bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the suitability of YY males and ZZ females as an invasive species population control method across life histories
Authors: Erickson Richard A. , Thompson Hannah M. , Kageyama Stacie A. , Andriacchi Grace M. , Cupp Aaron R. , Patiño Reynaldo , Amberg Jon J.
Published: August 2023

Natural resource managers use tools to control invasive species. In theory, stocking YY males or ZZ females would allow managers to skew sex ratios until populations collapse. In combination with other suppression methods, such as removal, this approach could be incorporated into Integrated Pest Management plans. For example, fishery managers have stocked YY males to control isolated non-native brook trout (Salvelinus fontinalis) populations. However, life histories and demographic factors (e.g., lifespans) vary across species and could affect the feasibility of skewing sex ratios as an effective control strategy for a given population. Likewise, some species may have sex determinations that do not allow population control through sex-skewing methods. We compared five representative aquatic invasive species with global invasion ranges for potential control by skewing the sex ratio through closed population simulations: red swamp crayfish (Procambarus clarkii), zebra mussels (Dreissena polymorpha), lake trout (Salvelinus namaycush), silver carp (Hypophthalmichthys molitrix), and Nile tilapia (Oreochromis niloticus). We determined that Nile tilapia, red swamp crayfish, and zebra mussels would be the most suitable to control through skewing the sex ratio assuming appropriate sex determination exists in the species. Lake trout could be eliminated by stocking YY males but would require either long stocking periods or high stocking numbers because of the long lifespan of the species. Silver carp populations were more difficult to crash because they live longer and produce many recruits. Broadly, these patterns demonstrated that short lived species lend themselves to control by skewing the sex ratio.
Mainstreaming the Blackpill: Understanding the Incel Community on TikTok
Authors: Solea Anda Iulia , Sugiura Lisa
Published: August 2023

Incels (involuntary celibates), a subgroup of the so called ‘manosphere,’ have become an increasing security concern for policymakers, researchers, and practitioners following their association with several violent attacks. Once mostly contained on niche men’s forums, redpilled and blackpilled communities and theories are gaining prominence on mainstream social media platforms. However, whilst previous research considerably enhanced our understanding of the incel phenomenon and their presence on Reddit and secluded incel forums, incel’s presence on mainstream social media platforms is understudied and their presence on TikTok is yet to be addressed. The present paper examines the incel subculture on TikTok, through an analysis of incel accounts, videos and their respective comments, to understand the role mainstream social media platforms play in the ‘normiefication’ and normalisation of incel ideology and discourse. The findings suggest that on TikTok the expression of incel ideology takes a covert form, employing emotional appeals and pseudo-science to disseminate common incelosphere tropes. Further, we demonstrate how the process of mainstreaming incel beliefs is facilitated by their interconnectedness with wider sexism and structural misogyny. The harms generating from this association are conducive to the normalisation of blackpill beliefs and the reinforcement of misogyny, sexism and justification of rape culture.
Experimental and field evidence suggests extreme salinity tolerances in Coxiella gastropods from Australian salt lakes
Authors: Lawrie Angus D’Arcy , Chaplin Jennifer , Rahman Mahabubur , Islam Md. Aminul , Pinder Adrian
Published: August 2023

This study aimed to determine salinity tolerances in Coxiella gastropods from Australian salt lakes and whether different species exhibit characteristically different tolerances. Controlled gradual accumulation experiments were conducted to estimate both the maximum and minimum salinity levels at which 50% of individuals (IC50) remained active for 25 populations representing six species. All studied species showed remarkable euryhalinity and were tolerant of very high levels of salinity, some more than others, while minimum salinity tolerance varied little among populations and species. The experimental trends in salinity tolerances were consistent with the salinity distributions of species in the field, although the former were typically broader than latter. The findings suggest that Coxiella comprises some of the most salt tolerant gastropods globally.
LC-QToF chemical profiling of Euphorbia grantii Oliv. and its potential to inhibit LPS-induced lung inflammation in rats via the NF-κB, CY450P2E1, and P38 MAPK14 pathways
Authors: Radi Mai Hussin , El-Shiekh Riham A. , Hegab Amany Mohammed , Henry Shirley Ragae , Avula Bharathi , Katragunta Kumar , Khan Ikhlas A. , El-Halawany Ali M. , Abdel-Sattar Essam
Published: August 2023

Acute lung injury (ALI) is a life-threatening syndrome that causes high morbidity and mortality worldwide. The aerial parts of Euphorbia grantii Oliv. were extracted with methanol to give a total methanolic extract (TME), which was further fractionated into dichloromethane (DCMF) and the remaining mother liquor (MLF) fractions. Biological guided anti-inflammatory assays in vitro revealed that the DCMF showed the highest activity (IC50 6.9 ± 0.2 μg/mL and 0.29 ± 0.01 μg/mL) compared to. celecoxib (IC50 of 88.0 ± 1 μg/mL and 0.30 ± 0.01 μg/mL) on COX-1 and COX-2, respectively. Additionally, anti-LOX activity was IC50 = 24.0 ± 2.5 μg/mL vs. zileuton with IC50 of 40.0 ± 0.5 μg/mL. LC-DAD-QToF analysis of TME and the active DCMF resulted in the tentative identification and characterization of 56 phytochemical compounds, where the diterpenes were the dominated metabolites. An LPS-induced inflammatory model of ALI (10 mg/kg i.p) was used to assess the anti-inflammatory potential of DCMF in vivo at dose of 200 mg/kg and 300 mg/kg compared to dexamethasone (5 mg/kg i.p). Our treatments significantly reduced the pro-inflammatory cytokines (TNF-α, IL-1, IL-6, and MPO), increased the activity of antioxidant enzymes (SOD, CAT, and GSH), decreased the activity of oxidative stress enzyme (MDA), and reduced the expression of inflammatory genes (p38.MAPK14 and CY450P2E1). The western blotting of NF-κB p65 in lung tissues was inhibited after orally administration of the DCMF. Histopathological study of the lung tissues, scoring, and immunohistochemistry of transforming growth factor-beta 1 (TGF-β1) were also assessed. In both dose regimens, DCMF of E. grantii prevented further lung damage and reduced the side effects of LPS on acute lung tissue injury.
Backward Partial Vertical Integration Through Private Placement
Authors: Gonçalves Ricardo
Published: August 2023

We analyze the market impact of a partial vertical integration whereby a subset of retail firms acquire, through a private placement operation, a non-controlling stake in the capital of an upstream firm, which supplies an essential input. In addition, we assume that this upstream firm can price discriminate between the retail firms which (now) own a stake in its capital and all of their retail rivals. We find that price discrimination is optimal and, compared to a vertical separation scenario, there is input foreclosure, a higher retail price, and lower social welfare, which suggests that, from a competition policy viewpoint, such partial vertical integrations should be analyzed with particular concern. On the other hand, incentives are such that conducting a private placement operation of the upstream firm’s capital yields gains from trade, and we are able to identify the optimal characteristics of such an operation.
The simple view of reading and its broad types of reading difficulties
Authors: Hoover Wesley A.
Published: August 2023

Common depictions of the simple view of reading (SVR), in both research and practice, describe reading comprehension difficulties by using the dichotomous variables of “poor” and “good” for each of its three constructs. But these fail to accurately capture the role the product of the two subcomponents of word recognition and language comprehension plays in defining such difficulties. When the skills in both subcomponents are “good,” most depictions show reading comprehension as “good” – but this is not what the SVR holds. This can lead users of the SVR to both overlook the great variation in reading comprehension skills that are possible within each of the SVR’s defined reading difficulty types as well as misunderstand that reading comprehension may still suffer even when both word recognition and language comprehension do not. This article first reviews the SVR and its main predictions, followed by an overview of the evidence bearing on these. The article then describes how reading comprehension difficulties are defined under the SVR, presenting graphics that employ continuous variables that accurately reflect these definitions. The article concludes with a discussion of classification studies that have investigated SVR-defined reading difficulties and their findings of cases of good skills in word recognition and language comprehension coupled with poor reading comprehension. The article argues that these can be interpreted as consistent with the SVR rather than counter to it.
Role of Air Staging in a Batch-Type Fixed Bed Biomass Combustor under Constant Primary Air
Authors: Junejo Awais , Al-Abdeli Yasir M. , Porteiro Jacobo
Published: August 2023

Staged combustion of biomass is the most suitable thermo-chemical conversion for achieving lower gaseous emissions and higher fuel conversion rates. In a staged fixed bed combustion of biomass, combustion air is supplied in two stages. In the first stage, primary air is provided below the fuel, whereas in the later stage, secondary air is supplied in the freeboard region. The available literature on the effects of air staging (secondary air location) at a constant primary air flow rate on combustion characteristics in a batch-type fixed bed combustor is limited and hence warrants further investigations. This study resolves the effect of air staging, by varying the location of secondary air in the freeboard at five secondary to total air ratios in a batch-type fixed bed combustor. Results are reported for the effects of these controlled parameters on fuel conversion rate, overall gaseous emissions (CO2, CO and NOx) and temperature distributions. The fuel used throughout was densified hardwood pellets.

Results show that a primary freeboard length (distance between fuel bed top and secondary air injection) of 200 mm has higher fuel conversion rates and temperatures as well as lower CO emissions, at a secondary to total air ratio of 0.75 as compared to primary freeboard length of 300 mm. However, NOx emissions were found to be lower for a primary freeboard length of 300 mm as compared to 200 mm. An increase in secondary to total air ratio from 0.33 to 0.75 resulted in higher freeboard temperatures and lower CO as well as NOx emissions. The outcomes of this study will be helpful in the effective design of commercial scale biomass combustors for more efficient and environmentally friendly combustion.
Circ_0067934: a circular RNA with roles in human cancer
Authors: Yu Liqing , Zheng Jiacheng , Yu Jiali , Zhang Yujun , Hu Huoli
Published: August 2023

A circular RNA (circRNA) is a non-coding RNA (ncRNA) derived from reverse splicing from pre-mRNA and is characterized by the absence of a cap structure at the 5′ end and a poly-adenylated tail at the 3′ end. Owing to the development of RNA sequencing and bioinformatics approaches in recent years, the important clinical value of circRNAs has been increasingly revealed. Circ_0067934 is an RNA molecule of 170 nucleotides located on chromosome 3q26.2. Circ_0067934 is formed via the reverse splicing of exons 15 and 16 in PRKCI (protein kinase C Iota). Recent studies revealed the upregulation or downregulation of circ_0067934 in various tumors. The expression of circ_0067934 was found to be correlated with tumor size, TNM stage, and poor prognosis. Based on experiments with cancer cells, circ_0067934 promotes cancer cell proliferation, migratory activity, and invasion when overexpressed or downregulated. The potential mechanism involves the binding of circ_0067934 to microRNAs (miRNAs; miR-545, miR-1304, miR-1301-3p, miR-1182, miR-7, and miR-1324) to regulate the post-transcriptional expression of genes. Other mechanisms include inhibition of the Wnt/β-catenin and PI3K/AKT signaling pathways. Here, we summarized the biological functions and possible mechanisms of circ_0067934 in different tumors to enable further exploration of its translational applications in clinical diagnosis, therapy, and prognostic assessments.
Active broad learning with multi-objective evolution for data stream classification
Authors: Cheng Jian , Zheng Zhiji , Guo Yinan , Pu Jiayang , Yang Shengxiang
Published: August 2023

In a streaming environment, the characteristics and labels of instances may change over time, forming concept drifts. Previous studies on data stream learning generally assume that the true label of each instance is available or easily obtained, which is impractical in many real-world applications due to expensive time and labor costs for labeling. To address the issue, an active broad learning based on multi-objective evolutionary optimization is presented to classify non-stationary data stream. The instance newly arrived at each time step is stored to a chunk in turn. Once the chunk is full, its data distribution is compared with previous ones by fast local drift detection to seek potential concept drift. Taking diversity of instances and their relevance to new concept into account, multi-objective evolutionary algorithm is introduced to find the most valuable candidate instances. Among them, representative ones are randomly selected to query their ground-truth labels, and then update broad learning model for drift adaption. More especially, the number of representative is determined by the stability of adjacent historical chunks. Experimental results for 7 synthetic and 5 real-world datasets show that the proposed method outperforms five state-of-the-art ones on classification accuracy and labeling cost due to drift regions accurately identified and the labeling budget adaptively adjusted.
A Thermal Conductivity Model for Deformable and Unsaturated Soils to Assess the Thermal Behaviour of Energy Piles
Authors: Bruno Agostino Walter , Najdi Abdallah , Balzano Brunella
Published: August 2023

This paper presents an empirical model that predicts the thermal conductivity of soils by accounting for the effect of both the degree of saturation and void ratio on the heat exchange capacity of shallow geothermal reservoirs. The model is generated by the product of two terms: the former accounts for the effect of void ratio on the dry thermal conductivity, whereas the latter describes the influence of the degree of saturation on the moisture-dependent thermal conductivity. The model is a function of three parameters, which are easy to calibrate based on their physical meaning. Model predictions are validated against five different sets of experimental data from literature by means of two alternative approaches: blind prediction of thermal conductivity measurements not employed during calibration and numerical simulations of thermal tests performed on energy piles. Results show that the proposed model is capable of accurately predicting both the thermal conductivity of deformable unsaturated soils as well as reproducing the thermal behaviour of energy piles.
A One-Size-Fits-Three Representation Learning Framework for Patient Similarity Search
Authors: Huang Yefan , Luo Feng , Wang Xiaoli , Di Zhu , Li Bohan , Luo Bin
Published: August 2023

Patient similarity search is an essential task in healthcare. Recent studies adopted electronic health records (EHRs) to learn patient representations for measuring the clinical similarities. These methods outperformed traditional methods, by capturing more information from various sources consisting of multi-modal EHRs, external knowledge and correlations among medical concepts. They often concerned certain type of data without taking full advantage of various information. We propose a graph representation learning framework, denoted by One-Size-Fits-Three (OSFT), that takes into account fusion-attention, neighbor-attention and global-attention from three types of information. Extensive experiments are conducted on two real datasets of MIMIC-III and MIMIC-IV, and the results verified the effectiveness and generality of our framework. When compared with baselines on patient similarity search, our framework achieved good effectiveness and comparative efficiency. The results provide new insights about whether the use of various information can better measure the patient similarity. The source codes are available at https://github.com/emmali808/ADDS/tree/master/EHRDeepHelper.
Agape in the Workplace. A Survey Among Medium and Large Dutch Companies
Authors: Hummels Harry , van der Put Anne
Published: August 2023

The concepts of love and business do not seem to match very well, despite attempts to operationalize love as agape or neighborly love. In line with the emerging literature, this contribution uses a profane and analytical approach to agape as an ‘Agenda for Growth and Affirmation of People and the Environment’. Within this agenda we define agape as ‘the commitment to the well-being and flourishing of others’ and operationalized it to measure the concept in a substantial sample of 420 medium-sized and large companies in The Netherlands. At the core of the research lies the question whether and to what extent companies, represented by senior managers and members of the works council, are committed to the well-being of their employees. This article analyses the concept of agape and its application in a business context and presents the results of a survey. The results show that, on average, respondents report that their organization is committed to employees’ well-being in line with the organization’s values. Though not the aim of agape, since organizations that apply the concept reap tangible business benefits from it, the concept becomes suitable to a wider range of businesses.
Embedding Research on Emotion Duration in a Network Model
Authors: Lange Jens
Published: August 2023

Contrary to early theorizing, emotions often last for longer periods of time. Variability in people’s emotion duration contributes to psychopathologies. Therefore, emotion theories need to account for this variability. So far, reviews only list predictors of emotion duration without integrating them in a theoretical framework. Mechanisms explaining why these predictors relate to emotion duration remain unknown. I propose to embed research on emotion duration in a network model of emotions and illustrate the central ideas with simulations using a formal network model. In the network model, the components of an emotion have direct causal effects on each other. According to the model, emotions last longer (a) when the components are more strongly connected or (b) when the components have higher thresholds (i.e., they are more easily activated). High connectivity prolongs emotions because components are constantly reactivated. Higher thresholds prolong emotions because components are more easily reactivated even when connectivity is lower. Indirect evidence from research on emotion coherence and research on the relationship of predictors of emotion duration with components outside of emotional episodes supports the usefulness of the network model. I further argue and show in simulations that a common cause model, in which a latent emotion causes changes in emotion components, cannot account for research on emotion duration. Finally, I describe future directions for research on emotion duration and emotion dynamics from a network perspective.
The Voice of the Indian Mona Lisa
Authors: Pauwels Heidi Rika Maria
Published: August 2023

The 'Indian Mona Lisa' is an eighteenth-century portrait of the goddess Radha from the Kishangarh school of Rajput Painting. It was purportedly modelled after a young enslaved woman and court-performer, Banī-ṭhanī, who became a concubine of the patron of the painting, crown-prince Savant Singh. Tracing her career, Heidi Pauwels recovers her role as a composer of devotional songs in multiple registers of Classical Hindi and shows how she was a conduit for trend-setting styles from Delhi, including the new vogue of Urdu. Through a combination of literary, historical, and art-historical analysis, she brings to life the vibrant cultural production center of Kishangarh in the eighteenth century by reconstructing how Banī-ṭhanī came to be acclaimed as the devotional poetess Rasikbihārī and as 'India's Mona Lisa'. This major new study conveys important new insights in the history of Hindi literature and devotion, the family, palace women and the social mobility of the enslaved.
Mental Content
Authors: Schulte Peter
Published: August 2023

This Element provides a comprehensive introduction to contemporary theories of mental content. After clarifying central concepts and identifying the questions that dominate the current debate, it presents and discusses the principal accounts of the nature of mental content (or mental representation), which include causal, informational, teleological and structuralist approaches, alongside the phenomenal intentionality approach and the intentional stance theory. Additionally, it examines anti-representationalist accounts which question either the existence or the explanatory relevance of mental content. Finally, the Element concludes by considering some recent developments in the debate about mental content, specifically the “explanatory turn” and its implications for questions about representations in basic cognitive systems and the representational character of current empirical theories of cognition.
Resources for finance lawyers
Authors: Hunter Ian
Published: August 2023

Financing work is an important source of revenue for many law firms, so it's no surprise that the finance practice group is often one of the largest in a City firm. But what is finance and what do finance lawyers do? Ian Hunter, Content & Research Manager (EMEA) at Shearman & Sterling (London) LLP, gives LIM the benefit of his wide experience in the sector.
Effects of Composite Rheology on Plate‐Like Behavior in Global‐Scale Mantle Convection
Authors: Arnould Maëlis , Rolf Tobias , Manjón‐Cabeza Córdoba Antonio
Published: August 2023

Earth's upper mantle rheology controls lithosphere‐asthenosphere coupling and thus surface tectonics. Rock deformation experiments and seismic anisotropy measurements indicate that composite rheology (co‐existing diffusion and dislocation creep) occurs in the Earth's uppermost mantle, potentially affecting convection and surface tectonics. Here, we investigate how the spatio‐temporal distribution of dislocation creep in an otherwise diffusion‐creep‐controlled mantle impacts the planform of convection and the planetary tectonic regime as a function of the lithospheric yield strength in numerical models of mantle convection self‐generating plate‐like tectonics. The low upper‐mantle viscosities caused by zones of substantial dislocation creep produce contrasting effects on surface dynamics. For strong lithosphere (yield strength > 35 MPa), the large lithosphere‐asthenosphere viscosity contrasts promote stagnant‐lid convection. In contrast, the increase of upper mantle convective vigor enhances plate mobility for lithospheric strength <35 MPa. For the here‐used model assumptions, composite rheology does not facilitate the onset of plate‐like behavior at large lithospheric strength.
MMS Observation of Two‐Step Electron Acceleration at Earth's Bow Shock
Authors: Lindberg M. , Vaivads A. , Raptis S. , Karlsson T.
Published: August 2023

We use the Magnetospheric Multiscale mission to observe a bi‐directional electron acceleration event in the electron foreshock upstream of Earth's quasi‐perpendicular collisionless bow shock. The acceleration region is associated with a decrease in wave activity, inconsistent with common electron acceleration mechanisms such as Diffusive Shock Acceleration and Stochastic Shock Drift Acceleration. We propose a two‐step acceleration process where an electron field‐aligned beam acts as a seed population further accelerated by a shrinking magnetic bottle process, with the shock acting as the magnetic mirror(s).
Continental Tip With Thinned Lithosphere and Thickened Crust Is a Favorable Location for Subduction Initiation
Authors: Zhang Shengxing , Leng Wei , Chen Ling
Published: August 2023

The collapse of passive margins and subsequent subduction initiation (SI) are key steps in the Wilson Cycle. However, the occurrence and mechanism of SI at passive margins have long been questioned due to the lack of Cenozoic observations. In this study, we propose that the continental tip, where arc/plateau blocks with thinned lithosphere and thickened crust accrete beside the passive margin, is a favorable location for SI. Our three‐dimensional numerical model and force analysis demonstrate that the continental tip, with its reduced frictional resistance and increased gravitational instability, is better suited for SI than other parts of the passive margin. Upon completion of SI, the retreat of self‐sustained subduction can create a transform plate boundary by tearing the passive margin. Our model explains why SI can occur at continental tips such as the Scotia and the Caribbean, as well as locations with similar tectonic settings, while most parts of the Atlantic margin remain stable over long geological periods.
Evaluating a Poroelastic Model via Pore Pressure Signals in Seafloor Sediments
Authors: Billings William Z. , Simeonov Julian , Calantoni Joseph
Published: August 2023

Below a certain threshold of wave energy for a given depth, unconsolidated sediment should respond to wave action poroelastically. To this end, a generalized simple poroelastic model was applied to in situ data collected in coastal sediments near Oceanside, California. Pore pressure data were recorded by sensors attached to cylindrical unexploded ordinance surrogates, and water pressure sensors on bottom moorings. Orientation data were collected from inertial motion units attached to the surrogates, which were placed on the seabed and subsequently shallow buried during a high‐energy event on 13 February 2021. The model is characterized by two parameters. A consolidation coefficient controls the depth of diffusive flow, and Skempton's coefficient represents the ratio of the original signal into components transmitted by the sediment matrix and the pore fluid. The model assumes that the pore pressure signal is coherent with the seafloor signal; spectral coherence above 0.75 was used to select the frequency range from 0.05 to 0.2 Hz for the analysis. Spectral analysis methods were then applied to obtain averaged auto spectral densities of the pore pressure and bottom mooring signals over the coherent frequency band. Attenuation between sensor pairs was calculated. The results yielded burial depths over time for the surrogates that agreed with changes in significant wave heights, liquefaction, and recovery depths.
Persistently Southward of the South Asian High During the Radiative Forcing Stabilization
Authors: Hou Hongyu , Qu Xia , Huang Gang
Published: August 2023

The South Asian high (SAH), a large‐scale anticyclone at 100 and 200 hPa on the Asian continent, is driven by South Asian summer monsoon rainfall and heating over the Tibetan Plateau. As one member of the Asian summer monsoon system, the changes of its location and intensity may cause other climate responses. Rainfall‐induced latent heating can affect the SAH change. Previous study revealed that rainfall responses in Indian Ocean are opposite in periods of increased and stabilizing radiative forcing (RF) due to the deep ocean warming over the Southern Ocean. SAH responses during RF increase and stabilization are studied with 13 models from the Extended Representative Concentration Pathway scenario 4.5 (ECP4.5) experiment. At 100 hPa, the SAH intensifies and moves equatorward in increased RF scenario; when RF stabilizing, SAH still shifts southward but with little change in intensity. At 200 hPa, the SAH changes little in both RF increase and stabilization. These opposite responses at different altitudes may be due to the maximum potential temperature at 150–200 hPa, leading to the opposite changes in vertical motion. Results of the linear baroclinic model indicate that (a) during RF increase, diabatic heating () contributes to SAH strengthening, both and the mean advection of stratification change (MASC) lead to SAH southward movement; (b) during RF stabilization, and MASC, contribute to the SAH equatorward displacement. Two components of , the latent heating and residual heating, are canceled out and lead to little change in SAH intensity.
Clinical impact of the genomic landscape and leukemogenic trajectories in non-intensively treated elderly acute myeloid leukemia patients
Authors: Jahn Ekaterina , Saadati Maral , Fenaux Pierre , Gobbi Marco , Roboz Gail J. , Bullinger Lars , Lutsik Pavlo , Riedel Anna , Plass Christoph , Jahn Nikolaus , Walter Claudia , Holzmann Karlheinz , Hao Yong , Naim Sue , Schreck Nicholas , Krzykalla Julia , Benner Axel , Keer Harold N. , Azab Mohammad , Döhner Konstanze , Döhner Hartmut
Published: August 2023

To characterize the genomic landscape and leukemogenic pathways of older, newly diagnosed, non-intensively treated patients with AML and to study the clinical implications, comprehensive genetics analyses were performed including targeted DNA sequencing of 263 genes in 604 patients treated in a prospective Phase III clinical trial. Leukemic trajectories were delineated using oncogenetic tree modeling and hierarchical clustering, and prognostic groups were derived from multivariable Cox regression models. Clonal hematopoiesis-related genes (ASXL1, TET2, SRSF2, DNMT3A) were most frequently mutated. The oncogenetic modeling algorithm produced a tree with five branches with ASXL1, DDX41, DNMT3A, TET2, and TP53 emanating from the root suggesting leukemia-initiating events which gave rise to further subbranches with distinct subclones. Unsupervised clustering mirrored the genetic groups identified by the tree model. Multivariable analysis identified FLT3 internal tandem duplications (ITD), SRSF2, and TP53 mutations as poor prognostic factors, while DDX41 mutations exerted an exceptionally favorable effect. Subsequent backwards elimination based on the Akaike information criterion delineated three genetic risk groups: DDX41 mutations (favorable-risk), DDX41wildtype/FLT3-ITDneg/TP53wildtype (intermediate-risk), and FLT3-ITD or TP53 mutations (high-risk). Our data identified distinct trajectories of leukemia development in older AML patients and provide a basis for a clinically meaningful genetic outcome stratification for patients receiving less intensive therapies.
E4orf1 improves adipose tissue-specific metabolic risk factors and indicators of cognition function in a mouse model of Alzheimer’s disease
Authors: Khan Md Shahjalal Hossain , Hefner Marleigh , Reddy Arubala , Dhurandhar Nikhil V. , Hegde Vijay
Published: August 2023

Objective

Obesity, impaired glycemic control, and hepatic steatosis often coexist and are risk factors for developing dementia, and Alzheimer’s disease (AD). We hypothesized that a therapeutic agent that improves glycemic control and steatosis may attenuate obesity-associated progression of dementia. We previously identified that adenoviral protein E4orf1 improves glycemic control and reduces hepatic steatosis despite obesity in mice. Here, we determined if this metabolic improvement by E4orf1 will ameliorate cognitive decline in a transgenic mouse model of AD.

Methods

Fourteen- to twenty-month-old APP/PS1/E4orf1 and APP/PS1 (control) mice were fed a high-fat diet. Cognition was determined by Morris Water Maze (MWM). Systemic glycemic control and metabolic signaling changes in adipose tissue, liver, and brain were determined.

Results

Compared to control, E4orf1 expression significantly improved glucose clearance, reduced endogenous insulin requirement and lowered body-fat, enhanced glucose and lipid metabolism in adipose tissue, and reduced de novo lipogenesis in the liver. In the brain, E4orf1 mice displayed significantly greater expression of genes involved in neurogenesis and amyloid-beta degradation and performed better in MWM testing.

Conclusion

This study opens-up the possibility of addressing glycemic control and steatosis for attenuating obesity-related cognitive decline. It also underscores the potential of E4orf1 for the purpose, which needs further investigations.
FANCA deficiency promotes leukaemic progression by allowing the emergence of cells carrying oncogenic driver mutations
Authors: Pawlikowska Patrycja , Delestré Laure , Gregoricchio Sebastian , Oppezzo Alessia , Esposito Michela , Diop M’ Boyba , Rosselli Filippo , Guillouf Christel
Published: August 2023

Leukaemia is caused by the clonal evolution of a cell that accumulates mutations/genomic rearrangements, allowing unrestrained cell growth. However, recent identification of leukaemic mutations in the blood cells of healthy individuals revealed that additional events are required to expand the mutated clones for overt leukaemia. Here, we assessed the functional consequences of deleting the Fanconi anaemia A (Fanca) gene, which encodes a DNA damage response protein, in Spi1 transgenic mice that develop preleukaemic syndrome. FANCA loss increases SPI1-associated disease penetrance and leukaemic progression without increasing the global mutation load of leukaemic clones. However, a high frequency of leukaemic FANCA-depleted cells display heterozygous activating mutations in known oncogenes, such as Kit or Nras, also identified but at low frequency in FANCA-WT mice with preleukaemic syndrome, indicating that FANCA counteracts the emergence of oncogene mutated leukaemic cells. A unique transcriptional signature is associated with the leukaemic status of FANCA-depleted cells, leading to activation of MDM4, NOTCH and Wnt/β-catenin pathways. We show that NOTCH signalling improves the proliferation capacity of FANCA-deficient leukaemic cells. Collectively, our observations indicate that loss of the FANC pathway, known to control genetic instability, fosters the expansion of leukaemic cells carrying oncogenic mutations rather than mutation formation. FANCA loss may contribute to this leukaemogenic progression by reprogramming transcriptomic landscape of the cells.
Commonalities and differences in the mutational signature and somatic driver mutation landscape across solid and hollow viscus organs
Authors: Ng Aik Seng , Chan Dedrick Kok Hong
Published: August 2023

Advances in sequencing have revealed a highly variegated landscape of mutational signatures and somatic driver mutations in a range of normal tissues. Normal tissues accumulate mutations at varying rates ranging from 11 per cell per year in the liver, to 1879 per cell per year in the bladder. In addition, some normal tissues are also comprised of a large proportion of cells which possess driver mutations while appearing phenotypically normal, as in the oesophagus where a majority of cells harbour driver mutations. Individual tissue proliferation and mutation rate, unique mutagenic stimuli, and local tissue architecture contribute to this highly variegated landscape which confounds the functional characterization of driver mutations found in normal tissue. In particular, our understanding of the relationship between normal tissue somatic mutations and tumour initiation or future cancer risk remains poor. Here, we describe the mutational signatures and somatic driver mutations in solid and hollow viscus organs, highlighting unique characteristics in a tissue-specific manner, while simultaneously seeking to describe commonalities which can bring forward a basic unified theory on the role of these driver mutations in tumour initiation. We discuss novel findings which can be used to inform future research in this field.
Geospatial mapping of distribution grid with machine learning and publicly-accessible multi-modal data
Authors: Wang Zhecheng , Majumdar Arun , Rajagopal Ram
Published: August 2023

Detailed and location-aware distribution grid information is a prerequisite for various power system applications such as renewable energy integration, wildfire risk assessment, and infrastructure planning. However, a generalizable and scalable approach to obtain such information is still lacking. In this work, we develop a machine-learning-based framework to map both overhead and underground distribution grids using widely-available multi-modal data including street view images, road networks, and building maps. Benchmarked against the utility-owned distribution grid map in California, our framework achieves > 80% precision and recall on average in the geospatial mapping of grids. The framework developed with the California data can be transferred to Sub-Saharan Africa and maintain the same level of precision without fine-tuning, demonstrating its generalizability. Furthermore, our framework achieves a R2 of 0.63 in measuring the fraction of underground power lines at the aggregate level for estimating grid exposure to wildfires. We offer the framework as an open tool for mapping and analyzing distribution grids solely based on publicly-accessible data to support the construction and maintenance of reliable and clean energy systems around the world.
On-shelf circulation of warm water toward the Totten Ice Shelf in East Antarctica
Authors: Hirano Daisuke , Tamura Takeshi , Kusahara Kazuya , Fujii Masakazu , Yamazaki Kaihe , Nakayama Yoshihiro , Ono Kazuya , Itaki Takuya , Aoyama Yuichi , Simizu Daisuke , Mizobata Kohei , Ohshima Kay I. , Nogi Yoshifumi , Rintoul Stephen R. , van Wijk Esmee , Greenbaum Jamin S. , Blankenship Donald D. , Saito Koji , Aoki Shigeru
Published: August 2023

The Totten Glacier in East Antarctica, with an ice volume equivalent to >3.5 m of global sea-level rise, is grounded below sea level and, therefore, vulnerable to ocean forcing. Here, we use bathymetric and oceanographic observations from previously unsampled parts of the Totten continental shelf to reveal on-shelf warm water pathways defined by deep topographic features. Access of warm water to the Totten Ice Shelf (TIS) cavity is facilitated by a deep shelf break, a broad and deep depression on the shelf, a cyclonic circulation that carries warm water to the inner shelf, and deep troughs that provide direct access to the TIS cavity. The temperature of the warmest water reaching the TIS cavity varies by ~0.8 °C on an interannual timescale. Numerical simulations constrained by the updated bathymetry demonstrate that the deep troughs play a critical role in regulating ocean heat transport to the TIS cavity and the subsequent basal melt of the ice shelf.
Characterization of the pig lower respiratory tract antibiotic resistome
Authors: Zhou Yunyan , Li Jingquan , Huang Fei , Ai Huashui , Gao Jun , Chen Congying , Huang Lusheng
Published: August 2023

Respiratory diseases and its treatments are highly concerned in both the pig industry and human health. However, the composition and distribution of antibiotic resistance genes (ARGs) in swine lower respiratory tract microbiome remain unknown. The relationships of ARGs with mobile genetic elements (MGEs) and lung health are unclear. Here, we characterize antibiotic resistomes of the swine lower respiratory tract microbiome containing 1228 open reading frames belonging to 372 ARGs using 745 metagenomes from 675 experimental pigs. Twelve ARGs conferring resistance to tetracycline are related to an MGE Tn916 family, and multiple types of ARGs are related to a transposase gene tnpA. Most of the linkage complexes between ARGs and MGEs (the Tn916 family and tnpA) are also observed in pig gut microbiomes and human lung microbiomes, suggesting the high risk of these MGEs mediating ARG transfer to both human and pig health. Gammaproteobacteria are the major ARG carriers, within which Escherichia coli harbored >50 ARGs and >10 MGEs. Although the microbial compositions structure the compositions of ARGs, we identify 73 ARGs whose relative abundances are significantly associated with the severity of lung lesions. Our results provide the first overview of ARG profiles in the swine lower respiratory tract microbiome.
p21-activated kinase 4 suppresses fatty acid β-oxidation and ketogenesis by phosphorylating NCoR1
Authors: Shi Min Yan , Yu Hwang Chan , Han Chang Yeob , Bang In Hyuk , Park Ho Sung , Jang Kyu Yun , Lee Sangkyu , Son Jeong Bum , Kim Nam Doo , Park Byung-Hyun , Bae Eun Ju
Published: August 2023

PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. However, its regulatory mechanism is largely unknown. Here, we report that oncoprotein p21-activated kinase 4 (PAK4) is an NCoR1 kinase. Specifically, PAK4 phosphorylates NCoR1 at T1619/T2124, resulting in an increase in its nuclear localization and interaction with PPARα, thereby repressing the transcriptional activity of PPARα. We observe impaired ketogenesis and increases in PAK4 protein and NCoR1 phosphorylation levels in liver tissues of high fat diet-fed mice, NAFLD patients, and hepatocellular carcinoma patients. Forced overexpression of PAK4 in mice represses ketogenesis and thereby increases hepatic fat accumulation, whereas genetic ablation or pharmacological inhibition of PAK4 exhibites an opposite phenotype. Interestingly, PAK4 protein levels are significantly suppressed by fasting, largely through either cAMP/PKA- or Sirt1-mediated ubiquitination and proteasome degradation. In this way, our findings provide evidence for a PAK4-NCoR1/PPARα signaling pathway that regulates fatty acid β-oxidation and ketogenesis.
A reflection on polymer electrolytes for solid-state lithium metal batteries
Authors: Song Ziyu , Chen Fangfang , Martinez-Ibañez Maria , Feng Wenfang , Forsyth Maria , Zhou Zhibin , Armand Michel , Zhang Heng
Published: August 2023

Before the debut of lithium-ion batteries (LIBs) in the commodity market, solid-state lithium metal batteries (SSLMBs) were considered promising high-energy electrochemical energy storage systems before being almost abandoned in the late 1980s because of safety concerns. However, after three decades of development, LIB technologies are now approaching their energy content and safety limits imposed by the rocking chair chemistry. These aspects are prompting the revival of research activities in SSLMB technologies at both academic and industrial levels. In this perspective article, we present a personal reflection on solid polymer electrolytes (SPEs), spanning from early development to their implementation in SSLMBs, highlighting key milestones. In particular, we discuss the SPEs’ characteristics taking into account the concept of coupled and decoupled SPEs proposed by C. Austen Angell in the early 1990s. Possible remedies to improve the physicochemical and electrochemical properties of SPEs are also examined. With this article, we also aim to highlight the missing blocks in building ideal SSLMBs and stimulate research towards innovative electrolyte materials for future rechargeable high-energy batteries.
Divergent sequences of tetraspanins enable plants to specifically recognize microbe-derived extracellular vesicles
Authors: Zhu Jinyi , Qiao Qian , Sun Yujing , Xu Yuanpeng , Shu Haidong , Zhang Zhichao , Liu Fan , Wang Haonan , Ye Wenwu , Dong Suomeng , Wang Yan , Ma Zhenchuan , Wang Yuanchao
Published: August 2023

Extracellular vesicles (EVs) are important for cell-to-cell communication in animals. EVs also play important roles in plant–microbe interactions, but the underlying mechanisms remain elusive. Here, proteomic analyses of EVs from the soybean (Glycine max) root rot pathogenPhytophthora sojaeidentify the tetraspanin family proteins PsTET1 and PsTET3, which are recognized byNicotiana benthamianato trigger plant immune responses. Both proteins are required for the full virulence ofP. sojae. The large extracellular loop (EC2) of PsTET3 is the key region recognized byN. benthamianaand soybean cells in a plant receptor-like kinase NbSERK3a/b dependent manner. TET proteins from oomycete and fungal plant pathogens are recognized byN. benthamianathus inducing immune responses, whereas plant-derived TET proteins are not due to the sequence divergence of sixteen amino acids at the C-terminal of EC2. This feature allows plants to distinguish self and non-self EVs to trigger active defense responses against pathogenic eukaryotes.
Constructing multiple active sites in iron oxide catalysts for improving carbonylation reactions
Authors: Liu Shujuan , Li Teng , Shi Feng , Ma Haiying , Wang Bin , Dai Xingchao , Cui Xinjiang
Published: August 2023

Surface engineering is a promising strategy to improve the catalytic activities of heterogeneous catalysts. Nevertheless, few studies have been devoted to investigate the catalytic behavior differences of the multiple metal active sites triggered by the surface imperfections on catalysis. Herein, oxygen vacancies induced Fe2O3 catalyst are demonstrated with different Fe sites around one oxygen vacancy and exhibited significant catalytic performance for the carbonylation of various aryl halides and amines/alcohols with CO. The developed catalytic system displays excellent activity, selectivity, and reusability for the synthesis of carbonylated chemicals, including drugs and chiral molecules, via aminocarbonylation and alkoxycarbonylation. Combined characterizations disclose the formation of oxygen vacancies. Control experiments and density functional theory calculations demonstrate the selective combination of the three Fe sites is vital to improve the catalytic performance by catalyzing the elemental steps of PhI activation, CO insertion and C-N/C-O coupling respectively, endowing combinatorial sites catalyst for multistep reactions.
NHC-catalyzed enantioselective access to β-cyano carboxylic esters via in situ substrate alternation and release
Authors: Wang Qingyun , Wu Shuquan , Zou Juan , Liang Xuyang , Mou Chengli , Zheng Pengcheng , Chi Yonggui Robin
Published: August 2023

A carbene-catalyzed asymmetric access to chiral β-cyano carboxylic esters is disclosed. The reaction proceeds between β,β-disubstituted enals and aromatic thiols involving enantioselective protonation of enal β-carbon. Two main factors contribute to the success of this reaction. One involves in situ ultrafast addition of the aromatic thiol substrates to the carbon-carbon double bond of the enal substrate. This reaction converts almost all enal substrate to a Thiol-click Intermediate, significantly reducing aromatic thiol substrates concentration and suppressing the homo-coupling reaction of enals. Another factor is an in situ release of enal substrate from the Thiol-click Intermediate for the desired reaction to proceed effectively. The optically enriched β-cyano carboxylic esters from our method can be readily transformed to medicines that include γ-aminobutyric acids derivatives such as Rolipram. In addition to synthetic utilities, our control of reaction outcomes via in situ substrate modulation and release can likely inspire future reaction development.