bluuebunny/crossref_metadata_2025 huggingface dataset:
Groundwater quality assessment along the West of New Damietta Coastal City of Egypt using an integrated geophysical and hydrochemical approaches
Authors: Gamal Gehad , Hassan Taher Mohammed , Gaber Ahmed , Abdelfattah Mohamed
Published: February 2023

Recently, the groundwater became very important source for the Egyptian water balance. Therefore, assessing its quality and quantity is necessary before initiating any developmental plans using this resource. In this research, a new operated power plant, which is located in the coastal area of West New Damietta City, north-east of Egypt was designed to work using the coastal groundwater aquifer. Therefore, an integrated approaches of both geophysical methods and hydrochemical analysis were applied to identify the subsurface lithology, the water-bearing layers and determine the potential use of such coastal groundwater. Therefore, a total of seventeen vertical electrical soundings (VES) and five time-domain electromagnetic soundings (TEM) were performed. Moreover, groundwater samples were collected from seven existing wells to be analyzed for water quality assessment. The geophysical results identified five geoelectric layers. The first geoelectric layer has a resistivity of 1–7.9 Ω m and a thickness range of 7–9 m. The second layer has a resistivity of 0.9–4.4 Ω m and a thickness range of 7–8 m. The third layer is 10–21 m thick with a resistivity value of 0.5–2 Ω m. The fourth layer, which is thicker (29 to 42 m), has a resistivity of 0.7–3 Ω m, while the last layer has a resistivity of 1.7–9 Ω m. According to the hydrochemical analysis, the aquifer is dominated by Na–Cl water type. The brackish nature of the water is revealed by the TDS range of 7035 mg/l to 7735 mg/l. The results collected demonstrate the groundwater's quantity and quality availability for the power plant’s sustainable use.
Examples of twice differentiable functions with continuous Laplacian and unbounded Hessian
Authors: Pan Yifei , Yan Yu
Published: February 2023

We construct examples of twice differentiable functions in $${\mathbb {R}}^n$$

R

n

with continuous Laplacian and unbounded Hessian. The same construction is also applicable to higher order differentiability.
Blown away? Wind speed and foraging success in an acoustic predator
Authors: Renda Samantha , Périquet Stéphanie , le Roux Aliza
Published: February 2023

Foraging animals must contend with fluctuating environmental variables that affect foraging success, including conditions like wind noise, which could diminish the usefulness of particular sensory modes. Although the documented impact of anthropogenic noise on animal behavior has become clear, there is limited research on natural noise and its potential influence on mammalian behavior. We investigated foraging behavior in the myrmecophagous bat-eared fox (Otocyon megalotis), a species known to rely predominantly on hearing for prey detection. For a year, we monitored the foraging behavior of 18 bat-eared foxes from a habituated population in South Africa, amidst varying wind speeds (0–15.5 km/h). In contrast to expectations, foraging rates did not generally decline with increasing wind speed, except for foraging rate outside termite patches in fall. Furthermore, wind speed had little correlation with time spent in patches. In winter, however, we observed an increase in foraging rate with increasing wind speed both within and outside patches. At the observed wind speeds, these acoustically driven insectivores continue to forage effectively despite potentially distracting or masking noises. With anthropogenic noise producing sound across a broader frequency range, it is important to examine the responses of these canids to artificial sources of acoustic disturbance as well.
‘Teachers are the guinea pigs’: teacher perspectives on a sudden reopening of schools during the COVID-19 pandemic
Authors: Ryan Jillian , Koehler Nicole , Cruickshank Travis , Rogers Shane L. , Stanley Mandy
Published: February 2023

Primary and secondary education systems experienced substantial disruption during the COVID-19 pandemic. However, little is known about how public health policy has affected Australian teachers during the pandemic. This study examines teacher perspectives on a sudden change of policy, whereby schools were abruptly opened to students at the beginning of the pandemic. At the same time, strict social distancing rules applied to the remainder of the population. Qualitative data from 372 Western Australian schoolteachers were analysed using thematic analysis. Results highlight substantial impacts on teachers’ workloads and adverse effects on wellbeing. Perceptions that they were acting as guinea pigs and subjected to different social distancing rules than other citizens were particular stressors. Findings highlight substantial consequences of public health policies on the roles and wellbeing of teachers.
Biomass gasification to syngas in thermal water vapor arc discharge plasma
Authors: Tamošiūnas Andrius , Gimžauskaitė Dovilė , Aikas Mindaugas , Uscila Rolandas , Snapkauskienė Vilma , Zakarauskas Kęstutis , Praspaliauskas Marius
Published: February 2023

This study investigated biomass (wood pellets) gasification to syngas using direct current (DC) thermal arc plasma at atmospheric pressure. Water vapor was used as a main gasifying agent and a plasma-forming gas. The biomass gasification system was quantified in terms of the producer gas composition, the tar content, the H2/CO ratio, the carbon conversion efficiency, the energy conversion efficiency and the specific energy requirements. It was found that the gasification performance efficiency was highest at the water vapor-to-biomass ratio of 0.97. The producer gas was mostly composed of H2 (43.86 vol.%) and CO (30.93 vol.%), giving the H2/CO ratio of 1.42 and the LHV of 10.23 MJ/Nm3. However, high content of tars of 13.81 g/Nm3 was obtained in the syngas. The yield of H2 and CO was 48.31% and 58.13%, respectively, with the highest producer gas yield of 2.42 Nm3/kg biomass. The carbon conversion efficiency and the energy conversion efficiency were 100% and 48.83%, respectively, and the production of 1 kg of syngas required 1.78 kWh of electric energy input. Finally, the obtained results were compared with different plasma methods, including plasma-assisted application coupled with conventional gasification.
Effects of Probiotic and Selenium Co-supplementation on Lipid Profile and Glycemia Indices: A Systematic Review and Meta-analysis of Randomized Clinical Trials
Authors: Mohammadparast Vida , Mohammadi Tanin , Karimi Elham , Mallard Beth L.
Published: February 2023

Purpose of Review

The current systematic review and meta-analysis was done to evaluate the effects of selenium and probiotic co-supplementation on lipid profile and glycemia indices of the adult population using randomized controlled clinical trials (RCTs).

Recent Findings

Five studies involving 282 participants with a sample size ranging from 38 to 79 were eligible to be enrolled in the current study. Co-supplementation with probiotic and selenium reduced fasting plasma glucose (WMD =  −4.02 mg/dL; 95% CI: −5.87 to −2.18; P < 0.001), insulin (WMD =  −2.50 mIU/mL; 95% CI: −3.11 to −1.90; P < 0.001), homeostatic model assessment for insulin resistance (WMD =  −0.59; 95% CI: −0.74 to −0.43; P < 0.001), quantitative insulin sensitivity check index (WMD = 0.01; 95% CI: 0.01 to 0.02; P < 0.001), total cholesterol (WMD =  −12.75 mg/dL; 95% CI: −19.44 to −6.07; P < 0.001), low-density lipoprotein cholesterol (WMD =  −7.09 mg/dL; 95% CI: −13.45 to −0.73; P = 0.029), and triglyceride (WMD =  −14.38 mg/dL; 95% CI: −23.13 to −5.62; P = 0.001).

The findings of the current systematic review and meta-analysis suggested that co-supplementation with probiotics and selenium may benefit adults in terms of glycemia indices and lipid profile. However, due to the small number of included studies, further trials are needed to confirm our findings.
Strengthening Global Legislative Actions to Protect Children from the Harmful Impacts of Unhealthy Food and Non-alcoholic Beverage Marketing
Authors: Sing Fiona , Backholer Kathryn
Published: February 2023

Purpose of Review

Drawing on current global food marketing policies and the academic literature, we illustrate why and how existing legislative approaches can be strengthened to better achieve the goal of protecting children from the harmful impacts of unhealthy food and non-alcoholic beverage marketing.

Recent Findings

Around the world, governments are starting to implement legislative actions to protect children from exposure to unhealthy food and non-alcoholic beverage marketing. However, the scope of these approaches is limited and unlikely to meet their objective of safeguarding children from harmful marketing practices. The key opportunities for strengthening legislative design include increasing the age threshold of a child to 18 years; the broadening of focus from ‘child-directed’ marketing to all marketing that children are exposed to; designing tailored regulations for multiple settings, media and techniques; strengthening underlying food classification systems; balancing a comprehensive approach with stepwise regulatory implementation; and strengthening monitoring and enforcement systems.

Our review and recommendations can aid policymakers when designing legislative approaches to protect children from the harmful impacts of unhealthy food and non-alcoholic beverage marketing.
Are the ecotoxicological tools viable to evaluate the effectiveness of wastewater treatment plant effluents?
Authors: Diogo B. S. , Rodrigues S. , Lage O. M. , Antunes S. C.
Published: February 2023

Ecotoxicological tools have proved to be sensitive and appropriate for the evaluation of the effectiveness of treatments used in wastewater treatment plants (WWTP). The objective of this study was to assess the applicability of bioassays and biomarkers to evaluate the efficiency of different treatments throughout WWTP samples[A—raw influent, B—preliminary effluent, C—final effluent, and D—receiving stream], seasonally over 1 year, through a multispecies approach: i) bacterial cell viability [Escherichia coli, Rhodopirellulla rubra, Arthrobacter sp., and Pseudomonas putida]; ii) microalgae Raphidocelis subcapitata and the macrophyte Lemna minor growth inhibition; and iii) microcrustacean Daphnia magna acute and feeding rate assays. Total chlorophyll, malondialdehyde, and proline levels were evaluated in L. minor, and catalase, glutathione-S-transferase activities, and thiobarbituric acid reactive substances levels were quantified in D. magna, after exposure to wastewater samples. Overall, the tested species showed different sensitivities, P. putida = Arthrobacter sp. = R. rubra < R. subcapitata < E. coli = D. magna = L. minor, to the collected samples. The results obtained in D. magna and L. minor assays demonstrated that these organisms can be used in programs for monitoring and environmental assessment of wastewater effluents. The present study demonstrates the usefulness of ecotoxicological tools, with multispecies and different endpoints, to assess the effectiveness of WWTPs. Moreover, it is important to ensure that WWTP implements a monitoring program to minimize the discharge of effluents that compromise the environment in order to guarantee the good ecological quality of the environmental ecosystems.
Fatigue strength of shot-peened as-welded joints and post-weld-treated and subsequently clean-blasted fillet weld joints
Authors: Ahola A. , Lipiäinen K. , Riski J. , Koskimäki M. , Pyörret J. , Björk T.
Published: February 2023

Surface treatment methods, such as shot peening and clean blasting, can improve the fatigue strength of welded joints. The aim of the current work is to experimentally evaluate the effects of clean blasting on the fatigue performance of post-weld-treated joints made of normal, high-strength, and ultra-high-strength steels, as well as obtain the fatigue strength improvement gained by the shot peening processes in welded connections made of different steel grades using literature data. A literature review was carried out to extract fatigue test data of welded joints, considering both clean blasting and shot peening processes. This data was statistically re-evaluated and used for a comparison to the results obtained in the current experimental work which focuses on evaluating the improvement gained by the clean blasting after post-weld treatments. Experimental fatigue tests were carried out on non-load-carrying transverse attachment joints prepared with gas metal arc welding, and made of S355, S700, and S1100 structural steels. TIG dressing and HFMI treatment post-weld treatments were implemented and, subsequently, the specimens were blast-cleaned using two different abrasives: corundum and sand. The re-analysis of existing fatigue test data indicated higher improvement by shot peening, i.e., average improvements of 1.71 and 1.52 in the fatigue strength for butt weld and fillet weld joints, respectively, than by clean blasting process for which an average improvement of 1.19 in fatigue strength was obtained. The enhancement factors, however, highly varied among different data sets indicating a clear impact of processing parameters on the improvement level. The statistical re-analyses considering all data sets of shot-peened specimens (butt weld and fillet weld joints) showed that one fatigue (FAT) class higher fatigue strength could be recommended for shot-peened joints compared to the as-welded condition with weld toe failures. The experimental work on the post-weld-treated joints indicated that the fatigue strength of clean-blasted joints was similar to that of non-blasted joints, and thus showing no major advantages or disadvantages by the clean blasting post-weld-treated joints with corundum and sand.
On the differential transcendentality of the Morita p-adic gamma function
Authors: Adamus Elżbieta
Published: February 2023

In p-adic analysis one can find an analog of the classical gamma function defined on the ring of p-adic integers. In 1975, Morita defined the p-adic gamma function $$\Gamma _p$$

Γ
p

by a suitable modification of the function $$n \mapsto n!$$

n
↦
n
!

. In this note we prove that for any given prime number p the Morita p-adic gamma function $$\Gamma _p$$

Γ
p

is differentially transcendental over $${\mathbb {C}}_p(X)$$

C
p

(
X
)

. The main result is an analog of the classical Hölder’s theorem, which states that Euler’s gamma function $$\Gamma $$
Γ
does not satisfy any algebraic differential equation whose coefficients are rational functions.
What Works for Whom? Evaluating Patterns and Mechanisms of Change Among Bullies, Victims, and Bully-Victims Participating in a School-Based Prevention Program
Authors: Strohmeier Dagmar , Stefanek Elisabeth , Yanagida Takuya
Published: February 2023

The effectiveness and program mechanisms of a whole-school anti-bullying program that builds on the socio-ecological framework were investigated by applying person-oriented methods of data analyses. A longitudinal cluster randomized control study was utilized comprising 1377 adolescents (48.5% girls, Mage = 11.7) who participated in a 1-year whole school anti-bullying program that was implemented in 13 schools and 665 adolescents (45.2% girls, Mage = 11.6) who attended 5 control schools. Student reports were collected at pre- and post-test within a 1-year interval. Applying latent profile analyses (LPA), students who were actively involved in bullying as perpetrators (e.g., bullies), who were the target of bullying (e.g., victims), who were both (e.g., bully-victims), and who were not involved either as perpetrators or victims (e.g., uninvolved) were identified. Latent transition analyses (LTA) investigated transition patterns between bully, victim, bully-victim, and uninvolved subgroups in the control and intervention group before and after the 1-year program implementation. Program effectiveness (e.g., a higher transition probability in the intervention compared to the control group) were found for victims and bully-victims. It was explored whether changes in program mechanisms were differently related to changes in these sub-group memberships in the intervention group. Victims transiting to the uninvolved sub-group increased in help-seeking and anti-bullying norms, while bully-victims transiting to the uninvolved sub-group increased help-seeking, perceived teacher intervention, and anti-bullying norms. It can be concluded that this program works differently for different sub-groups of students and that different mechanisms of change drive changes in different sub-groups of students.
Analysis of local system behavior in the foreign exchange-market using neural networks and Monte-Carlo method for predictıon and risk assessment
Authors: Aşırım Adil , Aşırım Özüm Emre , Salepçioğlu Murat Adil
Published: February 2023

In this study, we attempt to show the reason behind the poor estimation of the future values of foreign exchange-rate (FXR) signals under difference-equation modeling, using the neural network approach for evaluating the local system coefficients. To do this, we have splitted EUR/USD and AUD/CAD signals into many small-segments and modeled each segment as the signal representation of a linear time-invariant (LTI) system using the simple linear difference equation (LDE) formulation. After a precise segmentation of each FXR signal such that an LTI system based modeling is highly accurate in each segment, it is observed that the coefficient values of the corresponding LDEs are highly volatile, which indicates that a reliable estimation would be very difficult using LDE modeling. Although the LDE coefficients are usually observed to take values within a small range over a given FXR signal segment (sample-set), frequent sudden-jumps in coefficient values do occur, which subjects/forces the dynamics of FXR signals to undertake the dynamics of these sudden-jumps rather than the dynamics of any other deterministic or stochastic process. To support this observation, the range of variation of the LDE coefficients over each segment is analyzed to quantify the volatility of the foreign-exchange market for risk assessment.
Female students as victims of sexual abuse at institutions of higher learning: insights from Kwazulu-natal, South Africa
Authors: Makhaye Mandisa Samukelisiwe , Mkhize Sazelo Michael , Sibanyoni Ephraim Kevin
Published: February 2023

The focus of the wider study on which this paper is based was to uncover the social context of the sexual victimisation phenomenon in three selected institutions of higher learning in Durban, KwaZulu-Natal Province, South Africa. The objectives of the study were to examine the nature of sexual victimisation against female students in selected universities in Durban; to determine the factors that contribute to the sexual victimisation of female students; to investigate the effects of sexual victimisation on female students and to explore the reasons for female students’ reluctance to report sexual victimisation. The sample comprised a total of 60 participants  who had been purposively selected from three universities in the study area. The data were collected by means of interviews and were thematically analysed. The study found that incapacitated rape is more common on campuses than forcible rape, which is when perpetrators use threats and/or physical force. This could be attributed to the excessive use of alcohol and drugs by both victims and perpetrators. The study also confirmed that female students are reluctant to report sexual victimisation to the authorities. A key recommendation is that security measures need to be upgraded to ensure a safe environment for female students on campuses in the study area.
Extended producer responsibility’s effect on producers’ electronic waste management practices in Japan and Canada: drivers, barriers, and potential of the urban mine
Authors: Portugaise Mika Kaibara , Jóhannsdóttir Lára , Murakami Shinsuke
Published: February 2023

Electronic waste is the fastest-growing domestic waste stream globally, continuously outstripping projections. With increasing ubiquity of complex computing, many non-renewables are contained in end-of-life electronics, creating a vast urban mine, potentially hazardous, depending on treatment. The aim of this study is to compare how Extended Producer Responsibility (EPR) policy is applied in two case countries, Japan and Canada, the practical implications of EPR policy design on producer operations, and how EPR affects electronic waste management improvements in each case. These cases share international obligations for electronic waste management but employ contrasting EPR policies. These policies are widespread in both cases, yet are not presided over by larger, regional obligations. Therefore, country-level interviews with electronic waste management stakeholders focusing on how EPR regulation affects producer practice were conducted. The physical application of EPR, as seen in Japan, drives design changes by producers intending to simplify downstream treatment, while financial responsibility in Canada, creates greater concern with cost-savings for producers, complicating end-of-life processing. EPR implementation, along with specific geographical factors, also create contrasting resource recovery results between countries. Regulation primarily drives EPR implementation in both countries, which is consistent with the literature. This study presents new drivers and barriers, namely pre-emptive legislation, and no incentive to improve, classifying the Japanese and Canadian systems as suffering from externalities on an insular system, and lack of harmonization, respectively. This research addresses a gap in comparative studies across regions of physical and financial EPR effects on producer practice.
DPReLU: Dynamic Parametric Rectified Linear Unit and Its Proper Weight Initialization Method
Authors: Yang Donghun , Ngoc Kien Mai , Shin Iksoo , Hwang Myunggwon
Published: February 2023

Activation functions are essential in deep learning, and the rectified linear unit (ReLU) is the most widely used activation function to solve the vanishing gradient problem. However, owing to the dying ReLU problem and bias shift effect, deep learning models using ReLU cannot exploit the potential benefits of negative values. Numerous ReLU variants have been proposed to address this issue. In this study, we propose Dynamic Parametric ReLU (DPReLU), which can dynamically control the overall functional shape of ReLU with four learnable parameters. The parameters of DPReLU are determined by training rather than by humans, thereby making the formulation more suitable and flexible for each model and dataset. Furthermore, we propose an appropriate and robust weight initialization method for DPReLU. To evaluate DPReLU and its weight initialization method, we performed two experiments on various image datasets: one using an autoencoder for image generation and the other using the ResNet50 for image classification. The results show that DPReLU and our weight initialization method provide faster convergence and better accuracy than the original ReLU and the previous ReLU variants.
Melville's Mirrors
Authors: Yothers Brian
Published: February 2023

An accessible and highly readable guide to the story of Melville criticism as it has developed over the past century and a half.
Nyerere
Authors: Molony Thomas
Published: February 2023

A uniquely detailed portrayal of the formative years of Tanzania's first president and the influences that led him to enter politics.
The Maya Battle, 786–1519
Authors: Miller Mary E.
Published: February 2023

A careful reading of the battle in the Bonampak murals offers new insights into eighth-century strategies for warfare, and the importance of overwhelming force in both aggression and deterrence. These same two strategies were critical during the Spanish invasion, especially in defense of freshwater resources. The murals of Bonampak provide insights into the Maya battle, including the emphasis on teamwork in execution of battle tactics and the seemingly contradictory emphasis on the individual, in terms of hieroglyphics. Despite exhaustive study of the paintings, the potential consideration of color-defined and pattern shields also may reveal groupings of warriors previously unrecognized in both battle and presentation of captives. Sixteenth-century accounts by Spanish invaders confirm a practice that includes defense of water sources along the coast of Yucatan, with details that can be evaluated regarding eighth-century Maya practice.
Cannabis use and episodic memory performance among adolescents: Moderating effects of depression symptoms and sex
Authors: Lehman Sarah M. , Thompson Erin L. , Pacheco-Colón Ileana , Hawes Samuel W. , Adams Ashley R. , Granja Karen , Pulido William J. , Gonzalez Raul
Published: February 2023

Objective:

Cannabis use has been linked to poorer episodic memory. However, little is known about whether depression and sex may interact as potential moderators of this association, particularly among adolescents. The current study addresses this by examining interactions between depression symptoms and sex on the association between cannabis use and episodic memory in a large sample of adolescents.

Method:

Cross-sectional data from 360 adolescents (Mage = 17.38, SD = .75) were analyzed at the final assessment wave of a two-year longitudinal study. We used the Drug Use History Questionnaire to assess for lifetime cannabis use, and the Computerized Diagnostic Interview Schedule for Children, Fourth edition to assess the number of depression symptoms in the past year. Subtests from the Wechsler Memory Scale, Fourth Edition and the California Verbal Learning Test, Second Edition were used to assess episodic memory performance.

Results:

The effect of the three-way interaction among cannabis use, depression symptoms, and sex did not have a significant impact on episodic memory performance. However, follow-up analyses revealed a significant effect of the two-way interaction of cannabis use and depression symptoms on episodic memory, such that associations between cannabis use and episodic memory were only significant at lower and average levels of depression symptoms.

Conclusions:

Contrary to our hypotheses, we found that as depression symptoms increased, the negative association between cannabis use and episodic memory diminished. Given the use of a predominantly subsyndromic sample, future studies should attempt to replicate findings among individuals with more severe depression.
Sensitivity of the Relationship Between Antarctic Ice Shelves and Iron Supply to Projected Changes in the Atmospheric Forcing
Authors: Dinniman Michael S. , St‐Laurent Pierre , Arrigo Kevin R. , Hofmann Eileen E. , van Dijken Gert L.
Published: February 2023

Upward advection or mixing of iron‐rich deep waters due to circulation changes driven by the rate of basal ice shelf melt was shown to be a primary control on chlorophyll a production in coastal polynyas over the Antarctic continental shelf. Here, the effects of atmospheric changes projected in 2100 on this relationship were examined with a 5‐km resolution ocean/sea ice/ice shelf model of the Southern Ocean with different simulated dissolved iron sources and idealized biological uptake. The atmospheric changes are added as idealized increments to the forcing. Inclusion of a poleward shift and strengthening of the winds, increased precipitation, and warmer atmospheric temperatures resulted in doubling of the heat advected onto the continental shelf and an 83% increase in the total Antarctic ice shelf basal melt. The total dissolved iron supply to the surface waters over the continental shelf increased by 62%, while the surface iron supply due just to basal melt driven overturning increased by 48%. However, even though the ice shelf driven contribution becomes less important to the total iron supply on average (29% of total), the ice shelf involvement becomes relatively even more important in some locations, such as the Amundsen and Bellingshausen Seas. The modified atmospheric conditions also produced a reduction in summer sea ice extent and a shoaling of the summer mixed layers. These simulated responses to projected changes suggest relief of light and nutrient limitation for phytoplankton blooms over the Antarctic continental shelf and perhaps an increase in annual production in years to come.
Physics‐Informed Neural Networks of the Saint‐Venant Equations for Downscaling a Large‐Scale River Model
Authors: Feng Dongyu , Tan Zeli , He QiZhi
Published: February 2023

Large‐scale river models are being refined over coastal regions to improve the scientific understanding of coastal processes, hazards and responses to climate change. However, coarse mesh resolutions and approximations in physical representations of tidal rivers limit the performance of such models at resolving the complex flow dynamics especially near the river‐ocean interface, resulting in inaccurate simulations of flood inundation. In this research, we propose a machine learning (ML) framework based on the state‐of‐the‐art physics‐informed neural network (PINN) to simulate the downscaled flow at the subgrid scale. First, we demonstrate that PINN is able to assimilate observations of various types and solve the one‐dimensional (1‐D) Saint‐Venant equations (SVE) directly. We perform the flow simulations over a floodplain and along an open channel in several synthetic case studies. The PINN performance is evaluated against analytical solutions and numerical models. Our results indicate that the PINN solutions of water depth have satisfactory accuracy with limited observations assimilated. In the case of flood wave propagation induced by storm surge and tide, a new neural network architecture is proposed based on Fourier feature embeddings that seamlessly encodes the periodic tidal boundary condition in the PINN's formulation. Furthermore, we show that the PINN‐based downscaling can produce more reasonable subgrid solutions of the along‐channel water depth by assimilating observational data. The PINN solution outperforms the simple linear interpolation in resolving the topography and dynamic flow regimes at the subgrid scale. This study provides a promising path toward improving emulation capabilities in large‐scale models to characterize fine‐scale coastal processes.
Photoacoustic tomography reveals structural and functional cardiac images of animal models
Authors: Paltauf Guenther
Published: February 2023

Three-dimensional photoacoustic tomography synchronized with an electrocardiogram provides highly resolved images of a beating heart with optical absorption contrast and enables investigation of cardiovascular diseases in animal models.
Dasabuvir suppresses esophageal squamous cell carcinoma growth in vitro and in vivo through targeting ROCK1
Authors: Liu Xinning , Jiang Yanan , Zhou Hao , Zhao Xiaokun , Li Mingzhu , Bao Zhuo , Wang Zitong , Zhang Chenyang , Xie Zhenliang , Zhao Jimin , Dong Zigang , Liu Kangdong , Guo Zhiping
Published: February 2023

Esophageal squamous cell carcinoma (ESCC) is an upper gastrointestinal cancer with high morbidity and mortality. New strategies are urgently needed to prolong patients’ survival. Through screening FDA-approved drugs, we found dasabuvir, a drug approved for hepatitis C virus (HCV) treatment, suppressed ESCC proliferation. Dasabuvir could inhibit the growth of ESCC cells in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was further validated in vivo using patient-derived xenograft tumor models. In terms of mechanism, we unveil that dasabuvir is a Rho-associated protein kinase 1 (ROCK1) inhibitor. Dasabuvir can bind to ROCK1 and suppress its kinase activity, thus downregulating the phosphorylation of ERK1/2 by ROCK1 and the expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1. These results provide evidence that dasabuvir suppresses ESCC growth in vivo and in vitro through blocking ROCK1/ERK signaling pathway.
Rho A/ROCK1 signaling-mediated metabolic reprogramming of valvular interstitial cells toward Warburg effect accelerates aortic valve calcification via AMPK/RUNX2 axis
Authors: Liu Huiruo , Yin Hang , Wang Zhen , Yuan Qiuhuan , Xu Feng , Chen Yuguo , Li Chuanbao
Published: February 2023

The aberrant differentiation of valvular interstitial cells (VICs) to osteogenic lineages promotes calcified aortic valves disease (CAVD), partly activated by potentially destructive hemodynamic forces. These involve Rho A/ROCK1 signaling, a mechano-sensing pathway. However, how Rho A/ROCK1 signaling transduces mechanical signals into cellular responses and disrupts normal VIC homeostasis remain unclear. We examined Rho A/ROCK1 signaling in human aortic valves, and further detected how Rho A/ROCK1 signaling regulates mineralization in human VICs. Aortic valves (CAVDn = 22, normal control (NC)n = 12) from patients undergoing valve replacement were investigated. Immunostaining and western blotting analysis indicated that Rho A/ROCK1 signaling, as well as key transporters and enzymes involved in the Warburg effect, were markedly upregulated in human calcified aortic valves compared with those in the controls. In vitro, Rho A/ROCK1-induced calcification was confirmed as AMPK-dependent, via a mechanism involving metabolic reprogramming of human VICs to Warburg effect. Y-27632, a selective ROCK1 inhibitor, suppressed the Warburg effect, rescued AMPK activity and subsequently increased RUNX2 ubiquitin-proteasome degradation, leading to decreased RUNX2 protein accumulation in human VICs under pathological osteogenic stimulus. Rho A/ROCK1 signaling, which is elevated in human calcified aortic valves, plays a positive role in valvular calcification, partially through its ability to drive metabolic switching of VICs to the Warburg effect, leading to altered AMPK activity and RUNX2 protein accumulation. Thus, Rho A/ROCK1 signaling could be an important and unrecognized hub of destructive hemodynamics and cellular aerobic glycolysis that is essential to promote the CAVD process.
DNMT3a-dermatopontin axis suppresses breast cancer malignancy via inactivating YAP
Authors: Ye Danrong , Wang Yuying , Deng Xiaochong , Zhou Xiqian , Liu Diya , Zhou Baian , Zheng Wenfang , Wang Xuehui , Fang Lin
Published: February 2023

Breast cancer (BC) is the most common malignant tumor in women worldwide, and its recurrence and metastasis negatively affect patient prognosis. However, the mechanisms underlying its tumorigenesis and progression remain unclear. Recently, the influence of dermatopontin (DPT), which is an extracellular matrix protein, has been proposed in the development of cancer. Here we found that DNMT3a-mediated DPT, promoter hypermethylation results in the downregulation of DPT expression in breast cancer and its low expression correlated with poor prognosis. Notably, DPT directly interacted with YAP to promote YAP Ser127 phosphorylation, and restricted the translocation of endogenous YAP from the cytoplasm to the nucleus, thereby suppressing malignant phenotypes in BC cells. In addition, Ectopic YAP overexpression reversed the inhibitory effects of DPT on BC growth and metastasis. Our study showed the critical role of DPT in regulating BC progression, making it easier to explore the clinical potential of modulating DPT/YAP activity in BC targeted therapies.
Actin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives
Authors: Tee Yee Han , Goh Wei Jia , Yong Xianbin , Ong Hui Ting , Hu Jinrong , Tay Ignacius Yan Yun , Shi Shidong , Jalal Salma , Barnett Samuel F. H. , Kanchanawong Pakorn , Huang Wenmao , Yan Jie , Lim Yong Ann Ben , Thiagarajan Visalatchi , Mogilner Alex , Bershadsky Alexander D.
Published: February 2023

Deviations from mirror symmetry in the development of bilateral organisms are common but the mechanisms of initial symmetry breaking are insufficiently understood. The actin cytoskeleton of individual cells self-organises in a chiral manner, but the molecular players involved remain essentially unidentified and the relationship between chirality of an individual cell and cell collectives is unclear. Here, we analysed self-organisation of the chiral actin cytoskeleton in individual cells on circular or elliptical patterns, and collective cell alignment in confined microcultures. Screening based on deep-learning analysis of actin patterns identified actin polymerisation regulators, depletion of which suppresses chirality (mDia1) or reverses chirality direction (profilin1 and CapZβ). The reversed chirality  is mDia1-independent but requires the function of actin-crosslinker α−actinin1. A robust correlation between the effects of a variety of actin assembly regulators on chirality of individual cells and cell collectives is revealed. Thus, actin-driven cell chirality may underlie tissue and organ asymmetry.
Enzyme-like polyene cyclizations catalyzed by dynamic, self-assembled, supramolecular fluoro alcohol-amine clusters
Authors: Arnold Andreas M. , Dullinger Philipp , Biswas Aniruddha , Jandl Christian , Horinek Dominik , Gulder Tanja
Published: February 2023

Terpene cyclases catalyze one of the most powerful transformations with respect to efficiency and selectivity in natural product (bio)synthesis. In such polyene cyclizations, structurally highly complex carbon scaffolds are built by the controlled ring closure of linear polyenes. Thereby, multiple C,C bonds and stereocenters are simultaneously created with high precision. Structural pre-organization of the substrate carbon chain inside the active center of the enzyme is responsible for the product- and stereoselectivity of this cyclization. Here, we show that in-situ formed fluorinated-alcohol-amine supramolecular clusters serve as artificial cyclases by triggering enzyme-like reactivity and selectivity by controlling substrate conformation in solution. Because of the dynamic nature of these supramolecular assemblies, a broad range of terpenes can be produced diastereoselectively. Mechanistic studies reveal a finely balanced interplay of fluorinated solvent, catalyst, and substrate as key to establishing nature’s concept of a shape-selective polyene cyclization in organic synthesis.
T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles
Authors: Turco Verena , Pfleiderer Kira , Hunger Jessica , Horvat Natalie K. , Karimian-Jazi Kianush , Schregel Katharina , Fischer Manuel , Brugnara Gianluca , Jähne Kristine , Sturm Volker , Streibel Yannik , Nguyen Duy , Altamura Sandro , Agardy Dennis A. , Soni Shreya S. , Alsasa Abdulrahman , Bunse Theresa , Schlesner Matthias , Muckenthaler Martina U. , Weissleder Ralph , Wick Wolfgang , Heiland Sabine , Vollmuth Philipp , Bendszus Martin , Rodell Christopher B. , Breckwoldt Michael O. , Platten Michael
Published: February 2023

Glioblastoma, the most common and aggressive primary brain tumor type, is considered an immunologically “cold” tumor with sparse infiltration by adaptive immune cells. Immunosuppressive tumor-associated myeloid cells are drivers of tumor progression. Therefore, targeting and reprogramming intratumoral myeloid cells is an appealing therapeutic strategy. Here, we investigate a β-cyclodextrin nanoparticle (CDNP) formulation encapsulating the Toll-like receptor 7 and 8 (TLR7/8) agonist R848 (CDNP-R848) to reprogram myeloid cells in the glioma microenvironment. We show that intravenous monotherapy with CDNP-R848 induces regression of established syngeneic experimental glioma, resulting in increased survival rates compared with unloaded CDNP controls. Mechanistically, CDNP-R848 treatment reshapes the immunosuppressive tumor microenvironment and orchestrates tumor clearing by pro-inflammatory tumor-associated myeloid cells, independently of T cells and NK cells. Using serial magnetic resonance imaging, we identify a radiomic signature in response to CDNP-R848 treatment and ultrasmall superparamagnetic iron oxide (USPIO) imaging reveals that immunosuppressive macrophage recruitment is reduced by CDNP-R848. In conclusion, CDNP-R848 induces tumor regression in experimental glioma by targeting blood-borne macrophages without requiring adaptive immunity.
Interpretable design of Ir-free trimetallic electrocatalysts for ammonia oxidation with graph neural networks
Authors: Pillai Hemanth Somarajan , Li Yi , Wang Shih-Han , Omidvar Noushin , Mu Qingmin , Achenie Luke E. K. , Abild-Pedersen Frank , Yang Juan , Wu Gang , Xin Hongliang
Published: February 2023

The electrochemical ammonia oxidation to dinitrogen as a means for energy and environmental applications is a key technology toward the realization of a sustainable nitrogen cycle. The state-of-the-art metal catalysts including Pt and its bimetallics with Ir show promising activity, albeit suffering from high overpotentials for appreciable current densities and the soaring price of precious metals. Herein, the immense design space of ternary Pt alloy nanostructures is explored by graph neural networks trained on ab initio data for concurrently predicting site reactivity, surface stability, and catalyst synthesizability descriptors. Among a few Ir-free candidates that emerge from the active learning workflow, Pt3Ru-M (M: Fe, Co, or Ni) alloys were successfully synthesized and experimentally verified to be more active toward ammonia oxidation than Pt, Pt3Ir, and Pt3Ru. More importantly, feature attribution analyses using the machine-learned representation of site motifs provide fundamental insights into chemical bonding at metal surfaces and shed light on design strategies for high-performance catalytic systems beyond the d-band center metric of binding sites.
Subduction initiation triggered the Caribbean large igneous province
Authors: Riel Nicolas , Duarte João C. , Almeida Jaime , Kaus Boris J. P. , Rosas Filipe , Rojas-Agramonte Yamirka , Popov Anton
Published: February 2023

Subduction provides the primary driving force for plate tectonics. However, the mechanisms leading to the formation of new subduction zones remain debated. An example is the Lesser Antilles Arc in the Atlantic. Previous initiation mechanisms have implied the transmission of subduction from the Pacific Ocean or the impact of a plume head. Here, we use geodynamic models to simulate the evolution of the Caribbean region during the Cretaceous, where the eastern Pacific subduction triggered the formation of a new subduction zone in the Atlantic. The simulations show how the collision of the old Caribbean plateau with the Central America margin lead to the formation of a new Atlantic subduction zone by polarity reversal. The results further show how subduction renewal on the back of the old Caribbean plateau (present-day Central America) resulted in a major mantle flow reorganization that generated a subduction-induced plume consistent with the formation of the Caribbean Large Igneous Province.
Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer
Authors: Malagoli Tagliazucchi Guidantonio , Wiecek Anna J. , Withnell Eloise , Secrier Maria
Published: February 2023

The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.
Integrative proteomic characterization of adenocarcinoma of esophagogastric junction
Authors: Li Shengli , Yuan Li , Xu Zhi-Yuan , Xu Jing-Li , Chen Gui-Ping , Guan Xiaoqing , Pan Guang-Zhao , Hu Can , Dong Jinyun , Du Yi-An , Yang Li-Tao , Ni Mao-Wei , Jiang Rui-Bin , Zhu Xiu , Lv Hang , Xu Han-Dong , Zhang Sheng-Jie , Qin Jiang-Jiang , Cheng Xiang-Dong
Published: February 2023

The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing in recent decades, but its molecular alterations and subtypes are still obscure. Here, we conduct proteomics and phosphoproteomics profiling of 103 AEG tumors with paired normal adjacent tissues (NATs), whole exome sequencing of 94 tumor-NAT pairs, and RNA sequencing in 83 tumor-NAT pairs. Our analysis reveals an extensively altered proteome and 252 potential druggable proteins in AEG tumors. We identify three proteomic subtypes with significant clinical and molecular differences. The S-II subtype signature protein, FBXO44, is demonstrated to promote tumor progression and metastasis in vitro and in vivo. Our comparative analyses reveal distinct genomic features in AEG subtypes. We find a specific decrease of fibroblasts in the S-III subtype. Further phosphoproteomic comparisons reveal different kinase-phosphosubstrate regulatory networks among AEG subtypes. Our proteogenomics dataset provides valuable resources for understanding molecular mechanisms and developing precision treatment strategies of AEG.
Small molecule inhibitors of 15-PGDH exploit a physiologic induced-fit closing system
Authors: Huang Wei , Li Hongyun , Kiselar Janna , Fink Stephen P. , Regmi Sagar , Day Alexander , Yuan Yiyuan , Chance Mark , Ready Joseph M. , Markowitz Sanford D. , Taylor Derek J.
Published: February 2023

15-prostaglandin dehydrogenase (15-PGDH) is a negative regulator of tissue stem cells that acts via enzymatic activity of oxidizing and degrading PGE2, and related eicosanoids, that support stem cells during tissue repair. Indeed, inhibiting 15-PGDH markedly accelerates tissue repair in multiple organs. Here we have used cryo-electron microscopy to solve the solution structure of native 15-PGDH and of 15-PGDH individually complexed with two distinct chemical inhibitors. These structures identify key 15-PGDH residues that mediate binding to both classes of inhibitors. Moreover, we identify a dynamic 15-PGDH lid domain that closes around the inhibitors, and that is likely fundamental to the physiologic 15-PGDH enzymatic mechanism. We furthermore identify two key residues, F185 and Y217, that act as hinges to regulate lid closing, and which both inhibitors exploit to capture the lid in the closed conformation, thus explaining their sub-nanomolar binding affinities. These findings provide the basis for further development of 15-PGDH targeted drugs as therapeutics for regenerative medicine.
Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility
Authors: Li Shuxiang , Wei Tiejun , Panchenko Anna R.
Published: February 2023

Nucleosomes, containing histone variants H2A.Z, are important for gene transcription initiation and termination, chromosome segregation and DNA double-strand break repair, among other functions. However, the underlying mechanisms of how H2A.Z influences nucleosome stability, dynamics and DNA accessibility are not well understood, as experimental and computational evidence remains inconclusive. Our modeling efforts of human nucleosome stability and dynamics, along with comparisons with experimental data show that the incorporation of H2A.Z results in a substantial decrease of the energy barrier for DNA unwrapping. This leads to the spontaneous DNA unwrapping of about forty base pairs from both ends, nucleosome gapping and increased histone plasticity, which otherwise is not observed for canonical nucleosomes. We demonstrate that both N- and C-terminal tails of H2A.Z play major roles in these events, whereas the H3.3 variant exerts a negligible impact in modulating the DNA end unwrapping. In summary, our results indicate that H2A.Z deposition makes nucleosomes more mobile and DNA more accessible to transcriptional machinery and other chromatin components.