bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermoelastic damping in MEMS gyroscopes at high frequencies
Authors: Schiwietz Daniel , Weig Eva M. , Degenfeld-Schonburg Peter 
Published: January 2023

AbstractMicroelectromechanical systems (MEMS) gyroscopes are widely used, e.g., in modern automotive and consumer applications, and require signal stability and accuracy in rather harsh environmental conditions. In many use cases, device reliability must be guaranteed under large external loads at high frequencies. The sensitivity of the sensor to such external loads depends strongly on the damping, or rather quality factor, of the high-frequency mechanical modes of the structure. In this paper, we investigate the influence of thermoelastic damping on several high-frequency modes by comparing finite element simulations with measurements of the quality factor in an application-relevant temperature range. We measure the quality factors over different temperatures in vacuum, to extract the relevant thermoelastic material parameters of the polycrystalline MEMS device. Our simulation results show a good agreement with the measured quantities, therefore proving the applicability of our method for predictive purposes in the MEMS design process. Overall, we are able to uniquely identify the thermoelastic effects and show their significance for the damping of the high-frequency modes of an industrial MEMS gyroscope. Our approach is generic and therefore easily applicable to any mechanical structure with many possible applications in nano- and micromechanical systems.
Chemotherapy-induced tumor immunogenicity is mediated in part by megakaryocyte-erythroid progenitors
Authors: Vorontsova Avital , Cooper Tim J. , Haj-Shomaly Jozafina , Benguigui Madeleine , Levin Sapir , Manobla Bar , Menachem Rotem , Timaner Michael , Raviv Ziv , Shaked Yuval 
Published: January 2023

AbstractChemotherapy remains one of the main treatment modalities for cancer. While chemotherapy is mainly known for its ability to kill tumor cells directly, accumulating evidence indicates that it also acts indirectly by enhancing T cell-mediated anti-tumor immunity sometimes through immunogenic cell death. However, the role of immature immune cells in chemotherapy-induced immunomodulation has not been studied. Here, we utilized a mouse pancreatic cancer model to characterize the effects of gemcitabine chemotherapy on immature bone marrow cells in the context of tumor immunogenicity. Single cell RNA sequencing of hematopoietic stem and progenitor cells revealed a 3-fold increase in megakaryocyte-erythroid progenitors (MEPs) in the bone marrow of gemcitabine-treated mice in comparison to untreated control mice. Notably, adoptive transfer of MEPs to pancreatic tumor-bearing mice significantly reduced tumor growth and increased the levels of anti-tumor immune cells in tumors and peripheral blood. Furthermore, MEPs increased the tumor cell killing activity of CD8 + T cells and NK cells, an effect that was dependent on MEP-secreted CCL5 and CXCL16. Collectively, our findings demonstrate that chemotherapy-induced enrichment of MEPs in the bone marrow compartment contributes to anti-tumor immunity.
Discovery of IHMT-337 as a potent irreversible EZH2 inhibitor targeting CDK4 transcription for malignancies
Authors: Mei Husheng , Wu Hong , Yang Jing , Zhou Bin , Wang Aoli , Hu Chen , Qi Shuang , Jiang Zongru , Zou Fengming , Wang Beilei , Liu Feiyang , Chen Yongfei , Wang Wenchao , Liu Jing , Liu Qingsong 
Published: January 2023

AbstractEnhancer of zeste homolog 2 (EZH2), an enzymatic subunit of PRC2 complex, plays an important role in tumor development and progression through its catalytic and noncatalytic activities. Overexpression or gain-of-function mutations of EZH2 have been significantly associated with tumor cell proliferation of triple-negative breast cancer (TNBC) and diffuse large B-cell lymphoma (DLBCL). As a result, it has gained interest as a potential therapeutic target. The currently available EZH2 inhibitors, such as EPZ6438 and GSK126, are of benefit for clinical using or reached clinical trials. However, certain cancers are resistant to these enzymatic inhibitors due to its noncatalytic or transcriptional activity through modulating nonhistone proteins. Thus, it may be more effective to synergistically degrade EZH2 in addition to enzymatic inhibition. Here, through a rational design and chemical screening, we discovered a new irreversible EZH2 inhibitor, IHMT-337, which covalently bounds to and degrades EZH2 via the E3 ligase CHIP-mediated ubiquitination pathway. Moreover, we revealed that IHMT-337 affects cell cycle progression in TNBC cells through targeting transcriptional regulating of CDK4, a novel PRC2 complex- and enzymatic activity-independent function of EZH2. More significantly, our compound inhibits both DLBCL and TNBC cell proliferation in different preclinical models in vitro and in vivo. Taken together, our findings demonstrate that in addition to enzymatic inhibition, destroying of EZH2 by IHMT-337 could be a promising therapeutic strategy for TNBC and other malignancies that are independent of EZH2 enzymatic activity.
CRISPR/Cas9 therapeutics: progress and prospects
Authors: Li Tianxiang , Yang Yanyan , Qi Hongzhao , Cui Weigang , Zhang Lin , Fu Xiuxiu , He Xiangqin , Liu Meixin , Li Pei-feng , Yu Tao 
Published: January 2023

AbstractClustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during diseases. However, strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking, and nonviral vectors with target recognition functions may be the focus of future research. Pathological and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene editing. Diseases are both varied and complex, and the choice of appropriate gene-editing methods and delivery vectors for different diseases is important. Meanwhile, there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment. This paper reviews the current developments in three aspects, namely, gene-editing type, delivery vector, and disease characteristics. Additionally, this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.
Norepinephrine inhibits CD8+ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma
Authors: Geng Qishun , Li Lifeng , Shen Zhibo , Zheng Yuanyuan , Wang Longhao , Xue Ruyue , Xue Wenhua , Peng Mengle , Zhao Jie 
Published: January 2023

Abstract
Background
Mental stress-induced neurotransmitters can affect the immune system in various ways. Therefore, a better understanding of the role of neurotransmitters in the tumour immune microenvironment is expected to promote the development of novel anti-tumour therapies.

Methods
In this study, we analysed the plasma levels of neurotransmitters in anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb)-resistance patients and sensitive patients, to identify significantly different neurotransmitters. Subsequently, animal experiments and experiments in vitro were used to reveal the specific mechanism of norepinephrine’s (NE) effect on immunotherapy.

Results
The plasma NE levels were higher in anti-PD-1 mAb-resistance patients, which may be the main cause of anti-PD-1 mAb resistance. Then, from the perspective of the immunosuppressive microenvironment to explore the specific mechanism of NE-induced anti-PD-1 mAb resistance, we found that NE can affect the secretion of C-X-C Motif Chemokine Ligand 9 (CXCL9) and adenosine (ADO) in tumour cells, thereby inhibiting chemotaxis and function of CD8+ T cells. Notably, the WNT7A/β-catenin signalling pathway plays a crucial role in this progression.

Conclusion
NE can affect the secretion of CXCL9 and ADO in tumour cells, thereby inhibiting chemotaxis and the function of CD8+ T cells and inducing anti-PD-1 mAb resistance in lung adenocarcinoma (LUAD).
Regulatory T cell and macrophage crosstalk in acute lung injury: future perspectives
Authors: Guan Tianshu , Zhou Xv , Zhou Wenwen , Lin Hui 
Published: January 2023

AbstractAcute lung injury (ALI) describes the injury to endothelial cells in the lungs and associated vessels due to various factors. Furthermore, ALI accompanied by inflammation and thrombosis has been reported as a common complication of SARS-COV-2 infection. It is widely accepted that inflammation and the cytokine storm are main causes of ALI. Two classical anti-inflammatory cell types, regulatory T cells (Tregs) and M2 macrophages, are theoretically capable of resisting uncontrolled inflammation. Recent studies have indicated possible crosstalk between Tregs and macrophages involving their mutual activation. In this review, we discuss the current findings related to ALI pathogenesis and the role of Tregs and macrophages. In particular, we review the molecular mechanisms underlying the crosstalk between Tregs and macrophages in ALI pathogenesis. Understanding the role of Tregs and macrophages will provide the potential targets for treating ALI.
Inter-decadal climate variability induces differential ice response along Pacific-facing West Antarctica
Authors: Christie Frazer D. W. , Steig Eric J. , Gourmelen Noel , Tett Simon F. B. , Bingham Robert G. 
Published: January 2023

AbstractWest Antarctica has experienced dramatic ice losses contributing to global sea-level rise in recent decades, particularly from Pine Island and Thwaites glaciers. Although these ice losses manifest an ongoing Marine Ice Sheet Instability, projections of their future rate are confounded by limited observations along West Antarctica’s coastal perimeter with respect to how the pace of retreat can be modulated by variations in climate forcing. Here, we derive a comprehensive, 12-year record of glacier retreat around West Antarctica’s Pacific-facing margin and compare this dataset to contemporaneous estimates of ice flow, mass loss, the state of the Southern Ocean and the atmosphere. Between 2003 and 2015, rates of glacier retreat and acceleration were extensive along the Bellingshausen Sea coastline, but slowed along the Amundsen Sea. We attribute this to an interdecadal suppression of westerly winds in the Amundsen Sea, which reduced warm water inflow to the Amundsen Sea Embayment. Our results provide direct observations that the pace, magnitude and extent of ice destabilization around West Antarctica vary by location, with the Amundsen Sea response most sensitive to interdecadal atmosphere-ocean variability. Thus, model projections accounting for regionally resolved ice-ocean-atmosphere interactions will be important for predicting accurately the short-term evolution of the Antarctic Ice Sheet.
mGluR5 is transiently confined in perisynaptic nanodomains to shape synaptic function
Authors: Scheefhals Nicky , Westra Manon , MacGillavry Harold D. 
Published: January 2023

AbstractThe unique perisynaptic distribution of postsynaptic metabotropic glutamate receptors (mGluRs) at excitatory synapses is predicted to directly shape synaptic function, but mechanistic insight into how this distribution is regulated and impacts synaptic signaling is lacking. We used live-cell and super-resolution imaging approaches, and developed molecular tools to resolve and acutely manipulate the dynamic nanoscale distribution of mGluR5. Here we show that mGluR5 is dynamically organized in perisynaptic nanodomains that localize close to, but not in the synapse. The C-terminal domain of mGluR5 critically controlled perisynaptic confinement and prevented synaptic entry. We developed an inducible interaction system to overcome synaptic exclusion of mGluR5 and investigate the impact on synaptic function. We found that mGluR5 recruitment to the synapse acutely increased synaptic calcium responses. Altogether, we propose that transient confinement of mGluR5 in perisynaptic nanodomains allows flexible modulation of synaptic function.
High-performance Kerr microresonator optical parametric oscillator on a silicon chip
Authors: Perez Edgar F. , Moille Grégory , Lu Xiyuan , Stone Jordan , Zhou Feng , Srinivasan Kartik 
Published: January 2023

AbstractOptical parametric oscillation (OPO) is distinguished by its wavelength access, that is, the ability to flexibly generate coherent light at wavelengths that are dramatically different from the pump laser, and in principle bounded solely by energy conservation between the input pump field and the output signal/idler fields. As society adopts advanced tools in quantum information science, metrology, and sensing, microchip OPO may provide an important path for accessing relevant wavelengths. However, a practical source of coherent light should additionally have high conversion efficiency and high output power. Here, we demonstrate a silicon photonics OPO device with unprecedented performance. Our OPO device, based on the third-order (χ(3)) nonlinearity in a silicon nitride microresonator, produces output signal and idler fields widely separated from each other in frequency ( > 150 THz), and exhibits a pump-to-idler conversion efficiency up to 29 % with a corresponding output idler power of > 18 mW on-chip. This performance is achieved by suppressing competitive processes and by strongly overcoupling the output light. This methodology can be readily applied to existing silicon photonics platforms with heterogeneously-integrated pump lasers, enabling flexible coherent light generation across a broad range of wavelengths with high output power and efficiency.
Micro and macroevolution of sea anemone venom phenotype
Authors: Smith Edward G. , Surm Joachim M. , Macrander Jason , Simhi Adi , Amir Guy , Sachkova Maria Y. , Lewandowska Magda , Reitzel Adam M. , Moran Yehu 
Published: January 2023

AbstractVenom is a complex trait with substantial inter- and intraspecific variability resulting from strong selective pressures acting on the expression of many toxic proteins. However, understanding the processes underlying toxin expression dynamics that determine the venom phenotype remains unresolved. By interspecific comparisons we reveal that toxin expression in sea anemones evolves rapidly and that in each species different toxin family dictates the venom phenotype by massive gene duplication events. In-depth analysis of the sea anemone,Nematostella vectensis, revealed striking variation of the dominant toxin (Nv1) diploid copy number across populations (1-24 copies) resulting from independent expansion/contraction events, which generate distinct haplotypes.Nv1copy number correlates with expression at both the transcript and protein levels with one population having a near-complete loss of Nv1 production. Finally, we establish the dominant toxin hypothesis which incorporates observations in other venomous lineages that animals have convergently evolved a similar strategy in shaping their venom.
Preferential molecular recognition of heterochiral guests within a cyclophane receptor
Authors: Weh Manuel , Shoyama Kazutaka , Würthner Frank 
Published: January 2023

AbstractThe discrimination of enantiomers by natural receptors is a well-established phenomenon. In contrast the number of synthetic receptors with the capability for enantioselective molecular recognition of chiral substrates is scarce and for chiral cyclophanes indicative for a preferential binding of homochiral guests. Here we introduce a cyclophane composed of two homochiral core-twisted perylene bisimide (PBI) units connected by p-xylylene spacers and demonstrate its preference for the complexation of [5]helicene of opposite helicity compared to the PBI units of the host. The pronounced enantio-differentiation of this molecular receptor for heterochiral guests can be utilized for the enrichment of the P-PBI-M-helicene-P-PBI epimeric bimolecular complex. Our experimental results are supported by DFT calculations, which reveal that the sterically demanding bay substituents attached to the PBI chromophores disturb the helical shape match of the perylene core and homochiral substrates and thereby enforce the formation of syndiotactic host-guest complex structures. Hence, the most efficient substrate binding is observed for those aromatic guests, e. g. perylene, [4]helicene, phenanthrene and biphenyl, that can easily adapt in non-planar axially chiral conformations due to their inherent conformational flexibility. In all cases the induced chirality for the guest is opposed to those of the embedding PBI units, leading to heterochiral host-guest structures.
Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol
Authors: Yang Ming , Qi Xiaoqiang , Li Nan , Kaifi Jussuf T. , Chen Shiyou , Wheeler Andrew A. , Kimchi Eric T. , Ericsson Aaron C. , Rector R. Scott , Staveley-O’Carroll Kevin F. , Li Guangfu 
Published: January 2023

AbstractThe interplay between western diet and gut microbiota drives the development of non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. However, the specific microbial and metabolic mediators contributing to non-alcoholic steatohepatitis remain to be identified. Here, a choline-low high-fat and high-sugar diet, representing a typical western diet, named CL-HFS, successfully induces male mouse non-alcoholic steatohepatitis with some features of the human disease, such as hepatic inflammation, steatosis, and fibrosis. Metataxonomic and metabolomic studies identify Blautia producta and 2-oleoylglycerol as clinically relevant bacterial and metabolic mediators contributing to CL-HFS-induced non-alcoholic steatohepatitis. In vivo studies validate that both Blautia producta and 2-oleoylglycerol promote liver inflammation and hepatic fibrosis in normal diet- or CL-HFS-fed mice. Cellular and molecular studies reveal that the GPR119/TAK1/NF-κB/TGF-β1 signaling pathway mediates 2-oleoylglycerol-induced macrophage priming and subsequent hepatic stellate cell activation. These findings advance our understanding of non-alcoholic steatohepatitis pathogenesis and provide targets for developing microbiome/metabolite-based therapeutic strategies against non-alcoholic steatohepatitis.
Deep mutational scanning of essential bacterial proteins can guide antibiotic development
Authors: Dewachter Liselot , Brooks Aaron N. , Noon Katherine , Cialek Charlotte , Clark-ElSayed Alia , Schalck Thomas , Krishnamurthy Nandini , Versées Wim , Vranken Wim , Michiels Jan 
Published: January 2023

AbstractDeep mutational scanning is a powerful approach to investigate a wide variety of research questions including protein function and stability. Here, we perform deep mutational scanning on three essential E. coli proteins (FabZ, LpxC and MurA) involved in cell envelope synthesis using high-throughput CRISPR genome editing, and study the effect of the mutations in their original genomic context. We use more than 17,000 variants of the proteins to interrogate protein function and the importance of individual amino acids in supporting viability. Additionally, we exploit these libraries to study resistance development against antimicrobial compounds that target the selected proteins. Among the three proteins studied, MurA seems to be the superior antimicrobial target due to its low mutational flexibility, which decreases the chance of acquiring resistance-conferring mutations that simultaneously preserve MurA function. Additionally, we rank anti-LpxC lead compounds for further development, guided by the number of resistance-conferring mutations against each compound. Our results show that deep mutational scanning studies can be used to guide drug development, which we hope will contribute towards the development of novel antimicrobial therapies.
A database of experimentally measured lithium solid electrolyte conductivities evaluated with machine learning
Authors: Hargreaves Cameron J. , Gaultois Michael W. , Daniels Luke M. , Watts Emma J. , Kurlin Vitaliy A. , Moran Michael , Dang Yun , Morris Rhun , Morscher Alexandra , Thompson Kate , Wright Matthew A. , Prasad Beluvalli-Eshwarappa , Blanc Frédéric , Collins Chris M. , Crawford Catriona A. , Duff Benjamin B. , Evans Jae , Gamon Jacinthe , Han Guopeng , Leube Bernhard T. , Niu Hongjun , Perez Arnaud J. , Robinson Aris , Rogan Oliver , Sharp Paul M. , Shoko Elvis , Sonni Manel , Thomas William J. , Vasylenko Andrij , Wang Lu , Rosseinsky Matthew J. , Dyer Matthew S. 
Published: January 2023

AbstractThe application of machine learning models to predict material properties is determined by the availability of high-quality data. We present an expert-curated dataset of lithium ion conductors and associated lithium ion conductivities measured by a.c. impedance spectroscopy. This dataset has 820 entries collected from 214 sources; entries contain a chemical composition, an expert-assigned structural label, and ionic conductivity at a specific temperature (from 5 to 873 °C). There are 403 unique chemical compositions with an associated ionic conductivity near room temperature (15–35 °C). The materials contained in this dataset are placed in the context of compounds reported in the Inorganic Crystal Structure Database with unsupervised machine learning and the Element Movers Distance. This dataset is used to train a CrabNet-based classifier to estimate whether a chemical composition has high or low ionic conductivity. This classifier is a practical tool to aid experimentalists in prioritizing candidates for further investigation as lithium ion conductors.