Journal Article Etching Dynamics of Geometrically Confined Silicon Nanostructure Get access Kunmo Koo, Kunmo Koo Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea Search for other works by this author on: Oxford Academic Google Scholar Joon Ha Chang, Joon Ha Chang Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea Search for other works by this author on: Oxford Academic Google Scholar Sanghyeon Ji, Sanghyeon Ji Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea Search for other works by this author on: Oxford Academic Google Scholar Jacob Choe, Jacob Choe Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea Search for other works by this author on: Oxford Academic Google Scholar Seungmin Shin, Seungmin Shin Advanced Core Equipment Engineering & Development P/J, Semiconductor R&D Center, Samsung Electronics, Hwaseong, Republic of Korea Search for other works by this author on: Oxford Academic Google Scholar Geun-Taek Lee, Geun-Taek Lee Advanced Core Equipment Engineering & Development P/J, Semiconductor R&D Center, Samsung Electronics, Hwaseong, Republic of Korea Search for other works by this author on: Oxford Academic Google Scholar Tae-Hong Kim, Tae-Hong Kim Advanced Core Equipment Engineering & Development P/J, Semiconductor R&D Center, Samsung Electronics, Hwaseong, Republic of Korea Search for other works by this author on: Oxford Academic Google Scholar Jong Min Yuk Jong Min Yuk Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea Corresponding author: jongmin.yuk@kaist.ac.kr Search for other works by this author on: Oxford Academic Google Scholar Microscopy and Microanalysis, Volume 28, Issue S1, 1 August 2022, Pages 126–127, https://doi.org/10.1017/S1431927622001404 Published: 01 August 2022
The Active Mount (AM) controls the vibrations caused by the movement of a mechanical system resting on top of it. Vibration caused by mechanical systems often consists of several dominant frequency components. Therefore, we need an adaptive algorithm controlling tonal vibration components effectively. The FxLMS algorithm widely used for active vibration control raises several issues as the tone number and control channel increase. This paper proposes an efficient narrowband FxLMS algorithm for controlling multiple tonal vibrations occurring in a 3-axis AM. To this end, the secondary path's magnitude and phase responses are modeled tone-by-tone, independently using two-tap filters. Narrowband control filters are constructed for each tone using a narrowband signal model. In addition, a reference sensor is mounted on top of AM, from which tonal references are estimated using adaptive notch filters (ANFs). The proposed algorithm was simulated using transfer functions obtained in a 3-axis AM. Results show that the proposed algorithm effectively controls multiple tonal components by minimizing total errors measured along the 3-axis.
Abstract Oncogenic Ras mutants, and most frequently KRas mutants (86% of Ras-driven cancers), are found in approximately 25% of human cancers and are high-priority anticancer drug targets. Despite 30 years of effort to develop drugs that directly target oncogenic Ras mutants, no effective pharmacologic inhibitors for these mutants are clinically available, mainly because of the lack of suitable surface binding pockets for small molecules. More than 50 therapeutic antibodies have been clinically approved against many extracellular proteins. However, such antibodies do not have the capacity to localize in intracellular cytosolic regions after receptor-mediated endocytosis, restricting their therapeutic application for targeting cytosolic proteins. Our group recently developed a platform technology of cytosol-penetrating antibody, which in the IgG format can reach the cytosolic space of living cells owing to its endosomal escaping ability after receptor-mediated endocytosis. Exploiting the cytosol-penetrating antibody technology, we have engineered a human IgG1 format antibody, named iMab (internalizing and protein-protein interaction [PPI] interfering monoclonal antibody), which internalizes into the cytosol of living cells and selectively binds to the activated GTP-bound form of oncogenic Ras mutants. iMab specifically binds to the PPI interfaces of activated Ras with effector proteins to block the associations, thereby inhibiting the Ras downstream oncogenic signaling and exerting antiproliferation effects on oncogenic Ras mutant tumor cells. For in vivo antitumor efficacy assessment, we further engineer iMab to have tumor tissue-homing ability by fusion of tumor-associated integrin αvβ3/αvβ5 binding cyclic peptide to the N-terminus of light chain. When systemically administered, the iMab variant significantly inhibited the in vivo growth of oncogenic Ras-mutated tumor xenografts in mice, but not wild-type Ras-harboring tumors. Our results demonstrate the feasibility of developing antibody therapeutics that directly target cytosolic proteins involved in disease-associated PPIs, such as oncogenic Ras mutants, by systemic administration, similar to conventional therapeutic antibody regimens. Because the oncogenic Ras targeting antibody holds many desirable features of the conventional IgG antibody, it shows great potential for development as a first-in-class anticancer antibody. Citation Format: Seung-Min Shin, Ji-Sun Kim, Jin-Sun Hong, Seong-wook Park, Sei-Yong Jun, Hye-Jin Kweon, Dong-Ki Choi, Yong-Sung Kim. Direct targeting oncogenic Ras mutants by IgG-format cytosol-penetrating antibody [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B28.
Prostate stem cell antigen (PSCA) is expressed in all stages of prostate cancer, including in advanced androgen-independent tumors and bone metastasis. PSCA may associate with prostate carcinogenesis and lineage plasticity in prostate cancer. PSCA is also a promising theranostic marker for a variety of other solid tumors, including pancreatic adenocarcinoma and renal cell carcinoma. Here, we identified a novel fully human PSCA antibody using phage display methodology. The structure-based affinity maturation yielded a high-affinity binder, F12, which is highly specific and does not bind to 6,000 human membrane proteins based on a membrane proteome array assay. F12 targets PSCA amino acids 63-69 as tested by the peptide scanning microarray, and it cross-reacts with the murine PSCA. IgG1 F12 efficiently internalizes into PSCA-expressing tumor cells. The antimitotic reagent monomethyl auristatin E (MMAE)-conjugated IgG1 F12 (ADC, F12-MMAE) exhibits dose-dependent efficacy and specificity in a human prostate cancer PC-3-PSCA xenograft NSG mouse model. This is a first reported ADC based on a fully human PSCA antibody and MMAE that is characterized in a xenograft murine model, which warrants further optimizations and investigations in additional preclinical tumor models, including prostate and other solid tumors.
Introduction: Prolyl-tRNA synthetase (PRS) is an enzyme that conjugates proline to tRNA, which is an essential process in protein translation. Daewoong is developing a novel PRS inhibitor, DWN12088, as an anti-fibrotic agent. In this study, we investigated anti-fibrotic effects of DWN12088 in Bleomycin-induced skin fibrosis model. Method: In vitro anti-fibrotic activity of DWN12088 was assessed using human dermal fibroblasts. In vivo efficacy of DWN12088 was investigated using Bleomycin (BLM) -induced mouse pulmonary fibrosis model. BLM was introduced by osmotic pump implantation for 7 days. Skin thickness was assessed as a primary endpoint, and total collagen amount in skin was measured using hydroxyproline assay. Lung function was measured using pulse oximetry, and total collagen amount in lung was measured using Second Harmonic Generation imaging analysis. Results: Treatment of DWN12088 in human dermal fibroblast inhibited collagen and αSMA. In BLM-induced mouse skin fibrosis model, oral administration of DWN12088 significantly reduced skin thickness and collagen amount in dose-dependent manner. Interestingly, the lung function in these mice was significantly impaired and DWN12088 significantly improved lung function as well as Nintedanib. Collagen deposition was increased in the BLM-induced mouse skin fibrosis model lung, and DWN12088 reduced collagen deposition in the lung. Conclusion: Inhibition of PRS has anti-fibrotic effects by inhibiting collagen synthesis and down-regulating pro-fibrotic markers. Therefore, DWN12088 may serve as a potential therapeutic agent for Systemic Sclerosis (SSc and SSc-ILD).
Cellular internalization of bacteriophage by surface-displayed cell penetrating peptides has been reported, though the underlying mechanism remains elusive. Here we describe in detail the internalization mechanism and intracellular trafficking and stability of filamentous M13 phages, the cellular entry of which is mediated by surface-displayed cell-penetrating light chain variable domain 3D8 VL transbody (3D8 VL-M13) or TAT peptide (TAT-M13). Recombinant 3D8 VL-M13 and TAT-M13 phages were efficiently internalized into living mammalian cells via physiologically relevant, energy-dependent endocytosis and were recovered from the cells in their infective form with the yield of 3D8 VL-M13 being higher (0.005∼0.01%) than that of TAT-M13 (0.001∼0.005%). Biochemical and genetic studies revealed that 3D8 VL-M13 was internalized principally by caveolae-mediated endocytosis via interaction with heparan sulfate proteoglycans as cell surface receptors, whereas TAT-M13 was internalized by clathrin- and caveolae-mediated endocytosis utilizing chondroitin sulfate proteoglycans as cell surface receptors, suggesting that phage internalization occurs by physiological endocytotic mechanism through specific cell surface receptors rather than non-specific transcytotic pathways. Internalized 3D8 VL-M13 phages routed to the cytosol and remained stable for more than 18 h without further trafficking to other subcellular compartments, whereas TAT-M13 phages routed to several subcellular compartments before being degraded in lysosomes even after 2 h of internalization. Our results suggest that the internalizing mechanism and intracellular trafficking of filamentous M13 bacteriophages largely follow the attributes of the displayed cell-penetrating moiety. Efficient internalization and cytosolic localization of 3D8 VL transbody-displayed phages will provide a useful tool for intracellular delivery of polar macromolecules such as proteins, peptides, and siRNAs.
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)
