bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fully Coupled Photochemistry of the Deuterated Ionosphere of Mars and Its Effects on Escape of H and D
Authors: Cangi Eryn , Chaffin Michael , Yelle Roger , Gregory Bethan , Deighan Justin 
Published: June 2023

AbstractAlthough deuterium (D) on Mars has received substantial attention, the deuterated ionosphere remains relatively unstudied. This means that we also know very little about non‐thermal D escape from Mars, since it is primarily driven by excess energy imparted to atoms produced in ion‐neutral reactions. Most D escape from Mars is expected to be non‐thermal, highlighting a gap in our understanding of water loss from Mars. In this work, we set out to fill this knowledge gap. To accomplish our goals, we use an upgraded 1D photochemical model that fully couples ions and neutrals and does not assume photochemical equilibrium. To our knowledge, such a model has not been applied to Mars previously. We model the atmosphere during solar minimum, mean, and maximum, and find that the deuterated ionosphere behaves similarly to the H‐bearing ionosphere, but that non‐thermal escape on the order of 8,000–9,000 cm−2 s−1 dominates atomic D loss under all solar conditions. The total fractionation factor, f, is f = 0.04–0.07, and integrated water loss is 147–158 m global equivalent layer. This is still less than geomorphological estimates. Deuterated ions at Mars are likely difficult to measure with current techniques due to low densities and mass degeneracies with more abundant H ions. Future missions wishing to measure the deuterated ionosphere in situ will need to develop innovative techniques to do so.
Extensive Lunar Surface Disturbance at the Chang'e‐5 Mission Landing Site: Implications for Future Lunar Base Design and Construction
Authors: Qiao Le , Hess Marcel , Xu Luyuan , Wöhler Christian , Head James W. , Chen Jian , Wang Yiran , Bugiolacchi Roberto , Xiao Ayang , Zhang Feng , Ling Zongcheng 
Published: June 2023

AbstractLunar surface disturbances by spacecraft engine jets are of particular concern in the current new phase of lunar exploration, when dozens of landing missions and permanent bases are being planned. Some of these exploration efforts will involve multiple landings and liftoffs around the same lunar site; thus, it is essential to evaluate their effect on astronauts and assets on the lunar surface. Here, we assess the surface disturbances during the Chang'e‐5 landing and liftoff procedures through the photometric analysis of high‐resolution multi‐temporal surface and orbital images. Centimeter‐scale surface images reveal a four‐stage evolution of the landing plume impingement over a period of ∼50 s, which involves phenomena such as dust devils and streaks, and displacement of cobbles. Temporal‐ratio calculation of orbital images (including one acquired between landing and liftoff) enables the first direct observation of ascent plume effects. The ascent blast zone consists of two separated sub‐areas (∼3,400 m2 in total), which is nearly twice larger than that of the landing blast zone. The final disturbed surface is characterized by a central main zone (∼2,300 m2) surrounded by a marginal diffuse zone (∼15,300 m2). Phase‐ratio analyses suggest that plume impingement destroys the micro‐porous structure of the uppermost regolith. We estimate that future lunar landers (e.g., SpaceX's Starship) may cause significant lunar surface disturbances over an area of square kilometers. Our results provide unique insights into Chang'e‐5 mission activities, and instructive references for the planning of future lunar endeavors, including the design and construction of surface experiment packages and permanent lunar bases.
Disentangling Shallow Subsidence Sources by Data Assimilation in a Reclaimed Urbanized Coastal Plain, South Flevoland Polder, the Netherlands
Authors: Verberne Manon , Koster Kay , Lourens Aris , Gunnink Jan , Candela Thibault , Fokker Peter A. 
Published: June 2023

AbstractThis research targets disentangling shallow causes of anthropogenically induced subsidence in a reclaimed and urbanized coastal plain. The study area is the city of Almere, in the South Flevoland polder, the Netherlands, which is among the countries' fastest subsiding areas. The procedure consists of integrating Interferometric Synthetic Aperture Radar (InSAR) data with high‐resolution phreatic groundwater and lithoclass models, and a database containing construction details. The InSAR data were derived from Sentinel‐1, one ascending and one descending track, over a period from March 2015 until June 2020. The two main parts of the workflow are isolation of the InSAR points of structures without a pile foundation and a data assimilation procedure. The shrinkage of surficial clay beds by phreatic groundwater level lowering is identified as the main cause of subsidence in the area, with an average contribution of 6 mm per year. The history‐matched physics‐based model predicts that 1 m drop in phreatic groundwater level now translates into 10 mm of subsidence in the next 5 years. Additionally, a groundwater deficiency due to severe dry periods should be considered as an accelerator of subsidence. To ensure a robust network to estimate subsidence, we recommend a consistent monitoring strategy of the phreatic groundwater level.
Nonlinear Equilibrium Structure of Super Thin Current Sheets: Influence of Quasi‐Adiabatic Electron Population
Authors: Tsareva Olga O. , Leonenko Makar V. , Grigorenko Elena E. , Malova Helmi V. , Popov Victor Yu. , Zelenyi Lev M. 
Published: June 2023

AbstractRecent MMS observations confirmed the existence of the quasi‐stationary electron‐scale super‐thin current sheets (STCSs) with a half‐thickness of few electron gyroradii. STCSs contain the electron population consisting of magnetized and demagnetized particles. To study the role of the demagnetized electrons, we developed a self‐consistent combined model of a STCS in which the dynamics of a part of the electron population is described by the quasi‐adiabatic approximation, while the motion of the other part is described by the guiding center approximation. Demagnetized ion population can be described in a frame of quasi‐adiabatic approach. In the presented model we introduced the weight coefficient of the demagnetized electron plasma density χ depending on the magnetic field normal component Bn/B0 and compared the characteristic profiles of two STCSs differing by the presence (χ ≠ 0) and absence (χ = 0) of demagnetized electrons. It is shown that the presence of demagnetized electrons makes the current density profile of STCS significantly more intense and narrower. The thickness and intensity of STCS depend on the anisotropy coefficient of magnetized electrons and the incoming drift velocity of demagnetized electrons. The maximum current density continuously increases with the growth of the demagnetized electron population and is controlled by the ratio of the thermal to the incoming drift electron velocities. Thus intense current sheets can be formed even in the absence of strong electron anisotropy, which is confirmed by MMS observations.
Rayleigh‐Taylor Instability Observed at the Dayside Magnetopause Under Northward Interplanetary Magnetic Field
Authors: Yan G. Q. , Parks G. K. , Mozer F. S. , Goldstein M. L. , Chen T. , Liu Y. 
Published: June 2023

AbstractUnder northward interplanetary magnetic field, periodical fluctuations with the period of 85 s have been observed by one of the Time History of Events and Macroscale Interactions during Substorms spacecraft at the dayside magnetopause when the solar wind dynamic pressure suddenly dropped. The observed magnetic field distortions, characterized by the compression of the main component as well as the flapping of the perpendicular components, are in line with the theoretical predictions of the Rayleigh‐Taylor (R‐T) instability excited at the magnetopause. With the convective electric field and the mean electric field removed, the perturbations in the electric field are identified as typical two sinusoidal signals with a 90° phase difference, consistent with previous prediction of the attendant electrostatic field arising from the R‐T instability. The transverse motions of the plasmas resulting from the electric drifting driven by the electrostatic field are observed both in pitch‐angle distributions and in distribution functions. The growth rate of the R‐T instability is about 43 s, implying that the instability has time to grow during the disturbances. Using the Gauss theorem, the calculated net charge density based on the electric field observation is one part of 27 compared to the totally observed plasma density, indicating that only a tiny fraction of the charge separates to set up the electrostatic field, which is due to a collective effect in the plasma.
Epigenetic reprogramming of cell cycle genes by ACK1 promotes breast cancer resistance to CDK4/6 inhibitor
Authors: Sawant Mithila , Wilson Audrey , Sridaran Dhivya , Mahajan Kiran , O’Conor Christopher J. , Hagemann Ian S. , Luo Jingqin , Weimholt Cody , Li Tiandao , Roa Juan Carlos , Pandey Akhilesh , Wu Xinyan , Mahajan Nupam P. 
Published: June 2023

AbstractHormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes,CCNB1, CCNB2andCDC20, which in turn initiated their efficient transcription. Pharmacological inhibition of ACK1 using its inhibitor, (R)-9bdampenedCCNB1, CCNB2andCDC20expression, caused G2/M arrest, culminating in regression of palbociclib-resistant breast tumor growth. Further, (R)-9bsuppressed expression of CXCR4 receptor, which resulted in significant impairment of metastasis of breast cancer cells to lung. Overall, our pre-clinical data identifies activated ACK1 as an oncogene that epigenetically controls the cell cycle genes governing the G2/M transition in breast cancer cells. ACK1 inhibitor, (R)-9bcould be a novel therapeutic option for the breast cancer patients that have developed resistance to CDK4/6 inhibitors.
Differences in white blood cell proportions between schizophrenia cases and controls are influenced by medication and variations in time of day
Authors: Villar Jonelle D. , Stavrum Anne-Kristin , Spindola Leticia M. , Torsvik Anja , Bjella Thomas , Steen Niels Eiel , Djurovic Srdjan , Andreassen Ole A. , Steen Vidar M. , Le Hellard Stephanie 
Published: June 2023

AbstractCases with schizophrenia (SCZ) and healthy controls show differences in white blood cell (WBC) counts and blood inflammation markers. Here, we investigate whether time of blood draw and treatment with psychiatric medications are related to differences in estimated WBC proportions between SCZ cases and controls. DNA methylation data from whole blood was used to estimate proportions of six subtypes of WBCs in SCZ patients (n = 333) and healthy controls (n = 396). We tested the association of case-control status with estimated cell-type proportions and the neutrophil-to-lymphocyte ratio (NLR) in 4 models: with/without adjusting for time of blood draw, and then compared results from blood samples drawn during a 12-h (07:00–19:00) or 7-h (07:00-14:00) period. We also investigated WBC proportions in a subgroup of medication-free patients (n = 51). Neutrophil proportions were significantly higher in SCZ cases (mean=54.1%) vs. controls (mean=51.1%; p = <0.001), and CD8+T lymphocyte proportions were lower in SCZ cases (mean=12.1%) vs. controls (mean=13.2%; p = 0.001). The effect sizes in the 12-h sample (07:00–19:00) showed a significant difference between SCZ vs. controls for neutrophils, CD4+T, CD8+T, and B-cells, which remained significant after adjusting for time of blood draw. In the samples matched for time of blood draw during 07.00–14.00, we also observed an association with neutrophils, CD4+T, CD8+T, and B-cells that was unaffected by further adjustment for time of blood draw. In the medication-free patients, we observed differences that remained significant in neutrophils (p = 0.01) and CD4+T (p = 0.01) after adjusting for time of day. The association of SCZ with NLR was significant in all models (range: p < 0.001 to p = 0.03) in both medicated and unmedicated patients. In conclusion, controlling for pharmacological treatment and circadian cycling of WBC is necessary for unbiased estimates in case-control studies. Nevertheless, the association of WBC with SCZ remains, even after adjusting for the time of day.
Epigenetically modified AP-2α by DNA methyltransferase facilitates glioma immune evasion by upregulating PD-L1 expression
Authors: Long Shengwen , Huang Guixiang , Ouyang Mi , Xiao Kai , Zhou Hao , Hou Anyi , Li Zhiwei , Zhong Zhe , Zhong Dongmei , Wang Qinghao , Xiang Shuanglin , Ding Xiaofeng 
Published: June 2023

AbstractProgrammed death-ligand 1 (PD-L1) ensures that tumor cells escape T-cell-mediated tumor immune surveillance. However, gliomas are characteristic of the low immune response and high-resistance therapy, it is necessary to understand molecular regulatory mechanisms in glioblastoma, especially the limited regulation of PD-L1 expression. Herein, we show that low expression of AP-2α is correlated with high expression of PD-L1 in high-grade glioma tissues. AP-2α binds directly to the promoter of the CD274 gene, not only inhibits the transcriptional activity of PD-L1 but enhances endocytosis and degradation of PD-L1 proteins. Overexpression of AP-2α in gliomas enhances CD8+ T cell-mediated proliferation, effector cytokine secretion, and cytotoxicity in vitro. Tfap2a could increase the cytotoxic effect of Cd8+ T cells in CT26, B16F10, and GL261 tumor-immune models, improve anti-tumor immunity, and promote the efficacy of anti-PD-1 therapy. Finally, the EZH2/H3K27Me3/DNMT1 complex mediates the methylation modification of AP-2α gene and maintains low expression of AP-2α in gliomas. 5-Aza-dC (Decitabine) treatment combines with anti-PD-1 immunotherapy to efficiently suppress the progression of GL261 gliomas. Overall, these data support a mechanism of epigenetic modification of AP-2α that contributes to tumor immune evasion, and reactivation of AP-2α synergizes with anti-PD-1 antibodies to increase antitumor efficacy, which may be a broadly applicable strategy in solid tumors.
Cathepsin K inhibition induces Raptor destabilization and mitochondrial dysfunction via Syk/SHP2/Src/OTUB1 axis-mediated signaling
Authors: Seo Seung Un , Woo Seon Min , Kwon Taeg Kyu 
Published: June 2023

AbstractThe Raptor signaling pathway is a critical point of intervention in the invasion and progression of cancer. The non-receptor tyrosine kinase Src-mediated phosphorylation of OTUB1-Y26 plays a critical role in Raptor stabilization, whereas cathepsin K inhibitor (odanacatib; ODN) and knockdown (siRNA) induce Raptor destabilization. However, the mechanisms involved in cathepsin K inhibition-induced OTUB1-Y26 phosphorylation in Raptor stabilization have not been yet elucidated. This study showed that cathepsin K inhibition activates SHP2, a tyrosine phosphatase, that dephosphorylates OTUB1 and destabilizes Raptor, whereas SHP2 deletion and pharmacological inhibition increase OTUB1-Y26 phosphorylation and Raptor expression. SHP2 deletion also led to the inhibition of ODN-induced mitochondrial ROS, fusion, and dysfunction. Furthermore, cathepsin K inhibition phosphorylated spleen tyrosine kinase (Syk) at Y525 and Y526, resulting in the SHP2-mediated dephosphorylation of OTUB1-Y26. Collectively, our findings identified Syk not only as an upstream tyrosine kinase required for SHP2 activation but also showed a critical mechanism that regulates ODN-induced Raptor downregulation and mitochondrial dysfunction. In conclusion, Syk/SHP2/Src/OTUB1 axis-mediated signaling can act as a therapeutic target in cancer management.
A data-driven approach for predicting the impact of drugs on the human microbiome
Authors: Algavi Yadid M. , Borenstein Elhanan 
Published: June 2023

AbstractMany medications can negatively impact the bacteria residing in our gut, depleting beneficial species, and causing adverse effects. To guide personalized pharmaceutical treatment, a comprehensive understanding of the impact of various drugs on the gut microbiome is needed, yet, to date, experimentally challenging to obtain. Towards this end, we develop a data-driven approach, integrating information about the chemical properties of each drug and the genomic content of each microbe, to systematically predict drug-microbiome interactions. We show that this framework successfully predicts outcomes of in-vitro pairwise drug-microbe experiments, as well as drug-induced microbiome dysbiosis in both animal models and clinical trials. Applying this methodology, we systematically map a large array of interactions between pharmaceuticals and human gut bacteria and demonstrate that medications’ anti-microbial properties are tightly linked to their adverse effects. This computational framework has the potential to unlock the development of personalized medicine and microbiome-based therapeutic approaches, improving outcomes and minimizing side effects.
Cannabidiol inhibits Nav channels through two distinct binding sites
Authors: Huang Jian , Fan Xiao , Jin Xueqin , Jo Sooyeon , Zhang Hanxiong Bear , Fujita Akie , Bean Bruce P. , Yan Nieng 
Published: June 2023

AbstractCannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most relevant for clinical actions is still unclear. Here we show that CBD interacts with Nav1.7 channels at sub-micromolar concentrations in a state-dependent manner. Electrophysiological experiments show that CBD binds to the inactivated state of Nav1.7 channels with a dissociation constant of about 50 nM. The cryo-EM structure of CBD bound to Nav1.7 channels reveals two distinct binding sites. One is in the IV-I fenestration near the upper pore. The other binding site is directly next to the inactivated “wedged” position of the Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV, which mediates fast inactivation. Consistent with producing a direct stabilization of the inactivated state, mutating residues in this binding site greatly reduced state-dependent binding of CBD. The identification of this binding site may enable design of compounds with improved properties compared to CBD itself.
Optically induced electrothermal microfluidic tweezers in bio-relevant media
Authors: Gupta Kshitiz , Moon Hye-Ran , Chen Zhengwei , Han Bumsoo , Green Nicolas G. , Wereley Steven T. 
Published: June 2023

AbstractNon-contact micro-manipulation tools have enabled invasion-free studies of fragile synthetic particles and biological cells. Rapid electrokinetic patterning (REP) traps target particles/cells, suspended in an electrolyte, on an electrode surface. This entrapment is electrokinetic in nature and thus depends strongly on the suspension medium’s properties. REP has been well characterized for manipulating synthetic particles suspended in low concentration salt solutions (~ 2 mS/m). However, it is not studied as extensively for manipulating biological cells, which introduces an additional level of complexity due to their limited viability in hypotonic media. In this work, we discuss challenges posed by isotonic electrolytes and suggest solutions to enable REP manipulation in bio-relevant media. Various formulations of isotonic media (salt and sugar-based) are tested for their compatibility with REP. REP manipulation is observed in low concentration salt-based media such as 0.1× phosphate buffered saline (PBS) when the device electrodes are passivated with a dielectric layer. We also show manipulation of murine pancreatic cancer cells suspended in a sugar-based (8.5% w/v sucrose and 0.3% w/v dextrose) isotonic medium. The ability to trap mammalian cells and deposit them in custom patterns enables high-impact applications such as determining their biomechanical properties and 3D bioprinting for tissue scaffolding.
Red narrow-linewidth lasing and frequency comb from gain-switched self-injection-locked Fabry–Pérot laser diode
Authors: Shitikov Artem E. , Galiev Ramzil R. , Min’kov Kirill N. , Kondratiev Nikita M. , Cordette Steevy J. , Lobanov Valery E. , Bilenko Igor A. 
Published: June 2023

AbstractNarrow-linewidth lasers are in extensive demand for numerous cutting-edge applications. Such lasers operating at the visible range are of particular interest. Self-injection locking of a laser diode frequency to a high-Q whispering gallery mode is an effective and universal way to achieve superior laser performance. We demonstrate ultranarrow lasing with less than 10 Hz instantaneous linewidth for 20 $$\mu$$
μ
s averaging time at 638 nm using a Fabry–Pérot laser diode locked to a crystalline MgF$$_2$$

2

microresonator. The linewidth measured with a $$\beta$$
β
-separation line technique that characterizes 10 ms stability is as low as 1.4 kHz. Output power exceeds 80 mW. Demonstrated results are among the best for visible-range lasers in terms of linewidth combined with solid output power. We additionally report the first demonstration of a gain-switched regime for such stabilized Fabry–Pérot laser diode showing a high-contrast visible frequency comb generation. Tunable linespacing from 10 MHz to 3.8 GHz is observed. We demonstrated that the beatnote between the lines has sub-Hz linewidth and experiences spectral purification in the self-injection locking regime. This result might be of special importance for spectroscopy in the visible range.
Predicting outcomes of acute kidney injury in critically ill patients using machine learning
Authors: Nateghi Haredasht Fateme , Viaene Liesbeth , Pottel Hans , De Corte Wouter , Vens Celine 
Published: June 2023

AbstractAcute Kidney Injury (AKI) is a sudden episode of kidney failure that is frequently seen in critically ill patients. AKI has been linked to chronic kidney disease (CKD) and mortality. We developed machine learning-based prediction models to predict outcomes following AKI stage 3 events in the intensive care unit. We conducted a prospective observational study that used the medical records of ICU patients diagnosed with AKI stage 3. A random forest algorithm was used to develop two models that can predict patients who will progress to CKD after three and six months of experiencing AKI stage 3. To predict mortality, two survival prediction models have been presented using random survival forests and survival XGBoost. We evaluated established CKD prediction models using AUCROC, and AUPR curves and compared them with the baseline logistic regression models. The mortality prediction models were evaluated with an external test set, and the C-indices were compared to baseline COXPH. We included 101 critically ill patients who experienced AKI stage 3. To increase the training set for the mortality prediction task, an unlabeled dataset has been added. The RF (AUPR: 0.895 and 0.848) and XGBoost (c-index: 0.8248) models have a better performance than the baseline models in predicting CKD and mortality, respectively Machine learning-based models can assist clinicians in making clinical decisions regarding critically ill patients with severe AKI who are likely to develop CKD following discharge. Additionally, we have shown better performance when unlabeled data are incorporated into the survival analysis task.