bluuebunny/crossref_metadata_2025 huggingface dataset:
Life cycle assessment of the manufacturing and operation of distillation column for eliminating volatile and organic halogen compounds from process wastewater
Authors: Do Thi Huyen Trang , Toth Andras Jozsef
Published: October 2023

Distillation serves as the foremost method for commercial-scale separation of fluid mixtures. Widely applied in wastewater treatment, it is the preferred choice for isolating volatile multi-component mixtures into pure substances. Distillation technology offers notable economic benefits due to its easy implementation, high efficiency, productivity, and robust safety features. This study examines the environmental impacts associated with the production and usage of a distillation, specifically in treating pharmaceutical process wastewater containing organic halogen compounds (AOX). The analysis adopts a 'gate-to-gate' approach, with the specified functional unit (FU) set at 1 kg of treated effluent containing no more than 8 ppm of AOX and less than 1000 mg O2/L of Chemical Oxygen Demand (COD). In this work, Life Cycle Assessment (LCA) is conducted using Product Environmental Footprint (PEF) and Recipe 2016 Endpoint (H) V1.06 methodologies, utilizing the SimaPro V9.3.0.3 software in conjunction with the Ecoinvent V3.8 database. Analysis results have shown the emission of 1.11 × 10–2 kg CO2-eq, in which operational and production processes contribute 91.9% and 8.1%, respectively. To mitigate adverse effects, alternative energy sources, i.e., solar, offshore wind, and onshore wind are integrated into the distillation procedure. The substitution of hard coal with solar, offshore wind, and onshore wind energy displays the potential to significantly reduce climate change impact by 64.3%, 62.9%, and 62.8%, respectively.

Article Highlights

Distillation process undergoes a thorough life cycle assessment from production to application.

Distillation process requires high energy and emits 1.11 × 10–2 kg CO2-eq per functional unit.

The operational phase dominates over 90% in three damage categories: human health, ecosystems, and resources.
ACTIV-6: Operationalizing a decentralized, outpatient randomized platform trial to evaluate efficacy of repurposed medicines for COVID-19
Authors:   The Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group
Published: October 2023

Despite the availability of vaccinations, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause Coronavirus Disease 2019 (COVID-19) infection with a spectrum of disease in the acute setting. Transmission, infection, and severe disease remain common. There is a critical need to establish treatment regimens in the ambulatory setting that can reduce symptom burden and potentially prevent progression to severe disease and death. Many existing medicines previously approved for other uses may have benefit but remain unproven in informative clinical trials.

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 is a decentralized, placebo-controlled, double-blind, randomized, platform trial that has now enrolled more than 7500 participants and has reported on the effectiveness of ivermectin at two doses, fluticasone, and fluvoxamine for helping people with COVID-19. With additional repurposed therapies added to the platform, ACTIV-6 continues to enroll symptomatic outpatients aged ≥ 30 years with a confirmed positive PCR or antigen test for SARS-CoV-2. Potential participants are screened and enrolled online, through a call center, or facilitated by local study sites. Participants consent electronically and are randomized to placebo or to one of the open study drugs for which they are eligible at the time of enrollment. A shared, contemporary placebo approach is used. Participants receive study drug in the mail and remain on study for up to 180 days. While enrolled, electronic patient-reported outcome assessments are used to monitor symptoms, healthcare utilization, and mortality. The primary endpoint is time to recovery or a composite of hospitalization and mortality within 28 days. Symptoms, acute healthcare utilization, and the Patient-Reported Outcomes Measurement Information System-29 are collected for up to 180 days.

Using a decentralized trial approach allowed the ACTIV-6 platform to increase both reach and rate of enrollment. The decentralized approach did not simplify regulatory oversight, and we found unanticipated challenges in patient behavior and the study drug delivery process. Despite challenges, ACTIV-6 has enrolled thousands of participants from across the USA and continues to test the effectiveness of repurposed medicines for treating COVID-19. Our lessons learned contribute to the emerging understanding of how to optimize decentralized trials.
The CJEU’s give-and-give relationship with executive actors in times of crisis
Authors: Wallerman Ghavanini Anna
Published: October 2023

In a crisis, ordinary rules must often give way to a more expedient approach. Such emergency competences tend to favour executive decision-making over legislative procedures. In a European Union (EU) shaken by successive crises, this situation risks leading to permanent competence creep. While considerable attention has been devoted to the impact of crisis on legal and political decision-making within the Union, the position of the Court of Justice (CJEU) – and its impact on the distribution of powers within the EU – has been less researched. This Article fills the gap by exploring how the Court reviews the exercise of power in times of crisis by executive actors at the Union and Member State levels. Using migration law as a case study, it qualitatively and quantitatively examines how the CJEU has responded to crisis both in its scrutiny of measures of containment, and through its adjudication of migration cases in general before and after the acute phase of the 2015 refugee crisis. The Article shows that the crisis has led the CJEU to take a more lenient approach towards the executive powers at both the Union and the Member State level. It argues that this effectively amounts to a withdrawal from the judicial control function and enables an expansion of executive power that is likely to have effects lasting beyond any given emergency.
The EU Court of Justice as a relational actor: an introduction
Authors: Wallerman Ghavanini Anna
Published: October 2023

This introductory Article sets out the background and summarises the content of the Symposium on ‘The Court of Justice of the European Union (CJEU) as a Relational Actor’. Observing that the CJEU has been a key player in shaping European legal integration, the Symposium takes as its starting point that courts – and the CJEU is no exception in this regard – are unable to drive developments in isolation. For the Court to carry out its role as guarantor of the Treaties and guardian of the rule of law in the Union, it needs not to isolate itself but to interact with other European Union (EU) and national institutions. Relations, the Symposium argues, are not only unavoidable but also legitimate and even vital for the adequate execution of the judicial function. This introduction briefly explores six of the Court’s most important relationships: those with the other EU institutions; the courts of the Member States; the Member States themselves; the parties appearing before it; other international courts; and the general public. It then summarises the contributions and highlights how they complement each other in examining the CJEU as a relational actor.
Religious Institutions’ Stances towards Autocratization in the Post-Third Wave Period
Authors: Lotfy Dina Osama
Published: October 2023

While scholars have devoted significant attention to religious institutions’ role in democratization, less attention has been given to their role in autocratization. Moreover, religious economy approaches suggest that religious institutions are flexible to offer whatever is of interest to the marketplace, but here the role the institutions played in the third wave of democratization suggests a stable commitment. I test the impact of religious monopoly and the historical pro-democratizing role on 52 dominant religious institutions’ stances towards autocratic practices related to regime survival in the post-third wave period. Logistic regression models reveal that stronger religious monopolies decrease the probability of opposing regime survival, while the historical pro-democratizing role of the dominant religious groups in the third wave increases the probability. Furthermore, when the religious market is highly monopolized, the commitment to a democratic role in the third wave is weak, and it is strengthened when there is intense religious competition.
THE SUPPRESSION OF THE DRUIDS IN CAESAR'S GALLIC WAR
Authors: Creer Tyler
Published: October 2023

Ancient testimonia on the Druids are few in number and sparse on details, and they have yielded a broad range of scholarly opinions on the Druids’ function among the Gauls. This article examines the suspiciously limited role played by the Druids in Julius Caesar's Gallic War (= BGall.). Considering the work of both classicists and archaeologists, it argues that, given Caesar's demonstrated propensity for tailoring his portrayals of northern Europeans to fit with his narrative objectives, he deliberately omitted the Druids from nearly all of the Gallic War save for a brief ethnographic digression on the Gauls. This he did in order to downplay the sophistication of the Gauls, and the threat they posed to the Romans, since the Druids were likely a potent source of anti-Roman sentiment during Caesar's time in Gaul, just as they seem to have been in the Early Imperial period.
Notes on hyperelliptic mapping class groups
Authors: Boggi Marco
Published: October 2023

Hyperelliptic mapping class groups are defined either as the centralizers of hyperelliptic involutions inside mapping class groups of oriented surfaces of finite type or as the inverse images of these centralizers by the natural epimorphisms between mapping class groups of surfaces with marked points. We study these groups in a systematic way. An application of this theory is a counterexample to the genus
$2$
case of a conjecture by Putman and Wieland on virtual linear representations of mapping class groups. In the last section, we study profinite completions of hyperelliptic mapping class groups: we extend the congruence subgroup property to the general class of hyperelliptic mapping class groups introduced above and then determine the centralizers of multitwists and of open subgroups in their profinite completions.
The Real Effects of Financing and Trading Frictions
Authors: Zucchi Francesca
Published: October 2023

I develop a model revealing the interplay between a stock’s liquidity and the policies and value of the issuing firm. The model shows that bid-ask spreads increase not only the firm’s cost of capital but also the opportunity cost of cash, then lowering cash reserves, increasing liquidation risk, and reducing firm value. These outcomes are stronger when internalized by liquidity providers, simultaneously leading to a wider bid-ask spread. A two-way relation between the firm and the liquidity of its stock arises, implying that shocks arising within the firm or in the stock market have more complex implications than previously understood.
News and Markets in the Time of COVID-19
Authors: Mamaysky Harry
Published: October 2023

The onset of COVID-19 was characterized by voluminous, negative news. Higher narrativity news topics (measured by textual proximity to articles describing the 1987 stock market crash and textual distance from Federal Reserve communications) were systematically associated with contemporaneous market responses, which were larger on high volatility days (hypersensitivity), and with markets–news feedback. Hypersensitive news topic-market pairs were associated with next-day reversals. A test using the news–markets relationship identifies a mid-March 2020 structural break, which was knowable by the end of April. Post break, markets and news became considerably less coupled, and hypersensitivity and reversals abated.
Inseparable operations and the human operation of Christ
Authors: Duby Steven J.
Published: October 2023

The recent recovery of the teaching that the three divine persons share one operation in their outward works raises the question of whether or in what sense the human operation of Christ belongs to the Son alone. My thesis is that all three divine persons move and support the Son's human operation while the Son alone is the proper subject of his human operation. In order to substantiate this thesis, I will consider two main issues: (1) the relationship between divine movement and human energy and (2) the relationship between nature and person in Christ's human action.
Contrasting the semantic typology biases of Deaf and hearing nonsigners in their conceptualization of time and space
Authors: Macedo María Noel , Yerro Matías , Vivas Jorge , Castillo Mauricio , Meliande Maximiliano , de León Adriana , Fojo Alejandro , Aguirre Roberto
Published: October 2023

The mental lexicon offers a window into the configuration of conceptual domains such as space and time, which has been labeled as concrete the former and abstract the latter in the current embodiment approach to cognition. Space has a phonological and semantic value in sign languages, but not in spoken languages. Additionally, the representation of time by spatial means is robust in oral and sign languages. This research asks if Deaf signers and hearing nonsigners have the same conceptual organization of those domains. In their respective languages, sixty-two participants made a repeated free word association task. These results showed that the studied populations have a little overlap in the associates evocated for each clue. The analysis of the preferences of the semantic relations of the pairs clue-associate showed a greater tendency of the Deaf signers to establish thematic relations. In contrast, the hearing participants indicated a bias toward taxonomic relations. The results suggest that the abstractness or concreteness of concepts may be modulated by factors associated with linguistic modalities. However, in this compared free association norms factors related to the language deprivation of Deaf, the asymmetries in the cross-modal language contact and cross-modal borrowing were not exhaustively controlled.
Organizing Dots and Lines: Eastern Hui and the Adaptation of the CCP's Nationalities Work in the Revolutionary Era
Authors: Glasserman Aaron Nathan
Published: October 2023

Although ethnic governance in the People's Republic of China is often portrayed as a matter of controlling “minority nationalities” in the country's frontier regions, the ethnic affairs bureaucracy operates in every province. The origins of “nationalities work” as a discrete domain of governance can be traced to the Chinese Communist Party's efforts to mobilize scattered Hui communities in the eastern provinces of Shandong and Hebei in the 1930s–1940s. Thanks to the initiative of Hui Communists, local Party leaders came to understand that Hui were not simply scattered but interconnected. They adapted and replicated organizational methods to exploit Hui networks for gathering intelligence, smuggling goods and penetrating enemy-controlled cities. This history offers an instructive case of adaptive governance in the revolutionary period and the role of ethnic minority cadres in policy entrepreneurship. It also underscores the importance of the Party's experience in eastern China in the study of Chinese ethnic policy.
Giant early post-surgical aneurysm of the aortic arch in an infant
Authors: Cruz Hernández Angel , Ortiz José L. Colín , Silva Estrada Jorge A.
Published: October 2023

Ten-day-old neonate who underwent correction of interrupted aortic arch developed a giant early post-surgical aneurysm. To our knowledge, this unusual complication has been only reported as a late complication.
NON-FACTIVE KOLMOGOROV CONDITIONALIZATION
Authors: RESCORLA MICHAEL
Published: October 2023

Kolmogorov conditionalization is a strategy for updating credences based on propositions that have initial probability 0. I explore the connection between Kolmogorov conditionalization and Dutch books. Previous discussions of the connection rely crucially upon a factivity assumption: they assume that the agent updates credences based on true propositions. The factivity assumption discounts cases of misplaced certainty, i.e., cases where the agent invests credence 1 in a falsehood. Yet misplaced certainty arises routinely in scientific and philosophical applications of Bayesian decision theory. I prove a non-factive Dutch book theorem and converse Dutch book theorem for Kolmogorov conditionalization. The theorems do not rely upon the factivity assumption, so they establish that Kolmogorov conditionalization has unique pragmatic virtues that persist even in cases of misplaced certainty.
Quantifying the Contribution of Salinity Effect to the Seasonal Variability of the Makassar Strait Throughflow
Authors: Lu Xi , Hu Shijian , Guan Cong , Li Mingting , Sprintall Janet , Wang Fan
Published: October 2023

The Makassar Strait throughflow (MST) constitutes a significant component of the Indonesian throughflow (ITF) and plays a pivotal role in the interbasin exchange between the Indian and Pacific Oceans. While previous studies have suggested that the buoyancy forcing plays a role in influencing the seasonality of the MST, the quantitative contribution of salinity effect on MST seasonality remains unclear. Here we use the measurements from the Monitoring ITF program and the Global Ocean Physics Reanalysis product to investigate the seasonality of MST and quantify the impact of the salinity effect. We find that the halosteric variability due to the salinity effect contributes to approximately (69.6 ± 11.7) % of the total seasonal variability of surface dynamic height gradient along the Makassar Strait, and dominates the seasonality of the upper layer MST. The primary drivers for freshwater forcing are horizontal advection through the Karimata Strait and precipitation in the Java Sea.
Serpentinite Dehydration and Olivine Vein Formation During Ductile Shearing: Insights From 2D Numerical Modeling on Porosity Generation, Density Variations, and Transient Weakening
Authors: Schmalholz Stefan M. , Moulas Evangelos , Räss Ludovic , Müntener Othmar
Published: October 2023

Serpentinite dehydration is important for subduction zone dynamics and water cycling. Field observations suggest that en échelon olivine veins in serpentinite mylonites formed by dehydration during simultaneous shearing of antigorite serpentinite. Here, we test the hypothesis of shear‐driven formation of olivine dehydration veins with a novel two‐dimensional hydro‐mechanical‐chemical numerical model. Our model accounts for the reaction antigorite + brucite = forsterite + water, considering significant solid density changes of approximately 25%. We assume ductile shearing, a decrease of shear viscosity with increasing porosity, and initially homogeneous total and fluid pressures within the serpentinite stability field. Initial perturbations in porosity, and hence viscosity, cause fluid pressure perturbations during simple shearing. Dehydration nucleates where fluid pressure locally drops below the thermodynamic pressure controlling the reaction boundary. During shearing, dehydration veins grow and serpentinite transforms into olivine inside the veins. Simulations show that the ambient pressure and the relation between compaction length and porosity have a major impact on vein formation. Conversely, the orientation of the initial porosity perturbation, the pressure‐insensitive yield stress, the porosity dependence of compaction viscosity, the elastic effects during compaction, and the reaction kinetics have minor impacts on the simulations. We quantify the relative contribution of the rates of solid volume change, solid density change, and reactive mass transfer to the porosity generation. Vein growth is self‐limiting and eventually reaches a steady state. We discuss potential implications for natural olivine veins, slow slip and tremor, transient weakening, anisotropy generation, and formation of shear‐driven high‐porosity bands without a dehydration reaction.
Multiparity increases the risk of diabetes by impairing the proliferative capacity of pancreatic β cells
Authors: Moon Joon Ho , Lee Joonyub , Kim Kyun Hoo , Kim Hyun Jung , Kim Hyeongseok , Cha Hye-Na , Park Jungsun , Lee Hyeonkyu , Park So-young , Jang Hak Chul , Kim Hail
Published: October 2023

Pregnancy imposes a substantial metabolic burden on women, but little is known about whether or how multiple pregnancies increase the risk of maternal postpartum diabetes. In this study, we assessed the metabolic impact of multiple pregnancies in humans and in a rodent model. Mice that underwent multiple pregnancies had increased adiposity, but their glucose tolerance was initially improved compared to those of age-matched virgin mice. Later, however, insulin resistance developed over time, but insulin secretory function and compensatory pancreatic β cell proliferation were impaired in multiparous mice. The β cells of multiparous mice exhibited aging features, including telomere shortening and increased expression of Cdkn2a. Single-cell RNA-seq analysis revealed that the β cells of multiparous mice exhibited upregulation of stress-related pathways and downregulation of cellular respiration- and oxidative phosphorylation-related pathways. In humans, women who delivered more than three times were more obese, and their plasma glucose concentrations were elevated compared to women who had delivered three or fewer times, as assessed at 2 months postpartum. The disposition index, which is a measure of the insulin secretory function of β cells, decreased when women with higher parity gained body weight after delivery. Taken together, our findings indicate that multiple pregnancies induce cellular stress and aging features in β cells, which impair their proliferative capacity to compensate for insulin resistance.
Talin-1 inhibits Smurf1-mediated Stat3 degradation to modulate β-cell proliferation and mass in mice
Authors: Hou Xiaoting , Chen Yangshan , Zhou Bo , Tang Wanze , Ding Zhen , Chen Litong , Wu Yun , Yang Hongyu , Du Changzheng , Yang Dazhi , Ma Guixing , Cao Huiling
Published: October 2023

Insufficient pancreatic β-cell mass and reduced insulin expression are key events in the pathogenesis of diabetes mellitus (DM). Here we demonstrate the high expression of Talin-1 in β-cells and that deficiency of Talin-1 reduces β-cell proliferation, which leads to reduced β-cell mass and insulin expression, thus causing glucose intolerance without affecting peripheral insulin sensitivity in mice. High-fat diet fed exerbates these phenotypes. Mechanistically, Talin-1 interacts with the E3 ligase smad ubiquitination regulatory factor 1 (Smurf1), which prohibits ubiquitination of the signal transducer and activator of transcription 3 (Stat3) mediated by Smurf1, and ablation of Talin-1 enhances Smurf1-mediated ubiquitination of Stat3, leading to decreased β-cell proliferation and mass. Furthermore, haploinsufficiency of Talin-1 and Stat3 genes, but not that of either gene, in β-cell in mice significantly impairs glucose tolerance and insulin expression, indicating that both factors indeed function in the same genetic pathway. Finally, inducible deletion Talin-1 in β-cell causes glucose intolerance in adult mice. Collectively, our findings reveal that Talin-1 functions as a crucial regulator of β-cell mass, and highlight its potential as a therapeutic target for DM patients.
Targeting mPGES-2 to protect against acute kidney injury via inhibition of ferroptosis dependent on p53
Authors: Zhong Dandan , Quan Lingling , Hao Chang , Chen Jingshuo , Qiao Ranran , Lin Tengfei , Ying Changjiang , Sun Dong , Jia Zhanjun , Sun Ying
Published: October 2023

Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality but no specific therapy. Microsomal prostaglandin E synthase-2 (mPGES-2) is a PGE2 synthase but can metabolize PGH2 to malondialdehyde by forming a complex with heme. However, the role and mechanism of action of mPGES-2 in AKI remain unclear. To examine the role of mPGES-2, both global and tubule-specific mPGES-2-deficient mice were treated with cisplatin to induce AKI. mPGES-2 knockdown or overexpressing HK-2 cells were exposed to cisplatin to cause acute renal tubular cell injury. The mPGES-2 inhibitor SZ0232 was used to test the translational potential of targeting mPGES-2 in treating AKI. Additionally, mice were subjected to unilateral renal ischemia/reperfusion to further validate the effect of mPGES-2 on AKI. Interestingly, both genetic and pharmacological blockage of mPGES-2 led to decreased renal dysfunction and morphological damage induced by cisplatin and unilateral renal ischemia/reperfusion. Mechanistic exploration indicated that mPGES-2 deficiency inhibited ferroptosis via the heme-dependent regulation of the p53/SLC7A11/GPX4 axis. The present study indicates that mPGES-2 blockage may be a promising therapeutic strategy for AKI.
Continually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers
Authors: Merkenschlager Julia , Berz Riza-Maria , Ramos Victor , Uhlig Maximilian , MacLean Andrew J. , Nowosad Carla R. , Oliveira Thiago Y. , Nussenzweig Michel C.
Published: October 2023

Follicular helper T cells (TFH) mediate B cell selection and clonal expansion in germinal centers (GCs), and follicular regulatory T cells (TFR) prevent the emergence of self-reactive B cells and help to extinguish the reaction. Here we show that GC reactions continually recruit T cells from both the naïve conventional and naive thymic regulatory T cell (Treg) repertoires. In the early GC, newly recruited T cells develop into TFH, whereas cells entering during the contraction phase develop into TFR cells that contribute to GC dissolution. The TFR fate decision is associated with decreased antigen availability and is modulated by slow antigen delivery or mRNA vaccination. Thus, invasion of ongoing GCs by newly developing TFH and TFR helps remodel the GC based on antigen availability.
Extracting medicinal chemistry intuition via preference machine learning
Authors: Choung Oh-Hyeon , Vianello Riccardo , Segler Marwin , Stiefl Nikolaus , Jiménez-Luna José
Published: October 2023

The lead optimization process in drug discovery campaigns is an arduous endeavour where the input of many medicinal chemists is weighed in order to reach a desired molecular property profile. Building the expertise to successfully drive such projects collaboratively is a very time-consuming process that typically spans many years within a chemist’s career. In this work we aim to replicate this process by applying artificial intelligence learning-to-rank techniques on feedback that was obtained from 35 chemists at Novartis over the course of several months. We exemplify the usefulness of the learned proxies in routine tasks such as compound prioritization, motif rationalization, and biased de novo drug design. Annotated response data is provided, and developed models and code made available through a permissive open-source license.
A genome-scale metabolic model of parasitic whipworm
Authors: Bay Ömer F. , Hayes Kelly S. , Schwartz Jean-Marc , Grencis Richard K. , Roberts Ian S.
Published: October 2023

Genome-scale metabolic models are widely used to enhance our understanding of metabolic features of organisms, host-pathogen interactions and to identify therapeutics for diseases. Here we present iTMU798, the genome-scale metabolic model of the mouse whipworm Trichuris muris. The model demonstrates the metabolic features of T. muris and allows the prediction of metabolic steps essential for its survival. Specifically, that Thioredoxin Reductase (TrxR) enzyme is essential, a prediction we validate in vitro with the drug auranofin. Furthermore, our observation that the T. muris genome lacks gsr-1 encoding Glutathione Reductase (GR) but has GR activity that can be inhibited by auranofin indicates a mechanism for the reduction of glutathione by the TrxR enzyme in T. muris. In addition, iTMU798 predicts seven essential amino acids that cannot be synthesised by T. muris, a prediction we validate for the amino acid tryptophan. Overall, iTMU798 is as a powerful tool to study not only the T. muris metabolism but also other Trichuris spp. in understanding host parasite interactions and the rationale design of new intervention strategies.
Robust 2D layered MXene matrix–boron carbide hybrid films for neutron radiation shielding
Authors: Han Ju-Hyoung , Seok Shi-Hyun , Jin Young Ho , Park Jaeeun , Lee Yunju , Yeo Haeng Un , Back Jong-Ho , Sim Yeoseon , Chae Yujin , Wang Jaewon , Oh Geum-Yoon , Lee Wonjoo , Park Sung Hyun , Bang In-Cheol , Kim Ji Hyun , Kwon Soon-Yong
Published: October 2023

Large-scale fabrication of neutron-shielding films with flexible or complex shapes is challenging. Uniform and high boron carbide (B4C) filler loads with sufficient workability are needed to achieve good neutron-absorption capacity. Here, we show that a two-dimensional (2D) Ti3C2Tx MXene hybrid film with homogeneously distributed B4C particles exhibits high mechanical flexibility and anomalous neutron-shielding properties. Layered and solution-processable 2D Ti3C2Tx MXene flakes serve as an ideal robust and flexible matrix for high-content B4C fillers (60 wt.%). In addition, the preparation of a scalable neutron shielding MXene/B4C hybrid paint is demonstrated. This composite can be directly integrated with various large-scale surfaces (e.g., stainless steel, glass, and nylon). Because of their low thickness, simple and scalable preparation method, and an absorption capacity of 39.8% for neutrons emitted from a 241Am9Be source, the 2D Ti3C2Tx MXene hybrid films are promising candidates for use in wearable and lightweight applications.
Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease
Authors: Harada Takuya , Kikushige Yoshikane , Miyamoto Toshihiro , Uno Kazuko , Niiro Hiroaki , Kawakami Atsushi , Koga Tomohiro , Akashi Koichi , Yoshizaki Kazuyuki
Published: October 2023

Castleman disease (CD) is a rare lymphoproliferative disorder. Among subtypes of CD, idiopathic multicentric CD-not otherwise specified (iMCD-NOS) has a poor prognosis and its pathogenesis is largely unknown. Here we present a xenotransplantation model of iMCD-NOS pathogenesis. Immunodeficient mice, transplanted with lymph node (LN) cells from iMCD-NOS patients, develop iMCD-like lethal inflammation, while mice transplanted with LN cells from non-iMCD patients without inflammation serve as negative control. Grafts depleted of human CD3+ T cells fail to induce inflammation in vivo. Upon engraftment, peripheral helper T (Tph) cells expand and levels of human CXCL13 substantially increase in the sera of mice. A neutralizing antibody against human CXCL13 blocks development of inflammation and improves survival in the recipient mice. Our study thus indicates that Tph cells, producing CXCL13 play a critical role in the pathogenesis of iMCD-NOS, and establishes iMCD-NOS as an immunoregulatory disorder.
Organic photodiodes with bias-switchable photomultiplication and photovoltaic modes
Authors: Liu Qingxia , Li Lingfeng , Wu Jiaao , Wang Yang , Yuan Liu , Jiang Zhi , Xiao Jianhua , Gu Deen , Li Weizhi , Tai Huiling , Jiang Yadong
Published: October 2023

The limited sensitivity of photovoltaic-type photodiodes makes it indispensable to use pre-amplifier circuits for effectively extracting electrical signals, especially when detecting dim light. Additionally, the photomultiplication photodiodes with light amplification function suffer from potential damages caused by high power consumption under strong light. In this work, by adopting the synergy strategy of thermal-induced interfacial structural traps and blocking layers, we develop a dual-mode visible-near infrared organic photodiode with bias-switchable photomultiplication and photovoltaic operating modes, exhibiting high specific detectivity (~1012Jones) and fast response speed (0.05/3.03 ms for photomultiplication-mode; 8.64/11.14 μs for photovoltaic-mode). The device also delivers disparate external quantum efficiency in two optional operating modes, showing potential in simultaneously detecting dim and strong light ranging from ~10−9to 10−1 W cm−2. The general strategy and working mechanism are validated in different organic layers. This work offers an attractive option to develop bias-switchable multi-mode organic photodetectors for various application scenarios.
White matter changes in Parkinson’s disease
Authors: Yang Kai , Wu Zhengqi , Long Jie , Li Wenxin , Wang Xi , Hu Ning , Zhao Xinyue , Sun Taolei
Published: October 2023

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD). It is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the formation of Lewy bodies (LBs). Although PD is primarily considered a gray matter (GM) disease, alterations in white matter (WM) have gained increasing attention in PD research recently. Here we review evidence collected by magnetic resonance imaging (MRI) techniques which indicate WM abnormalities in PD, and discuss the correlations between WM changes and specific PD symptoms. Then we summarize transcriptome and genome studies showing the changes of oligodendrocyte (OLs)/myelin in PD. We conclude that WM abnormalities caused by the changes of myelin/OLs might be important for PD pathology, which could be potential targets for PD treatment.
Experimentally induced changes in authoritarian submission as a response to threat
Authors: Winter Taylor , Riordan Benjamin C. , Scarf Damian , Jose Paul E.
Published: October 2023

Authoritarianism is best conceptualised by three attitudinal clusters: Aggression, Submission, and Conventionalism. Once considered a fixed characteristic, recent observational research has demonstrated how the dimension of submission can fluctuate in response to COVID-19 threat as a means of maintaining collective security. However, this effect has not been investigated with other forms of threat, nor has it been supported experimentally. In the present study, we sought to test observational findings by priming 300 participants with either a COVID-19 threat, a domestic terrorism threat, or a non-threatening control. Levels of authoritarianism were tested before and after presentation of a prime and then the difference between the two measures could be compared between prime conditions. Results from a Bayesian multivariate regression analysis informed by observational findings suggested that participants who experienced the COVID-19 or terrorism primes reported higher levels of authoritarian submission after the prime compared to before the prime, relative to those who experienced the neutral control prime. In contrast, the aggression subfactor did not seem to elicit any change in response to threat, and the conventionalism subfactor showed a response only to the terrorism prime. We concluded that two different forms of societal threat could elicit changes in specific dimensions of authoritarianism over a very short time span. We caution against the common practice of treating authoritarianism as a unidimensional construct without careful consideration.
Morphological, physio-biochemical, and molecular indications of heat stress tolerance in cucumber
Authors: El-Remaly Eman
Published: October 2023

Global warming is a critical challenge limiting crop productivity. Heat stress during cucumber growing stages caused deterioration impacts on the flowering, fruit, and yield stages. In this study, “inbred line 1 and hybrid P1 × P2” (heat-tolerant) and “Barracuda” (heat-sensitive) were utilized to determine the heat tolerance in summer season. The heat injury index was used to exhibit the heat tolerance performance. The heat injury index for heat tolerant (HT) genotypes, on leaves (HIIL%) and female flowers (HIIF%), was less than 25 and 15 % in HT, compared to heat sensitive (HS) was more than 75 and 85%, respectively. Moreover, the content of leaf chlorophyll, proline, brassinosteroid (BRs), abscisic acid content (ABA), the activity of catalase (CAT, EC 1.11. 1.6), peroxidase (POD, EC 1.11.1.7) and superoxide dismutase (SOD, EC 1.15.1.1) increased with the heat stress responses in HT plants. Expression pattern analyses of eight genes, related to POD (CSGY4G005180 and CSGY6G015230), SOD (CSGY4G010750 and CSGY1G026400), CAT (CsGy4G025230 and CsGy4G025240), and BR (CsGy6G029150 and CsGy6G004930) showed a significant increase in HT higher than in HS plants. This study furnishes valuable markers for heat tolerance genotypes breeding in cucumber and provides a basis for understanding heat-tolerance mechanisms.
Plumage color degradation indicates reproductive effort: an experiment
Authors: Hegyi Gergely , Laczi Miklós , Szabó Gyula , Sarkadi Fanni , Török János
Published: October 2023

Plumage color has traditionally been regarded as a static ornamental trait, but evidence is accumulating for significant color changes without molt that typically reduce the conspicuousness of ornamentation. In some species, the social partner seems to increase its reproductive investment if the color trait is experimentally enhanced, suggesting that color change could act as a signal. However, the information content of this signal is so far unclear. For example, birds in poor condition or making greater effort may deteriorate more severely. We used brood size manipulations to alter the reproductive effort of male and female collared flycatchers Ficedula albicollis. Both sexes showed less severe decline in some reflectance attribute of their white breast when their brood was experimentally reduced. In each sex, greater deterioration of the reflectance trait affected by the manipulation was accompanied by increased feeding rate by the partner. These feeding patterns do not prove, but are consistent with, a compensatory response by the partner to induced degradation. The manipulation effects on color change we detected confirm for the first time that plumage color deterioration can indicate current reproductive effort, thereby providing a potential fitness advantage to social partners that react to such deterioration.
Correlation challenges for North Sea offshore wind power: a Norwegian case study
Authors: Hjelmeland Martin , Nøland Jonas Kristiansen
Published: October 2023

Offshore wind power projects are currently booming around the North Sea. However, there are inherent correlation challenges between wind farms in this area, which has implications for the optimal composition of locations and the scale-up of installed capacities. This paper is aimed at addressing the correlation problem by minimizing the variance of total wind power accumulated around the North Sea. We show that this nonlinear convex optimization problem can be solved by applying the Augmented Lagrangian Algorithm (ALA). The premise of the study is that more interconnections between the EU countries will be prioritized in order to optimize and smooth out the wind power production patterns. A publicly available dataset with historical hour-by-hour data spanning over 20 years was used for the analysis. We explore two distinct scenarios for Norwegian offshore wind development. In the first scenario, we consider the ongoing activities on the European continental side of the North Sea and their implications for Norway. Here, we illustrate the advantages of focusing on expanding wind power capacity in the northern regions of Norway to enhance the overall value of the generated wind power. In contrast, the second reference scenario neglects these interconnections, resulting in a significantly greater concentration of offshore wind development in the southern parts of Norway, particularly in Sørlige Nordsjø II. Additionally, our work estimates the wind power correlation coefficient in the North Sea as a function of distance. Furthermore, we analyze deviations and intermittencies in North Sea wind power over various time intervals, emphasizing that the perceived integration challenges are highly dependent on the chosen time resolution in the analysis.
Comparative RNA-seq analysis of resistant and susceptible banana genotypes reveals molecular mechanisms in response to banana bunchy top virus (BBTV) infection
Authors: Lantican Darlon V. , Nocum Jen Daine L. , Manohar Anand Noel C. , Mendoza Jay-Vee S. , Gardoce Roanne R. , Lachica Grace C. , Gueco Lavernee S. , Dela Cueva Fe M.
Published: October 2023

Bananas hold significant economic importance as an agricultural commodity, serving as a primary livelihood source, a favorite fruit, and a staple crop in various regions across the world. However, Banana bunchy top disease (BBTD), which is caused by banana bunchy top virus (BBTV), poses a considerable threat to banana cultivation. To understand the resistance mechanism and the interplay of host suitability factors in the presence of BBTV, we conducted RNA-seq-based comparative transcriptomics analysis on mock-inoculated and BBTV-inoculated samples from resistant (wild Musa balbisiana) and susceptible (Musa acuminata ‘Lakatan’) genotypes. We observed common patterns of expression for 62 differentially expressed genes (DEGs) in both genotypes, which represent the typical defense response of bananas to BBTV. Furthermore, we identified 99 DEGs exclusive to the 'Lakatan' banana cultivar, offering insights into the host factors and susceptibility mechanisms that facilitate successful BBTV infection. In parallel, we identified 151 DEGs unique to the wild M. balbisiana, shedding light on the multifaceted mechanisms of BBTV resistance, involving processes such as secondary metabolite biosynthesis, cell wall modification, and pathogen perception. Notably, our validation efforts via RT-qPCR confirmed the up-regulation of the glucuronoxylan 4-O-methyltransferase gene (14.28 fold-change increase), implicated in xylan modification and degradation. Furthermore, our experiments highlighted the potential recruitment of host's substrate adaptor ADO (30.31 fold-change increase) by BBTV, which may play a role in enhancing banana susceptibility to the viral pathogen. The DEGs identified in this work can be used as basis in designing associated gene markers for the precise integration of resistance genes in marker-assisted breeding programs. Furthermore, the findings can be applied to develop genome-edited banana cultivars targeting the resistance and susceptibility genes, thus developing novel cultivars that are resilient to important diseases.
Physiological mechanism of action and partial separation of herbicide–active compounds from the Diaporthe sp. extract on Amaranthus tricolor L.
Authors: Manichart Nutcha , Laosinwattana Chamroon , Somala Naphat , Teerarak Montinee , Chotsaeng Nawasit
Published: October 2023

Thirteen fungi that produce compounds with herbicidal activities were isolated, identified, and extracted under the assumption that the mechanism of action occurs during seed exposure to the extract. The extracts from all the fungal strains considerably decreased the growth parameters of Amaranthus tricolor L. The EC010 strain extracts showed the greatest effect. Through ITS region gene sequencing methods, the isolated EC010 was identified as a genus of Diaporthe. The results showed a significant (p < 0.05) inhibitory effect of 91.25% on germination and a decrease in shoot and root length by 91.28% and 95.30%, respectively. The mycelium of Diaporthe sp. was extracted using sequential extraction techniques for the partial separation of the herbicidal fraction. According to the bioassay activities, the EtOAc fraction showed the highest inhibitory activity. The osmotic stress of the A. tricolor seeds was studied. Although the extract increased the accumulation of proline and soluble protein, the treated seeds showed lower imbibition. While the activity of α-amylase was dramatically decreased after treatment. A cytogenetic assay in the treated Allium cepa L. root revealed a decrease in the mitotic index, an altered mitotic phase index, and a promotion of mitotic abnormalities. Accordingly, the Diaporthe sp. may serve as a potential herbicidal compound resource.
A novel tumor immunotherapy-related signature for risk stratification, prognosis prediction, and immune status in hepatocellular carcinoma
Authors: Sun Jianping , Xi Lefeng , Zhang Dechen , Gao Feipei , Wang Liqin , Yang Guangying
Published: October 2023

Immunotherapy as a strategy to deal with cancer is increasingly being used clinically, especially in hepatocellular carcinoma (HCC). We aim to create an immunotherapy-related signature that can play a role in predicting HCC patients’ survival and therapeutic outcomes. Immunotherapy-related genes were discovered first. Clinical information and gene expression data were extracted from GSE140901. By a series of bioinformatics methods to analyze, overlapping genes were used to build an immunotherapy-related signature that could contribute to predict both the prognosis of people with hepatocellular carcinoma and responder to immune checkpoint blockade therapy of them in TCGA database. Differences of the two groups in immune cell subpopulations were then compared. Furthermore, A nomogram was constructed, based on the immunotherapy-related signature and clinicopathological features, and proved to be highly predictive. Finally, immunohistochemistry assays were performed in HCC tissue and normal tissue adjacent tumors to verify the differences of the four genes expression. As a result of this study, a prognostic protein profile associated with immunotherapy had been created, which could be applied to predict patients' response to immunotherapy and may provide a new perspective as clinicians focus on non-apoptotic treatment for patients with HCC.
The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients
Authors: Åkerlund Emma , Gudoityte Greta , Moussaud-Lamodière Elisabeth , Lind Olina , Bwanika Henri Colyn , Lehti Kaisa , Salehi Sahar , Carlson Joseph , Wallin Emelie , Fernebro Josefin , Östling Päivi , Kallioniemi Olli , Joneborg Ulrika , Seashore-Ludlow Brinton
Published: October 2023

Most patients with advanced ovarian cancer (OC) relapse and progress despite systemic therapy, pointing to the need for improved and tailored therapy options. Functional precision medicine can help to identify effective therapies for individual patients in a clinically relevant timeframe. Here, we present a scalable functional precision medicine platform: DET3Ct (Drug Efficacy Testing in 3D Cultures), where the response of patient cells to drugs and drug combinations are quantified with live-cell imaging. We demonstrate the delivery of individual drug sensitivity profiles in 20 samples from 16 patients with ovarian cancer in both 2D and 3D culture formats, achieving over 90% success rate in providing results six days after operation. In this cohort all patients received carboplatin. The carboplatin sensitivity scores were significantly different for patients with a progression free interval (PFI) less than or equal to 12 months and those with more than 12 months (p < 0.05). We find that the 3D culture format better retains proliferation and characteristics of the in vivo setting. Using the DET3Ct platform we evaluate 27 tailored combinations with results available 10 days after operation. Notably, carboplatin and A-1331852 (Bcl-xL inhibitor) showed an additive effect in four of eight OC samples tested, while afatinib and A-1331852 led to synergy in five of seven OC models. In conclusion, our 3D DET3Ct platform can rapidly define potential, clinically relevant data on efficacy of existing drugs in OC for precision medicine purposes, as well as provide insights on emerging drugs and drug combinations that warrant testing in clinical trials.