bluuebunny/crossref_metadata_2025 huggingface dataset:
5α-Epoxyalantolactone from Inula macrophylla attenuates cognitive deficits in scopolamine-induced Alzheimer’s disease mice model
Authors: Ma Rui , Feng Xu-Yao , Tang Jiang-Jiang , Ha Wei , Shi Yan-Ping
Published: July 2024

Alzheimer’s disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla, has various pharmacological effects. This work supposed to investigate the improved impact of 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC50 of 6.2 μM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5α-EAL to penetrate the blood–brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile.

Graphical Abstract
Management Of The Pediatric Difficult Airway: New Strategies Unveiled
Authors: Khan Sabina Ali , Matuszczak Maria
Published: July 2024

Purpose of Review

This article outlines recent advancements in pediatric difficult airway management, driven by collaborative research and technology. It highlights challenges in newborns and infants, emphasizing initiatives like the Pediatric Difficult Intubation Registry (PeDI-R) and large-scale observational studies like APRICOT and NECTARINE. These endeavors aim to refine management strategies, enhancing approaches to both anticipated and unforeseen difficult pediatric airways.

Recent Findings

Studies have elucidated various facets of pediatric airway management, including difficult intubation incidence, contributing factors and efficacy of diverse techniques and devices. Noteworthy advancements include videolaryngoscopy, hybrid techniques, passive oxygenation, sedation, and muscle relaxation with a focus on reducing intubation attempts. Additionally, ultrasound’s utility and the significance of extubation planning are highlighted.

To summarize, continued research and collaboration refine strategies for difficult pediatric airway management, striving to enhance patient outcomes and safety through dissemination of knowledge and leveraging recent insights.
A novel fuzzy finite-horizon economic lot and delivery scheduling model with sequence-dependent setups
Authors: Sangari Esmat , Jolai Fariborz , Sangari Mohamad Sadegh
Published: July 2024

This paper addresses the economic lot and delivery scheduling problem (ELDSP) within three-echelon supply chains, focusing on the complexities of demand uncertainty, limited shelf-life of products, and sequence-dependency of setups. We develop a novel mixed-integer non-linear programming (MINLP) model for a supply chain comprising one supplier, multiple manufacturers with flexible flow shop (FFS) production systems, and multiple retailers, all operating over a finite planning horizon. The common cycle (CC) strategy is adopted as the synchronization policy. Our model employs fuzzy set theory, particularly the “Me measure,” to effectively handle the retailers’ demand uncertainty. Our findings indicate that total supply chain costs escalate with an increase in demand, final components’ holding costs, and sequence-dependent setup costs, but decrease with increasing production rates. Furthermore, while total costs are significantly sensitive to changes in demand, they are relatively insensitive to fluctuations in sequence-dependent setup times. The models developed offer valuable managerial insights for optimizing costs in synchronized multi-stage supply chains, aiding managers in making informed decisions about production lot sizes and delivery schedules under both deterministic and fuzzy demand scenarios. Additionally, the proposed models bridge key research gaps and provide robust decision-making tools for cost optimization, enhancing supply chain synchronization in practical settings.
Fatigue response of AlSi10Mg by laser powder bed fusion: influence of build orientation, heat, and surface treatments
Authors: Fini S. , Croccolo D. , De Agostinis M. , Olmi G. , Paiardini L. , Scapecchi C. , Mele M.
Published: July 2024

The aim of this study is to analyze how the fatigue behavior of AlSi10Mg by laser powder bed fusion is affected by build orientation, heat, and surface treatments. A three-by-three factorial plan has been arranged for this purpose. Particularly, regarding the heat treatment, three levels were considered (as built, age hardening, and stress relief); whereas, for the surface treatment, three levels were investigated (micro-shot-peening, micro-shot-peening plus fine blasting, and machining and lapping following laser powder bed fusion). Regarding the build orientation, the specimens were manufactured using three different build orientations (0°, 45°, and 90°). The obtained data have been statistically analyzed by a three-factor ANOVA-based method. The results, supported by fractographic and micrographic microscopy analyses, indicate that the age-hardening treatment yields the maximum benefits, whereas stress relief may even have a detrimental effect. As for surface treatments, a positive influence of shot-peening has been found.
Falsch informiert?! Die (Fehl‑)Einschätzungen der Bevölkerung über die Wirkungen eines Tempolimits auf deutschen Autobahnen
Authors: Maltritz Dominik
Published: July 2024

Basierend auf einer repräsentativen Befragung untersuchen wir die Informiertheit der Bevölkerung über die Wirkungen einer allgemeinen Geschwindigkeitsbeschränkung auf deutschen Autobahnen hinsichtlich der möglichen Reduktion des CO2-Ausstoßes im Verkehrssektor einerseits und der Vermeidung von Opfern tödlicher Verkehrsunfälle andererseits. Im Rahmen einer ökonomischen Analyse der Wirkungen eines Tempolimits müssen neben positiven Wirkungen auch dessen negativen Konsequenzen betrachtet werden. Wir stellen daher im ersten Teil des Papiers die Ergebnisse der wissenschaftlichen Literatur hinsichtlich der wichtigsten positiven und negativen Konsequenzen überblicksartig dar.

Die Ergebnisse der Befragung zeigen, dass die Bevölkerung sehr schlecht über die Wirkungen eines Tempolimits informiert ist. Deutlich weniger als die Hälfte der Befragten fühlt sich überhaupt in der Lage, eine Antwort zu geben. Die Teilnehmer der Befragung, die eine Antwort geben, überschätzen die tatsächlichen positiven Wirkungen, wie sie nach der wissenschaftlichen Literatur zu erwarten sind, im Mittel um ein Vielfaches. Hierbei sind die Einschätzungen der Wirksamkeit, und damit auch die Fehleinschätzungen, unter den Befürwortern deutlich höher als unter den Gegnern, bei denen ein Großteil Antworten in der richtigen Größenordnung gibt.

Die Einschätzung der Wirksamkeit hat dabei einen deutlich ausgeprägten Zusammenhang zur Befürwortung bzw. Ablehnung eines Tempolimits. Geht man von einem kausalen Einfluss der Einschätzung der Wirksamkeit auf die Präferenzen aus, deuten unsere Ergebnisse darauf hin, dass die Bevölkerung ein Tempolimit mehrheitlich ablehnen würde, wenn die Menschen die positiven Wirkungen ungefähr entsprechend den Ergebnissen der wissenschaftlichen Literatur einschätzen würden.
Network embedding based on DepDist contraction
Authors: Dopater Emanuel , Ochodkova Eliska , Kudelka Milos
Published: July 2024

Networks provide an understandable and, in the case of small size, visualizable representation of data, which allows us to obtain essential information about the relationships between pairs of nodes, e.g., their distances. In visualization, networks have an alternative two-dimensional vector representation to which various machine-learning methods can be applied. More generally, networks can be transformed into a low-dimensional space using so-called embedding methods, which bridge the gap between network analysis and traditional machine learning by creating numerical representations that capture the essence of the network structure. In this article, we present a new embedding method that uses non-symmetric dependency to find the distance between nodes and applies an iterative procedure to find a satisfactory distribution of nodes in space. For dimension 2 and the visualization of the result, we demonstrate the method’s effectiveness on small networks. For higher dimensions and several larger networks, we present the results of two experiments comparing our results with two well-established methods in the research community, namely node2vec and DeepWalk. The first experiment focuses on a qualitative comparison of the methods, while the second focuses on applying and comparing the classification results to embeddings in a higher dimension. Although the presented method does not outperform the two chosen methods, its results are still comparable. Therefore, we also explain the limitations of our method and a possible way to overcome them.
Soft Margin Spectral Normalization for GANs
Authors: Rogachev Alexander , Ratnikov Fedor
Published: July 2024

In this paper, we explore the use of Generative Adversarial Networks (GANs) to speed up the simulation process while ensuring that the generated results are consistent in terms of physics metrics. Our main focus is the application of spectral normalization for GANs to generate electromagnetic calorimeter (ECAL) response data, which is a crucial component of the LHCb. We propose an approach that allows to balance between model’s capacity and stability during training procedure, compare it with previously published ones and study the relationship between proposed method’s hyperparameters and quality of generated objects. We show that the tuning of normalization method’s hyperparameters boosts the quality of generative model.
An Anger-based Approach-Avoidance Modification Training Targeting Dysfunctional Beliefs in Adults with Elevated Stress – Results from a Randomized Controlled Pilot Study
Authors: Keinert Marie , Schindler-Gmelch Lena , Eskofier Bjoern M. , Berking Matthias
Published: July 2024

We examined the feasibility, acceptability, and clinical potential of a smartphone-based Approach-Avoidance Modification Training (AAMT) that required users to deliberately display anger and positive emotions (AAMT-AP) to move (dys-)functional stress-related beliefs away from and towards themselves, respectively. The per protocol sample consisted of N = 30 participants randomized to an AAMT-AP condition, a swipe control condition, or an inactive control condition. Feasibility and acceptability of the intervention and study design were assessed directly and changes in clinical outcomes (perceived stress (primary outcome), dysfunctional beliefs, symptoms of depression, and emotion regulation skills) one week after intervention completion. The results indicated that AAMT-AP was feasible and acceptable to participants. Moreover, notable effect sizes for clinical outcomes in comparison with both control conditions provided preliminary evidence for its therapeutic potential. Future research should evaluate the efficacy of AAMT-AP in sufficiently powered randomized controlled trials.
A survey of multi-population optimization algorithms for tracking the moving optimum in dynamic environments
Authors: Yazdani Delaram , Yazdani Danial , Blanco-Davis Eduardo , Nguyen Trung Thanh
Published: July 2024

The solution spaces of many real-world optimization problems change over time. Such problems are called dynamic optimization problems (DOPs), which pose unique challenges that necessitate adaptive strategies from optimization algorithms to maintain optimal performance and responsiveness to environmental changes. Tracking the moving optimum (TMO) is an important class of DOPs where the goal is to identify and deploy the best-found solution in each environments Multi-population dynamic optimization algorithms are particularly effective at solving TMOs due to their flexible structures and potential for adaptability. These algorithms are usually complex methods that are built by assembling multiple components, each of which is responsible for addressing a specific challenge or improving the tracking performance in response to changes. This survey provides an in-depth review of multi-population dynamic optimization algorithms, focusing on describing these algorithms as a set of multiple cooperating components, the synergy between these components, and their collective effectiveness and/or efficiency in addressing the challenges of TMOs. Additionally, this survey reviews benchmarking practices within this domain and outlines promising directions for future research.
Schreibflüssigkeit fördern in der Grundschule – Wirksamkeit eines Trainingsprogramms
Authors: Stephany Sabine , Griepentrog Anne , Koch Alina Marlene , Becker-Mrotzek Michael
Published: July 2024

Texte schreiben zu können gehört zu den Schlüsselkompetenzen in unserer Gesellschaft. Eine wesentliche Voraussetzung für eine entwickelte Schreibfähigkeit ist das mühelose Beherrschen der basalen Schreibfertigkeiten, insbesondere der Schreibflüssigkeit. Flüssiges Schreiben wird jedoch nicht von allen Schülerinnen und Schülern in der Grundschule in ausreichendem Maße beherrscht. Schreibflüssigkeit setzt sich aus zwei Teilprozessen zusammen: dem automatisierten Verschriften von Buchstaben, Wörtern und grammatikalisch korrekten Sätzen und dem zügigen Formulieren kohärenter sprachlicher Einheiten. Sind diese Fertigkeiten noch nicht automatisiert, stehen nicht genügend kognitive Ressourcen für hierarchiehohe Schreibprozesse zur Verfügung, wie das Planen des Textes. Unflüssiges Schreiben wirkt sich daher negativ auf die Textqualität aus. Trotz ihrer Relevanz steht die Schreibflüssigkeit bisher kaum im Fokus von schreibdidaktischer Forschung und Unterrichtspraxis. Es gibt kaum empirisch erprobte Förderkonzepte. Daher wurde ein Schreibflüssigkeitstraining entwickelt, das aus 18 Einheiten à 15 min bestand und in einem Prä-Post-Kontrollgruppendesign mit 469 Grundschülerinnen und Grundschülern durchgeführt wurde. Die Transkriptionsflüssigkeit wurde auf Buchstaben‑, Wort- und Satzebene gemessen. Die Formulierungsflüssigkeit wurde mit digitalen Smart-Pens in Form von Bursts erhoben. Zusätzlich wurde die Schreibkompetenz erfasst. Die Ergebnisse zeigen positive Effekte für die Transkriptionsflüssigkeit und die Schreibkompetenz. Der Beitrag gibt einen Einblick in das Training und berichtet die Effekte auf die Schreibflüssigkeit und die Schreibkompetenz. Darüber hinaus werden die Ergebnisse für verschiedene Untergruppen diskutiert.
Quantum state reconstruction in a noisy environment via deep learning
Authors: Morgillo Angela Rosy , Mangini Stefano , Piastra Marco , Macchiavello Chiara
Published: July 2024

Quantum noise is currently limiting efficient quantum information processing and computation, impacting on the fidelity and reliability of quantum states. In this work, we consider the tasks of reconstructing and classifying quantum states corrupted by the action of an unknown noisy channel using classical feed-forward neural networks. By framing reconstruction as a regression problem, we show how such an approach can be used to recover with fidelities exceeding 99% the noiseless density matrices of quantum states of up to three qubits undergoing noisy evolution, and we test its performance with both single-qubit (bit-flip, phase-flip, depolarizing, and amplitude damping) and two-qubit quantum channels (correlated amplitude damping). Furthermore, a critical aspect of our investigation involves also a comprehensive comparison between mean squared error and infidelity as loss functions. Our findings reveal that these two metrics yield comparable results in the context of state reconstruction. Moreover, we also consider the task of distinguishing between different quantum noisy channels, and show how a neural network-based classifier is able to solve such a classification problem with perfect accuracy.
Material Characterisation of Deflated Structured Fabrics
Authors: Rustighi E. , Gardonio P. , Baldini S. , Malacarne C. , Perini M.
Published: July 2024

Structured fabrics are made by interwoven rigid elements that form flexible garments such as chain mail armours. Traditionally, the mechanical properties of these materials were considered fixed. However, recent research has revealed their mechanical properties may be varied. Notably, studies have demonstrated that applying vacuum pressure between layers of 3D-printed chain mails enclosed in a bag induces particle and layer jamming of the elements, thereby affecting the material’s bending modulus. This arises from both compressive frictional forces and the complex geometrical interlocking of the rigid elements. This paper presents a comprehensive set of experimental tests for the characterisation of the stiffness and damping properties with respect to the type and number of fabrics and with respect to the vacuum pressure. More specifically, the study examines experimentally the changes in static properties in response to vacuum pressure changes evaluated on a four- and six-point bending setups. The outcome of this measurement campaign is then reported into the Ashby diagrams to compare the mechanical properties of the in-vacuum structured fabrics with those of classical materials. The potential applications of this research include the development of lightweight adaptive and semi-active vibration mitigation devices.
Early Season Wheat Response to Electrochemically Precipitated Struvite in Various Soils in the Greenhouse
Authors: Simms Tatum , Brye Kristofor R. , Roberts Trenton L. , Greenlee Lauren F.
Published: July 2024

Fertilizer-phosphorus (P) materials can be recovered from wastewater and used to supplement mined phosphate rock, where one such material is struvite [MgNH4PO4·6(H2O)]. This study aimed to compare electrochemically precipitated struvite (ECST) reclaimed from synthetic wastewater to other commercial fertilizer-P sources in cultivated soils from Arkansas [silty clay loam (AR-SiCL) and silt loam (AR-SiL)], Missouri [(silt loam; MO-SiL 1 and 2)], and Nebraska [silt loam (NE-SiL) and sandy loam (NE-SL)]. A greenhouse pot study was conducted for 60 days with unvernalized wheat (Triticum aestivum) using five fertilizer-P sources [ECST, chemically precipitated struvite (CPST), monoammonium phosphate (MAP), triple superphosphate (TSP), and an unamended control (UC)] to evaluate treatment effects on below (BG)- and aboveground (ABG) and total dry matter (DM) and tissue-N, -P, -K, -Ca, -Mg, and -Fe uptakes. The ECST treatment produced 44 g m−2 larger ABG-DM than CPST in the AR-SiCL, but 181 g m−2 larger than the UC in the MO-SiL 1. The ECST had similar or larger nutrient uptakes than CPST, MAP, TSP, and UC. Belowground-P, -N, and -Mg uptakes for ECST were generally similar for all soil-fertilizer-P source combinations, where ECST was 0.3 to 2.6 g m−2 larger than all other fertilizer-P sources. Plant property response from ECST was generally similar to or greater than CPST, MAP, TSP, and the UC across all soils. Results suggest that ECST is a prime candidate to be used as an effective, alternative fertilizer-P source, suitable for use in wheat production across multiple soil textures.
Algal-biochar and Chlorella vulgaris microalgae: a sustainable approach for textile wastewater treatment and biodiesel production
Authors: Rehman Rabia , Iqbal Javed , Ur Rehman Muhammad Saif , Hamid Shanawar , Wang Yuze , Rasool Kashif , Fazal Tahir
Published: July 2024

Microalgae technology is a viable solution for environmental conservation (carbon capture and wastewater treatment) and energy production. However, the nutrient cost, slow-kinetics, and low biosorption capacity of microalgae hindered its application. To overcome them, algal-biochar (BC) can be integrated with microalgae to treat textile wastewater (TWW) due to its low cost, its ability to rapidly adsorb pollutants, and its ability to serve as a nutrient source for microalgal-growth to capture CO2 and biodiesel production. Chlorella vulgaris (CV) and algal-BC were combined in this work to assess microalgal growth, carbon capture, TWW bioremediation, and biodiesel production. Results showed the highest optical density (3.70 ± 0.07 OD680), biomass productivity (42.31 ± 0.50 mg L−1 d−1), and dry weight biomass production (255.11 ± 6.01 mg L−1) in an integrated system of CV-BC-TWW by capturing atmospheric CO2 (77.57 ± 2.52 mg L−1 d−1). More than 99% bioremediation (removal of MB-pollutant, COD, nitrates, and phosphates) of TWW was achieved in CV-BC-TWW system due to biosorption and biodegradation processes. The addition of algal-BC and CV microalgae to TWW not only enhanced the algal growth but also increased the bioremediation of TWW and biodiesel content. The highest fatty acid methylesters (biodiesel) were also produced, up to 76.79 ± 2.01 mg g−1 from CV-BC-TWW cultivated-biomass. Biodiesel’s oxidative stability and low-temperature characteristics are enhanced by the presence of palmitoleic (C16:1) and linolenic (C18:3) acids. Hence, this study revealed that the integration of algal-biochar, as a biosorbent and source of nutrients, with living-microalgae offers an efficient, economical, and sustainable approach for microalgae growth, CO2 fixation, TWW treatment, and biodiesel production.

Graphical Abstract
Sustainability agency in unsustainable structures: rhetoric of a capable transformative individual
Authors: Salovaara Janne J. , Hagolani-Albov Sophia E.
Published: July 2024

While sustainability as a practice has been implemented in education for a long time, the conceptualisation of an impactful sustainability actor has not been as thoroughly formulated. The theory of structuration is relevant as a lens for critical reflection on the transformative potential of individuals educated in sustainability as a practice, who are often described as change-makers and mandated to enact sustainability. This paper examines sustainability agency using materials produced for a set of online sustainability courses. This text corpus is utilised as a representation of climate and sustainability education. The materials repeat systemic framings present in sustainability rhetoric, such as the contexts and targets in which sustainability transformation occurs. Additionally, through a qualitative content analysis of the textual corpus descriptions emerged as attributes of the agents to enact sustainability. This uncovers the juxtaposition between the often-repeated perception that sustainability must be achieved by capable agents and the capacities they possess. Further, our content analysis suggests a rhetorical process of othering within sustainability, for example by positioning “people”—the general population—as the cause of the sustainability crisis, and “us”—the educated—as the solution. Through our findings, the article concludes that when utilising the concept of sustainability agency—be it in theoretical, educational, or practical work—one ought to pay significant attention to the structures wherein the activities take place. The full comprehension of the transformative potential of individual agents ought to include an acknowledgement of the difference between educated capability and capacity—the latter of which necessitates dominance over the structural resources.
Fatal Errors with Fatalities Data: A Comment on Robertson's “An Instance of Effective Legal Regulation”
Authors: Cohen Roberta S. , Cohen Harvey S.
Published: July 2024

We noted with considerable interest Leon Robertson's article (1976), in a recent issue of this journal, dealing with statistical measures of the effectiveness of helmet and daytime headlight laws for motorcyclists. For some time, proponents and opponents of such legislation have been trading enthusiastic arguments and impassioned denials, often including misleading statistical presentations. The result has been that most followers of this debate are left with their personal views and little in the way of substantive support for either side. Robertson uses what appear to be promising data bearing on the safety controversy but, in our view, he does not perform the analyses required to clear the muddled waters and he seriously misinterprets the statistics he employs.
What Has Law to Offer Social Science?
Authors: Yegge Robert B.
Published: July 2024

In the last issue of this journal I asked, “What has social science to offer law?” When asking the converse (what has law to offer social science?), there is a repeated need for definition and translation: What social science? What law?
Reply to Max Gluckman
Authors: Abel Richard L.
Published: July 2024

I am writing in reaction to the article by Spaeth, Meltz, Rathjen and Haselswerdt, “Is Justice Blind: An Empirical Investigation of a Normative Ideal,” which appeared in vol. 7, no. 1. The authors attempt to support the Aristotelian myth that blind justice can systematically obtain. The premise in the myth is fallacious, and confirmation of the authors' research hypothesis in three of their five data sets cannot therefore be an adequate basis for concluding that justice is blind in the cases comprising the three sets.
Shallow Microtremor Array Survey Using Miniature and Small Arrays: Strategy for Efficient and Feasible Dense Survey
Authors: Cho I. , Nakazawa T.
Published: July 2024

We investigated the applicability of miniature microtremor arrays with a radius of a few meters or less to shallow surveys (up to a few tens of meters). It is shown that the upper limit wavelength normalized by the seismometer separation distance s that is analyzable by a miniature array does not depend on the observation instrument as long as the instrument has a self‐noise level that is sufficiently lower than the microtremor intensities; however, it generally depends on the average S‐wave velocity of the ground. This means that a miniature array is useful at soft‐soil sites but not hard‐soil sites. A statistical study in central Japan showed that the penetration depth by a miniature array with s = 1 m ranges from 6 to 12 m; specifically, the depth exceeds 12 m in one quarter of the cases but remains below 6 m in one quarter of the cases. This large variation is due to the variation in the average S‐wave velocity. A miniature array should thus be used in combination with a larger array with an s value of several meters to 20 m. In urbanized areas with high industrial activity, where the microtremor wavefield is likely isotropic, these arrays can be replaced by a linear array. In environments with extremely low signal‐to‐noise ratios, a less efficient zero‐crossing method should be applied to the larger array. An appropriate observation strategy should be selected for a given geoenvironment. Field examples show that our strategy enables efficient and feasible dense surveys.
Summer Hydrography Conditions at Proglacial Fjord Entrances Along East Greenland
Authors: Rysgaard S. , Mortensen J. , Haxen M. , Gillard L. C. , Risgaard‐Petersen N.
Published: July 2024

Climate change is causing widespread melting of land and sea ice in the Arctic, leading to an increase in freshwater input to the ocean. This may have an impact on ocean circulation, marine ecosystems, and biodiversity in the region. Our findings provide new insights into the summer hydrography conditions at proglacial fjord entrances along large parts of the east coast of Greenland. As most freshwater exits the Arctic Ocean through Fram Strait this study focuses on understanding the origin of spatial distribution of temperature and freshwater in the coastal waters in East Greenland. We find that Polar Water and the Atlantic Water variants (Eurasian Basin Atlantic Water/Subpolar Mode Water) dominate coastal waters north and south of Denmark Strait, respectively, and that coastal waters are influenced by advected meltwater from the Arctic Ocean, glacier meltwater and local precipitation. Combining hydrographic observations, water isotope data, and water source fraction analysis, we show that glacier meltwaters can be detected at fjord entrances and down to approximately 200 m. Integrated over the upper 200 m of the water column, glacial meltwater account for approximately 9%, precipitation for around 8% and Polar Water (including sea ice melt) for approximately 83% of the freshwater observed along the East Greenland coast. Below 200 m, Atlantic Water variants dominate the entire coastal section. The freshwater along East Greenland stays close to the coast and we could not detect any glacier meltwater at the slope.
Mechanisms of Suprapermafrost Groundwater Recharge Streamflow in Alpine Permafrost Regions: Insights From Young Water Fraction Analysis
Authors: Du Fa , Li Zongxing , Gui Juan , Zhang Baijuan , Xue Jian , Zhou Huiling
Published: July 2024

This study investigates the temporal processes of suprapermafrost groundwater (SPG)‐supplied streamflow in alpine permafrost regions, aiming to fill the gap in understanding this process from a water‐age perspective. Precipitation, streamflow, and SPG samples were collected from the Three‐Rivers Headwaters Region (TRHR). We defined the physical meaning of Fyw (the young water fraction) of the SPG and calculated it for the first time. The results showed that in the TRHR, the SPG mean travel time (MTT) was 159 days, and approximately 46.4% of SPG was younger than 77 days, whereas the streamflow MTT was 342 days, and approximately 12.2% of the streamflow was younger than 97 days. The correlation analysis revealed that various climatic factors played dominant roles in the recharge time variations of the SPG‐supplied streamflow within the TRHR. The SPG recharge rate did not significantly affect the streamflow Fyw; however, the thickness of the active layer ultimately controlled the SPG transit time distribution. Regression analysis further demonstrated the nonlinear impact of precipitation, average temperature, and average freezing days on SPG Fyw, which is closely related to seasonal freeze–thaw heat conduction and groundwater heat advection in the active layer. During the initial ablation period, the streamflow was primarily recharged by young SPG, resulting in a short‐tail travel time distribution. Our findings provide valuable insights into runoff generation and concentration processes in permafrost regions and have important implications for water resource management.
Neuroglia in cognitive reserve
Authors: Verkhratsky Alexei , Zorec Robert
Published: July 2024

The concept of cognitive reserve was born to account for the disjunction between the objective extent of brain damage in pathology and its clinical and intellectual outcome. The cognitive reserve comprises structural (brain reserve) and functional (brain maintenance, resilience, compensation) aspects of the nervous tissue reflecting exposome-driven life-long plasticity, which defines the ability of the brain to withstand aging and pathology. The mechanistic background of this concept was primarily focused on adaptive changes in neurones and neuronal networks. We present arguments favoring the more inclusive view, positing that neuroglia are fundamental for defining the cognitive reserve through homeostatic, neuroprotective, and neurodegenerative mechanisms. Neuroglia are critical for the life-long shaping of synaptically connected neuronal circuits as well as the brain connectome thus defining cognitive reserve. Neuroglial homeostatic and protective physiological responses define brain maintenance and resilience, while neuroglia regenerative capabilities are critical for brain compensation in pathology. Targeting neuroglia may represent an untrodden path for prolonging cognitive longevity.
Sex differences in the association between vitamin D and prediabetes in adults: A cross-sectional study
Authors: Ziyab Ali H. , Mohammad Anwar , Almousa Zainab , Mohammad Talal
Published: July 2024

Background/Objectives

Vitamin D status has been shown to be associated with prediabetes risk. However, epidemiologic evidence on whether sex modulates the association between vitamin D and prediabetes is limited. The present study investigated sex-specific associations between vitamin D and prediabetes.

Subjects/Methods

The Kuwait Wellbeing Study, a population-based cross-sectional study, enrolled nondiabetic adults. Prediabetes was defined as 5.7 ≤ HbA1c% ≤6.4; 25-hydroxyvitamin D (25(OH)D) was measured in venous blood and analyzed as a continuous, dichotomous (deficiency: <50 nmol/L vs. insufficiency/sufficiency ≥50 nmol/L), and categorical (tertiles) variable. Associations were evaluated by estimating adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), while stratifying by sex.

Results

A total of 384 participants (214 males and 170 females) were included in the current analysis, with a median age of 40.5 (interquartile range: 33.0–48.0) years. The prevalence of prediabetes was 35.2%, and 63.0% of participants had vitamin D deficiency. Assessments of statistical interaction between sex and 25(OH)D status were statistically significant (PSex × 25(OH)D Interaction < 0.05). In the sex-stratified analysis, after adjustment for confounding factors, decreased 25(OH)D levels were associated with increased prevalence of prediabetes in males (aPRDeficiency vs. In-/Sufficiency: 2.35, 95% CI: 1.36–4.07), but not in females (aPRDeficiency vs. In-/Sufficiency: 1.03, 95% CI: 0.60–1.77). Moreover, the prevalence of prediabetes differed between males and females at 25(OH)D levels of ≤35 nmol/L, with a higher prevalence of prediabetes in males compared to females. Such a sex-specific difference was not observed at 25(OH)D levels of >35 nmol/L.

Conclusions

Sex modified the association between vitamin D levels and prediabetes, with an inverse association observed among males, but not among females. Moreover, the observed sex-disparity in the prevalence of prediabetes was only pronounced at 25(OH)D levels of ≤35 nmol/L.
Development and optimization of expected cross value for mate selection problems
Authors: Ahadi Pouya , Balasundaram Balabhaskar , Borrero Juan S. , Chen Charles
Published: July 2024

In this study, we address the mate selection problem in the hybridization stage of a breeding pipeline, which constitutes the multi-objective breeding goal key to the performance of a variety development program. The solution framework we formulate seeks to ensure that individuals with the most desirable genomic characteristics are selected to cross in order to maximize the likelihood of the inheritance of desirable genetic materials to the progeny. Unlike approaches that use phenotypic values for parental selection and evaluate individuals separately, we use a criterion that relies on the genetic architecture of traits and evaluates combinations of genomic information of the pairs of individuals. We introduce the expected cross value (ECV) criterion that measures the expected number of desirable alleles for gametes produced by pairs of individuals sampled from a population of potential parents. We use the ECV criterion to develop an integer linear programming formulation for the parental selection problem. The formulation is capable of controlling the inbreeding level between selected mates. We evaluate the approach or two applications: (i) improving multiple target traits simultaneously, and (ii) finding a multi-parental solution to design crossing blocks. We evaluate the performance of the ECV criterion using a simulation study. Finally, we discuss how the ECV criterion and the proposed integer linear programming techniques can be applied to improve breeding efficiency while maintaining genetic diversity in a breeding program.
Ligand-enabled ruthenium-catalyzed meta-C−H alkylation of (hetero)aromatic carboxylic acids
Authors: Luo Xianglin , Hou Peichao , Shen Jiayi , Kuang Yifeng , Sun Fengchao , Jiang Huanfeng , Gooßen Lukas J. , Huang Liangbin
Published: July 2024

Carboxylates are ideal directing groups because they are widely available, readily cleavable and excellent linchpins for diverse follow-up reactions. However, their use in meta-selective C−H functionalizations remains a substantial unmet catalytic challenge. Herein, we report the ruthenium-catalyzed meta-C–H alkylation of aromatic carboxylic acids with various functionalized alkyl halides. A bidentate N-ligand increases the electron density at the metal center of ortho-benzoate ruthenacycles to the extent that single-electron reductions of alkyl halides can take place. The subsequent addition of alkyl radicals is exclusively directed to the position para to the CAr–Ru bond, i.e., meta to the carboxylate group. The resulting catalytic meta-C−H alkylation extends to a wide range of (hetero)aromatic carboxylic acids including benzofused five-membered ring heteroarenes but no pyridine derivatives in combination with secondary/tertiary alkyl halides, including fluorinated derivatives. It also allows site-selective C5−H alkylation of 1-naphthoic acids. The products are shown to be synthetic hubs en route to meta-alkylated aryl ketones, nitriles, amides, esters and other functionalized products.
RNA-guided RNA silencing by an Asgard archaeal Argonaute
Authors: Bastiaanssen Carolien , Bobadilla Ugarte Pilar , Kim Kijun , Finocchio Giada , Feng Yanlei , Anzelon Todd A. , Köstlbacher Stephan , Tamarit Daniel , Ettema Thijs J. G. , Jinek Martin , MacRae Ian J. , Joo Chirlmin , Swarts Daan C. , Wu Fabai
Published: July 2024

Argonaute proteins are the central effectors of RNA-guided RNA silencing pathways in eukaryotes, playing crucial roles in gene repression and defense against viruses and transposons. Eukaryotic Argonautes are subdivided into two clades: AGOs generally facilitate miRNA- or siRNA-mediated silencing, while PIWIs generally facilitate piRNA-mediated silencing. It is currently unclear when and how Argonaute-based RNA silencing mechanisms arose and diverged during the emergence and early evolution of eukaryotes. Here, we show that in Asgard archaea, the closest prokaryotic relatives of eukaryotes, an evolutionary expansion of Argonaute proteins took place. In particular, a deep-branching PIWI protein (HrAgo1) encoded by the genome of the Lokiarchaeon ‘Candidatus Harpocratesius repetitus’ shares a common origin with eukaryotic PIWI proteins. Contrasting known prokaryotic Argonautes that use single-stranded DNA as guides and/or targets, HrAgo1 mediates RNA-guided RNA cleavage, and facilitates gene silencing when expressed in human cells and supplied with miRNA precursors. A cryo-EM structure of HrAgo1, combined with quantitative single-molecule experiments, reveals that the protein displays structural features and target-binding modes that are a mix of those of eukaryotic AGO and PIWI proteins. Thus, this deep-branching archaeal PIWI may have retained an ancestral molecular architecture that preceded the functional and mechanistic divergence of eukaryotic AGOs and PIWIs.
Light-driven C–H activation mediated by 2D transition metal dichalcogenides
Authors: Li Jingang , Zhang Di , Guo Zhongyuan , Chen Zhihan , Jiang Xi , Larson Jonathan M. , Zhu Haoyue , Zhang Tianyi , Gu Yuqian , Blankenship Brian W. , Chen Min , Wu Zilong , Huang Suichu , Kostecki Robert , Minor Andrew M. , Grigoropoulos Costas P. , Akinwande Deji , Terrones Mauricio , Redwing Joan M. , Li Hao , Zheng Yuebing
Published: July 2024

C–H bond activation enables the facile synthesis of new chemicals. While C–H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C–H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C–C coupling mediated by 2D TMDCs to promote C–H activation and carbon dots synthesis. Our results shed light on 2D materials for C–H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.
Baseline levels and longitudinal changes in plasma Aβ42/40 among Black and white individuals
Authors: Xiong Chengjie , Luo Jingqin , Wolk David A. , Shaw Leslie M. , Roberson Erik D. , Murchison Charles F. , Henson Rachel L. , Benzinger Tammie L. S. , Bui Quoc , Agboola Folasade , Grant Elizabeth , Gremminger Emily N. , Moulder Krista L. , Geldmacher David S. , Clay Olivio J. , Babulal Ganesh , Cruchaga Carlos , Holtzman David M. , Bateman Randall J. , Morris John C. , Schindler Suzanne E.
Published: July 2024

Blood-based biomarkers of Alzheimer disease (AD) may facilitate testing of historically under-represented groups. The Study of Race to Understand Alzheimer Biomarkers (SORTOUT-AB) is a multi-center longitudinal study to compare AD biomarkers in participants who identify their race as either Black or white. Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics’ PrecivityAD test for Aβ42 and Aβ40. Compared to white individuals, Black individuals had higher average plasma Aβ42/40 levels at baseline, consistent with a lower average level of amyloid pathology. Interestingly, this difference resulted from lower average levels of plasma Aβ40 in Black participants. Despite the differences, Black and white individuals had similar longitudinal rates of change in Aβ42/40, consistent with a similar rate of amyloid accumulation. Our results agree with multiple recent studies demonstrating a lower prevalence of amyloid pathology in Black individuals, and additionally suggest that amyloid accumulates consistently across both groups.
Dimeric transport mechanism of human vitamin C transporter SVCT1
Authors: Kobayashi Takaaki A. , Shimada Hiroto , Sano Fumiya K. , Itoh Yuzuru , Enoki Sawako , Okada Yasushi , Kusakizako Tsukasa , Nureki Osamu
Published: July 2024

Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5–3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.
Unraveling dislocation-based strengthening in refractory multi-principal element alloys
Authors: Wang Tianyi , Li Jiuyin , Wang Mian , Li Chengzhi , Su Yanqing , Xu Shuozhi , Li Xiang-Guo
Published: July 2024

Refractory multi-principal element alloys (RMPEAs) draw great interest with their superior mechanical properties and extremely high melting points, yet the strengthening mechanism remains unclear. Here, we calculate the critical resolved shear stress (CRSS) for a single dislocation to move in RMPEAs consisting of 4 or 5 elements with or without short-range order (SRO) to represent strength by a machine learning-based interatomic potential. The increased CRSS is then attributed to high lattice distortion, elastic mismatch, and SRO strengthening, all of which originate from the solid solution strengthening theory. After detailed research of the CRSS across many RMPEAs systems with different composition ratios, we construct an XGBoost model to predict the CRSS from a few parameters and rank their importance. We find that lattice distortion strongly influences both dislocation types and reduces the screw-to-edge ratio in CRSS, while the elastic mismatch has a more significant impact on the screw dislocation than the edge one.
Identification of metabolites reproducibly associated with Parkinson’s Disease via meta-analysis and computational modelling
Authors: Luo Xi , Liu Yanjun , Balck Alexander , Klein Christine , Fleming Ronan M. T.
Published: July 2024

Many studies have reported metabolomic analysis of different bio-specimens from Parkinson’s disease (PD) patients. However, inconsistencies in reported metabolite concentration changes make it difficult to draw conclusions as to the role of metabolism in the occurrence or development of Parkinson’s disease. We reviewed the literature on metabolomic analysis of PD patients. From 74 studies that passed quality control metrics, 928 metabolites were identified with significant changes in PD patients, but only 190 were replicated with the same changes in more than one study. Of these metabolites, 60 exclusively increased, such as 3-methoxytyrosine and glycine, 54 exclusively decreased, such as pantothenic acid and caffeine, and 76 inconsistently changed in concentration in PD versus control subjects, such as ornithine and tyrosine. A genome-scale metabolic model of PD and corresponding metabolic map linking most of the replicated metabolites enabled a better understanding of the dysfunctional pathways of PD and the prediction of additional potential metabolic markers from pathways with consistent metabolite changes to target in future studies.
A modified mycobacterial growth inhibition assay for the functional assessment of vaccine-mediated immunity
Authors: Vergara Emil Joseph , Tran Andy Cano , Paul Matthew J. , Harrison Thomas , Cooper Andrea , Reljic Rajko
Published: July 2024

The Mycobacterial growth inhibition assay (MGIA) is an ex-vivo assay used to measure the overall functional immune response elicited by infection or vaccination. In tuberculosis (TB) vaccine development, MGIA is a potentially important tool for preclinical evaluation of early-stage vaccine candidates to complement existing assays, and to potentially reduce the need for lengthy and costly pathogenic Mycobacterium tuberculosis (Mtb) animal challenge experiments. The conventional method of MGIA in mice entails directly infecting mixed cell cultures, most commonly splenocytes, from immunised mice with mycobacteria. However, this direct infection of mixed cell populations may yield unreliable results and lacks sufficient sensitivity to discriminate well between different vaccines due to the low number of mycobacteria-permissive cells. Here, we modified the assay by inclusion of mycobacteria-infected congenic murine macrophage cell lines as the target cells, and by measuring the total number of killed cells rather than the relative reduction between different groups. Thus, using splenocytes from Mycobacterium bovis BCG immunised mice, and J774 and MH-S (BALB/c background) or BL/6-M (C57Bl/6 background) macrophage cell lines, we demonstrated that the modified assay resulted in at least 26-fold greater mycobacterial killing per set quantity of splenocytes as compared to the conventional method. This increased sensitivity of measuring mycobacterial killing was confirmed using both the standard culture forming unit (CFU) assay and luminescence readings of luciferase-tagged virulent and avirulent mycobacteria. We propose that the modified MGIA can be used as a highly calibrated tool for quantitating the killing capacity of immune cells in preclinical evaluation of vaccine candidates for TB.