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  1. Article ; Online: Exploiting Molecular Orders at the Interface of Microdroplets for Intelligent Materials.

    Liu, Mingzhu / Yang, Shu

    Accounts of chemical research

    2024  Volume 57, Issue 5, Page(s) 739–750

    Abstract: ConspectusThe intrinsic molecular order of liquid crystals (LCs) and liquid crystalline elastomers (LCEs) is the origin of their stimuli-responsive properties. The programmable responsiveness and functionality, such as shape morphing and color change ... ...

    Abstract ConspectusThe intrinsic molecular order of liquid crystals (LCs) and liquid crystalline elastomers (LCEs) is the origin of their stimuli-responsive properties. The programmable responsiveness and functionality, such as shape morphing and color change under external stimuli, are the key features that attract interest in designing LC- and LCE-based intelligent material platforms. Methods such as mechanical stretching and shearing, surface alignment, and field-assisted alignment have been exploited to program the order of LC molecules for the desired responsiveness. However, the huge size mismatch between the nanometer-sized LC mesogens and the targeted macroscopic objects calls for questions about how to delicately control molecular order for desired performance. Microparticles that can be synthesized with intrinsic molecular order precisely controlled to micrometer size can be used as building blocks for bulk materials, thus offering opportunities to bridge the gap and transcend molecular orders across scales. By taking advantage of the interfacial anchoring effects, we can control and engineer the molecular orders inside the microdroplets, allowing for the realization of various responsive behaviors. Furthermore, designer LC microparticles with multiple responsiveness can be assembled and confined within a matrix, opening a new pathway to engineering LC-enabled intelligent materials.In this Account, we present our recent work on exploiting the molecular order inside microdroplets for the construction of intelligent materials. We briefly introduce the typical chemicals used in the synthesis and the methods developed to control LC molecular alignment within a microdroplets. We then present examples of microparticles synthesized from microdroplets that can transform into complex morphologies upon cooling from the isotropic to nematic phase or due to phase separation within the droplets coupled with the segregation of LC oligomers (LCOs) with polydisperse chain lengths. Furthermore, we show the synthesis of elliptical LCE microparticles and exploit their thermal and magnetic responsiveness to program shape-morphing behaviors and microarrays with switchable optical polarization. By mixing magnetic nanoparticles in cholesteric liquid crystals (CLCs) and silicone oils, we created Janus microparticles capable of color switching for camouflage and information encryption. Moreover, we can engineer complex molecular orders in LCE microparticles by mixing different surfactants, yielding microparticles of diverse anisotropic, temperature-responsive shapes after photopolymerization and extraction of the template LC molecules with different solvents. We conclude the Account with an outlook on the design of intelligent material systems via the design of unprecedented molecular ordering within the microparticles and their coupling with bulk materials.
    Language English
    Publishing date 2024-02-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1483291-4
    ISSN 1520-4898 ; 0001-4842
    ISSN (online) 1520-4898
    ISSN 0001-4842
    DOI 10.1021/acs.accounts.3c00761
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Distributional imputation for the analysis of censored recurrent events.

    Fairfax, Sarah R / Yang, Shu

    Statistics in medicine

    2024  

    Abstract: Longitudinal clinical trials for which recurrent events endpoints are of interest are commonly subject to missing event data. Primary analyses in such trials are often performed assuming events are missing at random, and sensitivity analyses are ... ...

    Abstract Longitudinal clinical trials for which recurrent events endpoints are of interest are commonly subject to missing event data. Primary analyses in such trials are often performed assuming events are missing at random, and sensitivity analyses are necessary to assess robustness of primary analysis conclusions to missing data assumptions. Control-based imputation is an attractive approach in superiority trials for imposing conservative assumptions on how data may be missing not at random. A popular approach to implementing control-based assumptions for recurrent events is multiple imputation (MI), but Rubin's variance estimator is often biased for the true sampling variability of the point estimator in the control-based setting. We propose distributional imputation (DI) with corresponding wild bootstrap variance estimation procedure for control-based sensitivity analyses of recurrent events. We apply control-based DI to a type I diabetes trial. In the application and simulation studies, DI produced more reasonable standard error estimates than MI with Rubin's combining rules in control-based sensitivity analyses of recurrent events.
    Language English
    Publishing date 2024-04-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 843037-8
    ISSN 1097-0258 ; 0277-6715
    ISSN (online) 1097-0258
    ISSN 0277-6715
    DOI 10.1002/sim.10087
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Semiparametric estimation of structural nested mean models with irregularly spaced longitudinal observations.

    Yang, Shu

    Biometrics

    2021  Volume 78, Issue 3, Page(s) 937–949

    Abstract: Structural nested mean models (SNMMs) are useful for causal inference of treatment effects in longitudinal observational studies. Most existing works assume that the data are collected at prefixed time points for all subjects, which, however, may be ... ...

    Abstract Structural nested mean models (SNMMs) are useful for causal inference of treatment effects in longitudinal observational studies. Most existing works assume that the data are collected at prefixed time points for all subjects, which, however, may be restrictive in practice. To deal with irregularly spaced observations, we assume a class of continuous-time SNMMs and a martingale condition of no unmeasured confounding (NUC) to identify the causal parameters. We develop the semiparametric efficiency theory and locally efficient estimators for continuous-time SNMMs. This task is nontrivial due to the restrictions from the NUC assumption imposed on the SNMM parameter. In the presence of ignorable censoring, we show that the complete-case estimator is optimal among a class of weighting estimators including the inverse probability of censoring weighting estimator, and it achieves a double robustness feature in that it is consistent if at least one of the models for the potential outcome mean function and the treatment process is correctly specified. The new framework allows us to conduct causal analysis respecting the underlying continuous-time nature of data processes. The simulation study shows that the proposed estimator outperforms existing approaches. We estimate the effect of time to initiate highly active antiretroviral therapy on the CD4 count at year 2 from the observational Acute Infection and Early Disease Research Program database.
    MeSH term(s) Causality ; Computer Simulation ; Humans ; Longitudinal Studies ; Models, Statistical ; Probability
    Language English
    Publishing date 2021-04-29
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 213543-7
    ISSN 1541-0420 ; 0099-4987 ; 0006-341X
    ISSN (online) 1541-0420
    ISSN 0099-4987 ; 0006-341X
    DOI 10.1111/biom.13471
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Semiparametric estimation of structural nested mean models with irregularly spaced longitudinal observations

    Yang, Shu

    Biometrics. 2022 Sept., v. 78, no. 3 p.937-949

    2022  

    Abstract: Structural nested mean models (SNMMs) are useful for causal inference of treatment effects in longitudinal observational studies. Most existing works assume that the data are collected at prefixed time points for all subjects, which, however, may be ... ...

    Abstract Structural nested mean models (SNMMs) are useful for causal inference of treatment effects in longitudinal observational studies. Most existing works assume that the data are collected at prefixed time points for all subjects, which, however, may be restrictive in practice. To deal with irregularly spaced observations, we assume a class of continuous‐time SNMMs and a martingale condition of no unmeasured confounding (NUC) to identify the causal parameters. We develop the semiparametric efficiency theory and locally efficient estimators for continuous‐time SNMMs. This task is nontrivial due to the restrictions from the NUC assumption imposed on the SNMM parameter. In the presence of ignorable censoring, we show that the complete‐case estimator is optimal among a class of weighting estimators including the inverse probability of censoring weighting estimator, and it achieves a double robustness feature in that it is consistent if at least one of the models for the potential outcome mean function and the treatment process is correctly specified. The new framework allows us to conduct causal analysis respecting the underlying continuous‐time nature of data processes. The simulation study shows that the proposed estimator outperforms existing approaches. We estimate the effect of time to initiate highly active antiretroviral therapy on the CD4 count at year 2 from the observational Acute Infection and Early Disease Research Program database.
    Keywords antiretroviral agents ; databases ; probability ; research programs ; therapeutics
    Language English
    Dates of publication 2022-09
    Size p. 937-949.
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 213543-7
    ISSN 0099-4987 ; 0006-341X
    ISSN 0099-4987 ; 0006-341X
    DOI 10.1111/biom.13471
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Germline masculinization by Phf7 in D. melanogaster requires its evolutionarily novel C-terminus and the HP1-family protein HP1D3csd.

    Yang, Shu Yuan

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 6308

    Abstract: Germ cells in Drosophila melanogaster need intrinsic factors along with somatic signals to activate proper sexual programs. A key factor for male germline sex determination is PHD finger protein 7 (Phf7), a histone reader expressed in the male germline ... ...

    Abstract Germ cells in Drosophila melanogaster need intrinsic factors along with somatic signals to activate proper sexual programs. A key factor for male germline sex determination is PHD finger protein 7 (Phf7), a histone reader expressed in the male germline that can trigger sex reversal in female germ cells and is also important for efficient spermatogenesis. Here we find that the evolutionarily novel C-terminus in Phf7 is necessary to turn on the complete male program in the early germline of D. melanogaster, suggesting that this domain may have been uniquely acquired to regulate sexual differentiation. We further looked for genes regulated by Phf7 related to sex determination in the embryonic germline by transcriptome profiling of FACS-purified embryonic gonads. One of the genes positively-regulated by Phf7 in the embryonic germline was an HP1family member, Heterochromatin Protein 1D3 chromoshadow domain (HP1D3csd). We find that this gene is needed for Phf7 to induce male-like development in the female germline, indicating that HP1D3csd is an important factor acting downstream of Phf7 to regulate germline masculinization.
    MeSH term(s) Animals ; Chromosomal Proteins, Non-Histone/genetics ; Drosophila Proteins/genetics ; Drosophila melanogaster/genetics ; Drosophila melanogaster/growth & development ; Embryonic Development/genetics ; Female ; Gene Expression Regulation, Developmental/genetics ; Germ Cells/growth & development ; Gonads/growth & development ; Homeodomain Proteins/genetics ; Male ; Sex Determination Processes/genetics ; Sex Differentiation/genetics ; Transcriptome/genetics
    Chemical Substances Chromosomal Proteins, Non-Histone ; Drosophila Proteins ; Homeodomain Proteins ; PHF7 protein, Drosophila ; rhi protein, Drosophila
    Language English
    Publishing date 2021-03-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-85560-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: RWD-INTEGRATED RANDOMIZED CLINICAL TRIAL ANALYSIS.

    Yang, Shu / Wang, Xiaofei

    Biopharmaceutical report

    2023  Volume 29, Issue 2, Page(s) 15–21

    Language English
    Publishing date 2023-02-28
    Publishing country United States
    Document type Journal Article
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: ScRNA analysis and ferroptosis-related ceRNA regulatory network investigation in microglia cells at different time points after spinal cord injury.

    Bao, Junping / Yang, Shu

    Journal of orthopaedic surgery and research

    2023  Volume 18, Issue 1, Page(s) 701

    Abstract: Spinal cord injuries (SCI) are usually caused by mechanical trauma that leads to serious physical and psychological damage to the patient as well as a huge economic burden to the whole society. The prevention, treatment, and rehabilitation of spinal cord ...

    Abstract Spinal cord injuries (SCI) are usually caused by mechanical trauma that leads to serious physical and psychological damage to the patient as well as a huge economic burden to the whole society. The prevention, treatment, and rehabilitation of spinal cord injuries have become a major issue for the medical community today due to the enormous social and economic expenditure induced via spinal cord injuries. Therefore, in-depth research into SCI is necessary. Microglia have been shown to be the key player in the immune inflammatory response after spinal cord injury, but the mechanisms of immune regulation at different time points after spinal cord injury remain unclear. To investigate the inflammatory biomarkers associated with microglia at different time points after SCI, we downloaded single-cell RNA sequencing data from mouse spinal cords 3- and 14-days after the injury and identified subpopulations associated with microglia. Further functional enrichment analysis also confirmed that microglia are associated with immune system regulation at different time points and that both can modulate cytokine production. As ferroptosis is a newly identified non-apoptotic programmed cell death, microglia establish a bridge between ferroptosis and CNS inflammation and may play an important role in spinal cord injury. We then screened for genes differentially expressed in microglia during 3- and 14-days after spinal cord injury and associated with iron death, named Stmn1 and Fgfbr1, respectively, and verified that these pivotal genes are closely related to the immune cells. Finally, we also screened for drug fractions associated with these pivotal genes. Our results predict key genes in the immune inflammatory process associated with microglia at different time points after spinal cord injury at the single-cell level and provide a molecular basis for better treatment of SCI.
    MeSH term(s) Animals ; Mice ; Microglia ; Ferroptosis ; Spinal Cord Injuries/genetics ; Inflammation/genetics ; Single-Cell Analysis
    Language English
    Publishing date 2023-09-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2252548-8
    ISSN 1749-799X ; 1749-799X
    ISSN (online) 1749-799X
    ISSN 1749-799X
    DOI 10.1186/s13018-023-04195-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Engineering Kirigami Frameworks Toward Real-World Applications.

    Jin, Lishuai / Yang, Shu

    Advanced materials (Deerfield Beach, Fla.)

    2023  Volume 36, Issue 9, Page(s) e2308560

    Abstract: The surge in advanced manufacturing techniques has led to a paradigm shift in the realm of material design from developing completely new chemistry to tailoring geometry within existing materials. Kirigami, evolved from a traditional cultural and ... ...

    Abstract The surge in advanced manufacturing techniques has led to a paradigm shift in the realm of material design from developing completely new chemistry to tailoring geometry within existing materials. Kirigami, evolved from a traditional cultural and artistic craft of cutting and folding, has emerged as a powerful framework that endows simple 2D sheets with unique mechanical, thermal, optical, and acoustic properties, as well as shape-shifting capabilities. Given its flexibility, versatility, and ease of fabrication, there are significant efforts in developing kirigami algorithms to create various architectured materials for a wide range of applications. This review summarizes the fundamental mechanisms that govern the transformation of kirigami structures and elucidates how these mechanisms contribute to their distinctive properties, including high stretchability and adaptability, tunable surface topography, programmable shape morphing, and characteristics of bistability and multistability. It then highlights several promising applications enabled by the unique kirigami designs and concludes with an outlook on the future challenges and perspectives of kirigami-inspired metamaterials toward real-world applications.
    Language English
    Publishing date 2023-12-05
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1474949-X
    ISSN 1521-4095 ; 0935-9648
    ISSN (online) 1521-4095
    ISSN 0935-9648
    DOI 10.1002/adma.202308560
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Graph Spatio-Temporal Networks for Manufacturing Sales Forecast and Prevention Policies in Pandemic Era.

    Lee, Chia-Yen / Yang, Shu-Huei

    Computers & industrial engineering

    2023  , Page(s) 109413

    Abstract: Worldwide manufacturing industries are significantly affected by COVID-19 pandemic because of their production characteristics with low-cost country sourcing, globalization, and inventory level. To analyze the correlated time series, spatial-temporal ... ...

    Abstract Worldwide manufacturing industries are significantly affected by COVID-19 pandemic because of their production characteristics with low-cost country sourcing, globalization, and inventory level. To analyze the correlated time series, spatial-temporal model becomes more attractive, and the graph convolution network (GCN) is also commonly used to provide more information to the nodes and its neighbors in the graph. Recently, attention-adjusted graph spatio-temporal network (AGSTN) was proposed to address the problem of pre-defined graph in GCN by combining multi-graph convolution and attention adjustment to learn spatial and temporal correlations over time. However, AGSTN may show potential problem with limited small non-sensor data; particularly, convergence issue. This study proposes several variants of AGSTN and applies them to non-sensor data. We suggest data augmentation and regularization techniques such as edge selection, time series decomposition, prevention policies to improve AGSTN. An empirical study of worldwide manufacturing industries in pandemic era was conducted to validate the proposed variants. The results show that the proposed variants significantly improve the prediction performance at least around 20% on mean squared error (MSE) and convergence problem.
    Language English
    Publishing date 2023-06-27
    Publishing country England
    Document type Journal Article
    ISSN 1879-0550
    ISSN (online) 1879-0550
    DOI 10.1016/j.cie.2023.109413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs.

    Yang, Shu / Ting, Chun-Yuan / Lilly, Mary A

    Molecular cell

    2024  Volume 84, Issue 4, Page(s) 727–743.e8

    Abstract: Lysosomes are central to metabolic homeostasis. The microphthalmia bHLH-LZ transcription factors (MiT/TFEs) family members MITF, TFEB, and TFE3 promote the transcription of lysosomal and autophagic genes and are often deregulated in cancer. Here, we show ...

    Abstract Lysosomes are central to metabolic homeostasis. The microphthalmia bHLH-LZ transcription factors (MiT/TFEs) family members MITF, TFEB, and TFE3 promote the transcription of lysosomal and autophagic genes and are often deregulated in cancer. Here, we show that the GATOR2 complex, an activator of the metabolic regulator TORC1, maintains lysosomal function by protecting MiT/TFEs from proteasomal degradation independent of TORC1, GATOR1, and the RAG GTPase. We determine that in GATOR2 knockout HeLa cells, members of the MiT/TFEs family are ubiquitylated by a trio of E3 ligases and are degraded, resulting in lysosome dysfunction. Additionally, we demonstrate that GATOR2 protects MiT/TFE proteins in pancreatic ductal adenocarcinoma and Xp11 translocation renal cell carcinoma, two cancers that are driven by MiT/TFE hyperactivation. In summary, we find that the GATOR2 complex has independent roles in TORC1 regulation and MiT/TFE protein protection and thus is central to coordinating cellular metabolism with control of the lysosomal-autophagic system.
    MeSH term(s) Humans ; HeLa Cells ; Microphthalmia-Associated Transcription Factor/genetics ; Microphthalmia-Associated Transcription Factor/metabolism ; Proteolysis ; Autophagy/genetics ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Proteins/metabolism ; Kidney Neoplasms/metabolism ; Lysosomes/genetics ; Lysosomes/metabolism ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
    Chemical Substances Microphthalmia-Associated Transcription Factor ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Proteins ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
    Language English
    Publishing date 2024-02-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2024.01.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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