bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum K-theory of incidence varieties
Authors: Xu Weihong
Published: March 2024

We prove a conjecture of Buch and Mihalcea in the case of the incidence variety $$X=\textrm{Fl}\hspace{0.55542pt}(1,n-1;n)$$

X
=
Fl

(
1
,
n
-
1
;
n
)

and determine the structure of its (T-equivariant) quantum K-theory ring. Our results are an interplay between geometry and combinatorics. The geometric side concerns Gromov–Witten varieties of 3-pointed genus 0 stable maps to X with markings sent to Schubert varieties, while on the combinatorial side are formulas for the (equivariant) quantum K-theory ring of X. We prove that the Gromov–Witten variety is rationally connected when one of the defining Schubert varieties is a divisor and another is a point. This implies that the (equivariant) K-theoretic Gromov–Witten invariants defined by two Schubert classes and a Schubert divisor class can be computed in the ordinary (equivariant) K-theory ring of X. We derive a positive Chevalley formula for the equivariant quantum K-theory ring of X and a positive closed formula for Littlewood–Richardson coefficients in the non-equivariant quantum K-theory ring of X. The Littlewood–Richardson rule in turn implies that non-empty Gromov–Witten varieties given by Schubert varieties in general position have arithmetic genus 0.
Learning to cooperate in the shadow of the law
Authors: Galbiati Roberto , Henry Emeric , Jacquemet Nicolas
Published: March 2024

Formal enforcement punishing defectors can sustain cooperation by changing incentives. In this paper, we introduce a second effect of enforcement: it can also affect the capacity to learn about the group's cooperativeness. Indeed, in contexts with strong enforcement, it is difficult to tell apart those who cooperate because of the threat of fines from those who are intrinsically cooperative types. Whenever a group is intrinsically cooperative, enforcement will thus have a negative dynamic effect on cooperation because it slows down learning about prevalent values in the group that would occur under a weaker enforcement. We provide theoretical and experimental evidence in support of this mechanism. Using a lab experiment with independent interactions and random rematching, we observe that, in early interactions, having faced an environment with fines in the past decreases current cooperation. We further show that this results from the interaction between enforcement and learning: the effect of having met cooperative partners has a stronger effect on current cooperation when this happened in an environment with no enforcement. Replacing one signal of deviation without fine by a signal of cooperation without fine in a player's history increases current cooperation by 10%; while replacing it by a signal of cooperation with fine increases current cooperation by only 5%.
Evaluation and formulation of Spirulina platensis proteins for potential applications in hair care products
Authors: Elkady Omar A. , Mannaa Islam M. , El Bishbishy Mahitab H.
Published: March 2024

Spirulina platensis, a blue-green algae belonging to family Phormidiaceae, is well-known for its unique nutritional profile and high protein content. This study aims to isolate its proteins, formulate them into a cream and evaluate its potential as a hair treatment. S. platensis were collected from Nuweiba, Egypt and its protein was extracted, analyzed and used to prepare a cream. The cream was applied on natural hair strands compared to a control cream containing no protein. Both hair strands groups were observed via Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM) and evaluated by Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, as well as, thermal analysis tests including thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC). The SEM images of the test group showed more intact cuticle with the absence of cracks and holes, also, the TEM images showed stronger non-porous cuticle compared to the control group. The AFM images of the test group was smoother with lower roughness average and step height compared to the control group. On the other hand, the raman spectra showed different band intensities for disulfide bonds and C-S bonds as well as increased number of b sheet conformations in the test group which is responsible for the smoothing effect. The thermal analysis tests revealed a clear difference between both groups as an indication of improved keratin structure on the test group. S. platensis proteins could be introduced as a potential candidate for hair care products.
Metabolomics and gut metagenomics profile of the healthy adults on consumption of whey protein supplemented with enzymes-probiotics blend
Authors: Rathi Abhijit , Gaonkar Tejal , Dhar Debojyoti , Kallapura Gopalakrishna , Jadhav Swati
Published: March 2024

In this randomized, crossover, pilot clinical study, we aimed to evaluate the effect of supplementation of enzymes-probiotics blend with whey protein on the amino acid absorption and gut microbiota. Healthy subjects were supplemented with the whey protein and test i.e. Pepzyme Pro (enzymes-probiotics blend) or placebo i.e. maltodextrin for 15 days with the washout period of 30 days. Blood samples were analyzed for plasma free amino acids, insulin, and CRP. Additionally, urine nitrogen, fecal nitrogen, and gut microbiota were evaluated. On day 15, the test arm showed upward trend in rate of amino acid absorption than placebo arm within 30 min of post ingestion of protein. Moreover, rate of absorption of few essential and branched chain amino acids were significantly higher (methionine (p = 0.049), leucine (p = 0.014), isoleucine (p = 0.053)) in the test arm on day 15. Total branched chain amino acids absorption were found to be significantly higher (p ≤ 0.05) in the test arm than the placebo arm within 30 min of post ingestion on day 15. Uptrend in total amino acid absorption and Cmax, and downtrend in Tmax was observed on day 15 in the test arm. The CRP, fecal nitrogen, and urine nitrogen remained unaltered after supplementation. Microbiota profiling showed significant change in abundance of species of genus Bacteroides and phylum Bacteroidetes. Overall, metagenomics and metabolomics based assessments demonstrated that the consumption of Pepzyme Pro with whey protein could potentially improve protein digestion, amino acid absorption, and modulate gut microbiota.

Clinical trial registration The clinical trial registry of India CTRI/2021/09/036169 [Registered on: 02/09/2021]
Traits impacting water crisis management
Authors: Yasmeen Kausar , Yasmin Kashifa , Adnan Muhammad
Published: March 2024

Water scarcity and its geopolitical implications have been a cornerstone of scholarly discourse. However, literature often overlooks the nuanced relationship between human traits and water management. Addressing this oversight, this study synthesized data from 149 articles (1991–2023), revealing a substantial connection between human actions and water management dynamics. From this data, a unique comprehensive framework was developed, focusing on the intricate interplay of human behaviors, leadership dynamics, economic factors, and technological advancements in water management. Unlike previous works, this framework holistically integrates these components, offering a fresh lens through which to understand the human-centric factors underpinning global water scarcity. This study underscores the framework’s vital role in guiding sustainable water management and strategy, making it an indispensable tool for stakeholders, from policymakers to environmentalists. In essence, this research not only bridges a knowledge gap but also serves as a beacon for addressing pressing water scarcity challenges in today’s world.
Pragmatic Inference
Authors: Elder Chi-Hé
Published: March 2024

The concept of inference is foundational to the study of pragmatics; however, the way it is theoretically conceptualised and methodologically operationalised is far from uniform. This Element investigates the role that inference plays in pragmatic models of communication, bringing together a range of scholarship that characterises inference in different ways for different purposes. It addresses the nature of 'faulty inferences', promoting the study of misunderstandings as crucial for understanding inferential processes, and looking at sociopragmatic issues such as the role of commitment, accountability and deniability of inferences in interpersonal communication. This Element highlights that the question of where the locus of meaning lies is not only relevant to pragmatic theory but is also of paramount importance for understanding and managing real-life interpersonal communication conflict.
Culturomics: A critical approach in studying the roles of human and animal microbiota
Authors: Howe Samantha , Liu Ziyu , Zuo Bin , Zhao Jiangchao
Published: March 2024

The rise of sequencing technologies has greatly contributed to our knowledge of the microbiota and its role in animal health and production. However, many members of the microbiota have historically been considered “unculturable.” Culturomics can be utilized to bring these fastidious microbes into cultivation and can be used in conjunction with culture-independent methods to study the microbiota in a more comprehensive manner. This review paper details culturomics’ role in revolutionizing human, swine, and bovine microbiota research and how its use has greatly increased the bacterial repertoire. Additionally, it describes how culturomics can be applied to develop microbiota-derived therapeutics, such as next-generation probiotics, and to study the role of the microbiota. Finally, this review provides potential methods and considerations for designing future culturomics studies.
Labor Rights and Dispute System Design: Assessing the Legal Legacy of the 2022 Qatar World Cup
Authors: Calo Zachary R.
Published: March 2024

The aim of this paper is not to relitigate Qatar’s human rights record but to assess the effectiveness of its labor reforms: the principal concern is dispute resolution and enforceability. While Qatar instituted a broad suite of labor law reforms in the years preceding the World Cup, questions remain about whether they have improved access to justice for migrant workers. More attention needs to be given to the dispute settlement system established by Law No. 13 of 2017 to assess if new legal norms translate into enforceable rights. It is argued that the labor dispute system has largely failed by not taking into account the circumstances that define the employer-employee relationship in Qatar, especially the stark imbalance in power. While reforms might endure at the level of formal law, the dispute system will fail to deliver genuine justice to workers unless it is refashioned.
RETREATMENT OF BONE MATERIAL IN THE GLIWICE RADIOCARBON LABORATORY USING ULTRAFILTRATION
Authors: Pawełczyk Fatima , Niedziałkowska Magdalena , Pawełczyk Sławomira , Piotrowska Natalia , Sykut Maciej
Published: March 2024

Preparation of bones for radiocarbon (14C) dating is still quite a challenge for researchers. The methods are being tested and improved, to increase reliability of dating results and to verify the previous ones. In this work, a set of gelatine samples, extracted from Cervus elaphus and Cervus canadensis bones from various sites in Europe and a set of human bones from archaeological sites in Poland were subjected to retreatment using ultrafiltration in Gliwice Radiocarbon Laboratory. The tested samples represent a wide range of ages, from older than 40,000 14C years BP to modern. The prepared material was subjected to the measurement of C/N atomic ratios and 14C dating using the accelerator mass spectrometry (AMS) technique. Also, the stable isotopes (δ13C and δ15N) values were determined. In a few cases ultrafiltration allows to improve gelatine quality for long-stored samples, by increasing the %C and %N as well as decreasing C/Nat ratios. Nevertheless, this effect was not observed for majority of the samples. Remeasurements of long-term stored samples give mostly the same 14C ages for ultrafiltered ones and for those without ultrafiltration.
Personality disorder coverage, prevalence, and convergence: do the DSM-5's two models of personality disorder identify the same patients?
Authors: Clark Lee Anna , Ro Eunyoe , Nuzum Hallie , Vanderbleek Emily N. , Allen Xia
Published: March 2024

Background

Research on the Alternative DSM-5 Model for Personality Disorders (AMPD) in DSM-5's Section-III has demonstrated acceptable interrater reliability, a largely consistent latent structure, substantial correlations with theoretically and clinically relevant measures, and evidence for incremental concurrent and predictive validity after controlling for DSM-5's Section II categorical personality disorders (PDs). However, the AMPD is not yet widely used clinically. One clinician concern may be caseness – that the new model will diagnose a different set of PD patients from that with which they are familiar. The primary aim of this study is to determine whether this concern is valid, by testing how well the two models converge in terms of prevalence and coverage.

Method

Participants were 305 psychiatric outpatients and 302 community residents not currently in mental-health treatment who scored above threshold on the Iowa Personality Disorder Screen (Langbehn et al., 1999). Participants were administered a semi-structured interview for DSM-5 PD, which was scored for both Section II and III PDs.

Results

Convergence across the two PD models was variable for specific PDs, Good when specific PDs were aggregated, and Very Good for ‘any PD.’

Conclusions

Results provide strong evidence that the AMPD yields the same overall prevalence of PD as the current model and, further, identifies largely the same overall population. It also addresses well-known problems of the current model, is more consistent with the ICD-11 PD model, and provides more complete, individualized characterizations of persons with PD, thereby offering multiple reasons for its implementation in clinical settings.
The non-religious and the European city in the nineteenth century: the development of crematories in Milan and Gotha
Authors: Kosuch Carolin
Published: March 2024

While our knowledge of the entanglements of cities and religions is growing, the ‘other’ of religion and its impact on the city has not received the same level of attention in research so far. This article explores how this lacuna could start to be filled. Its focus is on the history of modern cremation that unfolded with strong secularist leanings during the long nineteenth century. I will look into the history of the first European crematories that were built in Milan and Gotha, the construction of the first cremation furnaces and the infrastructures necessary to make them work. My hypothesis is that what I call ‘worldview technologies’ and related infrastructures changed the faces of cities and were in turn influenced by these cities’ histories and self-images.
(-)-epicatechin treatment did not modify the thermogenic pathway in the gastrocnemius muscle of male rat offspring obeses by programming
Authors: Tejeda María Elena , De los Santos Sergio , Coral-Vázquez Ramón Mauricio , Álvarez-Chávez Ana , Palma Flores Carlos , Zambrano Elena , Méndez Juan Pablo , Canto Patricia
Published: March 2024

The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln. Epi significantly increased the Pgc-1α protein in the MO group of offspring at 110 pnd (p < 0.036, MO vs. MO+Epi), while at 245 pnd, Epi increased Fndc5/irisin mRNA expression in the MO+Epi group versus the MO group (p = 0.006).

No differences were detected in Fndc5/irisin, Ucp3 or Sln mRNA or protein levels (including Pgc-1α mRNA) in the offspring at 110 pnd or in Pgc-1α, Ucp3, or Sln mRNA or protein levels (including Fndc5/irisin protein) at 245 pnd among the experimental groups. In conclusion, (-)-epicatechin treatment increased Fndc5/irisin mRNA expression and Pgc-α protein levels in the gastrocnemius muscle of offspring at postnatal days 110 and 245. Furthermore, it is suggested that the flavonoid effect in a model of obesity and its impact on thermogenesis in skeletal muscle are regulated by a different pathway than Fndc5/irisin.
Comparative political process theory II
Authors: Gardbaum Stephen
Published: March 2024

This article aims to continue the recent neo-Elyean turn in comparative constitutional scholarship by further exploring the role of the courts in supporting and protecting democracy. In so doing, it refines and develops my previous work on the topic, and applies this fuller version to a highly visible current dispute. The article first examines the underlying conception of democracy that comparative political process theory is designed to protect; namely, constitutional democracy. It asks what this is and what role courts have in supporting it. The article then introduces the idea of ‘semi-substantive review’ as an integral and output-oriented part of a comprehensive comparative political process theory, alongside and in addition to the types of more purely procedural review I primarily emphasized in my previous work. Finally, the article employs the recent, highly controversial judicial reforms in Israel as a case study in applying the criteria for, and limits of, court intervention in my account. It analyses whether, why and how, in the event that the deeply contested bills become law (as so far one did), judges would be justified in acting to support and protect constitutional democracy.
Resonances of Fluid‐Filled Cracks With Complex Geometry and Application to Very Long Period (VLP) Seismic Signals at Mayotte Submarine Volcano
Authors: Liang Chao , Peng Junjun , Ampuero Jean‐Paul , Shauer Nathan , Dai Kaoshan
Published: March 2024

Fluid‐filled cracks sustain a slow guided wave (Krauklis wave or crack wave) whose resonant frequencies are widely used for interpreting long period (LP) and very long period (VLP) seismic signals at active volcanoes. Significant efforts have been made to model this process using analytical developments along an infinite crack or numerical methods on simple crack geometries. In this work, we develop an efficient hybrid numerical method for computing resonant frequencies of complex‐shaped fluid‐filled cracks and networks of cracks and apply it to explain the ratio of spectral peaks in the VLP signals from the Fani Maoré submarine volcano that formed in Mayotte in 2018. By coupling triangular boundary elements and the finite volume method, we successfully handle complex geometries and achieve computational efficiency by discretizing solely the crack surfaces. The resonant frequencies are directly determined through eigenvalue analysis. After proper verification, we systematically analyze the resonant frequencies of rectangular and elliptical cracks, quantifying the effect of aspect ratio and crack stiffness. We then discuss theoretically the contribution of fluid viscosity and seismic radiation to energy dissipation. Finally, we obtain a crack geometry that successfully explains the characteristic ratio between the first two modes of the VLP seismic signals from the Fani Maoré submarine volcano in Mayotte. Our work not only reveals rich eigenmodes in complex‐shaped cracks but also contributes to illuminating the subsurface plumbing system of active volcanoes. The developed model is readily applicable to crack wave resonances in other geological settings, such as glacier hydrology and hydrocarbon reservoirs.
Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together
Authors: Guo Hong-Li , Wu Dan-Dan , Fu Di , Li Yue , Wang Jie , Zhang Yuan-Yuan , Wang Wei-Jun , Huang Jian , Fang Wei-Rong , Xu Jing , Hu Ya-Hui , Liu Qian-Qi , Chen Feng
Published: March 2024

Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children’s Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.
Post-traumatic stress disorder in a national sample of preadolescent children 9 to 10 years old: Prevalence, correlates, clinical sequelae, and treatment utilization
Authors: Levin Rachel Y. , Liu Richard T.
Published: March 2024

Although posttraumatic stress disorder (PTSD) has been well characterized in adults, its epidemiology in children is unclear. The current study provides the first population-based examination of the prevalence of PTSD, sociodemographic and psychiatric correlates, clinical sequelae, and associations with psychiatric treatment in preadolescents 9-10 years old in the United States. Data from the Adolescent Brain and Cognitive Development (ABCD) Study (release 5.0) was analyzed. Participants (unweighted n = 11,875) were recruited from 21 sites across the United States. Current and lifetime PTSD prevalence were estimated, as was treatment use among children with PTSD. Sociodemographic, psychiatric correlates and sequelae of PTSD were analyzed using logistic regression, as was the association between PTSD and psychiatric treatment. After the application of propensity weights, lifetime prevalence of PTSD was 2.17%. Sexual minority status, being multiracial, having unmarried parents, and family economic insecurity were associated with greater odds of PTSD. Among psychiatric disorders, separation anxiety was most strongly associated with PTSD, although general comorbid psychopathology was associated with greater odds of PTSD. Prior history of PTSD predicted a new onset of other psychiatric disorders after PTSD remission. Nearly one in three children with lifetime PTSD did not receive psychiatric treatment, despite negative long-term outcomes of PTSD and significant psychiatric comorbidity. Even among preadolescents who experience full remission of PTSD, a significant risk for future psychiatric illness remains. Further, the current findings underscore the need for improved efforts to reduce unmet treatment needs among those with PTSD at this age.
Exemestane plus everolimus and palbociclib in metastatic breast cancer: clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial
Authors: Gómez Tejeda Zañudo Jorge , Barroso-Sousa Romualdo , Jain Esha , Jin Qingchun , Li Tianyu , Buendia-Buendia Jorge E. , Pereslete Alyssa , Abravanel Daniel L. , Ferreira Arlindo R. , Wrabel Eileen , Helvie Karla , Hughes Melissa E. , Partridge Ann H. , Overmoyer Beth , Lin Nancy U. , Tayob Nabihah , Tolaney Sara M. , Wagle Nikhil
Published: March 2024

The landscape of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) resistance is still being elucidated and the optimal subsequent therapy to overcome resistance remains uncertain. Here we present the final results of a phase Ib/IIa, open-label trial (NCT02871791) of exemestane plus everolimus and palbociclib for CDK4/6i-resistant metastatic breast cancer. The primary objective of phase Ib was to evaluate safety and tolerability and determine the maximum tolerated dose/recommended phase II dose (100 mg palbociclib, 5 mg everolimus, 25 mg exemestane). The primary objective of phase IIa was to determine the clinical benefit rate (18.8%, n = 6/32), which did not meet the predefined endpoint (65%). Secondary objectives included pharmacokinetic profiling (phase Ib), objective response rate, disease control rate, duration of response, and progression free survival (phase IIa), and correlative multi-omics analysis to investigate biomarkers of resistance to CDK4/6i. All participants were female. Multi-omics data from the phase IIa patients (n = 24 tumor/17 blood biopsy exomes; n = 27 tumor transcriptomes) showed potential mechanisms of resistance (convergent evolution of HER2 activation, BRAFV600E), identified joint genomic/transcriptomic resistance features (ESR1 mutations, high estrogen receptor pathway activity, and a Luminal A/B subtype; ERBB2/BRAF mutations, high RTK/MAPK pathway activity, and a HER2-E subtype), and provided hypothesis-generating results suggesting that mTOR pathway activation correlates with response to the trial’s therapy. Our results illustrate how genome and transcriptome sequencing may help better identify patients likely to respond to CDK4/6i therapies.
Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers
Authors: Iyer R. Sumanth , Needham Sarah R. , Galdadas Ioannis , Davis Benjamin M. , Roberts Selene K. , Man Rico C. H. , Zanetti-Domingues Laura C. , Clarke David T. , Fruhwirth Gilbert O. , Parker Peter J. , Rolfe Daniel J. , Gervasio Francesco L. , Martin-Fernandez Marisa L.
Published: March 2024

The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Oncogenic EGFR has been successfully targeted by tyrosine kinase inhibitors, but acquired drug resistance eventually overcomes the efficacy of these treatments. Attempts to surmount this therapeutic challenge are hindered by a poor understanding of how and why cancer mutations specifically amplify ligand-independent EGFR auto-phosphorylation signals to enhance cell survival and how this amplification is related to ligand-dependent cell proliferation. Here we show that drug-resistant EGFR mutations manipulate the assembly of ligand-free, kinase-active oligomers to promote and stabilize the assembly of oligomer-obligate active dimer sub-units and circumvent the need for ligand binding. We reveal the structure and assembly mechanisms of these ligand-free, kinase-active oligomers, uncovering oncogenic functions for hitherto orphan transmembrane and kinase interfaces, and for the ectodomain tethered conformation of EGFR. Importantly, we find that the active dimer sub-units within ligand-free oligomers are the high affinity binding sites competent to bind physiological ligand concentrations and thus drive tumor growth, revealing a link with tumor proliferation. Our findings provide a framework for future drug discovery directed at tackling oncogenic EGFR mutations by disabling oligomer-assembling interactions.
The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome
Authors: Gersteuer Felix , Morici Martino , Gabrielli Sara , Fujiwara Keigo , Safdari Haaris A. , Paternoga Helge , Bock Lars V. , Chiba Shinobu , Wilson Daniel N.
Published: March 2024

Nascent polypeptide chains can induce translational stalling to regulate gene expression. This is exemplified by the E. coli secretion monitor (SecM) arrest peptide that induces translational stalling to regulate expression of the downstream encoded SecA, an ATPase that co-operates with the SecYEG translocon to facilitate insertion of proteins into or through the cytoplasmic membrane. Here we present the structure of a ribosome stalled during translation of the full-length E. coli SecM arrest peptide at 2.0 Å resolution. The structure reveals that SecM arrests translation by stabilizing the Pro-tRNA in the A-site, but in a manner that prevents peptide bond formation with the SecM-peptidyl-tRNA in the P-site. By employing molecular dynamic simulations, we also provide insight into how a pulling force on the SecM nascent chain can relieve the SecM-mediated translation arrest. Collectively, the mechanisms determined here for SecM arrest and relief are also likely to be applicable for a variety of other arrest peptides that regulate components of the protein localization machinery identified across a wide range of bacteria lineages.
Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer
Authors: Bi Guoshu , Liang Jiaqi , Bian Yunyi , Shan Guangyao , Huang Yiwei , Lu Tao , Zhang Huan , Jin Xing , Chen Zhencong , Zhao Mengnan , Fan Hong , Wang Qun , Gan Boyi , Zhan Cheng
Published: March 2024

Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour’s metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H2O2-dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal——iron overload——through WNT/MYC signalling, as well as the subsequent elevated polyamine synthesis, thus forming a ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H2O2 positive feedback loop that amplifies ferroptosis. Meanwhile, we notice that ferroptotic cells release enhanced polyamine-containing extracellular vesicles into the microenvironment, thereby further sensitizing neighbouring cells to ferroptosis and accelerating the “spread” of ferroptosis in the tumour region. Besides, polyamine supplementation also sensitizes cancer cells or xenograft tumours to radiotherapy or chemotherapy through inducing ferroptosis. Considering that cancer cells are often characterized by elevated intracellular polyamine pools, our results indicate that polyamine metabolism exposes a targetable vulnerability to ferroptosis and represents an exciting opportunity for therapeutic strategies for cancer.
A topographical atlas of α-synuclein dosage and cell type-specific expression in adult mouse brain and peripheral organs
Authors: Geertsma Haley M. , Fisk Zoe A. , Sauline Lillian , Prigent Alice , Kurgat Kevin , Callaghan Steve M. ,   aSCENT-PD Consortium, Arenkiel Benjamin R. , Mollenhauer Brit , Schlossmacher Michael G. , Stadelmann Christine , Tomlinson Julianna J. , Henderson Michael X. , Rousseaux Maxime W. C.
Published: March 2024

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and presents pathologically with Lewy pathology and dopaminergic neurodegeneration. Lewy pathology contains aggregated α-synuclein (αSyn), a protein encoded by the SNCA gene which is also mutated or duplicated in a subset of familial PD cases. Due to its predominant presynaptic localization, immunostaining for the protein results in a diffuse reactivity pattern, providing little insight into the types of cells expressing αSyn. As a result, insight into αSyn expression-driven cellular vulnerability has been difficult to ascertain. Using a combination of knock-in mice that target αSyn to the nucleus (SncaNLS) and in situ hybridization of Snca in wild-type mice, we systematically mapped the topography and cell types expressing αSyn in the mouse brain, spinal cord, retina, and gut. We find a high degree of correlation between αSyn protein and RNA levels and further identify cell types with low and high αSyn content. We also find high αSyn expression in neurons, particularly those involved in PD, and to a lower extent in non-neuronal cell types, notably those of oligodendrocyte lineage, which are relevant to multiple system atrophy pathogenesis. Surprisingly, we also found that αSyn is relatively absent from select neuron types, e.g., ChAT-positive motor neurons, whereas enteric neurons universally express some degree of αSyn. Together, this integrated atlas provides insight into the cellular topography of αSyn, and provides a quantitative map to test hypotheses about the role of αSyn in network vulnerability, and thus serves investigations into PD pathogenesis and other α-synucleinopathies.
Calculation of solar ultraviolet influx in the eye considering the field of view and pupillary dilation due to sunglasses
Authors: Masili Mauro , Duarte Fernanda O. , Ventura Liliane
Published: March 2024

The media and even the specialized literature report that the ultraviolet (UV) protection for sunglasses is critical, on the grounds that sunglasses can have a counter effect if the lenses do not provide adequate UV protection. They reason that the primary and natural mechanism is that the pupil of the eye contracts to attenuate radiation and protect the inner eye under sun exposure. Therefore, if dark lenses do not provide appropriate UV protection, there is an increased UV incidence in the inner eye due to pupil dilation, which enhances the adverse effects and impacts the ocular tissues more severely than in situations without UV protection. However, no existing literature properly quantified or supported this argument. In this work, the influx of solar UV throughout the pupil of the eye was calculated in two situations: when a person wear sunglasses and when he/she does not. In both situations, the pupil dilation and the field of view (squint) were considered with their dependence on the brightness of the ambient, calculated by modeling the solar irradiation. Finally, it was assessed whether sunglasses with poor UV protection actually increase the UV influx throughout the dilated pupil compared to the non-dilated pupil. A set of 214 sunglasses lenses were tested and the results show that pupil dilation does not play an important role in the UV influx throughout the pupil. It was observed that the FOV is the main player, surpassing the pupil size contribution by up to 314.3%, disproving the common explanation. Because of the major role of the FOV, our results show that sunglasses with UV-A protection below 86% may have a slight potential to increase hazards to the eye compared to not wearing sunglasses at all. These results can have direct impact on sunglasses standards regarding the UV protection linked to the category of the lenses.
Persistence of collective memory of corporate bankruptcy events discussed on X (Twitter) is influenced by pre-bankruptcy public attention
Authors: Jagodnik Kathleen M. , Dekel Sharon , Bartal Alon
Published: March 2024

Collective attention and memory involving significant events can be quantitatively studied via social media data. Previous studies analyzed user attention to discrete events that do not change post-event, and assume universal public attention patterns. However, dynamic events with ongoing updates are common, yielding varied individual attention patterns. We explore memory of U.S. companies filing Chapter 11 bankruptcy and being mentioned on X (formerly Twitter). Unlike discrete events, Chapter 11 entails ongoing financial changes as the company typically remains operational, influencing post-event attention dynamics. We collected 248,936 X mentions for 74 companies before and after each bankruptcy. Attention surged after bankruptcy, with distinct Low and High persistence levels compared with pre-bankruptcy attention. The two tweeting patterns were modeled using biexponential models, successfully predicting (F1-score: 0.81) post-bankruptcy attention persistence. Studying bankruptcy events on social media reveals diverse attention patterns, demonstrates how pre-bankruptcy attention affects post-bankruptcy recollection, and provides insights into memory of dynamic events.
Antibacterial and sunlight-driven photocatalytic activity of graphene oxide conjugated CeO2 nanoparticles
Authors: Fauzia  , Khan Mo Ahamad , Chaman Mohd , Azam Ameer
Published: March 2024

This work focuses on the structural, morphological, optical, photocatalytic, antibacterial properties of pure CeO2 nanoparticles (NPs) and graphene oxide (GO) based CeO2 nanocomposites (GO-1/CeO2, GO-5/CeO2, GO-10/CeO2, GO-15/CeO2), synthesized using the sol–gel auto-combustion and subsequent sonication method, respectively. The single-phase cubic structure of CeO2 NPs was confirmed by Rietveld refined XRD, HRTEM, FTIR and Raman spectroscopy. The average crystallite size was calculated using Debye Scherrer formula and found to increase from 20 to 25 nm for CeO2 to GO-15/CeO2 samples, respectively. The related functional groups were observed from Fourier transform infrared (FTIR) spectroscopy, consistent with the outcomes of Raman spectroscopy. The optical band gap of each sample was calculated by using a Tauc plot, which was observed to decrease from 2.8 to 1.68 eV. The valence state of Ce (Ce3+ and Ce4+) was verified using X-ray photoelectron spectroscopy (XPS) for CeO2 and GO-10/CeO2. The poisonous methylene blue (MB) dye was used to evaluate the photocatalytic activity of each sample in direct sunlight. The GO-15/CeO2 nanocomposite showed the highest photocatalytic activity with rate constant (0.01633 min–1), and it degraded the MB dye molecules by 100% within 120 min. The high photocatalytic activity of this material for degrading MB dye establishes it as an outstanding candidate for wastewater treatment. Further, these nanocomposites also demonstrated excellent antimicrobial activity against Pseudomonas aeruginosa PAO1.
SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme
Authors: Mustafov D. , Siddiqui S. S. , Klena L. , Karteris E. , Braoudaki M.
Published: March 2024

Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This study aimed to assess the prognostic significance of miRNAs and their gene targets in GBM. An in silico approach was employed to investigate the differentially expressed miRNAs in GBM. The most dysregulated miRNAs were identified and analysed via Sfold in association with their gene target. The candidate gene was studied via multi-omics approaches, followed by in vitro and in vivo experiments. The in silico analyses revealed that miR-128a and miR-34a were significantly downregulated within GBM. Both miRNAs displayed high binding affinity to the synaptic vesicle glycoprotein 2B (SV2B) 3′ untranslated region (3′UTR). SV2B exhibited upregulation within brain regions with high synaptic activity. Significantly higher SV2B levels were observed in high grade brain malignancies in comparison to their normal counterparts. SV2B expression was observed across the cytoplasm of GBM cells. Our findings underscored the downregulated expression patterns of miR-128a and miR-34a, alongside the upregulation of SV2B in GBM suggesting the importance of the SV2B/miR-34a/miR-128 axis as a potential prognostic approach in GBM management.
Automatic berthing of unmanned surface vessels with predetermined performance
Authors: Wang Qiwen , Zhang Qiang , Zhao Enrui , Liu Yang , Zhang Yan
Published: March 2024

To solve the problem of ship automatic berthing control due to unknown time-varying disturbance and dynamic uncertainty of model parameters, an automatic berthing control law based on predefined performance time function is proposed. First, a predefined performance time function is designed and coupled with tracking error to achieve the predetermined performance of tracking error. Secondly, radial basis function neural network is used to approach the dynamic uncertainty of ship model parameters, and the complex uncertainty of model parameters and unknown time-varying disturbance is represented by linearized parameter form with single virtual parameter, which makes the calculation simple and easy to implement in engineering. On this basis, the reverse step control law is designed. Thirdly, the stability of the system is proved based on Lyapunov stability theory. Finally, the simulation results show that the control law can make the ship reach the desired position and heading angle, and realize the automatic berthing of the ship. The control law and berthing controller designed in this paper have good applicability and robustness, which provides a theoretical basis for the subsequent control research of surface intelligent ships.
Renal biopsies from donors with acute kidney injury show different molecular patterns according to the post-transplant function
Authors: Neri Flavia , Lo Faro Maria Letizia , Kaisar Maria , Tam Ka Ho , Borak Martyna , Lindeman Jan , Angelini Annalisa , Fedrigo Marny , Kers Jesper , Hunter James , Ploeg Rutger
Published: March 2024

The utilization of kidneys from donors with acute kidney injury (AKI) is often limited by unpredictable post-transplantation outcomes. The aim of our study was to identify protein mediators implicated in either recovery or failure of these organs. Forty kidney biopsies from donors with (20) and without AKI (20) were selected and then subdivided according to the post-transplant outcome defined as a threshold of 45 ml/min for the eGFR at 1 year from transplantation. Tissue homogenates were analysed by western blot to assess how the levels of 17 pre-selected proteins varied across the four groups. Samples from AKI kidneys with a poor outcome showed a fourfold increase in the levels of PPARg and twofold reduction of STAT1 compared to the other groups (p < 0.05). On the contrary, antioxidant enzymes including TRX1 and PRX3 were increased in the AKI kidneys with a good outcome (p < 0.05). An opposite trend was observed for the detoxifying enzyme GSTp which was significantly increased in the AKI group with poor versus good outcome (p < 0.05). The importance of lipid metabolism (PPARg) and inflammatory signals (STAT1) in the function recovery of these kidneys hints to the therapeutical targeting of the involved pathways in the setting of organ reconditioning.
The estimated mediating roles of anemia-related variables in the association between kidney function and mortality: a National Health and Nutrition Examination Survey (NHANES) study
Authors: Kim Yae Hyun , Lee Whanhee , Kim Kyun Young , Kim Yaerim , Ko Ara , Weon Boram , Lee Jeonghwan , Jin Wencheng , Kim Dong Ki , Kim Yon Su , Lim Chun Soo , Lee Jung Pyo ,   Korean Association for the study of Renal Anemia, artificial Intelligence (KARAI), Kim Sung Gyun , Ko Gang Jee , Park Jung Tak , Chang Tae Ik , Chung Sungjin , Lee Sang Ho , Choi Bum Soon , Jeon Jin Seok , Song Sangheon , Choi Dae Eun , Ryu Dong‑Ryeol , Jung Woo Kyung
Published: March 2024

Anemia is a common complication of chronic kidney disease (CKD), impacting long-term outcomes such as mortality and morbidity. Analyzing NHANES data from 1999 through 2016 for adults aged ≥ 20 years, we assessed the mediating effects of anemia biomarkers (hemoglobin, hematocrit, red cell distribution width [RDW], and mean corpuscular hemoglobin concentration [MCHC]) on CKD-related outcomes by using hazard ratios from a biomarker-adjusted model. Of 44,099 participants, 7463 experienced all-cause death. Cox proportional hazard models revealed a higher all-cause mortality risk in the > 45 years and CKD groups than in the early CKD group. Hemoglobin, hematocrit and MCHC were inversely related to all-cause mortality; RDW was related to mortality. Single mediation analysis showed greater mediating effects of anemia indicators on CKD and mortality in the elderly (> 65 years) population than those in the general population. In the multimediation analysis, the combined mediating effect of anemia was higher in the CKD population than in the general population. This study showed a proportional increase in the mediating effect of anemia with CKD stage, suggesting potential therapeutic avenues. However, further exploration of other mediating factors on kidney outcomes is necessary.
A novel group decision making method based on CoCoSo and interval-valued Q-rung orthopair fuzzy sets
Authors: Zheng Yan , Qin Hongwu , Ma Xiuqin
Published: March 2024

Interval-valued q-rung orthopair fuzzy set (IVq-ROFS) is a powerful tool for dealing with uncertainty. In this paper, we first propose a new method for aggregating multiple IVq-ROFSs, which is easier to understand and implement in the multi-attribute group decision making process compared to current aggregation operators. Secondly, this paper introduces a new fuzzy entropy with parameters based on IVq-ROFS, which is highly flexible due to its adjustable parameters. Based on this, the IVq-ROFS-based attribute weight calculation method is proposed to obtain the objective weights of the attributes, which is more reasonable and objective than the existing methods. Then, for the dimensional differences between the three compromise scores in the original Combined Compromise Solution (CoCoSo) method, the enhanced compromise scores are proposed. These scores are obtained by normalizing the three dependent compromise scores, ensuring that they fall within the same range. Finally, a novel CoCoSo mothed on IVq-ROFS using the proposed fuzzy entropy and enhanced compromise scores is presented. The proposed method is highly adaptable and scalable, not limited to IVq-ROFS. The excellent performance and robustness of the proposed method are verified in sepsis diagnosis applications.