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1.
Adv Sci (Weinh) ; 10(36): e2304598, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37888859

ABSTRACT

In the domains of wearable electronics, robotics, and the Internet of Things, there is a demand for devices with low power consumption and the capability of multiplex sensing, memory, and learning. Triboelectric nanogenerators (TENGs) offer remarkable versatility in this regard, particularly when integrated with synaptic transistors that mimic biological synapses. However, conventional TENGs, generating only two spikes per cycle, have limitations when used in synaptic devices requiring repetitive high-frequency gating signals to perform various synaptic plasticity functions. Herein, a multi-layered micropatterned TENG (M-TENG) consisting of a polydimethylsiloxane (PDMS) film and a composite film that includes 1H,1H,2H,2H-perfluorooctyltrichlorosilane/BaTiO3 /PDMS are proposed. The M-TENG generates multiple spikes from a single touch by utilizing separate triboelectric charges at the multiple friction layers, along with a contact/separation delay achieved by distinct spacers between layers. This configuration allows the maximum triboelectric output charge of M-TENG to reach up to 7.52 nC, compared to 3.69 nC for a single-layered TENG. Furthermore, by integrating M-TENGs with an organic electrochemical transistor, the spike number multiplication property of M-TENGs is leveraged to demonstrate an artificial synaptic device with low energy consumption. As a proof-of-concept application, a robotic hand is operated through continuous memory training under repeated stimulations, successfully emulating long-term plasticity.

2.
Cell ; 184(4): 1047-1063.e23, 2021 02 18.
Article in English | MEDLINE | ID: mdl-33539780

ABSTRACT

DNA has not been utilized to record temporal information, although DNA has been used to record biological information and to compute mathematical problems. Here, we found that indel generation by Cas9 and guide RNA can occur at steady rates, in contrast to typical dynamic biological reactions, and the accumulated indel frequency can be a function of time. By measuring indel frequencies, we developed a method for recording and measuring absolute time periods over hours to weeks in mammalian cells. These time-recordings were conducted in several cell types, with different promoters and delivery vectors for Cas9, and in both cultured cells and cells of living mice. As applications, we recorded the duration of chemical exposure and the lengths of elapsed time since the onset of biological events (e.g., heat exposure and inflammation). We propose that our systems could serve as synthetic "DNA clocks."


Subject(s)
CRISPR-Associated Protein 9/metabolism , Animals , Base Sequence , Cellular Microenvironment , Computer Simulation , HEK293 Cells , Half-Life , Humans , INDEL Mutation/genetics , Inflammation/pathology , Integrases/metabolism , Male , Mice, Nude , Promoter Regions, Genetic/genetics , RNA, Guide, Kinetoplastida/genetics , Reproducibility of Results , Time Factors
3.
Biochem Biophys Res Commun ; 505(1): 187-193, 2018 10 20.
Article in English | MEDLINE | ID: mdl-30243723

ABSTRACT

The human epidermal growth factor receptor 2 (HER2)-positive breast cancer with overexpression of HER2 accounts for approximately 25% of breast cancers and is more aggressive than other types of breast cancer. Lapatinib has been widely used as a HER2-targeted therapy, however, a number of patients develop lapatinib resistance and still suffer from poor prognosis. Therefore, it is essential to identify novel therapeutic targets that could overcome lapatinib resistance. In this study, we carried out phosphoproteomic analysis of lapatinib sensitive and resistant cell lines (SKBR3 and SKBR3-LR) using stable isotope labeling with amino acids in cell culture (SILAC). We identified 3808 phosphopeptides from 1807 proteins and then analyzed signaling pathways, Gene Ontology, and protein-protein interaction networks. Finally, we identified PAK2 as a therapeutic target from the network analysis and validated that PAK2 knockdown and PAK inhibitor treatment resensitize the lapatinib resistant cells to lapatinib. This results suggest that PAK2 is a potent therapeutic target to overcome acquired lapatinib resistance in HER2-positive breast cancer cells.


Subject(s)
Drug Resistance, Neoplasm/drug effects , Lapatinib/pharmacology , Phosphoproteins/metabolism , Proteomics/methods , p21-Activated Kinases/antagonists & inhibitors , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Drug Resistance, Neoplasm/genetics , Female , Humans , Phosphoproteins/genetics , Phosphorylation/drug effects , Protein Interaction Maps/drug effects , Protein Interaction Maps/genetics , Protein Kinase Inhibitors/pharmacology , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , p21-Activated Kinases/genetics , p21-Activated Kinases/metabolism
4.
Memory ; 26(6): 784-797, 2018 07.
Article in English | MEDLINE | ID: mdl-29226769

ABSTRACT

Spacing repetitions typically improves memory (the spacing effect). In three cued recall experiments, we explored the relationship between working memory capacity and the spacing effect. People with higher working memory capacity are more accurate on memory tasks that require retrieval relative to people with lower working memory capacity. The experiments used different retention intervals and lags between repetitions, but were otherwise similar. Working memory capacity and spacing of repetitions both improved memory in most of conditions, but they did not interact, suggesting additive effects. The results are consistent with the ACT-R model's predictions, and with a study-phase recognition process underpinning the spacing effect in cued recall.


Subject(s)
Cues , Memory, Short-Term , Mental Recall , Space Perception , Humans
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