bluuebunny/crossref_metadata_2025 huggingface dataset:
Petrogenesis and Geodynamic Evolution in the Northern Westfjords, Iceland, Elucidated by Iceland's Oldest Silicic Rocks
Authors: Banik Tenley J. , Coble Matthew A. , Miller Calvin F. , Fisher Christopher M. , Jordan Brennan T. , Vervoort Jeffrey D. , Carley Tamara L.
Published: May 2023

Iceland's oldest silicic rocks provide unique insight into the island's early crustal evolution. We present new zircon U‐Pb ages bolstered with zircon trace element and isotopic compositions, and whole rock Nd, Hf, and Pb isotope compositions, from three silicic magmatic centers—Hrafnsfjörður, Árnes, and Kaldalón—to understand the petrogenesis of large silicic volcanic centers in the northern Westfjords, Iceland. Our data confirm Hrafnsfjörður as the oldest known central volcano in Iceland (∼14 Ma) and establish an older age for Árnes (∼13 Ma) than previously estimated. We also report the first U‐Pb zircon dates from Kaldalón (∼13.5 Ma). Zircon oxygen isotope compositions range from δ18O∼+2 to +4‰ and indicate involvement of a low‐18O component in their source magmas. Hrafnsfjörður zircon Hf (mean sample εHf ∼ +15.3–16.0) and whole rock Hf and Nd (εHf = +14.5 to +15; εNd = +7.9 to +8.1) isotopic compositions are more radiogenic than those from Árnes (zircon sample εHf ∼ +11.8–13; whole rock εHf = +12.8 to +15.1; εNd = +7.3 to +7.7), but Hrafnsfjörður whole rock Pb isotope compositions (208/204Pb = 37.95–37.96; 206/204Pb = 18.33–18.35) are less radiogenic than those from Árnes (208/204Pb = 38.34–38.48; 206/204Pb = 18.64–18.78). Kaldalón has zircon Hf isotope compositions of εHf∼+14.8 and 15.5 (sample means). These age and isotopic differences suggest that interaction of rift and plume, and thus the geodynamic evolution of the Westfjords, is complex. Isotopic compositions of Hrafnsfjörður and Árnes support involvement of an enriched mantle (EM)‐like mantle component associated with a pulsing plume that resulted in variable spreading rates and magma fluxes and highlight the heterogeneity of the Icelandic mantle.
Absence of Large‐Scale Ice Masses in Central Northeast Siberia During the Late Pleistocene
Authors: Nørgaard Jesper , Margold Martin , Jansen John D. , Kurbanov Redzhep , Szuman Izabela , Andersen Jane Lund , Olsen Jesper , Faurschou Knudsen Mads
Published: May 2023

Ongoing speculation regarding the existence of large Late Pleistocene ice masses in Northeast Eurasia reflects the dearth of age constraints on glaciations across this vast region. Here, we report the first dates from the central part of Northeast Siberia, consisting of 22 cosmogenic 10Be exposure ages from boulders deriving from a sequence of three moraines in the Chersky Range. The dated moraine sequence indicates progressive contraction of maximum glacier extent from Marine Isotope Stage 6 to the Last Glacial Maximum, while the remotely‐sensed mapping indicates an older, more expansive glaciation in the region yet undated. Our results show that Late Pleistocene glaciations were limited to the highlands, and Northeast Siberia did not host a large, coalescent ice sheet during the Last Glacial Maximum or Marine Isotope Stage 6.
Circulating S100B levels at birth and risk of six major neuropsychiatric or neurological disorders: a two-sample Mendelian Randomization Study
Authors: Pan Mengyu , Roe James M. , Nudel Ron , Schork Andrew J. , Iakunchykova Olena , Fjell Anders M. , Walhovd Kristine B. , Werge Thomas , Chen Chi-hua , Benros Michael E. , Wang Yunpeng
Published: May 2023

Circulating levels of the astrocytic marker S100B have been associated with risk of neuropsychiatric or neurological disorders. However, reported effects have been inconsistent, and no causal relations have yet been established. We applied two-sample Mendelian Randomization (MR) on the association statistics from genome-wide association studies (GWAS) for circulating S100B levels measured 5-7 days after birth (the iPSYCH sample) and in an older adult sample (mean age, 72.5 years; the Lothian sample), upon those derived from major depression disorder (MDD), schizophrenia (SCZ), bipolar disorder (BIP), autism spectral disorder (ASD), Alzheimer’s disease (AD), and Parkinson’s disease (PD). We studied the causal relations in the two S100B datasets for risk of these six neuropsychiatric disorders. MR suggested increased S100B levels 5-7 days after birth to causally increase the risk of MDD (OR = 1.014; 95%CI = 1.007–1.022; FDR-corrected p = 6.43×10−4). In older adults, MR suggested increased S100B levels to have a causal relation to the risk of BIP (OR = 1.075; 95%CI = 1.026–1.127; FDR-corrected p = 1.35×10−2). No significant causal relations were found for the other five disorders. We did not observe any evidence for reverse causality of these neuropsychiatric or neurological disorders on altered S100B levels. Sensitivity analyses using more stringent SNP-selection criteria and three alternative MR models suggested the results are robust. Altogether, our findings imply a small cause-effect relation for the previously reported associations of S100B and mood disorders. Such findings may provide a novel avenue for the diagnosis and management of disorders.
FGF10 mitigates doxorubicin-induced myocardial toxicity in mice via activation of FGFR2b/PHLDA1/AKT axis
Authors: Zhou De-pu , Deng Lian-cheng , Feng Xiao , Xu Hui-jing , Tian Ye , Yang Wei-wei , Zeng Ping-ping , Zou Li-hui , Yan Xi-hua , Zhu Xia-yan , Shu Dan-hua , Guo Qiang , Huang Xiao-ying , Bellusci Saverio , Lou Zhenkun , Li Xiao-kun , Zhang Jin-San
Published: May 2023

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10+/− mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26rtTA; tet(O)sFgfr2b) were used to determine the effect of Fgf10 hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10+/− mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10+/+ control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment.
Inequalities in access to NHS primary care dental services in Scotland during the COVID-19 pandemic
Authors: Aminu Abodunrin Q. , McMahon Alex D. , Clark Claire , Sherriff Andrea , Buchanan Caroline , Watling Chris , Mahmoud Ahmed , Culshaw Shauna , Mackay William , Gorman Megan , Braid Raymond , Edwards Maura , Conway David I.
Published: May 2023

Introduction This study aimed to quantify the impact of the COVID-19 pandemic on access and inequalities in primary care dental services among children and adults in Scotland.

Methods Access was measured as any NHS Scotland primary care dental contacts derived from administrative data from January 2019 to May 2022, linked to the area-based Scottish Index of Multiple Deprivation for children and adults, and related to population denominator estimates from National Record Scotland. Inequalities for pre-pandemic (January 2019-January 2020) and recent (December 2021-February 2022, and March 2022-May 2022) periods for both children and adults were calculated and compared using the slope index of inequality and relative index of inequality.

Results Following the first lockdown (March 2020) there was a dramatic fall to near zero dental contacts, followed by a slow recovery to 64.8% of pre-pandemic levels by May 2022. There was initial widening of relative inequalities in dental contacts in early 2022, which, more recently, had begun to return to pre-pandemic levels.

Conclusion COVID-19 had a major impact on access to NHS primary dental care, and while inequalities in access are apparent as services recover from lockdown, these inequalities are not a new phenomenon.
Chemotherapy impairs ovarian function through excessive ROS-induced ferroptosis
Authors: Zhang Shenghui , Liu Qin , Chang Mengyuan , Pan Ying , Yahaya Badrul Hisham , Liu Yanli , Lin Juntang
Published: May 2023

Chemotherapy was conventionally applied to kill cancer cells, but regrettably, they also induce damage to normal cells with high-proliferative capacity resulting in cardiotoxicity, nephrotoxicity, peripheral nerve toxicity, and ovarian toxicity. Of these, chemotherapy-induced ovarian damages mainly include but are not limited to decreased ovarian reserve, infertility, and ovarian atrophy. Therefore, exploring the underlying mechanism of chemotherapeutic drug-induced ovarian damage will pave the way to develop fertility-protective adjuvants for female patients during conventional cancer treatment. Herein, we firstly confirmed the abnormal gonadal hormone levels in patients who received chemotherapy and further found that conventional chemotherapeutic drugs (cyclophosphamide, CTX; paclitaxel, Tax; doxorubicin, Dox and cisplatin, Cis) treatment significantly decreased both the ovarian volume of mice and the number of primordial and antral follicles and accompanied with the ovarian fibrosis and reduced ovarian reserve in animal models. Subsequently, Tax, Dox, and Cis treatment can induce the apoptosis of ovarian granulosa cells (GCs), likely resulting from excessive reactive oxygen species (ROS) production-induced oxidative damage and impaired cellular anti-oxidative capacity. Thirdly, the following experiments demonstrated that Cis treatment could induce mitochondrial dysfunction through overproducing superoxide in GCs and trigger lipid peroxidation leading to ferroptosis, first reported in chemotherapy-induced ovarian damage. In addition, N-acetylcysteine (NAC) treatment could alleviate the Cis-induced toxicity in GCs by downregulating cellular ROS levels and enhancing the anti-oxidative capacity (promoting the expression of glutathione peroxidase, GPX4; nuclear factor erythroid 2-related factor 2, Nrf2 and heme oxygenase-1, HO-1). Our study confirmed the chemotherapy-induced chaotic hormonal state and ovarian damage in preclinical and clinical examination and indicated that chemotherapeutic drugs initiated ferroptosis in ovarian cells through excessive ROS-induced lipid peroxidation and mitochondrial dysfunction, leading to ovarian cell death. Consequently, developing fertility protectants from the chemotherapy-induced oxidative stress and ferroptosis perspective will ameliorate ovarian damage and further improve the life quality of cancer patients.
The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation
Authors: Li Jiaying , Pei Miaomiao , Xiao Wushuang , Liu Xuehua , Hong Linjie , Yu Zhen , Peng Ying , Zhang Jieming , Yang Ping , Lin Jianjiao , Wu Xiaosheng , Lin Zhizhao , Tang Weimei , Zhi Fachao , Li Guoxin , Xiang Li , Li Aimin , Liu Side , Chen Ye , Wang Jide
Published: May 2023

Long non-coding RNAs (lncRNAs) have been functionally characterised in various diseases. LncRNA PAX-interacting protein 1-antisense RNA 1 (PAXIP1-AS1) has reportedly been associated with cancer development. However, its role in gastric cancer (GC) remains poorly understood. Here, we showed that PAXIP1-AS1 was transcriptionally repressed by homeobox D9 (HOXD9) and was significantly downregulated in GC tissues and cells. Decreased expression of PAXIP1-AS1 was positively correlated with tumour progression, while PAXIP1-AS1 overexpression inhibited cell growth and metastasis both in vitro and in vivo. PAXIP1-AS1 overexpression significantly attenuated HOXD9-enhanced epithelial-to-mesenchymal transition (EMT), invasion and metastasis in GC cells. Poly(A)-binding protein cytoplasmic 1 (PABPC1), an RNA-binding protein, was found to enhance the stability of PAK1 mRNA, leading to EMT progress and GC metastasis. PAXIP1-AS1 was found to directly bind to and destabilise PABPC1, thereby regulating EMT and metastasis of GC cells. In summary, PAXIP1-AS1 suppressed metastasis, and the HOXD9/PAXIP1-AS1/PABPC1/PAK1 signalling axis may be involved in the progression of GC.
Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion
Authors: Eser Tabea M. , Baranov Olga , Huth Manuel , Ahmed Mohammed I. M. , Deák Flora , Held Kathrin , Lin Luming , Pekayvaz Kami , Leunig Alexander , Nicolai Leo , Pollakis Georgios , Buggert Marcus , Price David A. , Rubio-Acero Raquel , Reich Jakob , Falk Philine , Markgraf Alissa , Puchinger Kerstin , Castelletti Noemi , Olbrich Laura , Vanshylla Kanika , Klein Florian , Wieser Andreas , Hasenauer Jan , Kroidl Inge , Hoelscher Michael , Geldmacher Christof
Published: May 2023

Despite intensive research since the emergence of SARS-CoV-2, it has remained unclear precisely which components of the early immune response protect against the development of severe COVID-19. Here, we perform a comprehensive immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples obtained during the acute phase of infection with SARS-CoV-2. We find that soluble and transcriptional markers of systemic inflammation peak during the first week after symptom onset and correlate directly with upper airways viral loads (UA-VLs), whereas the contemporaneous frequencies of circulating viral nucleocapsid (NC)-specific CD4+ and CD8+ T cells correlate inversely with various inflammatory markers and UA-VLs. In addition, we show that high frequencies of activated CD4+ and CD8+ T cells are present in acutely infected nasopharyngeal tissue, many of which express genes encoding various effector molecules, such as cytotoxic proteins and IFN-γ. The presence of IFNG mRNA-expressing CD4+ and CD8+ T cells in the infected epithelium is further linked with common patterns of gene expression among virus-susceptible target cells and better local control of SARS-CoV-2. Collectively, these results identify an immune correlate of protection against SARS-CoV-2, which could inform the development of more effective vaccines to combat the acute and chronic illnesses attributable to COVID-19.
Redefining the role of AMPK in autophagy and the energy stress response
Authors: Park Ji-Man , Lee Da-Hye , Kim Do-Hyung
Published: May 2023

Autophagy maintains cellular homeostasis during low energy states. According to the current understanding, glucose-depleted cells induce autophagy through AMPK, the primary energy-sensing kinase, to acquire energy for survival. However, contrary to the prevailing concept, our study demonstrates that AMPK inhibits ULK1, the kinase responsible for autophagy initiation, thereby suppressing autophagy. We found that glucose starvation suppresses amino acid starvation-induced stimulation of ULK1-Atg14-Vps34 signaling via AMPK activation. During an energy crisis caused by mitochondrial dysfunction, the LKB1-AMPK axis inhibits ULK1 activation and autophagy induction, even under amino acid starvation. Despite its inhibitory effect, AMPK protects the ULK1-associated autophagy machinery from caspase-mediated degradation during energy deficiency, preserving the cellular ability to initiate autophagy and restore homeostasis once the stress subsides. Our findings reveal that dual functions of AMPK, restraining abrupt induction of autophagy upon energy shortage while preserving essential autophagy components, are crucial to maintain cellular homeostasis and survival during energy stress.
Neural crest E-cadherin loss drives cleft lip/palate by epigenetic modulation via pro-inflammatory gene–environment interaction
Authors: Alvizi Lucas , Nani Diogo , Brito Luciano Abreu , Kobayashi Gerson Shigeru , Passos-Bueno Maria Rita , Mayor Roberto
Published: May 2023

Gene–environment interactions are believed to play a role in multifactorial phenotypes, although poorly described mechanistically. Cleft lip/palate (CLP), the most common craniofacial malformation, has been associated with both genetic and environmental factors, with little gene–environment interaction experimentally demonstrated. Here, we study CLP families harbouring CDH1/E-Cadherin variants with incomplete penetrance and we explore the association of pro-inflammatory conditions to CLP. By studying neural crest (NC) from mouse, Xenopus and humans, we show that CLP can be explained by a 2-hit model, where NC migration is impaired by a combination of genetic (CDH1 loss-of-function) and environmental (pro-inflammatory activation) factors, leading to CLP. Finally, using in vivo targeted methylation assays, we demonstrate that CDH1 hypermethylation is the major target of the pro-inflammatory response, and a direct regulator of E-cadherin levels and NC migration. These results unveil a gene–environment interaction during craniofacial development and provide a 2-hit mechanism to explain cleft lip/palate aetiology.
Intracellular RNA and DNA tracking by uridine-rich internal loop tagging with fluorogenic bPNA
Authors: Liang Yufeng , Willey Sydney , Chung Yu-Chieh , Lo Yi-Meng , Miao Shiqin , Rundell Sarah , Tu Li-Chun , Bong Dennis
Published: May 2023

The most widely used method for intracellular RNA fluorescence labeling is MS2 labeling, which generally relies on the use of multiple protein labels targeted to multiple RNA (MS2) hairpin structures installed on the RNA of interest (ROI). While effective and conveniently applied in cell biology labs, the protein labels add significant mass to the bound RNA, which potentially impacts steric accessibility and native RNA biology. We have previously demonstrated that internal, genetically encoded, uridine-rich internal loops (URILs) comprised of four contiguous UU pairs (8 nt) in RNA may be targeted with minimal structural perturbation by triplex hybridization with 1 kD bifacial peptide nucleic acids (bPNAs). A URIL-targeting strategy for RNA and DNA tracking would avoid the use of cumbersome protein fusion labels and minimize structural alterations to the RNA of interest. Here we show that URIL-targeting fluorogenic bPNA probes in cell media can penetrate cell membranes and effectively label RNAs and RNPs in fixed and live cells. This method, which we call fluorogenic U-rich internal loop (FLURIL) tagging, was internally validated through the use of RNAs bearing both URIL and MS2 labeling sites. Notably, a direct comparison of CRISPR-dCas labeled genomic loci in live U2OS cells revealed that FLURIL-tagged gRNA yielded loci with signal to background up to 7X greater than loci targeted by guide RNA modified with an array of eight MS2 hairpins. Together, these data show that FLURIL tagging provides a versatile scope of intracellular RNA and DNA tracking while maintaining a light molecular footprint and compatibility with existing methods.
Robust cortical encoding of 3D tongue shape during feeding in macaques
Authors: Laurence-Chasen Jeffrey D. , Ross Callum F. , Arce-McShane Fritzie I. , Hatsopoulos Nicholas G.
Published: May 2023

Dexterous tongue deformation underlies eating, drinking, and speaking. The orofacial sensorimotor cortex has been implicated in the control of coordinated tongue kinematics, but little is known about how the brain encodes—and ultimately drives—the tongue’s 3D, soft-body deformation. Here we combine a biplanar x-ray video technology, multi-electrode cortical recordings, and machine-learning-based decoding to explore the cortical representation of lingual deformation. We trained long short-term memory (LSTM) neural networks to decode various aspects of intraoral tongue deformation from cortical activity during feeding in male Rhesus monkeys. We show that both lingual movements and complex lingual shapes across a range of feeding behaviors could be decoded with high accuracy, and that the distribution of deformation-related information across cortical regions was consistent with previous studies of the arm and hand.
Near-lifespan longitudinal tracking of brain microvascular morphology, topology, and flow in male mice
Authors: Walek Konrad W. , Stefan Sabina , Lee Jang-Hoon , Puttigampala Pooja , Kim Anna H. , Park Seong Wook , Marchand Paul J. , Lesage Frederic , Liu Tao , Huang Yu-Wen Alvin , Boas David A. , Moore Christopher , Lee Jonghwan
Published: May 2023

In age-related neurodegenerative diseases, pathology often develops slowly across the lifespan. As one example, in diseases such as Alzheimer’s, vascular decline is believed to onset decades ahead of symptomology. However, challenges inherent in current microscopic methods make longitudinal tracking of such vascular decline difficult. Here, we describe a suite of methods for measuring brain vascular dynamics and anatomy in mice for over seven months in the same field of view. This approach is enabled by advances in optical coherence tomography (OCT) and image processing algorithms including deep learning. These integrated methods enabled us to simultaneously monitor distinct vascular properties spanning morphology, topology, and function of the microvasculature across all scales: large pial vessels, penetrating cortical vessels, and capillaries. We have demonstrated this technical capability in wild-type and 3xTg male mice. The capability will allow comprehensive and longitudinal study of a broad range of progressive vascular diseases, and normal aging, in key model systems.
A positive statistical benchmark to assess network agreement
Authors: Hao Bingjie , Kovács István A.
Published: May 2023

Current computational methods for validating experimental network datasets compare overlap, i.e., shared links, with a reference network using a negative benchmark. However, this fails to quantify the level of agreement between the two networks. To address this, we propose a positive statistical benchmark to determine the maximum possible overlap between networks. Our approach can efficiently generate this benchmark in a maximum entropy framework and provides a way to assess whether the observed overlap is significantly different from the best-case scenario. We introduce a normalized overlap score, Normlap, to enhance comparisons between experimental networks. As an application, we compare molecular and functional networks, resulting in an agreement network of human as well as yeast network datasets. The Normlap score can improve the comparison between experimental networks by providing a computational alternative to network thresholding and validation.
Compact optical convolution processing unit based on multimode interference
Authors: Meng Xiangyan , Zhang Guojie , Shi Nuannuan , Li Guangyi , Azaña José , Capmany José , Yao Jianping , Shen Yichen , Li Wei , Zhu Ninghua , Li Ming
Published: May 2023

Convolutional neural networks are an important category of deep learning, currently facing the limitations of electrical frequency and memory access time in massive data processing. Optical computing has been demonstrated to enable significant improvements in terms of processing speeds and energy efficiency. However, most present optical computing schemes are hardly scalable since the number of optical elements typically increases quadratically with the computational matrix size. Here, a compact on-chip optical convolutional processing unit is fabricated on a low-loss silicon nitride platform to demonstrate its capability for large-scale integration. Three 2 × 2 correlated real-valued kernels are made of two multimode interference cells and four phase shifters to perform parallel convolution operations. Although the convolution kernels are interrelated, ten-class classification of handwritten digits from the MNIST database is experimentally demonstrated. The linear scalability of the proposed design with respect to computational size translates into a solid potential for large-scale integration.
Uncertainty analysis and performance evaluation of thermophysical property measurement of liquid Au in microgravity
Authors: Nawer Jannatun , Ishikawa Takehiko , Oda Hirohisa , Saruwatari Hideki , Koyama Chihiro , Xiao Xiao , Schneider Stephan , Kolbe Matthias , Matson Douglas M.
Published: May 2023

A new method for quantifying facility performance has been discussed in this study that encompasses uncertainties associated with thermophysical property measurement. Four key thermophysical properties: density, volumetric thermal expansion coefficient, surface tension, and viscosity of liquid Au have been measured in microgravity environment using two different levitation facilities. Levitation experiments were conducted using the Electrostatic Levitation Furnace (ELF) onboard the ISS in Argon and air, and the TEMPUS Electromagnetic Levitation (EML) facility on a Novespace Zero-G aircraft parabolic flight in Argon. The traditional Maximum Amplitude method was augmented through the use of Frequency Crossover method to identify the natural frequency for oscillations induced on a molten sample during Faraday forcing in ESL. The EML tests were conducted using a pulse excitation method where two techniques, one imaging and one non-imaging, were used to study surface oscillations. The results from both facilities are in excellent agreement with the published literature values. A detailed study of the accuracy and precision of the measured values has also been presented in this work to evaluate facility performance.
Directly monitoring the shift in corrosion mechanisms of a model FeCrNi alloy driven by electric potential
Authors: Liu Tingkun , Li Cheng-Han , Olszta Matthew , Tao Jinhui , Devaraj Arun
Published: May 2023

Stainless steels are used in a myriad of engineering applications, including construction, automobiles, and nuclear reactors. Developing accurate, predictive mechanistic models for corrosion and electrochemical corrosion kinetics of stainless steels has been a topic of research studies over many decades. Herein, we quantified the aqueous corrosion kinetics of a model austenitic Fe–18Cr–14Ni (wt%) alloy in the presence and absence of applied potential using systematic in situ electrochemical atomic force microscopy (EC-AFM) and transmission electron microscopy (TEM). Without an applied bias, vertical dissolution of corrosion pits is controlled by the surface kinetics/diffusion hybrid mechanism, whereas lateral dissolution is diffusion controlled. When an electric bias is applied, the increase in corrosion rate is dominated by the nucleation of new pits. These insights gained by the in situ EC-AFM will allow applications of this method for a quantitative understanding of corrosion of a wider class of materials.
Influence of cementite coarsening on the corrosion resistance of high strength low alloy steel
Authors: Liu Chao , Li Can , Che Zhichao , Li Xuan , Yang Shufeng , Liu Zhiyong , Zhou Yigang , Cheng Xuequn
Published: May 2023

The impact of heat treatment on the initiation and progression of localized corrosion in E690 steel in a simulated marine environment was investigated systematically. The primary cause of localized corrosion was the presence of inclusions, which led to the dissolution of the distorted matrix surrounding them. In the initial stages of corrosion, localized corrosion resulting from inclusions was the predominant form. The chemical and electrochemical mechanisms underlying matrix deformation and localized corrosion caused by inclusions were meticulously elucidated. As the immersion time was extended, the galvanic contributions at the ferrite-austenite interfaces, as well as the coarsened carbides, reduced the polarization resistance in the annealed specimen, accelerating the corrosion rate compared to the lath martensite in the as-received specimen. Consequently, the heat-treated sample promoted a transition from localized to uniform corrosion. Finally, a model was established to describe the corrosion behavior of E690 steel in the marine environment.
Metagenomic insights into nutrient and hypoxic microbial communities at the macrofouling/steel interface leading to severe MIC
Authors: Wang Zhengquan , Wang Xiutong , Huang Yanliang , Hou Baorong
Published: May 2023

Adherent macrofouling in marine environments caused complex corrosion of steel surfaces, resulting in localized corrosion at the oyster/steel interface and uniform corrosion at the ascidian/steel interface. Sulfate-reducing bacteria (SRB) have been implicated in the microbiologically influenced corrosion (MIC) process at macrofouling-covered interfaces. To better understand the role of marine biofilms as key mediators in the MIC process, metagenomic techniques were used to study microbial communities and their response to macrofouling’s coverage. Compared to ascidians, the formed local anaerobic zone at oyster/steel interface stimulated the growth of SRBs, leading to higher FeS content and severe localized corrosion. SRB Desulfovibrio and Desulfobulbus, along with the SRB-related functional gene dsr, were found to increase, while oxygen-related function genes coxC, ccoN, ccoO, ccoP, and ccoQ decreased. In contrast, steel surfaces without macrofouling coverage had the richest microbial communities, yet experienced less severe MIC, suggesting no direct connection between microbial abundance/diversity and steel corrosion promotion.
Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy
Authors: Foronda Hector , Fu Yangxue , Covarrubias-Pinto Adriana , Bocker Hartmut T. , González Alexis , Seemann Eric , Franzka Patricia , Bock Andrea , Bhaskara Ramachandra M. , Liebmann Lutz , Hoffmann Marina E. , Katona Istvan , Koch Nicole , Weis Joachim , Kurth Ingo , Gleeson Joseph G. , Reggiori Fulvio , Hummer Gerhard , Kessels Michael M. , Qualmann Britta , Mari Muriel , Dikić Ivan , Hübner Christian A.
Published: May 2023

Membrane-shaping proteins characterized by reticulon homology domains play an important part in the dynamic remodelling of the endoplasmic reticulum (ER). An example of such a protein is FAM134B, which can bind LC3 proteins and mediate the degradation of ER sheets through selective autophagy (ER-phagy)1. Mutations in FAM134B result in a neurodegenerative disorder in humans that mainly affects sensory and autonomic neurons2. Here we report that ARL6IP1, another ER-shaping protein that contains a reticulon homology domain and is associated with sensory loss3, interacts with FAM134B and participates in the formation of heteromeric multi-protein clusters required for ER-phagy. Moreover, ubiquitination of ARL6IP1 promotes this process. Accordingly, disruption of Arl6ip1 in mice causes an expansion of ER sheets in sensory neurons that degenerate over time. Primary cells obtained from Arl6ip1-deficient mice or from patients display incomplete budding of ER membranes and severe impairment of ER-phagy flux. Therefore, we propose that the clustering of ubiquitinated ER-shaping proteins facilitates the dynamic remodelling of the ER during ER-phagy and is important for neuronal maintenance.
Histone modifications regulate pioneer transcription factor cooperativity
Authors: Sinha Kalyan K. , Bilokapic Silvija , Du Yongming , Malik Deepshikha , Halic Mario
Published: May 2023

Pioneer transcription factors have the ability to access DNA in compacted chromatin1. Multiple transcription factors can bind together to a regulatory element in a cooperative way, and cooperation between the pioneer transcription factors OCT4 (also known as POU5F1) and SOX2 is important for pluripotency and reprogramming2–4. However, the molecular mechanisms by which pioneer transcription factors function and cooperate on chromatin remain unclear. Here we present cryo-electron microscopy structures of human OCT4 bound to a nucleosome containing human LIN28B or nMATN1 DNA sequences, both of which bear multiple binding sites for OCT4. Our structural and biochemistry data reveal that binding of OCT4 induces changes to the nucleosome structure, repositions the nucleosomal DNA and facilitates cooperative binding of additional OCT4 and of SOX2 to their internal binding sites. The flexible activation domain of OCT4 contacts the N-terminal tail of histone H4, altering its conformation and thus promoting chromatin decompaction. Moreover, the DNA-binding domain of OCT4 engages with the N-terminal tail of histone H3, and post-translational modifications at H3K27 modulate DNA positioning and affect transcription factor cooperativity. Thus, our findings suggest that the epigenetic landscape could regulate OCT4 activity to ensure proper cell programming.
Path loss modeling and performance evaluation of double IRSs-aided wireless communication systems based on spatial scattering channel model
Authors: Wang Jihong , Ni Hao
Published: May 2023

Intelligent reflecting surface (IRS) is a key enabling technology to reshape the electromagnetic propagation environment and enhance the communication performance. Current single IRS-aided or multiple distributed IRSs-aided wireless communication systems leave inter-IRSs collaboration out of consideration, and as a result, the system performance may be severely restricted. For cooperative double IRSs-aided wireless communication systems, dyadic backscatter channel model is widely used in the performance analysis and optimization. However, the impact of factors such as the size and gain of IRS elements is omitted. As a result, the performance quantification and evaluation are inaccurate. In order to avoid the above limitations, spatial scattering channel model is leveraged to quantify the path loss of the double reflection link in typical application scenarios of double IRSs-aided wireless communication systems. When the near-field condition is satisfied, the electromagnetic wave signal transmitted between IRSs is a spherical wave, which leads to high-rank channel and a lower signal to noise ratio. This paper considers the rank-1 inter-IRSs equivalent channel and derives the closed-form received signal power which reveals its relationship with the deployment of IRSs and the physical and electromagnetic properties of IRSs. Taking the impact of near/far-field effects of IRS on signal propagation further into consideration, the network configurations under which double cooperative IRSs can enhance the system performance are recognized. Simulation results show that whether double IRSs should be selected to assist in the communication between the transmitter and the receiver depends on practical network configurations, and the same number of elements should be assigned to the two IRSs to maximize the system performance if they are adopted.
Study on emotion recognition bias in different regional groups
Authors: Lukac Martin , Zhambulova Gulnaz , Abdiyeva Kamila , Lewis Michael
Published: May 2023

Human-machine communication can be substantially enhanced by the inclusion of high-quality real-time recognition of spontaneous human emotional expressions. However, successful recognition of such expressions can be negatively impacted by factors such as sudden variations of lighting, or intentional obfuscation. Reliable recognition can be more substantively impeded due to the observation that the presentation and meaning of emotional expressions can vary significantly based on the culture of the expressor and the environment within which the emotions are expressed. As an example, an emotion recognition model trained on a regionally-specific database collected from North America might fail to recognize standard emotional expressions from another region, such as East Asia. To address the problem of regional and cultural bias in emotion recognition from facial expressions, we propose a meta-model that fuses multiple emotional cues and features. The proposed approach integrates image features, action level units, micro-expressions and macro-expressions into a multi-cues emotion model (MCAM). Each of the facial attributes incorporated into the model represents a specific category: fine-grained content-independent features, facial muscle movements, short-term facial expressions and high-level facial expressions. The results of the proposed meta-classifier (MCAM) approach show that a) the successful classification of regional facial expressions is based on non-sympathetic features b) learning the emotional facial expressions of some regional groups can confound the successful recognition of emotional expressions of other regional groups unless it is done from scratch and c) the identification of certain facial cues and features of the data-sets that serve to preclude the design of the perfect unbiased classifier. As a result of these observations we posit that to learn certain regional emotional expressions, other regional expressions first have to be “forgotten”.
Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice
Authors: Reid Kim , Daniels Eileen G. , Vasam Goutham , Kamble Rashmi , Janssens Georges E. , Hu Iman M. , Green Alexander E. , Houtkooper Riekelt H. , Menzies Keir J.
Published: May 2023

Maintaining mitochondrial function is critical to an improved healthspan and lifespan. Introducing mild stress by inhibiting mitochondrial translation invokes the mitochondrial unfolded protein response (UPRmt) and increases lifespan in several animal models. Notably, lower mitochondrial ribosomal protein (MRP) expression also correlates with increased lifespan in a reference population of mice. In this study, we tested whether partially reducing the gene expression of a critical MRP, Mrpl54, reduced mitochondrial DNA-encoded protein content, induced the UPRmt, and affected lifespan or metabolic health using germline heterozygous Mrpl54 mice. Despite reduced Mrpl54 expression in multiple organs and a reduction in mitochondrial-encoded protein expression in myoblasts, we identified few significant differences between male or female Mrpl54+/− and wild type mice in initial body composition, respiratory parameters, energy intake and expenditure, or ambulatory motion. We also observed no differences in glucose or insulin tolerance, treadmill endurance, cold tolerance, heart rate, or blood pressure. There were no differences in median life expectancy or maximum lifespan. Overall, we demonstrate that genetic manipulation of Mrpl54 expression reduces mitochondrial-encoded protein content but is not sufficient to improve healthspan in otherwise healthy and unstressed mice.
A case-based reasoning system for neonatal survival and LOS prediction in neonatal intensive care units: a development and validation study
Authors: Kermani Farzaneh , Zarkesh Mohammad Reza , Vaziri Mostafa , Sheikhtaheri Abbas
Published: May 2023

Early prediction of neonates' survival and Length of Stay (LOS) in Neonatal Intensive Care Units (NICU) is effective in decision-making. We developed an intelligent system to predict neonatal survival and LOS using the "Case-Based Reasoning” (CBR) method. We developed a web-based CBR system based on K-Nearest Neighborhood (KNN) on 1682 neonates and 17 variables for mortality and 13 variables for LOS and evaluated the system with 336 retrospectively collected data. We implemented the system in a NICU to externally validate the system and evaluate the system prediction acceptability and usability. Our internal validation on the balanced case base showed high accuracy (97.02%), and F-score (0.984) for survival prediction. The root Mean Square Error (RMSE) for LOS was 4.78 days. External validation on the balanced case base indicated high accuracy (98.91%), and F-score (0.993) to predict survival. RMSE for LOS was 3.27 days. Usability evaluation showed that more than half of the issues identified were related to appearance and rated as a low priority to be fixed. Acceptability assessment showed a high acceptance and confidence in responses. The usability score (80.71) indicated high system usability for neonatologists. This system is available athttp://neonatalcdss.ir/. Positive results of our system in terms of performance, acceptability, and usability indicated this system can be used to improve neonatal care.
Cholesterol efflux capacity is increased in subjects with familial hypercholesterolemia in a retrospective case–control study
Authors: Sanz Juana Maria , D’Amuri Andrea , Sergi Domenico , Angelini Sharon , Fortunato Valeria , Favari Elda , Vigna Giovanni , Zuliani Giovanni , Dalla Nora Edoardo , Passaro Angelina
Published: May 2023

Familial Hypercholesterolemia (FH) is characterized by an increase in Low-Density Lipoprotein Cholesterol (LDL-C) and by premature Cardiovascular Disease (CVD). However, it remains to be fully elucidated if FH impairs cholesterol efflux capacity (CEC), and whether CEC is related to lipoprotein subfraction distribution. This study aimed at comparing FH patients and age, sex and BMI matched controls in terms of LDL and HDL subfraction distribution as well as CEC. Forty FH patients and 80 controls, matched for age, sex and BMI, were enrolled in this case–control study. LDL and HDL subfractions were analyzed using the Quantimetrix Lipoprint System. CEC was evaluated as aq-CEC and ABCA1-CEC. FH subjects showed a significantly higher concentration of all LDL subfractions, and a shift from large to small HDL subfraction pattern relative to controls. FH subjects with previous CVD event had smaller LDL lipoproteins than controls and FH subjects without previous CVD event. Both aq-CEC and ABCA1-CEC were increased in FH patients with respect to controls. To conclude, FH subjects had a metabolic profile characterized not only by higher LDL-C but also by shift from large to small HDL subfraction phenotype. However, FH subjects showed an increase CEC than controls.
A study on computer vision for facial emotion recognition
Authors: Huang Zi-Yu , Chiang Chia-Chin , Chen Jian-Hao , Chen Yi-Chian , Chung Hsin-Lung , Cai Yu-Ping , Hsu Hsiu-Chuan
Published: May 2023

Artificial intelligence has been successfully applied in various fields, one of which is computer vision. In this study, a deep neural network (DNN) was adopted for Facial emotion recognition (FER). One of the objectives in this study is to identify the critical facial features on which the DNN model focuses for FER. In particular, we utilized a convolutional neural network (CNN), the combination of squeeze-and-excitation network and the residual neural network, for the task of FER. We utilized AffectNet and the Real-World Affective Faces Database (RAF-DB) as the facial expression databases that provide learning samples for the CNN. The feature maps were extracted from the residual blocks for further analysis. Our analysis shows that the features around the nose and mouth are critical facial landmarks for the neural networks. Cross-database validations were conducted between the databases. The network model trained on AffectNet achieved 77.37% accuracy when validated on the RAF-DB, while the network model pretrained on AffectNet and then transfer learned on the RAF-DB results in validation accuracy of 83.37%. The outcomes of this study would improve the understanding of neural networks and assist with improving computer vision accuracy.
On nature-inspired design optimization of antenna structures using variable-resolution EM models
Authors: Koziel Slawomir , Pietrenko-Dabrowska Anna
Published: May 2023

Numerical optimization has been ubiquitous in antenna design for over a decade or so. It is indispensable in handling of multiple geometry/material parameters, performance goals, and constraints. It is also challenging as it incurs significant CPU expenses, especially when the underlying computational model involves full-wave electromagnetic (EM) analysis. In most practical cases, the latter is imperative to ensure evaluation reliability. The numerical challenges are even more pronounced when global search is required, which is most often carried out using nature-inspired algorithms. Population-based procedures are known for their ability to escape from local optima, yet their computational efficiency is poor, which makes them impractical when applied directly to EM models. A common workaround is the utilization of surrogate modeling techniques, typically in the form of iterative prediction-correction schemes, where the accumulated EM simulation data is used to identify the promising regions of the parameter space and to refine the surrogate model predictive power at the same time. Notwithstanding, implementation of surrogate-assisted procedures is often intricate, whereas their efficacy may be hampered by the dimensionality issues and considerable nonlinearity of antenna characteristics. This work investigates the benefits of incorporating variable-resolution EM simulation models into nature-inspired algorithms for optimization of antenna structures, where the model resolution pertains to the level of discretization density of an antenna structure in the full-wave simulation model. The considered framework utilizes EM simulation models which share the same physical background and are selected from a continuous spectrum of allowable resolutions. The early stages of the search process are carried out with the use of the lowest fidelity model, which is subsequently automatically increased to finally reach the high-fidelity antenna representation (i.e., considered as sufficiently accurate for design purposes). Numerical validation is executed using several antenna structures of distinct types of characteristics, and a particle swarm optimizer as the optimization engine. The results demonstrate that appropriate resolution adjustment profiles permit considerable computational savings (reaching up to eighty percent in comparison to high-fidelity-based optimization) without noticeable degradation of the search process reliability. The most appealing features of the presented approach—apart from its computational efficiency—are straightforward implementation and versatility.
Bayesian network analysis of antidepressant treatment trajectories
Authors: Turner Rosanne J. , Hagoort Karin , Meijer Rosa J. , Coenen Femke , Scheepers Floortje E.
Published: May 2023

It is currently difficult to successfully choose the correct type of antidepressant for individual patients. To discover patterns in patient characteristics, treatment choices and outcomes, we performed retrospective Bayesian network analysis combined with natural language processing (NLP). This study was conducted at two mental healthcare facilities in the Netherlands. Adult patients admitted and treated with antidepressants between 2014 and 2020 were included. Outcome measures were antidepressant continuation, prescription duration and four treatment outcome topics: core complaints, social functioning, general well-being and patient experience, extracted through NLP of clinical notes. Combined with patient and treatment characteristics, Bayesian networks were constructed at both facilities and compared. Antidepressant choices were continued in 66% and 89% of antidepressant trajectories. Score-based network analysis revealed 28 dependencies between treatment choices, patient characteristics and outcomes. Treatment outcomes and prescription duration were tightly intertwined and interacted with antipsychotics and benzodiazepine co-medication. Tricyclic antidepressant prescription and depressive disorder were important predictors for antidepressant continuation. We show a feasible way of pattern discovery in psychiatry data, through combining network analysis with NLP. Further research should explore the found patterns in patient characteristics, treatment choices and outcomes prospectively, and the possibility of translating these into a tool for clinical decision support.