bluuebunny/crossref_metadata_2025 huggingface dataset:
The expanding universe of the geometric mean
Authors: Lawson Jimmie D. , Lim Yongdo
Published: May 2024

In this paper the authors seek to trace in an accessible fashion the rapid recent development of the theory of the matrix geometric mean in the cone of positive definite matrices up through the closely related operator geometric mean in the positive cone of a unital $$C^*$$

C
∗

-algebra. The story begins with the two-variable matrix geometric mean, moves to the breakthrough developments in the multivariable matrix setting, the main focus of the paper, and then on to the extension to the positive cone of the $$C^*$$

C
∗

-algebra of operators on a Hilbert space, even to general unital $$C^*$$

C
∗

-algebras, and finally to the consideration of barycentric maps that grow out of the geometric mean on the space of integrable probability measures on the positive cone. Besides expected tools from linear algebra and operator theory, one observes a surprisingly substantial interplay with geometrical notions in metric spaces, particularly the notion of nonpositive curvature. Added features include a glance at the probabilistic theory of random variables with values in a metric space of nonpositive curvature, and the appearance of related means such as the inductive and power means. The authors also consider in a much briefer fashion the extension of the theory to the setting of Lie groups and briefer still to the positive symmetric cones of finite-dimensional Euclidean Jordan algebras.
The impact of community-led conservation models on women's nature-based livelihood outcomes in semi-arid Northern Ghana
Authors: Pienaah Cornelius K. A. , Baruah Bipasha , Kansanga Moses , Luginaah Isaac
Published: May 2024

With increasing human-induced environmental degradation, women's nature-based livelihood activities are threatened. In semi-arid northern Ghana, shea processing (i.e., shea butter, a derivative of shea nut from the shea tree), a vital women-dominated economic activity, is at risk as naturally occurring shea trees continue to decline in numbers and productivity. The decline of the shea tree's number and productivity and the ensuing biodiversity loss have sparked conservation efforts by governments and local communities. This includes community-led conservation models, which have recently gained traction in the Global South. Ghana implemented the Community Resource Management Areas (CREMA)—a community-led conservation model to improve biodiversity and ecosystem services, including shea trees conservation in response to climate change. Research has not explored the impacts of community-led conservation efforts on women’s nature-based livelihoods in Ghana. Using a mixed-methods approach involving surveys (n = 517) and focus group discussions (n = 8), this study explored shea productivity outcomes under CREMAs. Findings show that women residing in CREMAs had significantly better shea harvesting outcomes than those outside CREMAs (α = −53.725; P < 0.01). These findings demonstrate the potential for targeted conservation initiatives that are community-led, such as the CREMAs, to improve the conservation of economically significant naturally occurring trees like Shea. With the increasing impacts of climate change and environmental degradation, such models would be instrumental in achieving sustainable development goals like SDG5-gender equality, SDG10-reduced inequalities, SDG13-Climate action, SDG14-life below water, and SDG14-life on land.
Geophysical and physicochemical assessment of groundwater and the implication on the public health in rural and semi-urban areas of Northern Nigeria
Authors: Alao Joseph Omeiza , Lawal Hammed A. , Abubakar Fahad , Abdulsalami Momohjimoh
Published: May 2024

Groundwater resource plays a central role in every sector of life globally. Unfortunately, the roles of groundwater are often unappreciated in many parts of the world, especially in developing nations. The paper applied a combined geo-electrical method and hydrochemical analysis alongside physical surveys to investigate aquifer promising zones, the quality and the source of water supply in the selected regions. The geo-electric resistivity data were used to select the most aquifer-promising zone for groundwater development with a key interest in groundwater potential and aquifer overburden protective capacity overlying the water-bearing unit. Seventeen (17) vertical electrical sounding (VES) acquired in four regions reveals that the regional weathered/fractured unit which constitutes the aquifer unity extends from 13.4 m to 41.3 m in depth with the subsurface resistivity value varying between 53 Ωm–1013 Ωm in terms of resistivity values. The overburdened thickness (protective soil layers) stretches from 2.5 m to 13 m with a resistive layer of resistivity values ranging from 111 Ωm to 2877 Ωm, which could provide high aquifer protective cover for the regional groundwater systems. The computed aquifer transmissivity and hydraulic conductivity range from 0.54 $${m}^{2}/h$$

m

2

/
h

–15.85 $${m}^{2}/h$$

m

2

/
h

, and 0.95 m/day–9.19 m/day, respectively. The estimated average longitudinal conductance (0.2 moh) reveals that the regional groundwater systems are moderately protective against surface contaminants. In addition, the physicochemical water analysis was examined, which exposes the level of heavy metals (HMs) compositions in the regional groundwater systems and the possible public health risks compared to WHO permissible drinking water limits. The sample water from the Rivers had the highest concentration of HMs (0.089 mg/I–2.012 mg/l), followed by the hand-dug wells (HWDs) (0.033 mg/l–1.555 mg/l) and the lowest in the borehole (0.011 mg/l–0.511 mg/l). In contrast, the borehole water sample shows a moderation where the HMs presence falls within the WHO standard for drinking water. The outcomes of the study show that 63% of the investigated region consumed water with a high concentration of HMs above the WHO permissible standard allowance for drinking water, while only 37% took water that falls within the WHO permissible standard. In conclusion, the study showed significant impacts of anthropogenic activities on the regional water quality, which provides vital information about the regional groundwater systems and the quality of water supply for adequate groundwater development and sustainability.
“We Are Happy Here”: Creating Communist Cuba and the Mariel Crisis of 1980
Authors: Guerra Lillian
Published: May 2024

At a time when Cuban immigrants are seeking political asylum at historically unprecedented rates, most press and scholarly accounts consistently mirror earlier portrayals of Cubans’ mass exodus from the island in one key aspect: they ascribe to refugees a primarily economic reason for their decision to leave and offer little discussion of political factors. To illuminate the need for such analysis, this article examines the Mariel Boatlift of 1980, when approximately 125,000 Cubans, most of them thirty years old or younger, left Cuba. No other exodus of Cubans was more demonized than the Mariel, both by Cuba’s supporters and leadership and by exile opponents of the communist state. Exploring how the intensification of ideological criteria for inclusion in the Cuban Revolution undermined the quality of Cubans’ liberation under socialism prior to Mariel, this article explores state policies and the deep politicization of everyday life and identity. Key political factors explain many young people’s alienation and the degree to which the Cuban state sanctioned and directed extreme measures of repression to discredit those who wanted to leave as lazy, sexually degenerate escoria (human trash).
Reduced-resolution beamforming: Lowering the computational cost for pulsar and technosignature surveys
Authors: Price D.C.
Published: May 2024

In radio astronomy, the science output of a telescope is often limited by computational resources. This is especially true for transient and technosignature surveys that need to search high-resolution data across a large parameter space. The tremendous data volumes produced by modern radio array telescopes exacerbate these processing challenges. Here, we introduce a ‘reduced-resolution’ beamforming approach to alleviate downstream processing requirements. Our approach, based on post-correlation beamforming, allows sensitivity to be traded against the number of beams needed to cover a given survey area. Using the MeerKAT and Murchison Widefield Array telescopes as examples, we show that survey speed can be vastly increased, and downstream signal processing requirements vastly decreased, if a moderate sacrifice to sensitivity is allowed. We show the reduced-resolution beamforming technique is intimately related to standard techniques used in synthesis imaging. We suggest that reduced-resolution beamforming should be considered to ease data processing challenges in current and planned searches; further, reduced-resolution beamforming may provide a path to computationally expensive search strategies previously considered infeasible.
The Causes and Consequences of Refugee Flows: A Contemporary Reanalysis
Authors: SHAVER ANDREW , KRICK BENJAMIN , BLANCAFLOR JUDY , LIU XAVIER , SAMARA GHASSAN , KU SARAH YEIN , HU SHENGKUO , ANGELO JOSHUA , CARREON MARTHA , LIM TRISHIA , RAPS RACHEL , VELASQUEZ ALYSSA , DE MELO SOFIA , ZUO ZHANYI
Published: May 2024

The world faces a forced displacement crisis. Tens of millions of individuals have been forced across international boundaries worldwide. Therefore, the causes and consequences of refugee flows are the subjects of significant social science inquiry. Unfortunately, the historical lack of reliable data on actual refugee flows, country-specific data reporting timelines, and more general pre-2000 data quality issues have significantly limited empirical inferences on these topics. We replicate 28 articles on these topics using data newly released after a multiyear collaboration with the United Nations on annual dyadic flows. We observe major inconsistencies between the newly released flow numbers and the stock-based flow estimates upon which decades of research are based; we also find widespread inappropriate treatment of missing historical values. When we replicate the existing literature using the newly introduced flow data, correcting the treatment of missing historical values, and temporally extending/restricting the study periods, we produce significantly different results.
STRAIGHT TALK ABOUT CURVED HORNS AND GAY MARRIAGE: A NEW READING OF JUVENAL'S SECOND SATIRE
Authors: Herz Zachary
Published: May 2024

This article argues that one of our only pieces of evidence for Roman marriage between cinaedi, Juvenal's second satire, has been consistently misread and in fact describes a marriage between a cinaedus and a sex worker. It begins by providing the context for the passage in question and its traditional reading, and then demonstrates that the critical phrase siue hic recto cantauerat aere refers to financial, not erotic, exchanges. The article finally discusses the implications of this correction, which are far more substantial than one might expect for a contentious ablative.
Minerals and trace elements in broad-leaved Geebung (Persoonia stradbrokensis), an underutilised native Australian fruit
Authors: Zhang J. , Sivakumar D. , Netzel M.E. , Sultanbawa Y.
Published: May 2024

Minerals and trace elements are essential for human health and wellness. Fruits can be an important dietary source of these micronutrients. For centuries, native Australian fruits have been a vital source of nutrition and well-being for the Indigenous Communities(1). However, comprehensive information on the mineral and trace element composition of these native fruits, including broad-leaved Geebung (Persoonia stradbrokensis), is lacking. Therefore, the aim of the present study was to determine the mineral and trace element composition of broad-leaved Geebung, an important but still underutilised native Australian fruit, at different maturity stages. Inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectroscopy (ICP-OES) were used to analyse the fruit. Statistical analysis was performed using one-way ANOVA and the means (n = 3) were compared by Tukey’s multiple comparison post hoc test with p < 0.05 as significant. Calcium and potassium could be identified as the main minerals, and iron, zinc and manganese as the main trace elements. The calcium content in broad-leaved Geebung was lower than Australian desert lime, kakadu plum, and riberry, respectively (35.7-271.5 vs. 384.2 vs. 282.5 vs. 307.7 mg/100g dry weight (DW))(2). Potassium has a vital role in the prevention of bone loss and is essential for the heart, kidney, and blood pressure. The potassium content of broad-leaved Geebung fruit was lower than Australian desert lime, kakadu plum, lemon aspen, quandong and riberry (average 516.4 vs. 1287.8 vs. 1905.5 vs. 1512.9 vs. 3456.2 vs. 1715.7 mg/100g DW)(2), which contributes to approximately 15% recommended dietary allowance (RDA). Iron is the main element in the production of hemoglobin and is important for maintaining healthy blood. Iron content in the fruit ranged from 0.8-2.6 mg/100g DW, which was higher than that of Davidson’s plum (1.2 mg/100g DW), but lower than the Green Plum, Australian desert lime, and kakadu plum (3.8 vs. 4.7 vs. 4.0 mg/100g DW) (2,3). Besides, the manganese levels were relatively high in broad-leaved Geebung fruit and considerably higher than in other native Australian fruits such as Kakadu plums, Desert limes and Quandongs (11.2-26.4 vs. 3.5 vs. 0.9 vs. 0.3 mg/100 g DW)(2). Interestingly, the mineral and trace element content decreased (p < 0.05) during fruit maturity. In general, broad-leaved Geebung fruit can provide considerable amounts of essential minerals and trace elements and its potential as a healthy “snack” alternative should be investigated further.
Overseas Trade and War. Reconstructing a Late Eighteenth-Century East India Company Voyage to Asia Between Routine and Unpredictability
Authors: Chiocchetti Filippo
Published: May 2024

The role played by the East India Company in European expansion in early modern Asia is of such importance that it has generated a large body of scholarly literature. However, the logbooks of the East Indiamen, compiled by their captains, are largely overlooked as a primary source for the history of navigation, despite the wealth of information such firsthand, “from below” documents could provide about those voyages. As part of the Global Sea Routes (GSR) project, this essay analyses the voyage of theNassau(1781–85) along four main themes: the peculiarities of navigation during the Age of Sail, when the duration of a voyage was difficult to predict and subject to a range of possible accidents; the concrete reality of life on board, oscillating between the various activities of the crew and the episodes of desertion and insubordination that broke its daily routine; her military deployment, as theNassauwas directly involved in operations related to the Second Anglo-Mysore War; and, finally, her commercial activities, from the port cities of India to the seas of China.
Spatial and Temporal Changes in Nutrient Source Contribution in a Lowland Catchment Within the Baltic Sea Region Under Climate Change Scenarios
Authors: Bojanowski Damian , Orlińska‐Woźniak Paulina , Wilk Paweł , Jakusik Ewa , Szalińska Ewa
Published: May 2024

Currently, climate change is considered as an important factor affecting nutrient loads introduced through riverine systems into the Baltic Sea. Although the prospect of a large increase in pollution has long seemed very real, it still does not translate into planning of effective remedial actions. One of the factors limiting the development of such activities is the scale of simulations, focusing generally on catchment outlet profiles. To fill this gap and enable a step forward in understanding responses toward future predictions in a higher resolution scale (subcatchment), we assessed nutrient load contribution using calculation profiles localized along a main watercourse and its tributaries. To track spatial and seasonal changes of total nitrogen and phosphorus for the Wełna River (central Poland), we used climate change data and the SWAT model. Having at our disposal a catchment model with a good performance we could follow not only total load changes in particular subcatchments, but also track localization of the pollution sources and their direct impact on load estimations. Our results showed an increase of the loads, especially from the agricultural land use type, up to 34% for TN and 85% for TP, in the most extreme scenario. Moreover, forest areas have been noted as highly reactive to climate change, and through their localisation are able to distinctly alter nutrient outflow. Finally, the contribution of urban areas should be further investigated since the dynamics of nitrogen and phosphorus release from impervious surfaces is noticeably different here than from the other diffuse sources.
Disambiguating Concepts of Fairness in Stormwater Management: A Review of Economic Efficiency and Equity
Authors: Arik Aida D.
Published: May 2024

To confront the converging challenges of failing infrastructure, climate change, degraded water quality, and fewer undeveloped lands, many municipalities are establishing stormwater utilities (SWUs) to allocate a dedicated funding source to stormwater management (SWM) services. As a public service, creating a “fair” SWU by defining collective values that reflect community and municipal needs is crucial. However, the prevalent professional discourse surrounding SWUs often conflates “equity” with “economic efficiency” when they are two theoretically separate concepts, which obscure concerns raised by service beneficiaries. This paper unpacks ideas of fairness based on a systematic literature review that frames SWM financing in terms of economic efficiency and SWM services in terms of distributional, procedural, and structural equity. The distinction of which is important to set appropriate expectations between SWUs and beneficiaries.
Predicting survival in patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis
Authors: Li Fuhui , Qin Tiejun , Li Bing , Qu Shiqiang , Pan Lijuan , Zhang Peihong , Sun Qi , Cai Wenyu , Gao Qingyan , Jiao Meng , Li Junjie , Ai Xiaofei , Ma Jiao , Gale Robert Peter , Xu Zefeng , Xiao Zhijian
Published: May 2024

We investigated data from 180 consecutive patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T) who were diagnosed according to the 2022 World Health Organization (WHO) classification of myeloid neoplasms to identify covariates associated with survival. At a median follow-up of 48 months (95% confidence interval [CI] 35–61 months), the median survival was 69 months (95% CI 59–79 months). Patients with bone marrow ring sideroblasts (RS) < 15% had shorter median overall survival (OS) than did those with bone marrow RS ≥ 15% (41 months [95% CI 32–50 months] versus 76 months [95% CI 59–93 months]; P < 0.001). According to the univariable analyses of OS, age ≥ 65 years (P < 0.001), hemoglobin concentration (Hb) < 80 g/L (P = 0.090), platelet count (PLT) ≥ 800 × 10E + 9/L (P = 0.087), bone marrow RS < 15% (P < 0.001), the Revised International Prognostic Scoring System (IPSS-R) cytogenetic category intermediate/poor/very poor (P = 0.005), SETBP1 mutation (P = 0.061) and SRSF2 mutation (P < 0.001) were associated with poor survival. Based on variables selected from univariable analyses, two separate survival prediction models, a clinical survival model, and a clinical-molecular survival model, were developed using multivariable analyses with the minimum value of the Akaike information criterion (AIC) to specifically predict outcomes in patients with MDS/MPN-SF3B1-T according to the 2022 WHO classification.
CRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements
Authors: Recinos Yocelyn , Ustianenko Dmytro , Yeh Yow-Tyng , Wang Xiaojian , Jacko Martin , Yesantharao Lekha V. , Wu Qiyang , Zhang Chaolin
Published: May 2024

Pre-mRNA splicing, a key process in gene expression, can be therapeutically modulated using various drug modalities, including antisense oligonucleotides (ASOs). However, determining promising targets is hampered by the challenge of systematically mapping splicing-regulatory elements (SREs) in their native sequence context. Here, we use the catalytically inactive CRISPR-RfxCas13d RNA-targeting system (dCas13d/gRNA) as a programmable platform to bind SREs and modulate splicing by competing against endogenous splicing factors. SpliceRUSH, a high-throughput screening method, was developed to map SREs in any gene of interest using a lentivirus gRNA library that tiles the genetic region, including distal intronic sequences. When applied to SMN2, a therapeutic target for spinal muscular atrophy, SpliceRUSH robustly identifies not only known SREs but also a previously unknown distal intronic SRE, which can be targeted to alter exon 7 splicing using either dCas13d/gRNA or ASOs. This technology enables a deeper understanding of splicing regulation with applications for RNA-based drug discovery.
Characterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and phenylketonuria
Authors: Baek Rena , Coughlan Kimberly , Jiang Lei , Liang Min , Ci Lei , Singh Harkewal , Zhang Hannah , Kaushal Neeraj , Rajlic Ivana Liric , Van Linh , Dimen Rain , Cavedon Alexander , Yin Ling , Rice Lisa , Frassetto Andrea , Guey Lin , Finn Patrick , Martini Paolo G. V.
Published: May 2024

Messenger RNA (mRNA) therapeutics delivered via lipid nanoparticles hold the potential to treat metabolic diseases caused by protein deficiency, including propionic acidemia (PA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Herein we report results from multiple independent preclinical studies of mRNA-3927 (an investigational treatment for PA), mRNA-3705 (an investigational treatment for MMA), and mRNA-3210 (an investigational treatment for PKU) in murine models of each disease. All 3 mRNA therapeutics exhibited pharmacokinetic/pharmacodynamic (PK/PD) responses in their respective murine model by driving mRNA, protein, and/or protein activity responses, as well as by decreasing levels of the relevant biomarker(s) when compared to control-treated animals. These preclinical data were then used to develop translational PK/PD models, which were scaled allometrically to humans to predict starting doses for first-in-human clinical studies for each disease. The predicted first-in-human doses for mRNA-3927, mRNA-3705, and mRNA-3210 were determined to be 0.3, 0.1, and 0.4 mg/kg, respectively.
FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma
Authors: Zhen Yuanli , Liu Kai , Shi Lei , Shah Simran , Xu Qin , Ellis Haley , Balasooriya Eranga R. , Kreuzer Johannes , Morris Robert , Baldwin Albert S. , Juric Dejan , Haas Wilhelm , Bardeesy Nabeel
Published: May 2024

Genomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to FGFR inhibition. However, the depth and duration of response is often limited. Here, we conduct integrative transcriptomics, metabolomics, and phosphoproteomics analysis of patient-derived models to define pathways downstream of oncogenic FGFR2 signaling that fuel ICC growth and to uncover compensatory mechanisms associated with pathway inhibition. We find that FGFR2-mediated activation of Nuclear factor-κB (NF-κB) maintains a highly glycolytic phenotype. Conversely, FGFR inhibition blocks glucose uptake and glycolysis while inciting adaptive changes, including switching fuel source utilization favoring fatty acid oxidation and increasing mitochondrial fusion and autophagy. Accordingly, FGFR inhibitor efficacy is potentiated by combined mitochondrial targeting, an effect enhanced in xenograft models by intermittent fasting. Thus, we show that oncogenic FGFR2 signaling drives NF-κB-dependent glycolysis in ICC and that metabolic reprogramming in response to FGFR inhibition confers new targetable vulnerabilities.
Pharmacological inhibition of α-synuclein aggregation within liquid condensates
Authors: Dada Samuel T. , Toprakcioglu Zenon , Cali Mariana P. , Röntgen Alexander , Hardenberg Maarten C. , Morris Owen M. , Mrugalla Lena K. , Knowles Tuomas P. J. , Vendruscolo Michele
Published: May 2024

Aggregated forms of α-synuclein constitute the major component of Lewy bodies, the proteinaceous aggregates characteristic of Parkinson’s disease. Emerging evidence suggests that α-synuclein aggregation may occur within liquid condensates formed through phase separation. This mechanism of aggregation creates new challenges and opportunities for drug discovery for Parkinson’s disease, which is otherwise still incurable. Here we show that the condensation-driven aggregation pathway of α-synuclein can be inhibited using small molecules. We report that the aminosterol claramine stabilizes α-synuclein condensates and inhibits α-synuclein aggregation within the condensates both in vitro and in a Caenorhabditis elegans model of Parkinson’s disease. By using a chemical kinetics approach, we show that the mechanism of action of claramine is to inhibit primary nucleation within the condensates. These results illustrate a possible therapeutic route based on the inhibition of protein aggregation within condensates, a phenomenon likely to be relevant in other neurodegenerative disorders.
Compensating affected parties necessary for rapid coal phase-out but expensive if extended to major emitters
Authors: Nacke Lola , Vinichenko Vadim , Cherp Aleh , Jakhmola Avi , Jewell Jessica
Published: May 2024

Coal power phase-out is critical for climate mitigation, yet it harms workers, companies, and coal-dependent regions. We find that more than half of countries that pledge coal phase-out have  “just transition” policies which compensate these actors. Compensation is larger in countries with more ambitious coal phase-out pledges and most commonly directed to national and regional governments or companies, with a small share going directly to workers. Globally, compensation amounts to over $200 billion (uncertainty 163-258), about half of which is funded through  international schemes, mostly through Just Energy Transition Partnerships and the European Union Just Transition Fund. If similar transfers are extended to China and India to phase out coal in line with the Paris temperature targets, compensation flows could become larger than current international climate financing. Our findings highlight that the socio-political acceptance of coal phase-out has a tangible economic component which should be factored into assessing the feasibility of achieving climate targets.
Cardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1
Authors: Scranton Kyle , John Scott , Angelini Marina , Steccanella Federica , Umar Soban , Zhang Rui , Goldhaber Joshua I. , Olcese Riccardo , Ottolia Michela
Published: May 2024

The Na+-Ca2+ exchanger (NCX1) is the dominant Ca2+ extrusion mechanism in cardiac myocytes. NCX1 activity is inhibited by intracellular Na+ via a process known as Na+-dependent inactivation. A central question is whether this inactivation plays a physiological role in heart function. Using CRISPR/Cas9, we inserted the K229Q mutation in the gene (Slc8a1) encoding for NCX1. This mutation removes the Na+-dependent inactivation while preserving transport properties and other allosteric regulations. NCX1 mRNA levels, protein expression, and protein localization are unchanged in K229Q male mice. However, they exhibit reduced left ventricular ejection fraction and fractional shortening, while displaying a prolonged QT interval. K229Q ventricular myocytes show enhanced NCX1 activity, resulting in action potential prolongation, higher incidence of aberrant action potentials, a faster decline of Ca2+ transients, and depressed cell shortening. The results demonstrate that NCX1 Na+-dependent inactivation plays an essential role in heart function by affecting both cardiac excitability and contractility.
Quantum fluctuations lead to glassy electron dynamics in the good metal regime of electron doped KTaO3
Authors: Ojha Shashank Kumar , Hazra Sankalpa , Bera Surajit , Gogoi Sanat Kumar , Mandal Prithwijit , Maity Jyotirmay , Gloskovskii Andrei , Schlueter Christoph , Karmakar Smarajit , Jain Manish , Banerjee Sumilan , Gopalan Venkatraman , Middey Srimanta
Published: May 2024

One of the central challenges in condensed matter physics is to comprehend systems that have strong disorder and strong interactions. In the strongly localized regime, their subtle competition leads to glassy electron dynamics which ceases to exist well before the insulator-to-metal transition is approached as a function of doping. Here, we report on the discovery of glassy electron dynamics deep inside the good metal regime of an electron-doped quantum paraelectric system: KTaO3. We reveal that upon excitation of electrons from defect states to the conduction band, the excess injected carriers in the conduction band relax in a stretched exponential manner with a large relaxation time, and the system evinces simple aging phenomena—a telltale sign of glassy dynamics. Most significantly, we observe a critical slowing down of carrier dynamics below 35 K, concomitant with the onset of quantum paraelectricity in the undoped KTaO3. Our combined investigation using second harmonic generation technique, density functional theory and phenomenological modeling demonstrates quantum fluctuation-stabilized soft polar modes as the impetus for the glassy behavior. This study addresses one of the most fundamental questions regarding the potential promotion of glassiness by quantum fluctuations and opens a route for exploring glassy dynamics of electrons in a well-delocalized regime.
Specific exercise patterns generate an epigenetic molecular memory window that drives long-term memory formation and identifies ACVR1C as a bidirectional regulator of memory in mice
Authors: Keiser Ashley A. , Dong Tri N. , Kramár Enikö A. , Butler Christopher W. , Chen Siwei , Matheos Dina P. , Rounds Jacob S. , Rodriguez Alyssa , Beardwood Joy H. , Augustynski Agatha S. , Al-Shammari Ameer , Alaghband Yasaman , Alizo Vera Vanessa , Berchtold Nicole C. , Shanur Sharmin , Baldi Pierre , Cotman Carl W. , Wood Marcelo A.
Published: May 2024

Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.
Harnessing noncanonical crRNA for highly efficient genome editing
Authors: Xun Guanhua , Zhu Zhixin , Singh Nilmani , Lu Jingxia , Jain Piyush K. , Zhao Huimin
Published: May 2024

The CRISPR-Cas12a system is more advantageous than the widely used CRISPR-Cas9 system in terms of specificity and multiplexibility. However, its on-target editing efficiency is typically much lower than that of the CRISPR-Cas9 system. Here we improved its on-target editing efficiency by simply incorporating 2-aminoadenine (base Z, which alters canonical Watson-Crick base pairing) into the crRNA to increase the binding affinity between crRNA and its complementary DNA target. The resulting CRISPR-Cas12a (named zCRISPR-Cas12a thereafter) shows an on-target editing efficiency comparable to that of the CRISPR-Cas9 system but with much lower off-target effects than the CRISPR-Cas9 system in mammalian cells. In addition, zCRISPR-Cas12a can be used for precise gene knock-in and highly efficient multiplex genome editing. Overall, the zCRISPR-Cas12a system is superior to the CRISPR-Cas9 system, and our simple crRNA engineering strategy may be extended to other CRISPR-Cas family members as well as their derivatives.
tauFisher predicts circadian time from a single sample of bulk and single-cell pseudobulk transcriptomic data
Authors: Duan Junyan , Ngo Michelle N. , Karri Satya Swaroop , Tsoi Lam C. , Gudjonsson Johann E. , Shahbaba Babak , Lowengrub John , Andersen Bogi
Published: May 2024

As the circadian clock regulates fundamental biological processes, disrupted clocks are often observed in patients and diseased tissues. Determining the circadian time of the patient or the tissue of focus is essential in circadian medicine and research. Here we present tauFisher, a computational pipeline that accurately predicts circadian time from a single transcriptomic sample by finding correlations between rhythmic genes within the sample. We demonstrate tauFisher’s performance in adding timestamps to both bulk and single-cell transcriptomic samples collected from multiple tissue types and experimental settings. Application of tauFisher at a cell-type level in a single-cell RNAseq dataset collected from mouse dermal skin implies that greater circadian phase heterogeneity may explain the dampened rhythm of collective core clock gene expression in dermal immune cells compared to dermal fibroblasts. Given its robustness and generalizability across assay platforms, experimental setups, and tissue types, as well as its potential application in single-cell RNAseq data analysis, tauFisher is a promising tool that facilitates circadian medicine and research.
Atomic-level polarization reversal in sliding ferroelectric semiconductors
Authors: Sui Fengrui , Li Haoyang , Qi Ruijuan , Jin Min , Lv Zhiwei , Wu Menghao , Liu Xuechao , Zheng Yufan , Liu Beituo , Ge Rui , Wu Yu-Ning , Huang Rong , Yue Fangyu , Chu Junhao , Duan Chungang
Published: May 2024

Intriguing “slidetronics” has been reported in van der Waals (vdW) layered non-centrosymmetric materials and newly-emerging artificially-tuned twisted moiré superlattices, but correlative experiments that spatially track the interlayer sliding dynamics at atomic-level remain elusive. Here, we address the decisive challenge to in-situ trace the atomic-level interlayer sliding and the induced polarization reversal in vdW-layered yttrium-doped γ-InSe, step by step and atom by atom. We directly observe the real-time interlayer sliding by a 1/3-unit cell along the armchair direction, corresponding to vertical polarization reversal. The sliding driven only by low energetic electron-beam illumination suggests rather low switching barriers. Additionally, we propose a new sliding mechanism that supports the observed reversal pathway, i.e., two bilayer units slide towards each other simultaneously. Our insights into the polarization reversal via the atomic-scale interlayer sliding provide a momentous initial progress for the ongoing and future research on sliding ferroelectrics towards non-volatile storages or ferroelectric field-effect transistors.
Biogenic synthesis, characterization, and in vitro biological investigation of silver oxide nanoparticles (AgONPs) using Rhynchosia capitata
Authors: Ullah Zakir , Iqbal Javed , Gul Farhat , Abbasi Banzeer Ahsan , Kanwal Sobia , Elsadek Mohamed Farouk , Ali M. Ajmal , Iqbal Rashid , Elsalahy Heba H. , Mahmood Tariq
Published: May 2024

The current research aimed to study the green synthesis of silver oxide nanoparticles (AgONPs) usingRhynchosia capitata(RC) aqueous extract as a potent reducing and stabilizing agent. The obtained RC-AgONPs were characterized using UV, FT-IR, XRD, DLS, SEM, and EDX to investigate the morphology, size, and elemental composition. The size of the RC-AgONPs was found to be ~ 21.66 nm and an almost uniform distribution was executed by XRD analysis. In vitro studies were performed to reveal biological potential. The AgONPs exhibited efficient DPPH free radical scavenging potential (71.3%), reducing power (63.8 ± 1.77%), and total antioxidant capacity (88.5 ± 4.8%) to estimate their antioxidative power. Antibacterial and antifungal potentials were evaluated using the disc diffusion method against various bacterial and fungal strains, and the zones of inhibition (ZOI) were determined. A brine shrimp cytotoxicity assay was conducted to measure the cytotoxicity potential (LC50: 2.26 μg/mL). In addition, biocompatibility tests were performed to evaluate the biocompatible nature of RC-AgONPs using red blood cells, HEK, and VERO cell lines (< 200 μg/mL). An alpha-amylase inhibition assay was carried out with 67.6% inhibition. Moreover, In vitro, anticancer activity was performed against Hep-2 liver cancer cell lines, and an LC50value of 45.94 μg/mL was achieved. Overall, the present study has demonstrated that the utilization ofR. capitataextract for the biosynthesis of AgONPs offers a cost-effective, eco-friendly, and forthright alternative to traditional approaches for silver nanoparticle synthesis. The RC-AgONPs obtained exhibited significant bioactive properties, positioning them as promising candidates for diverse applications in the spheres of medicine and beyond.
Motor learning in multijoint virtual arm movements with novel kinematics
Authors: Inubashiri Nagisa , Hagio Shota , Kouzaki Motoki
Published: May 2024

Humans move their hands toward precise positions, a skill supported by the coordination of multiple joint movements, even in the presence of inherent redundancy. However, it remains unclear how the central nervous system learns the relationship between redundant joint movements and hand positions when starting from scratch. To address this question, a virtual-arm reaching task was performed in which participants were required to move a cursor corresponding to the hand of a virtual arm to a target. The joint angles of the virtual arm were determined by the heights of the participants’ fingers. The results demonstrated that the participants moved the cursor to the target straighter and faster in the late phase than they did in the initial phase of learning. This improvement was accompanied by a reduction in the amount of angular changes in the virtual limb joint, predominantly characterized by an increased reliance on the virtual shoulder joint as opposed to the virtual wrist joint. These findings suggest that the central nervous system selects a combination of multijoint movements that minimize motor effort while learning novel upper-limb kinematics.
Effect of regionalized structures on rock fracture process
Authors: Yao Xulong , Liu Zhen , Zhang Yanbo , Tao Zhigang , Liang Peng , Zhao Jizhong
Published: May 2024

The structure of rocks plays a crucial role in their failure process. However, it is ignored that the interactions between rock internal structure and the effect of its own evolution on the rock fracture process. To investigate the effect between the evolution law of rock regionalized structures and their interaction relationships during failure. We conducted an experiment using visual acoustic imaging monitoring to study rock failure, introducing a new concept of characteristics of rock structure—regionalized structures. The findings reveal three main types of regionalized structures in rocks: skeleton regions, variable regions, and damage regions. These structures combine to form four categories of complex rock structures: block-type support skeletons, point column-type support skeletons, suspension-type weak support skeletons, and no skeletons. During the failure process, we found that these regionalized structures worked together synergistically to control rock failure. Although the evolutionary relationships among the structures show some similarities, the final fracture states vary significantly. Stress and strain distribution patterns clearly demonstrate that variations in the force capacities and roles of the regionalized structures influence the synergistic evolutionary relationships, ultimately impacting the mode of rock failure. This work provides new insights for further research on rock failure mechanisms and can significantly contribute to preventing rock engineering disasters related to regionalized structures.
Reliable smart models for estimating frictional pressure drop in two-phase condensation through smooth channels of varying sizes
Authors: Moradkhani M. A. , Hosseini S. H. , Song Mengjie , Abbaszadeh A.
Published: May 2024

Reliable and comprehensive predictive tools for the frictional pressure drop (FPD) are of particular importance for systems involving two-phase flow condensation. However, the available models are only applicable to specific operating conditions and channel sizes. Thus, this study aims at developing universal models to estimate the FPD during condensation inside smooth mini/micro and conventional (macro) channels. An extensive databank, comprising 8037 experimental samples and 23 working fluids from 50 reliable sources, was prepared to achieve this target. A comprehensive investigation on the literature models reflected the fact that all of them are associated with high deviations, and their average absolute relative errors (AAREs) exceed 26%. Hence, after identifying the most effective input variables through the Spearman's correlation analysis, three soft-computing paradigms, i.e., multilayer perceptron (MLP), gaussian process regression (GPR) and radial basis function (RBF) were employed to establish intelligent and dimensionless predictive tools for the FPD based on the separated model suggested by Lockhart and Martinelli. Among them, the most accurate results were presented by the GPR approach with AARE and $$R^{2}$$

R
2

values of 4.10%, 99.23% respectively, in the testing step. The truthfulness and applicability of the models were explored through an array of statistical and visual analyses, and the results affirmed the obvious superiority of the newly proposed approaches over the literature correlations. Furthermore, the novel predictive tools excellently described the physical variations of the condensation FPD versus the operating parameters. Ultimately, the order of importance of factors in controlling the condensation FPD was clarified by a sensitivity analysis.
Doxycycline protects against sepsis-induced endothelial glycocalyx shedding
Authors: de Oliveira João Gabriel Craveiro Gonçalves , Miranda Carlos Henrique
Published: May 2024

Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the “backbone” of this structure. Several studies have shown eGC shedding in sepsis and its involvement in organ dysfunction. Matrix metalloproteinases (MMP) contribute to eGC shedding through their ability for syndecan-1 cleavage. This study aimed to investigate if doxycycline, a potent MMP inhibitor, could protect against eGC shedding in lipopolysaccharide (LPS)-induced sepsis and if it could interrupt the vascular hyperpermeability, neutrophil transmigration, and microvascular impairment. Rats that received pretreatment with doxycycline before LPS displayed ultrastructural preservation of the eGC observed using transmission electronic microscopy of the lung and heart. In addition, these animals exhibited lower serum syndecan-1 levels, a biomarker of eGC injury, and lower perfused boundary region (PBR) in the mesenteric video capillaroscopy, which is inversely related to the eGC thickness compared with rats that only received LPS. Furthermore, this study revealed that doxycycline decreased sepsis-related vascular hyperpermeability in the lung and heart, reduced neutrophil transmigration in the peritoneal lavage and inside the lungs, and improved some microvascular parameters. These findings suggest that doxycycline protects against LPS-induced eGC shedding, and it could reduce vascular hyperpermeability, neutrophils transmigration, and microvascular impairment.
Changes in amino acids, catechins and alkaloids during the storage of oolong tea and their relationship with antibacterial effect
Authors: Cui Jilai , Wu Bin , Zhou Jie
Published: May 2024

The storage process has a significant impact on tea quality. Few is known about effect of storage on quality of oolong tea. This study aimed to assess the effect of different storage times on the key chemical components of oolong tea by measuring changes in catechin, free amino acid, and alkaloid content. Variation in the main substances was determined by principal component analysis and heat map analysis. The results revealed notable effects of the storage process on the levels of theanine, epigallocatechin gallate (EGCG), and glutamine. These findings suggest that these compounds could serve as indicators for monitoring changes in oolong tea quality during storage. Additionally, the study observed an increase in the antibacterial ability of tea over time. Correlation analysis indicated that the antibacterial ability against Micrococcus tetragenus and Escherichia coli was influenced by metabolites such as aspartic acid, threonine, serine, gamma-aminobutyric acid, ornithine, alanine, arginine, and EGCG. Overall, this study presents an approach for identifying key metabolites to monitor tea quality effectively with relatively limited data.
Design and validation of a wearable dynamometry system for knee extension-flexion torque measurement
Authors: Park Sungwoo , Myong Youho , Cho Minwoo , Cho Seung Yeon , Lee Woo Hyung , Oh Byung-Mo , Kim Sungwan
Published: May 2024

Muscle strength assessments are vital in rehabilitation, orthopedics, and sports medicine. However, current methods used in clinical settings, such as manual muscle testing and hand-held dynamometers, often lack reliability, and isokinetic dynamometers (IKD), while reliable, are not easily portable. The aim of this study was to design and validate a wearable dynamometry system with high accessibility, accuracy, and reliability, and to validate the device. Therefore, we designed a wearable dynamometry system (WDS) equipped with knee joint torque sensors. To validate this WDS, we measured knee extension and flexion strength in 39 healthy adults using both the IKD and WDS. Comparing maximal isometric torque measurements, WDS and IKD showed strong correlation and good reliability for extension (Pearson’s r: 0.900; intraclass correlation coefficient [ICC]: 0.893; standard error of measurement [SEM]: 9.85%; minimal detectable change [MDC]: 27.31%) and flexion (Pearson’s r: 0.870; ICC: 0.857; SEM: 11.93%; MDC: 33.07%). WDS demonstrated excellent inter-rater (Pearson’s r: 0.990; ICC: 0.993; SEM: 4.05%) and test–retest (Pearson’s r: 0.970; ICC: 0.984; SEM: 6.15%) reliability during extension/flexion. User feedback from 35 participants, including healthcare professionals, underscores WDS's positive user experience and clinical potential. The proposed WDS is a suitable alternative to IKD, providing high accuracy, reliability, and potentially greater accessibility.