bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation of soil behavior under longitudinal motion of underground pipeline in one-dimensional statement
Authors: Rikhsieva Barno , Khusanov Bakhtiyar
Published: April 2023

The process of shear interaction of an underground pipeline with soil is numerically modeled in a one-dimensional statement. The main attention is paid to the behavior of soil around the pipeline. The deformation characteristics of the pipeline are ignored. A technique for the numerical solution of a one-dimensional problem of soil behavior and shear wave propagation using the finite difference method was developed. The developed method of numerical research made it possible to take into account the nonlinear properties of soil strain and it was tested for elastic and viscoelastic simulation of soils. Numerical results were obtained for the shear wave propagation in elastic and viscoelastic soil under the longitudinal motion of an underground pipeline. The results obtained showed the attenuation of the wave parameters with distance from the cross section of the underground pipeline. The attenuation of waves with distance is justified by the dissipation of the deformation energy on an expanding cylindrical soil layer. In the case of viscoelastic soil, attenuation in time in fixed points of soil is also observed, the maximum shear stresses are reached near the contact surface of the underground pipeline, and in this area, an intensive decrease in the shear stress amplitude is observed.
Research of the influence of the volumetric-mass layout of the aircraft on the dynamics of rotational motion in the longitudinal plane
Authors: Sagalovich S.A. , Kremenchutsky V.V. , Strelets D.Yu.
Published: April 2023

In this paper, the influence of the volumetric-mass layout of the aircraft on the dynamics of rotational motion in the longitudinal plane is considered. The studies allow us to evaluate the relationship between the space-mass layout of the aircraft and the perturbing aerodynamic effects that occur during the transition process. The deviation of the empirical values of the aerodynamic moment from the linear dependence and the time of the transition process were considered to be quantitative estimates of the quality of the transient process. An original aerodynamic experiment with a moving aircraft model was proposed as a research method. The continuous change in the position of the aerodynamic model in the experiment made it possible to analyze the effects and their influence on the motion parameters in real time, and take into account the unsteadiness of the flow on the airframe surface. The conducted experiment shows that to reduce the time of the transient process, the value of the moment of inertia of the aircraft should be reduced but, in this case, the aerodynamic moments caused by the inertia of the medium and various unsteady flows will increase. As a result, when choosing the ratios of stability and controllability of an aircraft, one should pay attention not only to the geometric location of the center of mass and focus of the aircraft, but also to the mass-volume characteristics of the aircraft.
Optimization of secure workstation for manipulation of 35S-labelled molecules: a case of in vitro cell metabolic labelling
Authors: Audry M. , Coureuil M. , Hinzpeter A. , Frot P. , Saltiel O. , Kadri M. , Gaab M.-L. , Armand A.-S. , Servel N.
Published: April 2023

Pulse-chase and cell metabolic experiments involving 35S-labelled molecules can be detrimental to your health. Suppliers and literature suggest the use of activated charcoal to limit contamination without any precise specification. The aim of this study is to fill in this gap. Here, we perform the usual procedures, which consist in working with the available equipment according to recommendations of radioprotection. We carried out radiotoxicological exams as well as dosimetric follow-ups of the workers. As this procedure leads to internal contamination of the operators and of surface contamination at the workplace, we tested a more secure workstation with collective protection equipment that we validated as limiting contaminations for workers. This study proposes a method to use 35S-labelled molecules in a more secure way, which could be beneficial for the scientific community.
Leitlinie Myokarditis der Deutschen Gesellschaft für
Pädiatrische Kardiologie
Authors: Paul Thomas , Klingel Karin , Tschöpe Carsten , Bertram Harald , Seidel Franziska
Published: April 2023

Diese Leitlinie präsentiert die aktuellen Handlungsanweisungen zur
Diagnostik und Therapie der Myokardits im Kindesalter.
Besonderheiten in der Therapie des TTF-1-negativen Adenokarzinoms der Lunge
Authors: Frost Nikolaj , Reck Martin
Published: April 2023

Die Identifikation Biomarker-stratifizierter Behandlungen hat das Überleben eines relevanten Anteils an Patient*innen mit metastasiertem Lungenkrebs in den letzten Jahren teils erheblich verbessert. Hierzu zählen Treibermutationen und bei Treiber-negativen Tumoren die Expression des „programmed death ligand 1“ (PD-L1) hinsichtlich des Ansprechens auf eine Therapie mit Checkpoint-Inhibitoren. Aufgrund der beim Lungenkarzinom bestehenden Korrelation zwischen PD-L1-Expression und Behandlungseffektivität kommt insbesondere bei geringer oder fehlender Expression der zusätzlich applizierten Chemotherapie eine wichtige Rolle zu. Derzeitig erhalten Patient*innen im Stadium IV mit einer PD-L1-Expression <50% auf den Tumorzellen eine Chemoimmuntherapie zur Erstlinienbehandlung. Hierzu stehen Pemetrexed- und Taxan-basierte Regime zur Auswahl. In retrospektiven Analysen zeigte sich bei für den thyroidalen Transkriptionsfaktor 1 (TTF-1)-negativen Patient*in ein im Vergleich zu Pemetrexed-basierter Therapie verbessertes Überleben bei Verwendung Taxan-haltiger Regime. Diese Beobachtung wird aktuell prospektiv randomisiert untersucht.
Chemical Diversification of Carbocyclic Fluorinated Pyrimidine Nucleosides: Introducing 2′-Arabino Analogues and Ring Unsaturation
Authors: Miller Gavin J. , Benckendorff Caecilie M. M. , Hawes Chris S. , Smith Mark
Published: April 2023

Analogues of the canonical nucleosides have a longstanding presence and proven capability within medicinal chemistry and drug-discovery research. Herein, we report chemical diversification of carbocyclic pyrimidine nucleosides containing CF2 and CHF in place of the furanose oxygen to introduce ring unsaturation and 2′-epimers. Utilizing gram-scale access to 6′-(R)-monofluoro- and 6′-gem-difluorouridine, we explore the provision of 2′,3′-didehydro-2′,3′-dideoxy, and 1′,2′-didehydro-2′-deoxy analogues, alongside the first example of a 6′-(R)-fluoro arabino-carbauridine. Key stereochemistries and the presence of unsaturation are confirmed using X-ray crystallography and NMR, and an indicative conformational preference for a monofluoro 2′,3′-didehydro-2′,3′-dideoxy system is presented. This synthetic blueprint offers a potential to explore biological activity for these hitherto unavailable materials, including a direct comparison to established nucleoside analogue drugs.
Quantitative 2D 1H, 13C HSQC NMR Spectroscopy for the Determination of Chondroitin Sulfate and Dermatan Sulfate Content in Danaparoid Sodium
Authors: Gardini Cristina , Boccardi Giovanni , Guerrini Marco , Kellenbach Edwin , Lunenburg Maarten , van der Meer Jan-Ytzen , Naggi Annamaria , Urso Elena
Published: April 2023

Objective Danaparoid sodium is a biopolymeric complex drug composed of the most abundant heparan sulfate (HS) followed in descending order by dermatan sulfate (DS) and chondroitin sulfate (CS). This composite nature explains its peculiar antithrombotic and anticoagulant properties and make it particularly advantageous when the risk of heparin-induced thrombocytopenia occurs. A specific control of the danaparoid composition is required by the Ph. Eur. The monograph includes the CS and DS limit contents and describes the method for their quantification through selective enzymatic degradations.

Materials and Methods In this study, a quantitative two-dimensional nuclear magnetic resonance (NMR) method is proposed as a new method suitable for CS and DS quantification. Statistical comparison of the results provided by the analysis of a series of danaparoid samples with both NMR and enzymatic methods highlights a small systematic difference, likely derived from lyase-resistant sequences bearing oxidized terminals. Some modified structures, whose survival to the enzymatic action was confirmed by mass spectrometry, can be detected and quantified by NMR.

Conclusion and Results The proposed NMR method can serve for the determination of DS and CS contents, is an easy-to-apply method with no dependence from enzymes and standards, and provides extensive structural information on the overall glycosaminoglycans mixture.
Nurse job task analysis: a profile of medical and surgical nursing activities
Authors: Considine Julie , Omonaiye Olumuyiwa , Schlieff Jordana , Boyd Leanne
Published: April 2023

Objective We aim to examine the activities undertaken by medical and surgical ward nurses at a major health service in Victoria, Australia, to inform nursing and midwifery strategic workforce planning. Methods This descriptive, exploratory study was conducted on 17 wards from three acute care hospitals in one of Victoria’s largest health services. The Work Observation Method by Activity Timing tool was used to enable participants to document the time spent in each of 10 nursing activity domains. Results Data from 70 respondents across all shifts showed nurses spent one-third of their time in direct care. Registered nurses spent a lower proportion of time than enrolled nurses in direct care and medications overall. Compared with enrolled nurses, registered nurses spent less time in direct care on morning shifts and documentation on afternoon shifts, and more time on ward-related activities on afternoon shifts. Conclusions Medical and surgical enrolled nurses and registered nurses spent comparable proportions of time engaged in specific activities. Further research is required to understand the influences on the time devoted to direct care and how time spent in direct care intersects with other activities, and the relationship with patient outcomes and quality of care indicators.
Physicians’ legal duty to disclose more cost-effective treatment options: an examination of Australian civil law applied to personal importation
Authors: Ghinea Narcyz
Published: April 2023

Objective A significant proportion of Australians defer or do not fill prescriptions they require due to cost. This article explores whether, and under what circumstances, physicians have a duty to assist these patients by disclosing how they can access more affordable medicines via personal importation. Methods This study involved a critical examination of Australian statutory and case law pertaining to physicians’ duty to disclose material information to identify key principles applicable to the context of cost-motivated personal importation. Results There are several legal principles that suggest that physicians have a duty to advise patients of options for accessing more affordable medicines, including via personal importation. These include a duty to warn of inherent and non-inherent risks, a duty to disclose treatments that offer clear advantages, and a duty to facilitate access to the means for achieving patients’ health goals. However, it is unclear whether, and on what grounds, responsibility for harm arising from a patient's inability to afford prescribed medicines should be attributed to the prescribing physician. Arguments supporting attribution of such a responsibility are proposed to motivate further legal, policy and ethical debate. Conclusions Physicians have a duty to take reasonable steps to mitigate foreseeable harm to their patients, however the law is silent on whether this duty extends to taking steps to help patients access medicines that they can afford. This investigation provides a framework to guide the development of sound policy and law on informed financial consent and economically motivated prescribing.
Estimating the benefits of stream water quality improvements in urbanizing watersheds: An ecological production function approach
Authors: von Haefen Roger H. , Van Houtven George , Naumenko Alexandra , Obenour Daniel R. , Miller Jonathan W. , Kenney Melissa A. , Gerst Michael D. , Waters Hillary
Published: April 2023

Streams in urbanizing watersheds are threatened by economic development that can lead to excessive sediment erosion and surface runoff. These anthropogenic stressors diminish valuable ecosystem services and result in pervasive degradation commonly referred to as “urban stream syndrome.” Understanding how the public perceives and values improvements in stream conditions is necessary to support efforts to quantify the economic benefits of water quality improvements. We develop an ecological production framework that translates measurable indicators of stream water quality into ecological endpoints. Our interdisciplinary approach integrates a predictive hierarchical water quality model that is well suited for sparse data environments, an expert elicitation that translates measurable water quality indicators into ecological endpoints that focus group participants identified as most relevant, and a stated preference survey that elicits the public’s willingness to pay for changes in these endpoints. To illustrate our methods, we develop an application to the Upper Neuse River Watershed located in the rapidly developing Triangle region of North Carolina (the United States). Our results suggest, for example, that residents are willing to pay roughly $127 per household and $54 million per year in aggregate (2021 US$) for water quality improvements resulting from a stylized intervention that increases stream bank canopy cover by 25% and decreases runoff from impervious surfaces, leading to improvements in water quality and ecological endpoints for local streams. Although the three components of our analysis are conducted with data from North Carolina, we discuss how our findings are generalizable to urban and urbanizing areas across the larger Piedmont ecoregion of the Eastern United States.
Distribution of capitalized benefits from land conservation
Authors: Lang Corey , VanCeylon Jarron , Ando Amy W.
Published: April 2023

Land conservation efforts throughout the United States sustain ecological benefits while generating wealth in the housing market through capitalization of amenities. This paper estimates the benefits of conservation that are capitalized into proximate home values and quantifies how those benefits are distributed across demographic groups. Using detailed property and household-level data from Massachusetts, we estimate that new land conservation led to $62 million in new housing wealth equity. However, houses owned by low-income or Black or Hispanic households are less likely to be located near protected areas, and hence, these populations are less likely to benefit financially. Direct study of the distribution of this new wealth from capitalized conservation is highly unequal, with the richest quartile of households receiving 43%, White households receiving 91%, and the richest White households receiving 40%, which is nearly 140% more than would be expected under equal distribution. We extend our analysis using census data for the entire United States and observe parallel patterns. We estimate that recent land conservation generated $9.8 billion in wealth through the housing market and that wealthier and White households benefited disproportionately. These findings suggest regressive and racially disparate incidence of the wealth benefits of land conservation policy.
Investigation of the yielding transition in concentrated colloidal systems via rheo-XPCS
Authors: Donley Gavin J. , Narayanan Suresh , Wade Matthew A. , Park Jun Dong , Leheny Robert L. , Harden James L. , Rogers Simon A.
Published: April 2023

We probe the microstructural yielding dynamics of a concentrated colloidal system by performing creep/recovery tests with simultaneous collection of coherent scattering data via X-ray Photon Correlation Spectroscopy (XPCS). This combination of rheology and scattering allows for time-resolved observations of the microstructural dynamics as yielding occurs, which can be linked back to the applied rheological deformation to form structure–property relations. Under sufficiently small applied creep stresses, examination of the correlation in the flow direction reveals that the scattering response recorrelates with its predeformed state, indicating nearly complete microstructural recovery, and the dynamics of the system under these conditions slows considerably. Conversely, larger creep stresses increase the speed of the dynamics under both applied creep and recovery. The data show a strong connection between the microstructural dynamics and the acquisition of unrecoverable strain. By comparing this relationship to that predicted from homogeneous, affine shearing, we find that the yielding transition in concentrated colloidal systems is highly heterogeneous on the microstructural level.
Autocorrelation analysis for cryo-EM with sparsity constraints: Improved sample complexity and projection-based algorithms
Authors: Bendory Tamir , Khoo Yuehaw , Kileel Joe , Mickelin Oscar , Singer Amit
Published: April 2023

The number of noisy images required for molecular reconstruction in single-particle cryoelectron microscopy (cryo-EM) is governed by the autocorrelations of the observed, randomly oriented, noisy projection images. In this work, we consider the effect of imposing sparsity priors on the molecule. We use techniques from signal processing, optimization, and applied algebraic geometry to obtain theoretical and computational contributions for this challenging nonlinear inverse problem with sparsity constraints. We prove that molecular structures modeled as sums of Gaussians are uniquely determined by the second-order autocorrelation of their projection images, implying that the sample complexity is proportional to the square of the variance of the noise. This theory improves upon the nonsparse case, where the third-order autocorrelation is required for uniformly oriented particle images and the sample complexity scales with the cube of the noise variance. Furthermore, we build a computational framework to reconstruct molecular structures which are sparse in the wavelet basis. This method combines the sparse representation for the molecule with projection-based techniques used for phase retrieval in X-ray crystallography.
Chemical factors induce aggregative multicellularity in a close unicellular relative of animals
Authors: Ros-Rocher Núria , Kidner Ria Q. , Gerdt Catherine , Davidson W. Sean , Ruiz-Trillo Iñaki , Gerdt Joseph P.
Published: April 2023

Regulated cellular aggregation is an essential process for development and healing in many animal tissues. In some animals and a few distantly related unicellular species, cellular aggregation is regulated by diffusible chemical cues. However, it is unclear whether regulated cellular aggregation was part of the life cycles of the first multicellular animals and/or their unicellular ancestors. To fill this gap, we investigated the triggers of cellular aggregation in one of animals’ closest unicellular living relatives—the filasterean
Capsaspora owczarzaki
. We discovered that
Capsaspora
aggregation is induced by chemical cues, as observed in some of the earliest branching animals and other unicellular species. Specifically, we found that calcium ions and lipids present in lipoproteins function together to induce aggregation of viable
Capsaspora
cells. We also found that this multicellular stage is reversible as depletion of the cues triggers disaggregation, which can be overcome upon reinduction. Our finding demonstrates that chemically regulated aggregation is important across diverse members of the holozoan clade. Therefore, this phenotype was plausibly integral to the life cycles of the unicellular ancestors of animals.
A rapidly spreading deleterious aphid endosymbiont that uses horizontal as well as vertical transmission
Authors: Gu Xinyue , Ross Perran A. , Gill Alex , Yang Qiong , Ansermin Eloïse , Sharma Sonia , Soleimannejad Safieh , Sharma Kanav , Callahan Ashley , Brown Courtney , Umina Paul A. , Kristensen Torsten N. , Hoffmann Ary A.
Published: April 2023

Endosymbiotic bacteria that live inside the cells of insects are typically only transmitted maternally and can spread by increasing host fitness and/or modifying reproduction in sexual hosts. Transinfections ofWolbachiaendosymbionts are now being used to introduce useful phenotypes into sexual host populations, but there has been limited progress on applications using other endosymbionts and in asexual populations. Here, we develop a unique pathway to application in aphids by transferring the endosymbiontRickettsiella viridisto the major crop pestMyzus persicae.Rickettsiellainfection greatly reduced aphid fecundity, decreased heat tolerance, and modified aphid body color, from light to dark green. Despite inducing host fitness costs,Rickettsiellaspread rapidly through caged aphid populations via plant-mediated horizontal transmission. The phenotypic effects ofRickettsiellawere sensitive to temperature, with spread only occurring at 19 °C and not 25 °C. Body color modification was also lost at high temperatures despiteRickettsiellamaintaining a high density.Rickettsiellashows the potential to spread through naturalM. persicaepopulations by horizontal transmission and subsequent vertical transmission. Establishment ofRickettsiellain natural populations could reduce crop damage by modifying population age structure, reducing population growth and providing context-dependent effects on host fitness. Our results highlight the importance of plant-mediated horizontal transmission and interactions with temperature as drivers of endosymbiont spread in asexual insect populations.
In diverse conditions, intrinsic chromatin condensates have liquid-like material properties
Authors: Gibson Bryan A. , Blaukopf Claudia , Lou Tracy , Chen Lifeng , Doolittle Lynda K. , Finkelstein Ilya , Narlikar Geeta J. , Gerlich Daniel W. , Rosen Michael K.
Published: April 2023

Nuclear DNA in eukaryotes is wrapped around histone proteins to form nucleosomes on a chromatin fiber. Dynamic folding of the chromatin fiber into loops and variations in the degree of chromatin compaction regulate essential processes such as transcription, recombination, and mitotic chromosome segregation. Our understanding of the physical properties that allow chromatin to be dynamically remodeled even in highly compacted states is limited. Previously, we reported that chromatin has an intrinsic capacity to phase separate and form dynamic liquid-like condensates, which can be regulated by cellular factors [B. A. Gibsonet al.,Cell179, 470–484.e421 (2019)]. Recent contradictory reports claim that a specific set of solution conditions is required for fluidity in condensates that would otherwise be solid [J. C. Hansen, K. Maeshima, M. J. Hendzel,Epigenetics Chromatin14, 50 (2021); H. Strickfadenet al.,Cell183, 1772–1784.e1713 (2020)]. We sought to resolve these discrepancies, as our ability to translate with confidence these biophysical observations to cells requires their precise characterization. Moreover, whether chromatin assemblies are dynamic or static affects how processes such as transcription, loop extrusion, and remodeling will engage them inside cells. Here, we show in diverse conditions and without specific buffering components that chromatin fragments form phase separated fluids in vitro. We also explore how sample preparation and imaging affect the experimental observation of chromatin condensate dynamics. Last, we describe how liquid-like in vitro behaviors can translate to the locally dynamic but globally constrained chromatin movement observed in cells.
Electrical current modulation in wood electrochemical transistor
Authors: Tran Van Chinh , Mastantuoni Gabriella G. , Zabihipour Marzieh , Li Lengwan , Berglund Lars , Berggren Magnus , Zhou Qi , Engquist Isak
Published: April 2023

The nature of mass transport in plants has recently inspired the development of low-cost and sustainable wood-based electronics. Herein, we report a wood electrochemical transistor (WECT) where all three electrodes are fully made of conductive wood (CW). The CW is prepared using a two-step strategy of wood delignification followed by wood amalgamation with a mixed electron-ion conducting polymer, poly(3,4-ethylenedioxythiophene)–polystyrene sulfonate (PEDOT:PSS). The modified wood has an electrical conductivity of up to 69 Sm
−1
induced by the formation of PEDOT:PSS microstructures inside the wood 3D scaffold. CW is then used to fabricate the WECT, which is capable of modulating an electrical current in a porous and thick transistor channel (1 mm) with an on/off ratio of 50. The device shows a good response to gate voltage modulation and exhibits dynamic switching properties similar to those of an organic electrochemical transistor. This wood-based device and the proposed working principle demonstrate the possibility to incorporate active electronic functionality into the wood, suggesting different types of bio-based electronic devices.
Evidence for an emergent anomalous metallic state in compressed titanium
Authors: Wang Kui , Liu Chang , Liu Guangtao , Yu Xiaohui , Zhou Mi , Wang Hongbo , Chen Changfeng , Ma Yanming
Published: April 2023

The anomalous metallic state (AMS) emerging from a quantum superconductor-to-metal transition is a subject of great current interest since this exotic quantum state exhibits unconventional transport properties that challenge the core physics principles of Fermi liquid theory. As the AMS concept is historically derived from disordered two-dimensional (2D) systems, related studies have predominately concentrated on 2D materials. The AMS behaviors in three-dimensional (3D) systems have been rarely reported to date, which raises intriguing questions on the fundamental nature of pertinent physics. Here, we report experimental evidence for a 3D AMS in highly compressed titanium metal that exhibits superconductivity with a critical temperature (
T
c
) reaching near-record 25.1 K among elemental superconductors, offering a favorable material template for exploring 3D AMS. At sufficiently strong magnetic fields, unusual transport behaviors set in over a wide pressure range, showcasing AMS hallmarks of a low-temperature saturation resistance below the Drude value and giant positive magnetoresistance. These findings reveal a 3D AMS in simple elemental systems and, more importantly, provide a fresh platform for probing the decades-long enigmatic underlying physics.
High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation
Authors: Wang Anli , Wan Xuzhi , Zhuang Pan , Jia Wei , Ao Yang , Liu Xiaohui , Tian Yimei , Zhu Li , Huang Yingyu , Yao Jianxin , Wang Binjie , Wu Yuanzhao , Xu Zhongshi , Wang Jiye , Yao Weixuan , Jiao Jingjing , Zhang Yu
Published: April 2023

Western dietary patterns have been unfavorably linked with mental health. However, the long-term effects of habitual fried food consumption on anxiety and depression and underlying mechanisms remain unclear. Our population-based study with 140,728 people revealed that frequent fried food consumption, especially fried potato consumption, is strongly associated with 12% and 7% higher risk of anxiety and depression, respectively. The associations were more pronounced among male and younger consumers. Consistently, long-term exposure to acrylamide, a representative food processing contaminant in fried products, exacerbates scototaxis and thigmotaxis, and further impairs exploration ability and sociality of adult zebrafish, showing anxiety- and depressive-like behaviors. Moreover, treatment with acrylamide significantly down-regulates the gene expression of
tjp2a
related to the permeability of blood–brain barrier. Multiomics analysis showed that chronic exposure to acrylamide induces cerebral lipid metabolism disturbance and neuroinflammation. PPAR signaling pathway mediates acrylamide-induced lipid metabolism disorder in the brain of zebrafish. Especially, chronic exposure to acrylamide dysregulates sphingolipid and phospholipid metabolism, which plays important roles in the development of anxiety and depression symptoms. In addition, acrylamide promotes lipid peroxidation and oxidation stress, which participate in cerebral neuroinflammation. Acrylamide dramatically increases the markers of lipid peroxidation, including (±)5-HETE, 11(S)-HETE, 5-oxoETE, and up-regulates the expression of proinflammatory lipid mediators such as (±)12-HETE and 14(S)-HDHA, indicating elevated cerebral inflammatory status after chronic exposure to acrylamide. Together, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered anxiety and depression, and highlight the significance of reducing fried food consumption for mental health.
Targeting SWI/SNF ATPases in H3.3K27M diffuse intrinsic pontine gliomas
Authors: Mota Mateus , Sweha Stefan R. , Pun Matt , Natarajan Siva Kumar , Ding Yujie , Chung Chan , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Samajdar Susanta , Cao Xuhong , Xiao Lanbo , Parolia Abhijit , Chinnaiyan Arul M. , Venneti Sriram
Published: April 2023

Diffuse midline gliomas (DMGs) including diffuse intrinsic pontine gliomas (DIPGs) bearing lysine-to-methionine mutations in histone H3 at lysine 27 (H3K27M) are lethal childhood brain cancers. These tumors harbor a global reduction in the transcriptional repressive mark H3K27me3 accompanied by an increase in the transcriptional activation mark H3K27ac. We postulated that H3K27M mutations, in addition to altering H3K27 modifications, reprogram the master chromatin remodeling switch/sucrose nonfermentable (SWI/SNF) complex. The SWI/SNF complex can exist in two main forms termed BAF and PBAF that play central roles in neurodevelopment and cancer. Moreover, BAF antagonizes PRC2, the main enzyme catalyzing H3K27me3. We demonstrate that H3K27M gliomas show increased protein levels of the SWI/SNF complex ATPase subunits SMARCA4 and SMARCA2, and the PBAF component PBRM1. Additionally, knockdown of mutant H3K27M lowered SMARCA4 protein levels. The proteolysis targeting chimera (PROTAC) AU-15330 that simultaneously targets SMARCA4, SMARCA2, and PBRM1 for degradation exhibits cytotoxicity in H3.3K27M but not H3 wild-type cells. AU-15330 lowered chromatin accessibility measured by ATAC-Seq at nonpromoter regions and reduced global H3K27ac levels. Integrated analysis of gene expression, proteomics, and chromatin accessibility in AU-15330-treated cells demonstrated reduction in the levels of FOXO1, a key member of the forkhead family of transcription factors. Moreover, genetic or pharmacologic targeting of FOXO1 resulted in cell death in H3K27M cells. Overall, our results suggest that H3K27M up-regulates SMARCA4 levels and combined targeting of SWI/SNF ATPases in H3.3K27M can serve as a potent therapeutic strategy for these deadly childhood brain tumors.
SRC2 controls CD4
+
T cell activation via stimulating c-Myc-mediated upregulation of amino acid transporter
Slc7a5
Authors: Zhang Wencan , Cao Xu , Zhong Xiancai , Wu Hongmin , Shi Yun , Feng Mingye , Wang Yi-Chang , Ann David , Gwack Yousang , Yuan Yate-Ching , Shang Weirong , Sun Zuoming
Published: April 2023

T cell activation stimulates substantially increased protein synthesis activity to accumulate sufficient biomass for cell proliferation. The protein synthesis is fueled by the amino acids transported from the environment. Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. Here, we show that SRC2 recruited by c-Myc enhances CD4
+
T cell activation to stimulate immune responses via upregulation of amino acid transporter Slc7a5. Mice deficient of SRC2 in T cells (

SRC2
fl/fl
/CD4
Cre

) are resistant to the induction of experimental autoimmune encephalomyelitis (EAE) and susceptible to
Citrobacter rodentium
(
C. rodentium
) infection. Adoptive transfer of naive CD4
+
T cells from

SRC2
fl/fl
/CD4
Cre

mice fails to elicit EAE and colitis in

Rag1
/

 recipients. Further, CD4
+
T cells from

SRC2
fl/fl
/CD4
Cre

mice display defective T cell proliferation, cytokine production, and differentiation both in vitro and in vivo. Mechanically, SRC2 functions as a coactivator to work together with c-Myc to stimulate the expression of amino acid transporter Slc7a5 required for T cell activation. Slc7a5 fails to be up-regulated in CD4
+
T cells from

SRC2
fl/fl
/CD4
Cre

mice, and forced expression of
Slc7a5
rescues proliferation, cytokine production, and the ability of

SRC2
fl/fl
/CD4
Cre

CD4
+
T cells to induce EAE. Therefore, SRC2 is essential for CD4
+
T cell activation and, thus, a potential drug target for controlling CD4
+
T cell-mediated autoimmunity.
The cell envelope of
Thermotogae
suggests a mechanism for outer membrane biogenesis
Authors: Sexton Danielle L. , Hashimi Ameena , Beskrovnaya Polina , Sibanda Lloyd , Huan Tao , Tocheva Elitza I.
Published: April 2023

The presence of a cell membrane is one of the major structural components defining life. Recent phylogenomic analyses have supported the hypothesis that the last universal common ancestor (LUCA) was likely a diderm. Yet, the mechanisms that guided outer membrane (OM) biogenesis remain unknown. Thermotogae is an early-branching phylum with a unique OM, the toga. Here, we use cryo-electron tomography to characterize the in situ cell envelope architecture of
Thermotoga maritima
and show that the toga is made of extended sheaths of β-barrel trimers supporting small (~200 nm) membrane patches. Lipidomic analyses identified the same major lipid species in the inner membrane (IM) and toga, including the rare to bacteria membrane-spanning ether-bound diabolic acids (DAs). Proteomic analyses revealed that the toga was composed of multiple SLH-domain containing Ompα and novel β-barrel proteins, and homology searches detected variable conservations of these proteins across the phylum. These results highlight that, in contrast to the SlpA/OmpM superfamily of proteins, Thermotoga possess a highly diverse bipartite OM-tethering system. We discuss the implications of our findings with respect to other early-branching phyla and propose that a toga-like intermediate may have facilitated monoderm-to-diderm cell envelope transitions.
Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication
Authors: Williams Jeffrey M. , Chen Yu-Jie , Cho Woo Jung , Tai Andrew W. , Tsai Billy
Published: April 2023

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling viral replication, which leads to productive infection. Different SARS-CoV-2 variants, including the delta variant, use the RTN-dependent pathway to promote infection. Mechanistically, our results reveal that the membrane-embedded reticulon homology domain (RHD) of the RTNs is sufficient to functionally support viral replication and physically engage NSP3 and NSP4, two viral non-structural membrane proteins known to induce DMV formation. Our findings thus identify the ER morphogenic RTN3 and RTN4 membrane proteins as host factors that help promote the biogenesis of SARS-CoV-2-induced DMVs, which can act as viral replication platforms.
Heavy ion irradiation induced failure of gallium nitride high electron mobility transistors: effects of in-situ biasing
Authors: Rasel Md Abu Jafar , Schoell Ryan , Al-Mamun Nahid Sultan , Hattar Khalid , Harris C Thomas , Haque Aman , Wolfe Douglas E , Ren Fan , Pearton Stephen J
Published: April 2023

While radiation is known to degrade AlGaN/GaN high-electron-mobility transistors (HEMTs), the question remains on the extent of damage governed by the presence of an electrical field in the device. In this study, we induced displacement damage in HEMTs in both ON and OFF states by irradiating with 2.8 MeV Au4+ ion to fluence levels ranging from

1.72
×

10

10

to

3.745
×

10

13

ions cm−2, or 0.001–2 displacement per atom (dpa). Electrical measurement is done in situ, and high-resolution transmission electron microscopy (HRTEM), energy dispersive x-ray (EDX), geometrical phase analysis (GPA), and micro-Raman are performed on the highest fluence of Au4+ irradiated devices. The selected heavy ion irradiation causes cascade damage in the passivation, AlGaN, and GaN layers and at all associated interfaces. After just 0.1 dpa, the current density in the ON-mode device deteriorates by two orders of magnitude, whereas the OFF-mode device totally ceases to operate. Moreover, six orders of magnitude increase in leakage current and loss of gate control over the 2-dimensional electron gas channel are observed. GPA and Raman analysis reveal strain relaxation after a 2 dpa damage level in devices. Significant defects and intermixing of atoms near AlGaN/GaN interfaces and GaN layer are found from HRTEM and EDX analyses, which can substantially alter device characteristics and result in complete failure.
Particle behavior and trap design for ±320 kV gas-insulated power transmission line (GIL)
Authors: Zhuang Weijian , Liang Zuodong , Liang Fangwei , Fan Xianhao , Luo Hanhua , Hu Jun , Li Chuanyang , Zhang Bo , He Jinliang
Published: April 2023

The movement of metal particles in the electric field of the DC gas-insulated transmission line (GIL) may cause local electric field distortion on the surface of the spacer, which seriously affects the operation stability of the GIL. In this paper, based on a ±320 kV GIL platform, the movement characteristics of metal particles (aluminum blocks, aluminum wires, aluminum balls) inside the GIL are studied. The suppression effect of particle activity for particle trapping and surface coating are experimentally studied in DC electric field. The relationship between particle trap porosity and particle suppression effect are discussed and verified with experiments. The research results show that under negative voltage, the minimum take-off voltage of metal particles in ±320 kV GIL is −190 kV, which is far lower than the steady-state operating voltage of GIL. Once the spherical and blocky particles take off, they will continue to reciprocate rapidly between the conductors. When the block particles are close to the spacer, they might be attracted and adsorbed on the surface of the spacer. Metal wires after taking off tend to show ‘firefly’ movement near the high-voltage conductor. The coating has a significant effect on increasing the take-off electric field of metal particles. It is verified that the traditional AC GIL particle trap is not effective in inhibiting particles in DC voltage. The suppression of the DC GIL particle is positively related to the porosity of the particle trap to a certain extent. The conclusions of this paper can be reference for the development of future stable and reliable DC gas-insulated equipment.
Effective electromechanical properties and energy harvesting response in PMN-0.3PT/PDMS flexible piezoelectric composites: a combined experimental and theoretical study
Authors: Kumar Abhishek , Mishra Neelam , Das Kaushik , Roy Amritendu
Published: April 2023

In this work, lead magnesium niobate-lead titanate (PMN-0.3PT) and polydimethylsiloxane (PDMS)-based flexible piezoelectric-polymer composites are designd and developd for efficient mechanical energy harvesting through a combined experimental-theoretical approach. A solid-state reaction method was employed to synthesize PMN-0.3PT piezo-ceramic, which was subsequently used for the fabrication of

v

r

-PMN-0.3PT/PDMS piezoelectric-polymer 0–3 composite with different volume fractions,

v

r

= 0.03, 0.25, and 0.50 of PMN-0.3PT reinforcement. Uniformly distributed PMN-0.3PT particles were found to retain their structural symmetry across the volume fractions and are well adhered to the PDMS matrix. The effective electromechanical properties of the composites were measured and compared with model predictions employing the finite element method and Eshelby–Mori–Tanaka-based micromechanical models. Considering that flexibility is a critical design parameter, we propose a new figure-of-merit term that would consider both electromechanical conversion as well as the mechanical flexibility of the material. We show that at

v

r

= 0.5, PMN-0.3PT/PDMS 0–3 composite yields an optimum combination of energy harvesting performance and flexibility. Our study further demonstrates that the orientation of the PMN-0.3PT particles does not significantly influence the effective elastic and dielectric properties at low and moderate PMN-PT content, attributed to the lower aspect ratio of the reinforcement particles. The piezoelectric charge coefficient showed small yet finite change with increasing reinforcement content. A maximum current density, 35 nA cm−2, and electric field, 90 V cm−1, was obtained with a cyclic compressive stress of 0.22 MPa (force, 50 N) at 5 Hz, in a piezoelectric generator, based on

v

r

= 0.5.
Role of SSW on thermal-gradient induced domain-wall dynamics
Authors: Akanda M A S , Islam M T , Wang X R
Published: April 2023

We study the thermal gradient (TG) induced domain wall (DW) dynamics in a uniaxial nanowire in the framework of the Stochastic-Landau–Lifshitz–Gilbert equation. TG drives the DW in a certain direction, and DW (linear and rotational) velocities increase with TG linearly, which can be explained by the magnonic angular momentum transfer to the DW. Interestingly, from Gilbert damping dependence of DW dynamics for fixed TG, we find that the DW velocity is significantly smaller even for lower damping, and DW velocity increases with damping (for a certain range of damping) and reaches a maximal value for critical damping which is contrary to our usual desire. This can be attributed to the formation of standing spin wave (SSW) modes (from the superposition of the spin waves and their reflection) together with travelling spin wave (TSW) modes. SSW does not carry any net energy/momentum to the DW, while TSW does. Damping α compels the spin current polarization to align with the local spin, which reduces the magnon propagation length and thus α hinders to generate SSWs, and contrarily the number of TSWs increases, which leads to the increment of DW speed with damping. For a similar reason, we observe that DW velocity increases with nanowire length and becomes saturated to maximal value for a certain length. Therefore, these findings may enhance the fundamental understanding as well as provide a way of utilizing the Joule heat in the spintronics (e.g. racetrack memory) devices.
Theoretical and simulation analysis of the measurement of polarized fluid flow in a circular pipe with electric field excitation
Authors: Vadde Anusha , Kadambi Govind R , C Siddabasappa
Published: April 2023

Measurement of conductive fluid flow velocity is essential in applications such as measuring the velocity of water flow in the agriculture sector, sewage water treatment plants, and metal refining industries. This paper proposes a contactless flow measurement device for computing the flow velocity of conductive fluids based on movement of polarized fluid flow. The proposed simulation model of the flow meter can also determine the conductivity of the fluid for varying flow velocity. The obtained simulated results concur with the earlier theoretical studies. Based on the interpretations in the underlying assumptions and physics of a fluid flow under a source of an electric field, it reveals that it is possible to measure a flow velocity of 0.01–10 m s−1 for conductive fluids of 0.1–10 S m−1.
A computational building block approach towards multiscale architected materials analysis and design with application to hierarchical metal metamaterials
Authors: Buehler Markus J
Published: April 2023

In this study we report a computational approach towards multiscale architected materials analysis and design. A particular challenge in modeling and simulation of materials, and especially the development of hierarchical design approaches, has been to identify ways by which complex multi-level material structures can be effectively modeled. One way to achieve this is to use coarse-graining approaches, where physical relationships can be effectively described with reduced dimensionality. In this paper we report an integrated deep neural network architecture that first learns coarse-grained representations of complex hierarchical microstructure data via a discrete variational autoencoder and then utilizes an attention-based diffusion model solve both forward and inverse problems, including a capacity to solve degenerate design problems. As an application, we demonstrate the method in the analysis and design of hierarchical highly porous metamaterials within the context of nonlinear stress–strain responses to compressive deformation. We validate the mechanical behavior and mechanisms of deformation using embedded-atom molecular dynamics simulations carried out for copper and nickel, showing good agreement with the design objectives.
Quantum multicritical behavior for coupled optical cavities with driven laser fields
Authors: Hu Yutao , Zhou Yu , Luo Wenchen , Trombettoni Andrea , Huang Guoxiang
Published: April 2023

Quantum phase transitions with multicritical points are fascinating phenomena occurring in interacting quantum many-body systems. However, multicritical points predicted by theory have been rarely verified experimentally; finding multicritical points with specific behaviors and realizing their control remains a challenging topic. Here, we propose a system that a quantized light field interacts with a two-level atomic ensemble coupled by microwave fields in optical cavities, which is described by a generalized Dicke model. Multicritical points for the superradiant quantum phase transition are shown to occur. We determine the number and position of these critical points and demonstrate that they can be effectively manipulated through the tuning of system parameters. Particularly, we find that the quantum critical points can evolve into a Lifshitz point (LP) if the Rabi frequency of the light field is modulated periodically in time. Remarkably, the texture of atomic pseudo-spins can be used to characterize the quantum critical behaviors of the system. The magnetic orders of the three phases around the LP, represented by the atomic pseudo-spins, are similar to those of an axial next-nearest-neighboring Ising model. The results reported here are beneficial for unveiling intriguing physics of quantum phase transitions and pave the way towards to find novel quantum multicritical phenomena based on the generalized Dicke model.