h of reaction time, for instance, the QDs synthesized at 70, 80 and 90 °C exhibit emission maxima centered at 550, 600 and 655 nm. The in situ monitoring approach opens doors for a more precise achievement of the desired emission wavelength of QDs.
The high FKBP1A expression in WBCs as a potential screening biomarker for pancreatic cancer
Authors: Watcharanurak Papitchaya , Mutirangura Apiwat , Aksornkitti Vitavat , Bhummaphan Narumol , Puttipanyalears Charoenchai
Published: April 2024

Given the limitation of current routine approaches for pancreatic cancer screening and detection, the mortality rate of pancreatic cancer cases is still critical. The development of blood-based molecular biomarkers for pancreatic cancer screening and early detection which provide less-invasive, high-sensitivity, and cost-effective, is urgently needed. The goal of this study is to identify and validate the potential molecular biomarkers in white blood cells (WBCs) of pancreatic cancer patients. Gene expression profiles of pancreatic cancer patients from NCBI GEO database were analyzed by CU-DREAM. Then, mRNA expression levels of three candidate genes were determined by quantitative RT-PCR in WBCs of pancreatic cancer patients (N = 27) and healthy controls (N = 51). ROC analysis was performed to assess the performance of each candidate gene. A total of 29 upregulated genes were identified and three selected genes were performed gene expression analysis. Our results revealed high mRNA expression levels in WBCs of pancreatic cancer patients in all selected genes, including FKBP1A (p < 0.0001), PLD1 (p < 0.0001), and PSMA4 (p = 0.0002). Among candidate genes, FKBP1A mRNA expression level was remarkably increased in the pancreatic cancer samples and also in the early stage (p < 0.0001). Moreover, FKBP1A showed the greatest performance to discriminate patients with pancreatic cancer from healthy individuals than other genes with the 88.9% sensitivity, 84.3% specificity, and 90.1% accuracy. Our findings demonstrated that the alteration of FKBP1A gene in WBCs serves as a novel valuable biomarker for patients with pancreatic cancer. Detection of FKBP1A mRNA expression level in circulating WBCs, providing high-sensitive, less-invasive, and cost-effective, is simple and feasible for routine clinical setting that can be applied for pancreatic cancer screening and early detection.
Cross-correlations between currents and tunnel magnetoresistance in interacting double quantum dot-Majorana wire system
Authors: Wrześniewski Kacper , Weymann Ireneusz
Published: April 2024

We theoretically investigate the spin and charge transport properties of a double quantum dot coupled to distinct edges of the nanowire hosting Majorana zero-energy modes. The focus is on the analysis of the currents flowing through the left and right junctions and their cross-correlations. We show that the system reveals very different transport properties depending on the detuning protocol of the quantum dot energy levels. For the symmetric detuning, the current dependencies reveal only two maxima associated with resonant tunneling, and currents in the left and right arms of the system reveal weak positive cross-correlations. On the other hand, for antisymmetric detuning, the flow of electrons into drains is maximized and strongly correlated in one bias voltage direction, while for the opposite bias direction a spin blockade is predicted. Furthermore, we observe a suppression of the current cross-correlations at a highly symmetric detuning point, indicating the involvement of the Majorana zero-energy modes in the transport processes. To gain insight into the role of the spin polarization of the Majorana edge states, we analyze the spin-dependent transport characteristics by considering the relationship between the spin canting angle, which describes the coupling of the Majorana modes to the spin of the quantum dots, and the magnetic configurations of the ferromagnetic drains. Moreover, we examine the non-local zero bias anomaly in the differential conductance, detailed analysis of which revealed a specific operational mode of the device that can facilitate the identification of the Majorana presence in the quantum dot-Majorana wire system. Finally, we also consider the transport properties in different magnetic configurations of the system and discuss the behavior of the associated tunnel magnetoresistance.
Vagus nerve signal has an inhibitory influence on the development of peritoneal metastasis in murine gastric cancer
Authors: Futoh Yurie , Miyato Hideyo , Yamaguchi Hironori , Matsumiya Misaki , Takahashi Rei , Kaneko Yuki , Kimura Yuki , Ohzawa Hideyuki , Sata Naohiro , Kitayama Joji , Hosoya Yoshinori
Published: April 2024

The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.
Soil pore characteristics and the fate of new switchgrass-derived carbon in switchgrass and prairie bioenergy cropping systems
Authors: Kim Kyungmin , Juyal Archana , Kravchenko Alexandra
Published: April 2024

Monoculture switchgrass and restored prairie are promising perennial feedstock sources for bioenergy production on the lands unsuitable for conventional agriculture. Such lands often display contrasting topography that influences soil characteristics and interactions between plant growth and soil C gains. This study aimed at elucidating the influences of topography and plant systems on the fate of C originated from switchgrass plants and on its relationships with soil pore characteristics. For that, switchgrass plants were grown in intact soil cores collected from two contrasting topographies, namely steep slopes and topographical depressions, in the fields in multi-year monoculture switchgrass and restored prairie vegetation. The 13C pulse labeling allowed tracing the C of switchgrass origin, which X-ray computed micro-tomography enabled in-detail characterization of soil pore structure. In eroded slopes, the differences between the monoculture switchgrass and prairie in terms of total and microbial biomass C were greater than those in topographical depressions. While new switchgrass increased the CO2 emission in depressions, it did not significantly affect the CO2 emission in slopes. Pores of 18–90 µm Ø facilitated the accumulation of new C in soil, while > 150 µm Ø pores enhanced the mineralization of the new C. These findings suggest that polyculture prairie located in slopes can be particularly beneficial in facilitating soil C accrual and reduce C losses as CO2.
Dihydrotanshinone I exhibits antitumor effects via β-catenin downregulation in papillary thyroid cancer cell lines
Authors: Molteni Elisabetta , Baldan Federica , Damante Giuseppe , Allegri Lorenzo
Published: April 2024

Thyroid cancer is the most common endocrine carcinoma and, among its different subtypes, the papillary subtype (PTC) is the most frequent. Generally, PTCs are well differentiated, but a minor percentage of PTCs are characterized by a worse prognosis and more aggressive behavior. Phytochemicals, naturally found in plant products, represent a heterogeneous group of bioactive compounds that can interfere with cell proliferation and the regulation of the cell cycle, taking part in multiple signaling pathways that are often disrupted in tumor initiation, proliferation, and progression. In this work, we focused on 15,16-dihydrotanshinone I (DHT), a tanshinone isolated from Salvia miltiorrhiza Bunge (Danshen). We first evaluated DHT biological effect on PTC cells regarding cell viability, colony formation ability, and migration capacity. All of these parameters were downregulated by DHT treatment. We then investigated gene expression changes after DHT treatment by performing RNA-seq. The analysis revealed that DHT significantly reduced the Wnt signaling pathway, which plays a role in various diseases, including cancer. Finally, we demonstrate that DHT treatment decreases protein levels of β-catenin, a final effector of canonical Wnt signaling pathway. Overall, our data suggest a possible use of this nutraceutical as an adjuvant in the treatment of aggressive papillary thyroid carcinoma.
The application value of deep learning-based nomograms in benign–malignant discrimination of TI-RADS category 4 thyroid nodules
Authors: Zhang Xinru , Jia Cheng , Sun Meng , Ma Zhe
Published: April 2024

Thyroid nodules are a common occurrence, and although most are non-cancerous, some can be malignant. The American College of Radiology has developed the Thyroid Imaging Reporting and Data System (TI-RADS) to standardize the interpretation and reporting of thyroid ultrasound results. Within TI-RADS, a category 4 designation signifies a thyroid nodule with an intermediate level of suspicion for malignancy. Accurate classification of these nodules is crucial for proper management, as it can potentially reduce unnecessary surgeries and improve patient outcomes. This study utilized deep learning techniques to effectively classify TI-RADS category 4 thyroid nodules as either benign or malignant. A total of 500 patients were included in the study and randomly divided into a training group (350 patients) and a test group (150 patients). The YOLOv3 model was constructed and evaluated using various metrics, achieving an 84% accuracy in the classification of TI-RADS category 4 thyroid nodules. Based on the predictions of the model, along with clinical and ultrasound data, a nomogram was developed. The performance of the nomogram was superior in both the training and testing groups. Furthermore, the calibration curve demonstrated good agreement between predicted probabilities and actual outcomes. Decision curve analysis further confirmed that the nomogram provided greater net benefits. Ultimately, the YOLOv3 model and nomogram successfully improved the accuracy of distinguishing between benign and malignant TI-RADS category 4 thyroid nodules, which is crucial for proper management and improved patient outcomes.
An interaction graph approach to gain new insights into mechanisms that modulate cerebrovascular tone
Authors: Dempsey Sergio , Argus Finbar , Maso Talou Gonzalo Daniel , Safaei Soroush
Published: April 2024

Mechanisms to modulate cerebrovascular tone are numerous, interconnected, and spatially dependent, increasing the complexity of experimental study design, interpretation of action-effect pathways, and mechanistic modelling. This difficulty is exacerbated when there is an incomplete understanding of these pathways. We propose interaction graphs to break down this complexity, while still maintaining a holistic view of mechanisms to modulate cerebrovascular tone. These graphs highlight the competing processes of neurovascular coupling, cerebral autoregulation, and cerebral reactivity. Subsequent analysis of these interaction graphs provides new insights and suggest potential directions for research on neurovascular coupling, modelling, and dementia.
Rhythmicity of neuronal oscillations delineates their cortical and spectral architecture
Authors: Myrov Vladislav , Siebenhühner Felix , Juvonen Joonas J. , Arnulfo Gabriele , Palva Satu , Palva J. Matias
Published: April 2024

Neuronal oscillations are commonly analyzed with power spectral methods that quantify signal amplitude, but not rhythmicity or ‘oscillatoriness’ per se. Here we introduce a new approach, the phase-autocorrelation function (pACF), for the direct quantification of rhythmicity. We applied pACF to human intracerebral stereoelectroencephalography (SEEG) and magnetoencephalography (MEG) data and uncovered a spectrally and anatomically fine-grained cortical architecture in the rhythmicity of single- and multi-frequency neuronal oscillations. Evidencing the functional significance of rhythmicity, we found it to be a prerequisite for long-range synchronization in resting-state networks and to be dynamically modulated during event-related processing. We also extended the pACF approach to measure ’burstiness’ of oscillatory processes and characterized regions with stable and bursty oscillations. These findings show that rhythmicity is double-dissociable from amplitude and constitutes a functionally relevant and dynamic characteristic of neuronal oscillations.
MIM-CyCIF: masked imaging modeling for enhancing cyclic immunofluorescence (CyCIF) with panel reduction and imputation
Authors: Sims Zachary , Mills Gordon B. , Chang Young Hwan
Published: April 2024

Cyclic Immunofluorescence (CyCIF) can quantify multiple biomarkers, but panel capacity is limited by technical challenges. We propose a computational panel reduction approach that can impute the information content from 25 markers using only 9 markers, learning co-expression and morphological patterns while concurrently increasing speed and panel content and decreasing cost. We demonstrate strong correlations in predictions and generalizability across breast and colorectal cancer, illustrating applicability of our approach to diverse tissue types.
Effects of multi-functional additives during foam extrusion of wheat gluten materials
Authors: Bettelli Mercedes A. , Hu Qisong , Capezza Antonio J. , Johansson Eva , Olsson Richard T. , Hedenqvist Mikael S.
Published: April 2024

To broaden the range in structures and properties, and therefore the applicability of sustainable foams based on wheat gluten expanded with ammonium-bicarbonate, we show here how three naturally ocurring multifunctional additives affect their properties. Citric acid yields foams with the lowest density (porosity of ~50%) with mainly closed cells. Gallic acid acts as a radical scavenger, yielding the least crosslinked/ aggregated foam. The use of a low amount of this acid yields foams with the highest uptake of the body-fluid model substance (saline, ~130% after 24 hours). However, foams with genipin show a large and rapid capillary uptake (50% in one second), due to their high content of open cells. The most dense and stiff foam is obtained with one weight percent genipin, which is also the most crosslinked. Overall, the foams show a high energy loss-rate under cyclic compression (84-92% at 50% strain), indicating promising cushioning behaviour. They also show a low compression set, indicating promising sealability. Overall, the work here provides a step towards using protein biofoams as a sustainable alternative to fossil-based plastic/rubber foams in applications where absorbent and/or mechanical properties play a key role.
Pre-collapse spaceborne deformation monitoring of the Kakhovka dam, Ukraine, from 2017 to 2023
Authors: Tavakkoliestahbanati Amin , Milillo Pietro , Kuai Hao , Giardina Giorgia
Published: April 2024

The Kakhovka Dam on the Dnieper River in Kherson Oblast, Ukraine, was completed in 1956 as the final dam in the Dnieper reservoir cascade. On the morning of June 6th, 2023, a substantial portion of the dam suffered a collapse while under Russian control. This incident was documented through satellite optical and radar images, providing valuable evidence of the dam’s condition. Here we present the results of multi-temporal Interferometric Synthetic Aperture Radar (MT-InSAR) monitoring of the Kakhovka dam. The dam is vital for water management and hydroelectric power generation. Utilizing multi-temporal InSAR (MT-InSAR) data, we assessed the dam deformations prior to the collapse. Our findings indicate movements of the south side, facing the Dniprovska Gulf, compatible with several possible damage mechanisms. This study highlights the significance of employing spaceborne advanced monitoring techniques to detect signs of distress and ensure the stability of critical infrastructure.
California dominates U.S. emissions of the pesticide and potent greenhouse gas sulfuryl fluoride
Authors: Gaeta Dylan C. , Mühle Jens , Vimont Isaac J. , Crotwell Molly , Hu Lei , Miller John B. , McKain Kathryn , Baier Bianca C. , Zhang Mingyang , Bao Jianing , Miller Benjamin R. , Miller Scot M.
Published: April 2024

Sulfuryl fluoride (SO2F2) is a synthetic pesticide and a potent greenhouse gas that is accumulating in the global atmosphere. Rising emissions are a concern since SO2F2 has a relatively long atmospheric lifetime and a high global warming potential. The U.S. is thought to contribute substantially to global SO2F2 emissions, but there is a paucity of information on how emissions of SO2F2 are distributed across the U.S., and there is currently no inventory of SO2F2 emissions for the U.S. or individual states. Here we provide an atmospheric measurement-based estimate of U.S. SO2F2 emissions using high-precision SO2F2 measurements from the NOAA Global Greenhouse Gas Reference Network (GGGRN) and a geostatistical inverse model. We find that California has the largest SO2F2 emissions among all U.S. states, with the highest emissions from southern coastal California (Los Angeles, Orange, and San Diego counties). Outside of California, only very small and infrequent SO2F2 emissions are detected by our analysis of GGGRN data. We find that California emits 60-85% of U.S. SO2F2 emissions, at a rate of 0.26 ( ± 0.10) Gg yr−1. We estimate that emissions of SO2F2 from California are equal to 5.5–12% of global SO2F2 emissions.
Millennial-aged pyrogenic carbon in high-latitude mineral soils
Authors: Schiedung Marcus , Ascough Philippa , Bellè Severin-Luca , Bird Michael I. , Bröder Lisa , Haghipour Negar , Hilton Robert G. , Lattaud Julie , Abiven Samuel
Published: April 2024

Wildfires in the Arctic are producing pyrogenic carbon as product of incomplete biomass combustion. The storage and distribution of pyrogenic carbon in soils is poorly known, especially in carbon rich permafrost-affected mineral soils. Here, we extracted pyrogenic carbon in mineral soils from eleven forest sites across the North Canadian permafrost regions by hydrogen pyrolysis. We found pyrogenic carbon with millennial-scale ages that were older in continuous (1960–12,690 calibrated years before present) than in discontinuous (510–3560 calibrated years before present) permafrost-affected soils. In all cases, pyrogenic carbon showed longer residence times compared to bulk soil organic carbon. The proportions of pyrogenic carbon on total soil organic carbon were consistent at 6.9 ± 0.5% of total soil organic carbon. Thus, pyrogenic carbon forms a significant component of the total soil organic carbon and climatic as well as soil factors control the long residence times of pyrogenic carbon in vulnerable high-latitude forest mineral soils.