bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal shear layer and vortex shedding development of a structured porous coated cylinder using tomographic particle image velocimetry
Authors: Arcondoulis E.J.G. , Liu Y. , Ragni D. , Avallone F. , Rubio-Carpio A. , Sedaghatizadeh N. , Yang Y. , Li Z.
Published: July 2023

Vortex shedding in the wake of a cylinder in uniform flow can be suppressed via the application of a porous coating; however, the suppression mechanism is not fully understood. The internal flow field of a porous coated cylinder (PCC) can provide a deeper understanding of how the flow within the porous medium affects the wake development. A structured PCC (SPCC) was three-dimensionally printed using a transparent material and tested in water tunnel facilities using flow visualisation and tomographic particle image velocimetry at outer-diameter Reynolds numbers of

$Re = 7 \times 10^{3}$

and

$7.3 \times 10^{4}$

, respectively. The internal and near-wall flow fields are analysed at the windward and mid-circumference regions. Flow stagnation is observed in the porous layer on the windward side and its boundary is shown to fluctuate with time in the outermost porous layer. This stagnation region generates a quasi-aerodynamic body that influences boundary layer development on the SPCC inner diameter, that separates into a shear layer within the porous medium. For the first time via experiment, spectral content within the separated shear layer reveals vortex shedding processes emanating through single pores at the outer diameter, providing strong evidence that SPCC vortex shedding originates from the inner diameter. Velocity fluctuations linked to this vortex shedding propagate through the porous layers into the external flow field at a velocity less than that of the free stream. The Strouhal number linked to this velocity accurately predicts the SPCC vortex shedding frequency.
On land, memory, and masculinity: unearthing silences around myths of Gallipoli in Nuri Bilge Ceylan’s Ahlat Ağacı (The Wild Pear Tree)
Authors: Adak Hülya , Akser Murat
Published: July 2023

This article offers a critical reading of Nuri Bilge Ceylan’s Ahlat Ağacı (The Wild Pear Tree) through an exploration and critique of the mythmaking and monumentalization surrounding the Gallipoli Battle and the multiple ways in which Ceylan’s film unsettles the foundational myths of the last century in Turkey. Ceylan’s scenes and characters are constructed in such a way that the male characters and particularly Sinan (the main character) refuse to succumb to hegemonic codes of masculinity. Through this cinematic refusal by an anti-hero (Sinan), the film addresses the crisis of hegemonic masculinities in their interconnectedness to militarism, nationalism, capitalism, and heteronormativity. Through Sinan’s quest for self-realization, the film signals not only the impotence and vanity of nationalist masculinities but also the caesuras and instabilities in national myths. As the last film of Nuri Bilge Ceylan’s new Land of Ghosts trilogy, which started with Once Upon a Time in Anatolia and Winter Sleep, Ahlat Ağacı seems to close the cycle with a final scene that bespeaks the possibility of unearthing lost others of national mythmaking, bringing fertility and hope to the lands in which collective amnesia reigns supreme.
Asian American Racial Threat and Support for Racially Discriminatory Policy
Authors: Thompson Andrew Ifedapo
Published: July 2023

Across a series of experiments, I show that racial threat from a stereotypically nonthreatening racial minority group, Asian Americans, has a direct impact on white Americans' views of discrimination toward the group. When white Americans learn the group is growing, they feel a distinct racial threat which decreases support for the idea that Asian Americans experience discrimination while simultaneously increasing support for policy which actively discriminates against Asian Americans. I show this concept to be portable over context, examining support for discriminatory policy toward Asians in education policy and COVID-19 policy. I conclude by discussing the implications for how racial threat can drive more racial conflict while simultaneously decreasing the perception that this discrimination is occurring.
Quantification of pollen viability in Lantana camara by digital holographic microscopy
Authors: Kumar Vipin , Goyal Nishant , Prasad Abhishek , Babu Suresh , Khare Kedar , Yadav Gitanjali
Published: July 2023

Pollen grains represent the male gametes of seed plants and their viability is critical for sexual reproduction in the plant life cycle. Palynology and viability studies have traditionally been used to address a range of botanical, ecological and geological questions, but recent work has revealed the importance of pollen viability in invasion biology as well. Here, we report an efficient visual method for assessing the viability of pollen using digital holographic microscopy (DHM). Imaging data reveal that quantitative phase information provided by the technique can be correlated with viability as indicated by the outcome of the colorimetric test. We successfully test this method on pollen grains of Lantana camara, a well-known alien invasive plant in the tropical world. Our results show that pollen viability may be assessed accurately without the usual staining procedure and suggest potential applications of the DHM methodology to a number of emerging areas in plant science.
From Cisr-i Mustafa Paşa to Svilengrad: The Ethnic Homogenization of a Thracian Town in the Balkan Wars
Authors: Ginio Eyal
Published: July 2023

The transformation of Ottoman Cisr-i Mustafa Paşa to Bulgarian Svilengrad was the outcome of a combination of both local violence and state-policy that took place throughout the Balkan Wars (1912-13) and within the framework of state-building efforts in both Ottoman imperial and Bulgarian post-imperial contexts. This sequence of mass violence stands at the core of this article. Based on Ottoman, Jewish, international, and translated Bulgarian sources, this article discusses the everyday dynamics and events that took place in the town by placing them in the contexts of the macro-historical transformations generated by the Balkan Wars. It likewise turns to micro-historical analysis to study the violence perpetrated by locals. While it is evident that much of the violence was state-sponsored or, at least, tacitly accepted by the state, and reflected top-down planning, non-state players also took part in the retribution against those they deemed alien to the national cause.
The multi-generational familial aggregation of interstitial cystitis, other chronic nociplastic pain disorders, depression, and panic disorder
Authors: Allen-Brady Kristina , Fyer Abby J. , Weissman Myrna
Published: July 2023

Background

Interstitial cystitis/painful bladder syndrome (IC) is a chronic pelvic pain condition which has high comorbidity with other nociplastic, or unexplained, pain disorders [e.g. fibromyalgia (FM), irritable bowel syndrome (IBS), and myalgic encephalomyelitis/chronic fatigue (ME/CFS)] and some psychiatric conditions [major depressive disorder (MDD) and panic disorder (PD)]. Here we investigated the shared familiality of IC and these other nociplastic and psychiatric conditions.

Methods

Subjects were identified in the Utah Population Database, which links genealogy data back to the 1800s to medical record diagnosis billing code data back to 1995. We computed the relative risk of each of these disorders among first (FDR), second (SDR), and third-degree relatives (TDR) of six proband groups: IC, FM, IBS, ME/CFS, PD, and MDD. Given the known familial aggregation of each of these disorders, we conducted our analyses to test for heritable interrelationships using proband subgroups whose members did not have the diagnosis assessed in their relatives.

Results

We observed strong evidence for heritable interrelationships among all six disorders. Most analyses indicated significantly increased risk for each of the six disorders in FDR, SDR, and TDR of all or most proband groups. Out of 30 possible bidirectional disorder interrelationships, 26 were significant among FDR, 23 were significant among SDR, and 7 were significant among TDR. Clustering was observed in both close and distant relatives.

Conclusions

Our results support a common, heritable component to IC and other nociplastic and psychiatric conditions.
Choreography as Ideology: Dance Heritage, Performance Politics, and the Former Yugoslavia
Authors: Petkovski Filip
Published: July 2023

In this article I discuss the process of choreographing “traditional” and “folk” dances in the former Yugoslavia, aligned with Yugoslav socialist ideologies that glorified the collective cultural authorship of the people, which allowed for these dances to adopt a new dimension as they took the form of a choreographed spectacle. I explain how Yugoslav choreographers utilized archival research to create a repertoire of choreographic representations of Yugoslav identity in constructing what I theorize as heritage choreography. Reflecting on how ideology moved the collective body of the Yugoslav people through choreographed works deemed as heritage, I broaden the understanding of choreographing that differs from Western concert dance practices. Furthermore, I provide alternative examples of dance making that are rooted in local understandings of spectacle, thereby enriching the conversation about what the act of choreographing entails.
“What if?” in Probabilistic Logic Programming
Authors: KIESEL RAFAEL , RÜCKSCHLOß KILIAN , WEITKÄMPER FELIX
Published: July 2023

A ProbLog program is a logic program with facts that only hold with a specified probability. In this contribution, we extend this ProbLog language by the ability to answer “What if” queries. Intuitively, a ProbLog program defines a distribution by solving a system of equations in terms of mutually independent predefined Boolean random variables. In the theory of causality, Judea Pearl proposes a counterfactual reasoning for such systems of equations. Based on Pearl’s calculus, we provide a procedure for processing these counterfactual queries on ProbLog programs, together with a proof of correctness and a full implementation. Using the latter, we provide insights into the influence of different parameters on the scalability of inference. Finally, we also show that our approach is consistent with CP-logic, that is with the causal semantics for logic programs with annotated with disjunctions.
Belastungserleben durch Informations- und Kommunikationstechnologien bei Pflegefachpersonen in der ambulanten Pflege
Authors: Thielmann Beatrice , Schmidt Stefanie , Böckelmann Irina
Published: July 2023

Zusammenfassung: Hintergrund: Auch in der ambulanten Pflege hält die „Arbeit 4.0“ durch Informations- und Kommunikationstechnologien (IKT) fortwährend Einzug. Neben einer Vielzahl an Möglichkeiten, die die IKT dem Pflegepersonal bieten, führt der Umgang zu zusätzlichen Belastungen. Ziel: Ziel der Arbeit ist es, relevante Belastungskategorien zu bestimmen, die durch die Nutzung von IKT hervorgerufen werden können sowie unter Berücksichtigung der individuellen Ressourcen und Technikaffinität einen zusätzlichen Einfluss auf das Belastungserleben von Mitarbeitenden der ambulanten Pflege ausüben. Methoden: Im Rahmen einer qualitativen Studie wurden problemzentrierte Interviews mit acht Pflegefachpersonen aus drei Unternehmen der ambulanten Pflege durchgeführt. Im Anschluss daran wurden diese Interviews transkribiert und mithilfe der qualitativen Inhaltsanalyse nach Mayring ausgewertet. Ergebnisse: Es konnten zehn Kategorien ermittelt werden, die von den Pflegefachpersonen der ambulanten Pflege als Belastung wahrgenommen wurden: zum Beispiel unzureichende Beteiligung und Gebrauchstauglichkeit, erhöhter Dokumentationsaufwand, Informationsüberflutung. Hinsichtlich der Arbeitsfähigkeit und der Gesundheit der Beschäftigten ließen sich keine Beeinträchtigungen ableiten, die auf die identifizierten zusätzlichen Belastungen zurückzuführen sind. Schlussfolgerungen: Weitere Analysen möglicher Belastungssituationen, die zusätzlich aus der Nutzung von IKT hervorgehen könnten, sind notwendig, um diese Kenntnisse in die Primärprävention einzubauen. Es ist sinnvoll bedarfs- und beteiligungs- bzw. prozessorientierte Strukturen in Unternehmen der ambulanten Pflege zu schaffen. Die Anwendung von IKT kann auch ein Vorteil sein, da beispielsweise Informationen schneller beschafft werden können.
Trends, Shifting, or Oscillations? Stochastic Modeling of Nonstationary Time Series for Future Water‐Related Risk Management
Authors: Lee Taesam , Ouarda Taha B. M. J.
Published: July 2023

Hydrological time series often present nonstationarities such as trends, shifts, or oscillations due to anthropogenic effects and hydroclimatological variations, including global climate change. For water managers, it is crucial to recognize and define the nonstationarities in hydrological records. The nonstationarities must be appropriately modeled and stochastically simulated according to the characteristics of observed records to evaluate the adequacy of flood risk mitigation measures and future water resources management strategies. Therefore, in the current study, three approaches were suggested to address stochastically nonstationary behaviors, especially in the long‐term variability of hydrological variables: as an overall trend, shifting mean, or as a long‐term oscillation. To represent these options for hydrological variables, the autoregressive model with an overall trend, shifting mean level (SML), and empirical mode decomposition with nonstationary oscillation resampling (EMD‐NSOR) were employed in the hydrological series of the net basin supply in the Lake Champlain‐River Richelieu basin, where the International Joint Committee recently managed and significant flood damage from long consistent high flows occurred. The detailed results indicate that the EMD‐NSOR model can be an appropriate option by reproducing long‐term dependence statistics and generating manageable scenarios, while the SML model does not properly reproduce the observed long‐term dependence, that are critical to simulate sustainable flood events. The trend model produces too many risks for floods in the future but no risk for droughts. The overall results conclude that the nonstationarities in hydrological series should be carefully handled in stochastic simulation models to appropriately manage future water‐related risks.
Organic Matter Export Rates and the Pathways of Nutrient Supply in the Ocean
Authors: Quay Paul
Published: July 2023

Multiyear estimates of organic matter (OM) export based primarily on oxygen and dissolved inorganic carbon surface layer budgets applied basin‐wide for the Pacific, Atlantic, and S. Indian Oceans yield an inter‐basin range from 1 to 3 mol C/m2/yr with a global mean of 2.0 mol C/m2/yr (8.5 Gt C/yr). OM export rates per area in the Pacific and Atlantic oceans are twice than that in the Indian Ocean. The supply of nutrients from the Southern Ocean can potentially support ∼70% of the observed OM export in the ocean based on observed surface current velocities and PO4 distributions. Horizontal flux of PO4 and dissolved organic phosphorous in the surface layer can support ∼50%, 20%, and 15% of observed OM export in the Pacific, S. Indian and Atlantic oceans, respectively, with the remainder being supplied vertically from the subsurface. Potential utilization of unused surface PO4 in the subtropical gyre yields ∼0.1 mol C/m2/yr increase in OM export in the Pacific and Atlantic oceans but a ∼0.8 mol C/m2/yr increase in the S. Indian ocean suggesting that stronger nutrient limitation contributes to lower export rates observed in the Indian ocean.
Sediment Exchange Across Coastal Barrier Landscapes Alters Ecosystem Extents
Authors: Reeves I. R. B. , Moore L. J. , Valentine K. , Fagherazzi S. , Kirwan M. L.
Published: July 2023

Barrier coastlines and their associated ecosystems are rapidly changing. Barrier islands/spits, marshes, bays, and coastal forests are all thought to be intricately coupled, yet an understanding of how morphologic change in one part of the system affects the system altogether remains limited. Here we explore how sediment exchange controls the migration of different ecosystem boundaries and ecosystem extent over time using a new coupled model framework that connects components of the entire barrier landscape, from the ocean shoreface to mainland forest. In our experiments, landward barrier migration is the primary cause of back‐barrier marsh loss, while periods of barrier stability can allow for recovery of back‐barrier marsh extent. Although sea‐level rise exerts a dominant control on the extent of most ecosystems, we unexpectedly find that, for undeveloped barriers, bay extent is largely insensitive to sea‐level rise because increased landward barrier migration (bay narrowing) offsets increased marsh edge erosion (bay widening).
A Seasonally Varying Tree Physiological Response to Environmental Conditions: Results From Semi‐Arid China
Authors: Li Yao , Zeng Xiaomin , Liu Xiaohong , Evans Michael N. , Xu Guobao , Szejner Paul , Ni Ping
Published: July 2023

Drought is the primary limiting factor for tree growth in water‐stressed regions through its effects on xylem development. In this study, we developed intra‐annual series of tree‐ring stable carbon (δ13C) and oxygen (δ18O) isotopes from Chinese pine (Pinus tabuliformis) to investigate the ecophysiological responses of trees to drought during the growing season in a climatic transition zone between arid and semi‐arid areas in north‐central China. Distinct intra‐annual patterns of δ13C and δ18O were revealed, with average annual amplitude of 0.26 and 2.72‰, respectively. Tree‐ring δ13C values increased from the early‐ to mid‐growing season, peaked in the mid‐to‐late‐growing season, and decreased at the end of the growing season. In contrast, δ18O values continuously decreased throughout the growing season. As expected, drought significantly increased δ13C and altered its intra‐annual pattern, particularly toward the end of the growing season. However, there was no significant difference in the average intra‐annual pattern in δ18O between dry and wet years. The tree‐ring δ18O at the end of the growing season was significantly correlated with the September to October average soil water δ18O, as simulated by a global isotope‐enabled climate model, which is consistent with the high proportion of exchangeable oxygen atoms predicted by previous studies for cellulose synthesis in the late growing season.
Reconstructing Long‐Term Forest Age of China by Combining Forest Inventories, Satellite‐Based Forest Age and Forest Cover Data Sets
Authors: Xia Jiangzhou , Xia Xiaosheng , Chen Yang , Shen Ruoque , Zhang Zheyuan , Liang Boyi , Wang Jia , Yuan Wenping
Published: July 2023

Forest age is one of the most important ecosystem characters for accurately estimating the magnitude and potential of carbon sink in forest ecosystems. During the past 40 years, national ecological restoration projects have led to the near doubling of the forest cover area in China, which has also substantially affected the dynamics of forest age. Therefore, there is an urgent need to generate long‐term forest age maps for China. This study reconstructed China forest age datasets (CFAD) from 1980 to 2015 at five year intervals at a 1 km spatial resolution by merging a satellite‐based forest age map in 2010 and forest cover dynamic maps from 1980 to 2015. The random forest method was used to reconstruct the forest age where forest age could not be inferred from the forest age base map in 2010 directly. CFAD showed a good agreement with the province‐level mean forest age derived from the several national forest inventories (R2 ranged from 0.66 to 0.86). In general, the younger forests are mainly distributed in southern and eastern China. The older forests are mainly distributed in the mountain areas of northeast, northwest and southwest China. The average age of China's forests increased from 18.2 to 44.0 years old from 1980 to 2015. Based on the current forest age and future afforestation planning, the average forest age in China is predicted to reach 71.6 years old in 2060. The CFAD provides an alternative data set to obtain improved estimates of local and national forest carbon sinks in China.
Insights on Simulating Summer Warming of the Great Lakes: Understanding the Behavior of a Newly Developed Coupled Lake‐Atmosphere Modeling System
Authors: Kayastha Miraj B. , Huang Chenfu , Wang Jiali , Pringle William J. , Chakraborty TC , Yang Zhao , Hetland Robert D. , Qian Yun , Xue Pengfei
Published: July 2023

The Laurentian Great Lakes are the world's largest freshwater system and regulate the climate of the Great Lakes region, which has been increasingly experiencing climatic, hydrological, and ecological changes. An accurate mechanistic representation of the Great Lakes thermal structure in Regional Climate Models (RCMs) is paramount to studying the climate of this region. Currently, RCMs have primarily represented the Great Lakes through coupled one‐dimensional (1D) column lake models; this approach works well for small inland lakes but is unable to resolve the realistic hydrodynamics of the Great Lakes and leads to inaccurate representations of lake surface temperature (LST) that influence regional climate and weather patterns. This work overcomes this limitation by developing a fully two‐way coupled modeling system using the Weather Research and Forecasting model and a three‐dimensional (3D) hydrodynamic model. The coupled model system resolves the interactive physical processes between the atmosphere, lake, and surrounding watersheds; and validated against a range of observational data. The model is then used to investigate the potential impacts of lake‐atmosphere coupling on the simulated summer LST of Lake Superior. By evaluating the difference between our two‐way coupled modeling system and our observation‐driven modeling system, we find that coupled‐lake atmosphere dynamics can lead to a higher LST during June‐September through higher net surface heat flux entering the lake in June and July and a lower net surface heat flux entering the lake in August and September. The unstratified water in June distributes the entering surface heat flux throughout the water column leading to a minor LST increase, while the stratified waters of July create a conducive thermal structure for the water surface to warm rapidly under the higher incoming surface heat flux. This research provides insight into the coupled modeling system behavior, which is critical for enhancing our predictive understanding of the Great Lakes climate system.
How Well do We Understand the Planck Feedback?
Authors: Cronin Timothy W. , Dutta Ishir
Published: July 2023

A reference or “no‐feedback” radiative response to warming is fundamental to understanding how much global warming will occur for a given change in greenhouse gases or solar radiation incident on the Earth. The simplest estimate of this radiative response is given by the Stefan‐Boltzmann law as  W m−2 K−1 for Earth's present climate, where is a global effective emission temperature. The comparable radiative response in climate models, widely called the “Planck feedback,” averages −3.3 W m−2 K−1. This difference of 0.5 W m−2 K−1 is large compared to the uncertainty in the net climate feedback, yet it has not been studied carefully. We use radiative transfer models to analyze these two radiative feedbacks to warming, and find that the difference arises primarily from the lack of stratospheric warming assumed in calculations of the Planck feedback (traditionally justified by differing constraints on and time scales of stratospheric adjustment relative to surface and tropospheric warming). The Planck feedback is thus masked for wavelengths with non‐negligible stratospheric opacity, and this effect implicitly acts to amplify warming in current feedback analysis of climate change. Other differences between Planck and Stefan‐Boltzmann feedbacks arise from temperature‐dependent gas opacities, and several artifacts of nonlinear averaging across wavelengths, heights, and different locations; these effects partly cancel but as a whole slightly destabilize the Planck feedback. Our results point to an important role played by stratospheric opacity in Earth's climate sensitivity, and clarify a long‐overlooked but notable gap in our understanding of Earth's reference radiative response to warming.
Effects of Multiple Drivers of Environmental Change on Native and Invasive Macroalgae in Nearshore Groundwater Dependent Ecosystems
Authors: Okuhata B. K. , Delevaux J. M. S. , Richards Donà A. , Smith C. M. , Gibson V. L. , Dulai H. , El‐Kadi A. I. , Stamoulis K. , Burnett K. M. , Wada C. A. , Bremer L. L.
Published: July 2023

Groundwater dependent ecosystems (GDE) are increasingly recognized as critical components of sustainable groundwater management, but are threatened by multiple drivers of environmental change. Despite this importance, data that link drivers of hydrologic change to GDEs are scarce. This study adapts a land‐sea modeling framework by calibrating marine models with macroalgal experiments to quantitatively assess impacts of climate and land use change on submarine groundwater discharge (SGD) and subsequent habitat suitability for a native (Ulva lactuca) and an invasive (Hypnea musciformis) macroalgae in nearshore GDEs in Kona, Hawai'i. Lab analyses demonstrate that while U. lactuca grows optimally in low‐salinity, high‐nutrient waters, H. musciformis appears constrained to a salinity threshold and exhibits low growth in low salinity despite high nutrient concentrations. Land‐sea model results predict that while a dry future climate (Representative Concentration Pathway 8.5 mid‐century) coupled with increased urban development will likely reduce SGD, protecting native forests may prevent further loss of SGD quantity. This prevention thus partially mitigates the decline in habitat suitability of U. lactuca due to the combined effects of climate and land use change. Findings also suggest that, in contrast to the native U. lactuca, reductions in SGD may favor H. musciformis growth if introduced to Kona. Collectively, this study demonstrates the importance of considering multiple drivers of environmental change on GDEs. This study bridges experiments with models to spatially map changes in species abundance beyond their current habitat conditions, and thus informs management actions that can explicitly incorporate future human and climate‐related impacts.
Single-cell transcriptomic profiles in the pathophysiology within the microenvironment of early diabetic kidney disease
Authors: Tsai Yi-Chun , Kuo Mei-Chuan , Huang Juan-Chi , Chang Wei-An , Wu Ling-Yu , Huang Yung-Chi , Chang Chao-Yuan , Lee Su-Chu , Hsu Ya-Ling
Published: July 2023

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, resulting in a huge socio-economic impact. Kidney is a highly complex organ and the pathogenesis underlying kidney organization involves complex cell-to-cell interaction within the heterogeneous kidney milieu. Advanced single-cell RNA sequencing (scRNA-seq) could reveal the complex architecture and interaction with the microenvironment in early DKD. We used scRNA-seq to investigate early changes in the kidney of db/m mice and db/db mice at the 14th week. Uniform Manifold Approximation and Projection were applied to classify cells into different clusters at a proper resolution. Weighted gene co-expression network analysis was used to identify the key molecules specifically expressed in kidney tubules. Information of cell–cell communication within the kidney was obtained using receptor-ligand pairing resources. In vitro model, human subjects, and co-detection by indexing staining were used to identify the pathophysiologic role of the hub genes in DKD. Among four distinct subsets of the proximal tubule (PT), lower percentages of proliferative PT and PT containing AQP4 expression (PTAQP4+) in db/db mice induced impaired cell repair activity and dysfunction of renin-angiotensin system modulation in early DKD. We found that ferroptosis was involved in DKD progression, and ceruloplasmin acted as a central regulator of the induction of ferroptosis in PTAQP4+. In addition, lower percentages of thick ascending limbs and collecting ducts with impaired metabolism function were also critical pathogenic features in the kidney of db/db mice. Secreted phosphoprotein 1 (SPP1) mediated pathogenic cross-talk in the tubular microenvironment, as validated by a correlation between urinary SPP1/Cr level and tubular injury. Finally, mesangial cell-derived semaphorin 3C (SEMA3C) further promoted endothelium-mesenchymal transition in glomerular endothelial cells through NRP1 and NRP2, and urinary SEMA3C/Cr level was positively correlated with glomerular injury. These data identified the hub genes involved in pathophysiologic changes within the microenvironment of early DKD.
Super-enhancer-driven MLX mediates redox balance maintenance via SLC7A11 in osteosarcoma
Authors: Guo Weitang , Wang Xin , Lu Bing , Yu Jiaming , Xu Mingxian , Huang Renxuan , Cheng Mingzhe , Yang Meiling , Zhao Wei , Zou Changye
Published: July 2023

Osteosarcoma (OS) is a common type of bone tumor for which there has been limited therapeutic progress over the past three decades. The prevalence of transcriptional addiction in cancer cells emphasizes the biological significance and clinical relevance of super-enhancers. In this study, we found that Max-like protein X (MLX), a member of the Myc-MLX network, is driven by super-enhancers. Upregulation of MLX predicts a poor prognosis in osteosarcoma. Knockdown of MLX impairs growth and metastasis of osteosarcoma in vivo and in vitro. Transcriptomic sequencing has revealed that MLX is involved in various metabolic pathways (e.g., lipid metabolism) and can induce metabolic reprogramming. Furthermore, knockdown of MLX results in disturbed transport and storage of ferrous iron, leading to an increase in the level of cellular ferrous iron and subsequent induction of ferroptosis. Mechanistically, MLX regulates the glutamate/cystine antiporter SLC7A11 to promote extracellular cysteine uptake required for the biosynthesis of the essential antioxidant GSH, thereby detoxifying reactive oxygen species (ROS) and maintaining the redox balance of osteosarcoma cells. Importantly, sulfasalazine, an FDA-approved anti-inflammatory drug, can inhibit SLC7A11, disrupt redox balance, and induce massive ferroptosis, leading to impaired tumor growth in vivo. Taken together, this study reveals a novel mechanism in which super-enhancer-driven MLX positively regulates SLC7A11 to meet the alleviated demand for cystine and maintain the redox balance, highlighting the feasibility and clinical promise of targeting SLC7A11 in osteosarcoma.
Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England
Authors: Perez-Guzman Pablo N. , Knock Edward , Imai Natsuko , Rawson Thomas , Santoni Cosmo Nazzareno , Alcada Joana , Whittles Lilith K. , Thekke Kanapram Divya , Sonabend Raphael , Gaythorpe Katy A. M. , Hinsley Wes , FitzJohn Richard G. , Volz Erik , Verity Robert , Ferguson Neil M. , Cori Anne , Baguelin Marc
Published: July 2023

As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.4 (95% credible interval (CrI) 7.8-9.1). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of immunity in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (3.0%, 95% CrI 2.8-3.2), followed by Delta (2.1%, 95% CrI 1.9–2.4), Wildtype (1.2%, 95% CrI 1.1–1.2), and Omicron (0.7%, 95% CrI 0.6-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.
Epigenetic mechanisms to propagate histone acetylation by p300/CBP
Authors: Kikuchi Masaki , Morita Satoshi , Wakamori Masatoshi , Sato Shin , Uchikubo-Kamo Tomomi , Suzuki Takehiro , Dohmae Naoshi , Shirouzu Mikako , Umehara Takashi
Published: July 2023

Histone acetylation is important for the activation of gene transcription but little is known about its direct read/write mechanisms. Here, we report cryogenic electron microscopy structures in which a p300/CREB-binding protein (CBP) multidomain monomer recognizes histone H4 N-terminal tail (NT) acetylation (ac) in a nucleosome and acetylates non-H4 histone NTs within the same nucleosome. p300/CBP not only recognized H4NTac via the bromodomain pocket responsible for reading, but also interacted with the DNA minor grooves via the outside of that pocket. This directed the catalytic center of p300/CBP to one of the non-H4 histone NTs. The primary target that p300 writes by reading H4NTac was H2BNT, and H2BNTac promoted H2A-H2B dissociation from the nucleosome. We propose a model in which p300/CBP replicates histone N-terminal tail acetylation within the H3-H4 tetramer to inherit epigenetic storage, and transcribes it from the H3-H4 tetramer to the H2B-H2A dimers to activate context-dependent gene transcription through local nucleosome destabilization.
Acquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella
Authors: Morreale Daniel P. , Porsch Eric A. , Kern Brad K. , St. Geme Joseph W. , Planet Paul J.
Published: July 2023

The bacterial genusKingellaincludes two pathogenic species, namelyKingella kingaeandKingella negevensis, as well as strictly commensal species. BothK. kingaeandK. negevensissecrete a toxin called RtxA that is absent in the commensal species. Here we present a phylogenomic study of the genusKingella, including new genomic sequences for 88 clinical isolates, genotyping of another 131 global isolates, and analysis of 52 available genomes. The phylogenetic evidence supports that the toxin-encoding operonrtxCAwas acquired by a common ancestor of the pathogenicKingellaspecies, and that a preexisting type-I secretion system was co-opted for toxin export. Subsequent genomic reorganization distributed the toxin machinery across two loci, with 30-35% ofK. kingaestrains containing two copies of thertxAtoxin gene. ThertxAduplication is largely clonal and is associated with invasive disease. Assays with isogenic strains show that a single copy ofrtxAis associated with reduced cytotoxicity in vitro. Thus, our study identifies key steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer, co-option of an existing secretion system, and gene duplication.
Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma
Authors: Chen Xiao , Li Yinglu , Zhu Fang , Xu Xinjing , Estrella Brian , Pazos Manuel A. , McGuire John T. , Karagiannis Dimitris , Sahu Varun , Mustafokulov Mustafo , Scuoppo Claudio , Sánchez-Rivera Francisco J. , Soto-Feliciano Yadira M. , Pasqualucci Laura , Ciccia Alberto , Amengual Jennifer E. , Lu Chao
Published: July 2023

Interplay between chromatin-associated complexes and modifications critically contribute to the partitioning of epigenome into stable and functionally distinct domains. Yet there is a lack of systematic identification of chromatin crosstalk mechanisms, limiting our understanding of the dynamic transition between chromatin states during development and disease. Here we perform co-dependency mapping of genes using CRISPR-Cas9-mediated fitness screens in pan-cancer cell lines to quantify gene-gene functional relationships. We identify 145 co-dependency modules and further define the molecular context underlying the essentiality of these modules by incorporating mutational, epigenome, gene expression and drug sensitivity profiles of cell lines. These analyses assign new protein complex composition and function, and predict new functional interactions, including an unexpected co-dependency between two transcriptionally counteracting chromatin complexes - polycomb repressive complex 2 (PRC2) and MLL-MEN1 complex. We show that PRC2-mediated H3K27 tri-methylation regulates the genome-wide distribution of MLL1 and MEN1. In lymphoma cells with EZH2 gain-of-function mutations, the re-localization of MLL-MEN1 complex drives oncogenic gene expression and results in a hypersensitivity to pharmacologic inhibition of MEN1. Together, our findings provide a resource for discovery of trans-regulatory interactions as mechanisms of chromatin regulation and potential targets of synthetic lethality.
Long-term durability of metastable β-Fe2O3 photoanodes in highly corrosive seawater
Authors: Liu Changhao , Zhang Ningsi , Li Yang , Fan Rongli , Wang Wenjing , Feng Jianyong , Liu Chen , Wang Jiaou , Hao Weichang , Li Zhaosheng , Zou Zhigang
Published: July 2023

Durability is one prerequisite for material application. Photoelectrochemical decomposition of seawater is a promising approach to produce clean hydrogen by using solar energy, but it always faces the problem of serious Cl− corrosion. We find that the main deactivation mechanism of the photoanode is oxide surface reconstruction accompanied by the coordination of Cl− during seawater splitting, and the stability of the photoanode can be effectively improved by enhancing the metal-oxygen interaction. Taking the metastable β-Fe2O3 photoanode as an example, Sn added to the lattice can enhance the M–O bonding energy and hinder the transfer of protons to lattice oxygen, thereby inhibiting excessive surface hydration and Cl− coordination. Therefore, the bare Sn/β-Fe2O3 photoanode delivers a record durability for photoelectrochemical seawater splitting over 3000 h.
Enabling programmable dynamic DNA chemistry using small-molecule DNA binders
Authors: Xu Junpeng , Wang Guan Alex , Gao Lu , Wu Lang , Lei Qian , Deng Hui , Li Feng
Published: July 2023

The binding of small molecules to the double helical structure of DNA, through either intercalation or minor groove binding, may significantly alter the stability and functionality of DNA, which is a fundamental basis for many therapeutic and sensing applications. Here, we report that small-molecule DNA binders can also be used to program reaction pathways of a dynamic DNA reaction, where DNA strand displacement can be tuned quantitatively according to the affinity, charge, and concentrations of a given DNA binder. The binder-induced nucleic acid strand displacement (BIND) thus enables innovative technologies to accelerate the discovery and characterization of bioactive small molecules. Specifically, we demonstrate the comprehensive characterization of existing and newly discovered DNA binders, where critical parameters for binding affinity and sequence selectivity can be obtained in a single, unbiased molecular platform without the need for any specialized equipment. We also engineer a tandem BIND system as a high-throughput screening assay for discovering DNA binders, through which 8 DNA binders were successfully discovered from a library of 700 compounds.
In-sensor computing using a MoS2 photodetector with programmable spectral responsivity
Authors: Kwak Dohyun , Polyushkin Dmitry K. , Mueller Thomas
Published: July 2023

Optical spectroscopy is an indispensable technique in almost all areas of scientific research and industrial applications. After its acquisition, an optical spectrum is usually further processed using a mathematical algorithm to classify or quantify the measurement results. Here we present the design and realization of a smart photodetector that provides such information directly without the need to explicitly record a spectrum. This is achieved by tailoring the spectral responsivity of the device to a specific purpose. In-sensor computation is performed at the lowest possible level of the sensor system hierarchy – the physical level of photon detection – and does not require any external processing of the measurement data. The device can be programmed to cover different types of spectral regression or classification tasks. We present the analysis of spectral mixtures as an example, but the scheme can also be applied to any other algorithm that can be represented by a linear operator. Our prototype physical implementation utilizes an ensemble of optical cavity-enhanced MoS2 photodetectors with different center wavelengths and individually adjustable peak responsivities. This spectroscopy method represents a significant advance in miniaturized and energy-efficient optical sensing.
Wearable bioelectronics fabricated in situ on skins
Authors: Ershad Faheem , Patel Shubham , Yu Cunjiang
Published: July 2023

In recent years, wearable bioelectronics has rapidly expanded for diagnosing, monitoring, and treating various pathological conditions from the skin surface. Although the devices are typically prefabricated as soft patches for general usage, there is a growing need for devices that are customized in situ to provide accurate data and precise treatment. In this perspective, the state-of-the-art in situ fabricated wearable bioelectronics are summarized, focusing primarily on Drawn-on-Skin (DoS) bioelectronics and other in situ fabrication methods. The advantages and limitations of these technologies are evaluated and potential future directions are suggested for the widespread adoption of these technologies in everyday life.
Life-long phishing attack detection using continual learning
Authors: Ejaz Asif , Mian Adnan Noor , Manzoor Sanaullah
Published: July 2023

Phishing is an identity theft that employs social engineering methods to get confidential data from unwary users. A phisher frequently attempts to trick the victim into clicking a URL that leads to a malicious website. Many phishing attack victims lose their credentials and digital assets daily. This study demonstrates how the performance of traditional machine learning (ML)-based phishing detection models deteriorates over time. This failure is due to drastic changes in feature distributions caused by new phishing techniques and technological evolution over time. This paper explores continual learning (CL) techniques for sustained phishing detection performance over time. To demonstrate this behavior, we collect phishing and benign samples for three consecutive years from 2018 to 2020 and divide them into six datasets to evaluate traditional ML and proposed CL algorithms. We train a vanilla neural network (VNN) model in the CL fashion using deep feature embedding of HTML contents. We compare the proposed CL algorithms with the VNN model trained from scratch and with transfer learning (TL). We show that CL algorithms maintain accuracy over time with a tolerable deterioration of 2.45%. In contrast, VNN and TL-based models’ performance deteriorates by over 20.65% and 8%, respectively.
Estimating generation time of SARS-CoV-2 variants in Italy from the daily incidence rate
Authors: Lippiello Eugenio , Petrillo Giuseppe , Baccari Silvio , de Arcangelis Lucilla
Published: July 2023

The identification of the transmission parameters of a virus is fundamental to identify the optimal public health strategy. These parameters can present significant changes over time caused by genetic mutations or viral recombination, making their continuous monitoring fundamental. Here we present a method, suitable for this task, which uses as unique information the daily number of reported cases. The method is based on a time since infection model where transmission parameters are obtained by means of an efficient maximization procedure of the likelihood. Applying the method to SARS-CoV-2 data in Italy, we find an average generation time $${\overline{z}}=3.2 \pm 0.8$$

z
¯

=
3.2
±
0.8

days, during the temporal window when the majority of infections can be attributed to the Omicron variants. At the same time we find a significantly larger value $${\overline{z}}=6.2\pm 1.1$$

z
¯

=
6.2
±
1.1

days, in the temporal window when spreading was dominated by the Delta variant. We are also able to show that the presence of the Omicron variant, characterized by a shorter $${{\overline{z}}}$$

z
¯

, was already detectable in the first weeks of December 2021, in full agreement with results provided by sequences of SARS-CoV-2 genomes reported in national databases. Our results therefore show that the novel approach can indicate the existence of virus variants, resulting particularly useful in situations when information about genomic sequencing is not yet available. At the same time, we find that the standard deviation of the generation time does not significantly change among variants.
The animacy effect on free recall is equally large in mixed and pure word lists or pairs
Authors: Komar Gesa Fee , Mieth Laura , Buchner Axel , Bell Raoul
Published: July 2023

The cognitive mechanisms underlying the animacy effect on free recall have as yet to be identified. According to the attentional-prioritization account, animate words are better recalled because they recruit more attention at encoding than inanimate words. The account implies that the animacy effect should be larger when animate words are presented together with inanimate words in mixed lists or pairs than when animate and inanimate words are presented separately in pure lists or pairs. The present series of experiments served to systematically test whether list composition or pair composition modulate the animacy effect. In Experiment 1, the animacy effect was compared between mixed and pure lists. In Experiments 2 and 3, the words were presented in mixed or pure pairs to manipulate the direct competition for attention between animate and inanimate words at encoding. While encoding was intentional in Experiments 1 and 2, it was incidental in Experiment 3. In each experiment, a significant animacy effect was obtained, but the effect was equally large in mixed and pure lists or pairs of animate and inanimate words despite considerable sensitivity of the statistical test of the critical interaction. These findings provide evidence against the attentional-prioritization account of the animacy effect.