Publications by authors named "Yun-Chu Lin"

6 Publications

  • Page 1 of 1

Traction force microscopy by deep learning.

Biophys J 2021 08 30;120(15):3079-3090. Epub 2021 Jun 30.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania.

Cells interact mechanically with their surroundings by exerting and sensing forces. Traction force microscopy (TFM), purported to map cell-generated forces or stresses, represents an important tool that has powered the rapid advances in mechanobiology. However, to solve the ill-posed mathematical problem, conventional TFM involved compromises in accuracy and/or resolution. Here, we applied neural network-based deep learning as an alternative approach for TFM. We modified a neural network designed for image processing to predict the vector field of stress from displacements. Furthermore, we adapted a mathematical model for cell migration to generate large sets of simulated stresses and displacements for training and testing the neural network. We found that deep learning-based TFM yielded results that resemble those using conventional TFM but at a higher accuracy than several conventional implementations tested. In addition, a trained neural network is appliable to a wide range of conditions, including cell size, shape, substrate stiffness, and traction output. The performance of deep learning-based TFM makes it an appealing alternative to conventional methods for characterizing mechanical interactions between adherent cells and the environment.
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http://dx.doi.org/10.1016/j.bpj.2021.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390964PMC
August 2021

How Can an Na Channel Inhibitor Ameliorate Seizures in Lennox-Gastaut Syndrome?

Ann Neurol 2021 06 9;89(6):1099-1113. Epub 2021 Apr 9.

Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.

Objective: Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy frequently associated with multiple types of seizures. The classical Na channel inhibitors are in general ineffective against the seizures in LGS. Rufinamide is a new Na channel inhibitor, but approved for the treatment of LGS. This is not consistent with a choice of antiseizure drugs (ASDs) according to simplistic categorical grouping.

Methods: The effect of rufinamide on the Na channel, cellular discharges, and seizure behaviors was quantitatively characterized in native neurons and mammalian models of epilepsy, and compared with the other Na channel inhibitors.

Results: With a much faster binding rate to the inactivated Na channel than phenytoin, rufinamide is distinctively effective if the seizure discharges chiefly involve short bursts interspersed with hyperpolarized interburst intervals, exemplified by spike and wave discharges (SWDs) on electroencephalograms. Consistently, rufinamide, but not phenytoin, suppresses SWD-associated seizures in pentylenetetrazol or AY-9944 models, which recapitulate the major electrophysiological and behavioral manifestations in typical and atypical absence seizures, including LGS.

Interpretation: Na channel inhibitors shall have sufficiently fast binding to exert an action during the short bursts and then suppress SWDs, in which cases rufinamide is superior. For the epileptiform discharges where the interburst intervals are not so hyperpolarized, phenytoin could be better because of the higher affinity. Na channel inhibitors with different binding kinetics and affinity to the inactivated channels may have different antiseizure scope. A rational choice of ASDs according to in-depth molecular pharmacology and the attributes of ictal discharges is advisable. ANN NEUROL 2021;89:1099-1113.
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http://dx.doi.org/10.1002/ana.26068DOI Listing
June 2021

Cytogenetics and mutations could predict outcome in relapsed and refractory acute myeloid leukemia patients receiving BCL-2 inhibitor venetoclax.

Ann Hematol 2020 Mar 21;99(3):501-511. Epub 2020 Jan 21.

Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Venetoclax, a selective B cell leukemia/lymphoma-2 (BCL2) inhibitor, has recently shown activity in relapsed or refractory (R/R) acute myeloid leukemia (AML). Effective biomarkers for identifying patients most likely to respond to venetoclax-based treatment are of clinical utility. In this study, we aimed to evaluate the efficacy and safety profiles of venetoclax-based therapy in a total 40 R/R AML patients and identify the potentially predictive factors for response. Overall response rate was 50%, including 9 (22.5%) complete response (CR) or CR with incomplete hematologic recovery of either neutrophil or platelet counts (CRi). Median time to best response was 1.4 months and the median overall survival (OS) was 6.6 months. Presence of intermediate-risk cytogenetics predicted better OS compared to unfavorable-risk cytogenetics. Patients harboring NPM1, RUNX1, or SRSF2 mutations seemed to have higher CR/CRi rates and median OS was significantly longer in RUNX1-mutated patients. On the contrary, patients with FLT3-ITD, TP53, or DNMT3A mutations did not reach any objective response and had worse OS. No laboratory or clinical tumor lysis syndrome was observed and the most common adverse events were prolonged cytopenias which resulted in 67.5% of febrile neutropenia. Patients with concurrent use of azole antifungals had similar incidence of cytopenias compared with those without azole antifungals. In summary, we demonstrate that venetoclax is an effective and well-tolerated salvage option for R/R AML patients. Survival benefits were particularly remarkable in patients with intermediate-risk cytogenetics or RUNX1 mutations. In contrast, TP53, NRAS, and DNMT3A mutations as well as FLT3-ITD conferred negative impact on survival.
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http://dx.doi.org/10.1007/s00277-020-03911-zDOI Listing
March 2020

GATA2 mutations in patients with acute myeloid leukemia-paired samples analyses show that the mutation is unstable during disease evolution.

Ann Hematol 2015 Feb 21;94(2):211-21. Epub 2014 Sep 21.

Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Recently, mutations of the GATA binding protein 2 (GATA2) gene were identified in acute myeloid leukemia (AML) patients with CEBPA double mutations (CEBPA (double-mut)), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, 14 different missense GATA2 mutations, which were all clustered in the highly conserved N-terminal zinc finger 1 domain, were identified in 27.4, 6.7, and 1 % of patients with CEBPA (double-mut), CEBPA (single-mut), and CEBPA wild type, respectively. All but one patient with GATA2 mutation had concurrent CEBPA mutation. GATA2 mutations were closely associated with younger age, FAB M1 subtype, intermediate-risk cytogenetics, expression of HLA-DR, CD7, CD15, or CD34 on leukemic cells, and CEBPA mutation, but negatively associated with FAB M4 subtype, favorable-risk cytogenetics, and NPM1 mutation. Patients with GATA2 mutation had significantly better overall survival and relapse-free survival than those without GATA2 mutation. Sequential analysis showed that the original GATA2 mutations might be lost during disease progression in GATA2-mutated patients, while novel GATA2 mutations might be acquired at relapse in GATA2-wild patients. In conclusion, AML patients with GATA2 mutations had distinct clinic-biological features and a favorable prognosis. GATA2 mutations might be lost or acquired at disease progression, implying that it was a second hit in the leukemogenesis of AML, especially those with CEBPA mutation.
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http://dx.doi.org/10.1007/s00277-014-2208-8DOI Listing
February 2015

Examination of ceramic/enamel interfacial debonding using acoustic emission and optical coherence tomography.

Dent Mater 2014 Aug 21;30(8):910-6. Epub 2014 Jun 21.

Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Objective: This study investigates monitored micro-crack growth and damage in the ceramic/enamel adhesive interface using the acoustic emission (AE) technique with optical coherence tomography (OCT) under fatigue shear testing.

Methods: Shear bond strength (SBS) was measured first with eight prepared ceramic/enamel adhesive specimens under static loads. The fatigue shear testing was performed with three specimens at each cyclic load according to a modified ISO14801 method, applying at 80%, 75%, 70%, and 65% of the SBS to monitor interface debonding. The number of cycles at each load was recorded until ceramic/enamel adhesive interface debonding occurred. The AE technique was used to detect micro-crack signals in static and fatigue shear bond tests.

Results: The results showed that the average SBS value in the static tests was 18.07 ± 1.72 MPa (mean ± standard deviation), expressed in Newton's at 56.77 ± 5.40N. The average number of fatigue cycles in which ceramic/enamel interface damage was detected in 80%, 75%, 70% and 65% of the SBS were 41, 410, 8141 and 76,541, respectively. The acoustic behavior varied according to the applied load level. Events were emitted during 65% and 70% fatigue tests. A good correlation was observed between the crack location in OCT images and the number of AE signal hits.

Significance: The AE technique combined with OCT images as a pre-clinical assessment tool to determine the integrity of cemented load bearing restored ceramic material. Sustainable cyclic load stresses in ceramic/enamel bonded specimens were substantially lower than the measured SBS. Predicted S-N curve showed that the maximum endured load was 10.98 MPa (about 34.48 N) passing 10(6) fatigue cyclic.
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http://dx.doi.org/10.1016/j.dental.2014.05.023DOI Listing
August 2014
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