bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of shallow underground targets using electrical resistivity tomography and the implications in civil/environmental engineering
Authors: Alao Joseph Omeiza , Lawal Kolawole Muideen , Dewu Bala Bello Muhammad , Raimi Jimoh 
Published: August 2024

AbstractApplying the electrical resistivity tomography (ERT) technique in detecting very near-surface targets is quite challenging in geophysical investigation, especially in civil and environmental engineering for adequate planning and designing of structural foundations, contributing to the overall safety and efficiency of construction projects. However, locating the exact position and depth of underground targets such as faults, underground utilities, and contaminants is more challenging. Therefore, this study is aimed at examining the geophysical response of various buried targets and evaluating the ability of ERT to detect buried targets in terms of locations and depths of occurrence in the context of engineering investigation and environmental studies. A laboratory test was conducted on the targets to determine their electrical conductivity and resistivity before burial. The two-dimensional (2D) ERT survey was performed on thirteen targets buried at the site using both Wenner and dipole–dipole (DD) arrays. Both arrays captured the metallic targets with a low electrical resistivity contrast (< 0.1 Ωm) corresponding to the laboratory results. In comparison, the positions of the non-metallic buried targets were found to have a high resistivity contrast greater than 3000 Ωm, matching the laboratory results. The modelled pipes and the car engine block captured by both DD and Wenner arrays on 1.0 m electrode spacing were relatively smeared and poorly resolved in shapes, sizes and geometries, while some were not captured. The electrode spacing of 0.25 m and 0.50 m was explored on undetected targets, which provide a better resolution with sizes and depths compared to 1.0 m spacing but did not produce satisfactory results in some cases. The success and failure of ERT to detect a few targets were discussed alongside the environmental and engineering implications. The effectiveness of both arrays was assessed by their sensitivity in mapping the change in subsurface resistivity values. The DD array shows sensitivity to horizontal variations in resistivity values with low signal. In contrast, the Wenner array shows a good signal strength with a good change in the horizontal and vertical resistivity values. In addition, both arrays show capacity in mapping the geophysical signature of the buried targets and subsurface structures, which has significant application in engineering and environmental investigations.
Unravelling the tissue regenerative nature of marine polysaccharide chitosan embedded halloysite reinforced poly (vinyl alcohol) nanocomposite films
Authors: Shabeena M. , Kouser Sabia , Prabhu Ashwini , Warale Deepali , Manasa D. J. , Nagaraja G. K. 
Published: August 2024

AbstractThe study focuses on developing the poly (vinyl alcohol) (PVA) nanocomposite films reinforced with Halloysite Nano-Tubes (HNT) which were surface functionalised with chitosan forming a Schiff base structure. The work was aimed to traverse its way in tissue engineering. Modification of halloysite with sea polysaccharide chitosan enhanced its ability to bind to the PVA matrix. The modification was assisted by FTIR, XRD, FESEM, TEM, AFM and DSC-TGA techniques. The films could withstand a higher temperature and exhibited high ranges of tensile strength and Young’s modulus. In addition, biocompatible studies such as in-vitro swelling, enzymatic degradation, water contact angle and hemolysis presented extremely well compatibilities proving it to be viable in physiological pH (in phosphate buffered saline). The cell adhesion and proliferation studies conducted on NIH3T3 mouse fibroblasts revealed the cell proliferation and tissue regeneration properties of the films. Both the tests performed for cell growth- Trypan blue dye exclusion and Acridine Orange Ethidium bromide assays showed a doubled rate of cell growth on the films which proves its biomedical nature.
Graphical Abstract
More variations on Nagel and Gergonne analogues of the Steiner-Lehmus theorem
Authors: Abu-Saymeh Sadi , Hajja Mowaffaq 
Published: August 2024

The celebrated Steiner-Lehmus theorem states that if the internal bisectors of two angles of a triangle are equal then the corresponding sides have equal lengths. That is to say if P is the incentre of ΔABC and if BP and CP meet the sides AC and AB at B′ and C′, respectively, then
An elegant proof of this theorem appeared in [1] and is reproduced in [2].
Opportunities for use of neuroimaging in de-risking drug development and improving clinical outcomes in psychiatry: an industry perspective
Authors: Etkin Amit , Powell Jessica , Savitz Adam J. 
Published: August 2024

AbstractNeuroimaging, across positron emission tomography (PET), electroencephalography (EEG), and magnetic resonance imaging (MRI), has been a mainstay of clinical neuroscience research for decades, yet has penetrated little into psychiatric drug development beyond often underpowered phase 1 studies, or into clinical care. Simultaneously, there is a pressing need to improve the probability of success in drug development, increase mechanistic diversity, and enhance clinical efficacy. These goals can be achieved by leveraging neuroimaging in a precision psychiatry framework, wherein effects of drugs on the brain are measured early in clinical development to understand dosing and indication, and then in later-stage trials to identify likely drug responders and enrich clinical trials, ultimately improving clinical outcomes. Here we examine the key variables important for success in using neuroimaging for precision psychiatry from the lens of biotechnology and pharmaceutical companies developing and deploying new drugs in psychiatry. We argue that there are clear paths for incorporating different neuroimaging modalities to de-risk subsequent development phases in the near to intermediate term, culminating in use of select neuroimaging modalities in clinical care for prescription of new precision drugs. Better outcomes through neuroimaging biomarkers, however, require a wholesale commitment to a precision psychiatry approach and will necessitate a cultural shift to align biopharma and clinical care in psychiatry to a precision orientation already routine in other areas of medicine.
TAGLN2 induces resistance signature ISGs by activating AKT-YBX1 signal with dual pathways and mediates the IFN-related DNA damage resistance in gastric cancer
Authors: Zhuo Huiqin , Hou Jingjing , Hong Zhijun , Yu Shuqi , Peng Huifang , Zhang Lihua , Xie Wen , Hong Xuehui 
Published: August 2024

AbstractRecently, various cancer types have been identified to express a distinct subset of Interferon-stimulated genes (ISGs) that mediate therapy resistance. The mechanism through which cancer cells maintain prolonged Interferon stimulation effects to coordinate resistance remains unclear. Our research demonstrated that aberrant upregulation of TAGLN2 is associated with gastric cancer progression, and inhibiting its expression renders gastric cancer cells more susceptible to chemotherapy and radiation. We uncovered a novel role for TAGLN2 in the upregulation of resistance signature ISGs by enhancing YBX1-associated ssDNA aggregation and cGAS-STING pathway activation. TAGLN2 modulates YBX1 by recruiting c-Myc and SOX9 to YBX1 promoter region and directly interacting with AKT-YBX1, thereby enhancing YBX1 phosphorylation and nuclear translocation. Significantly, targeted downregulation of key proteins, inhibition of the TAGLN2-YBX1-AKT interaction (using Fisetin or MK2206) or disruption of the cGAS-STING pathway substantially reduced ssDNA accumulation, subsequent ISGs upregulation, and therapy resistance. The combination of Cisplatin with MK2206 displayed a synergistic effect in the higher TAGLN2-expressing xenograft tumors. Clinical analysis indicated that a derived nine-gene set effectively predicts therapeutic sensitivity and long-term prognosis in gastric cancer patients. These findings suggest that TAGLN2, YBX1 and induced ISGs are novel predictive markers for clinical outcomes, and targeting this axis is an attractive therapeutic sensitization strategy.
Small RNA activation of CDH13 expression overcome BCR-ABL1-independent imatinib-resistance and their signaling pathway studies in chronic myeloid leukemia
Authors: Su Rui , Wen Ziqi , Zhan Xingri , Long Yiling , Wang Xiuyuan , Li Chuting , Su Yubin , Fei Jia 
Published: August 2024

AbstractBCR-ABL1-independent resistance to imatinib has no effective treatment due to its complexity and diversity. We previously reported that the CDH13 oncogene was expressed at low levels in BCR-ABL1-independent resistant CML cell lines. However, its effects on CML resistant cells and mechanisms remain unknown. This study investigated the effects of saRNA-based CDH13 activation on BCR-ABL1-independent imatinib resistance in CML and its underlying mechanism, and proposes a unique treatment method to overcome imatinib resistance. Specifically, this study demonstrated that using the DSIR (Designer of Small Interfering RNA) website tool, saRNAs targeting the CDH13 promoter region were generated and validated using qPCR and western blotting. Among the predicted sequences, C2 and C3 efficiently elevated CDH13 mRNA and protein expression, as well as inhibited the relative vitality of cells and the ability to form clones. After promoting CDH13 expression in K562-IMR cells, it inhabited the NF-κB signaling pathway and induced apoptosis in imatinib-resistant CML cells. LNP-saRNA (C3) was also observed to limit the growth of K562-IMR cells in vivo. From the above, the activation of CDH13 expression by saRNA promotes cell apoptosis by inhibiting the NF-κB signaling pathway to overcome to BCR-ABL1-independent resistance to imatinib in patients with CML.
Structural basis of the bacterial flagellar motor rotational switching
Authors: Tan Jiaxing , Zhang Ling , Zhou Xingtong , Han Siyu , Zhou Yan , Zhu Yongqun 
Published: August 2024

AbstractThe bacterial flagellar motor is a huge bidirectional rotary nanomachine that drives rotation of the flagellum for bacterial motility. The cytoplasmic C ring of the flagellar motor functions as the switch complex for the rotational direction switching from counterclockwise to clockwise. However, the structural basis of the rotational switching and how the C ring is assembled have long remained elusive. Here, we present two high-resolution cryo-electron microscopy structures of the C ring-containing flagellar basal body–hook complex from Salmonella Typhimurium, which are in the default counterclockwise state and in a constitutively active CheY mutant-induced clockwise state, respectively. In both complexes, the C ring consists of four subrings, but is in two different conformations. The CheY proteins are bound into an open groove between two adjacent protomers on the surface of the middle subring of the C ring and interact with the FliG and FliM subunits. The binding of the CheY protein induces a significant upward shift of the C ring towards the MS ring and inward movements of its protomers towards the motor center, which eventually remodels the structures of the FliG subunits and reverses the orientations and surface electrostatic potential of the αtorque helices to trigger the counterclockwise-to-clockwise rotational switching. The conformational changes of the FliG subunits reveal that the stator units on the motor require a relocation process in the inner membrane during the rotational switching. This study provides unprecedented molecular insights into the rotational switching mechanism and a detailed overall structural view of the bacterial flagellar motors.
Inferring histology-associated gene expression gradients in spatial transcriptomic studies
Authors: Kueckelhaus Jan , Frerich Simon , Kada-Benotmane Jasim , Koupourtidou Christina , Ninkovic Jovica , Dichgans Martin , Beck Juergen , Schnell Oliver , Heiland Dieter Henrik 
Published: August 2024

AbstractSpatially resolved transcriptomics has revolutionized RNA studies by aligning RNA abundance with tissue structure, enabling direct comparisons between histology and gene expression. Traditional approaches to identifying signature genes often involve preliminary data grouping, which can overlook subtle expression patterns in complex tissues. We present Spatial Gradient Screening, an algorithm which facilitates the supervised detection of histology-associated gene expression patterns without prior data grouping. Utilizing spatial transcriptomic data along with single-cell deconvolution from injured mouse cortex, and TCR-seq data from brain tumors, we compare our methodology to standard differential gene expression analysis. Our findings illustrate both the advantages and limitations of cluster-free detection of gene expression, offering more profound insights into the spatial architecture of transcriptomes. The algorithm is embedded in SPATA2, an open-source framework written in R, which provides a comprehensive set of tools for investigating gene expression within tissue.
Molecular hydrogen in the N-doped LuH3 system as a possible path to superconductivity
Authors: Tresca Cesare , Forcella Pietro Maria , Angeletti Andrea , Ranalli Luigi , Franchini Cesare , Reticcioli Michele , Profeta Gianni 
Published: August 2024

AbstractThe discovery of ambient superconductivity would mark an epochal breakthrough long-awaited for over a century, potentially ushering in unprecedented scientific and technological advancements. The recent findings on high-temperature superconducting phases in various hydrides under high pressure have ignited optimism, suggesting that the realization of near-ambient superconductivity might be on the horizon. However, the preparation of hydride samples tends to promote the emergence of various metastable phases, marked by a low level of experimental reproducibility. Identifying these phases through theoretical and computational methods entails formidable challenges, often resulting in controversial outcomes. In this paper, we consider N-doped LuH3 as a prototypical complex hydride: By means of machine-learning-accelerated force-field molecular dynamics, we have identified the formation of H2 molecules stabilized at ambient pressure by nitrogen impurities. Importantly, we demonstrate that this molecular phase plays a pivotal role in the emergence of a dynamically stable, low-temperature, experimental-ambient-pressure superconductivity. The potential to stabilize hydrogen in molecular form through chemical doping opens up a novel avenue for investigating disordered phases in hydrides and their transport properties under near-ambient conditions.
Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy
Authors: Tabata Keisuke , Imai Kenta , Fukuda Koki , Yamamoto Kentaro , Kunugi Hayato , Fujita Toshiharu , Kaminishi Tatsuya , Tischer Christian , Neumann Beate , Reither Sabine , Verissimo Fatima , Pepperkok Rainer , Yoshimori Tamotsu , Hamasaki Maho 
Published: August 2024

AbstractAutophagy is a highly conserved process from yeast to mammals in which intracellular materials are engulfed by a double-membrane organelle called autophagosome and degrading materials by fusing with the lysosome. The process of autophagy is regulated by sequential recruitment and function of autophagy-related (Atg) proteins. Genetic hierarchical analyses show that the ULK1 complex comprised of ULK1-FIP200-ATG13-ATG101 translocating from the cytosol to autophagosome formation sites as a most upstream ATG factor; this translocation is critical in autophagy initiation. However, how this translocation occurs remains unclear. Here, we show that ULK1 is palmitoylated by palmitoyltransferase ZDHHC13 and translocated to the autophagosome formation site upon autophagy induction. We find that the ULK1 palmitoylation is required for autophagy initiation. Moreover, the ULK1 palmitoylated enhances the phosphorylation of ATG14L, which is required for activating PI3-Kinase and producing phosphatidylinositol 3-phosphate, one of the autophagosome membrane’s lipids. Our results reveal how the most upstream ULK1 complex translocates to the autophagosome formation sites during autophagy.
Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping
Authors: Ector Carolin , Schmal Christoph , Didier Jeff , De Landtsheer Sébastien , Finger Anna-Marie , Müller-Marquardt Francesca , Schulte Johannes H. , Sauter Thomas , Keilholz Ulrich , Herzel Hanspeter , Kramer Achim , Granada Adrián E. 
Published: August 2024

AbstractThe circadian clock, a fundamental biological regulator, governs essential cellular processes in health and disease. Circadian-based therapeutic strategies are increasingly gaining recognition as promising avenues. Aligning drug administration with the circadian rhythm can enhance treatment efficacy and minimize side effects. Yet, uncovering the optimal treatment timings remains challenging, limiting their widespread adoption. In this work, we introduce a high-throughput approach integrating live-imaging and data analysis techniques to deep-phenotype cancer cell models, evaluating their circadian rhythms, growth, and drug responses. We devise a streamlined process for profiling drug sensitivities across different times of the day, identifying optimal treatment windows and responsive cell types and drug combinations. Finally, we implement multiple computational tools to uncover cellular and genetic factors shaping time-of-day drug sensitivity. Our versatile approach is adaptable to various biological models, facilitating its broad application and relevance. Ultimately, this research leverages circadian rhythms to optimize anti-cancer drug treatments, promising improved outcomes and transformative treatment strategies.
Effect of vitamin E on energy metabolism indicators and gill tissue structure of crucian carp (Carassius auratus) under cooling stress
Authors: Tang Jiaming , Li Gongyan , Chen Dongjie , Jiang Lexia , Huang Baosheng , Jiang Peihong , Zhang Changfeng , Qin Xiaoming 
Published: August 2024

AbstractThe aim of this work is to examine the effects of vitamin E addition to water on the structure of the gill tissue and energy metabolism of crucian carp (Carassius auratus) under cooling stress. The crucian carp were chilled using a cold acclimation intelligent chilling equipment from 20 °C to 5 °C. They were divided into three groups: the control group (E1), the negative control group (E2), and the 100 mg/L vitamin E (E3) solution. Three different temperature points (20 °C, 10 °C, and 5 °C) were used to collect, test, and analyze the samples. The findings demonstrated that in the E3 treatment group, phosphoenolpyruvate carboxykinase, acetyl coenzyme A carboxylase, total cholesterol, urea nitrogen, triglyceride, and fatty acid synthase contents were significantly lower under cooling stress than those in the E1 and E2 treatment groups (P < 0.05). The E3 therapy group had significantly greater blood glucose, glycogen, and glycogen synthase levels than the E1 and E2 treatment groups (P < 0.05). The levels of pyruvate kinase in the E1, E2, and E3 treatment groups did not differ significantly. Crucian carp's gill tissue changed under cooling stress, including capillary dilatation, and the E3 treatment group experienced less damage overall than the E1 and E2 treatment groups. In conclusion, supplementing water with vitamin E to treat crucian carp can decrease damage, improve the body's ability to withstand cold, and slow down the stress response brought on by cooling stress. This provides a theoretical basis for supplementing water with vitamin E to fish stress relief.
Evaluating the Duke Criteria for infectious endocarditis in a single-center retrospective study
Authors: d’Almeida Sascha , Reischmann Kathrin , Andreß Stefanie , Felbel Dominik , Stephan Tilman , Hay Birgit , Rohlmann Friederike , Buckert Dominik , Rottbauer Wolfgang , Markovic Sinisa 
Published: August 2024

AbstractThe Duke Criteria have shaped the way infectious endocarditis (IE) is diagnosed in the last 30 years. This study aims to evaluate their current validity and importance in the diagnostic of IE. A retrospective cohort study was conducted on 163 consecutive patients who presented at the University Hospital in Ulm (Germany) with clinical suspicion of IE between 2009 and 2019. With patients’ medical records we differentiated between definitive endocarditis (DIE), possible endocarditis (PIE) and rejected endocarditis (RIE) and assessed the validity of the Duke Criteria in comparison to the final discharge diagnosis. We then tried to identify new potential parameters as an addition to the current valid Duke Criteria. The validity of the Duke Criteria improves with the length of hospitalization (especially cardiac imaging criterion, RIE 33.3%, PIE 31.6% and DIE 41.9%, p = 0.622 at admission and RIE 53.3%, PIE 68.4%, DIE 92.2%, p < 0.001 at discharge). At admission, overall sensitivity and specificity were respectively 29.5 and 91.2% in the DIE group. At discharge, sensitivity in the DIE group rose to 77.5% and specificity decreased to 79.4%. Of all screened metrics, microhematuria (p = 0.124), leukocyturia, (p = 0.075), younger age (p = 0.042) and the lack of rheumatoid disease (p = 0.011) showed a difference in incidence (p < 0.2) when comparing DIE and RIE group. In multivariate regression only microhematuria qualified as a potential sixth minor criterion at admission. Even with the latest technological breakthroughs our findings suggest that the Duke Criteria continue to hold value in the accurate assessment of IE. Future efforts must shorten the time until diagnosis.
Harnessing the acceptor substrate promiscuity of Clostridium botulinum Maf glycosyltransferase to glyco-engineer mini-flagellin protein chimeras
Authors: Sunsunwal Sonali , Khairnar Aasawari , Subramanian Srikrishna , Ramya T.N.C. 
Published: August 2024

Abstract
Several bacterial flagellins are O-glycosylated with nonulosonic acids on surface-exposed Serine/Threonine residues by Maf glycosyltransferases. The Clostridium botulinum Maf glycosyltransferase (CbMaf) displays considerable donor substrate promiscuity, enabling flagellin O-glycosylation with N-acetyl neuraminic acid (Neu5Ac) and 3-deoxy-D-manno-octulosonic acid in the absence of the native nonulosonic acid, a legionaminic acid derivative. Here, we have explored the sequence/structure attributes of the acceptor substrate, flagellin, required by CbMaf glycosyltransferase for glycosylation with Neu5Ac and KDO, by co-expressing C. botulinum flagellin constructs with CbMaf glycosyltransferase in an E. coli strain producing cytidine-5’-monophosphate (CMP)-activated Neu5Ac, and employing intact mass spectrometry analysis and sialic acid-specific flagellin biotinylation as readouts. We found that CbMaf was able to glycosylate mini-flagellin constructs containing shortened alpha-helical secondary structural scaffolds and reduced surface-accessible loop regions, but not non-cognate flagellin. Our experiments indicated that CbMaf glycosyltransferase recognizes individual Ser/Thr residues in their local surface-accessible conformations, in turn, supported in place by the secondary structural scaffold. Further, CbMaf glycosyltransferase also robustly glycosylated chimeric proteins constructed by grafting cognate mini-flagellin sequences onto an unrelated beta-sandwich protein. Our recombinant engineering experiments highlight the potential of CbMaf glycosyltransferase in future glycoengineering applications, especially for the neo-O-sialylation of proteins, employing E. coli strains expressing CMP-Neu5Ac (and not CMP-KDO).