Papers by Shih Hsin Huang
International Journal of Molecular Sciences
During this global pandemic, cryo-EM has made a great impact on the structure determination of CO... more During this global pandemic, cryo-EM has made a great impact on the structure determination of COVID-19 proteins. However, nearly all high-resolution results are based on data acquired on state-of-the-art microscopes where their availability is restricted to a number of centers across the globe with the studies on infectious viruses being further regulated or forbidden. One potential remedy is to employ multipurpose microscopes. Here, we investigated the capability of 200 kV multipurpose microscopes equipped with a direct electron camera in determining the structures of infectious particles. We used 30 nm particles of the grouper nerve necrosis virus as a test sample and obtained the cryo-EM structure with a resolution as high as ∼2.7 Å from a setting that used electron counting. For comparison, we tested a high-end cryo-EM (Talos Arctica) using a similar virus (Macrobrachium rosenbergii nodavirus) to obtain virtually the same resolution. Those results revealed that the resolution i...
Applied Microbiology and Biotechnology
Frontiers in Bioinformatics, 2021
The functions of biological macromolecules are often associated with conformational malleability ... more The functions of biological macromolecules are often associated with conformational malleability of the structures. This phenomenon of chemically identical molecules with different structures is coined structural polymorphism. Conventionally, structural polymorphism is observed directly by structural determination at the density map level from X-ray crystal diffraction. Although crystallography approach can report the conformation of a macromolecule with the position of each atom accurately defined in it, the exploration of structural polymorphism and interpreting biological function in terms of crystal structures is largely constrained by the crystal packing. An alternative approach to studying the macromolecule of interest in solution is thus desirable. With the advancement of instrumentation and computational methods for image analysis and reconstruction, cryo-electron microscope (cryo-EM) has been transformed to be able to produce “in solution” structures of macromolecules routi...
Taylor and Francis, Dec 5, 2014
Purpose: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the treatment of chor... more Purpose: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularization (CNV) in patents with age-related macular degeneration (ARMD). Methods: Fifty-six eyes of 48 patients with CNV secondary to ARMD were treated with diode laser (810nm) TTT. A variable spot size (0.5mm, 0.8mm, 1.2mm, 2.0mm or 3.0mm) was used depending on the size of lesion. Power setting ranged between 60mw and 400mw. Treatment was given in each lesion for 1 minute, and the end point was no visible color change or light-gray appearance of the retina. Outcome was assessed with Snellen visual acuity, fluorescein angiography and clinical examination. Retreatment was performed if persistent leakage was noted 2 months later. Results: Nineteen predominantly classic CNV and 37 predominantly occult membranes were followed up for a mean of 12.2 months (range 2-26). Five eyes (8.9%) showed a two-or-more-line improvement in visual acuity (VA). Visual acuity remained stable (V...
Political Party Systems and Democratic Development in East and Southeast Asia, 2018
Journal of Inorganic Biochemistry, 2021
In this focused review, we portray the recently reported 2.5 Å cyro-EM structure of the particula... more In this focused review, we portray the recently reported 2.5 Å cyro-EM structure of the particulate methane monooxygenase (pMMO) from M. capsulatus (Bath). The structure of the functional holo-pMMO near atomic resolution has uncovered the sites of the copper cofactors including the location of the active site in the enzyme. The three coppers seen in the original X-ray crystal structures of the enzyme are now augmented by additional coppers in the transmembrane domain as well as in the water-exposed C-terminal subdomain of the PmoB subunit. The cryo-EM structure offers the first glimpse of the catalytic machinery capable of methane oxidation with high selectivity and efficiency. The findings are entirely consistent with the biochemical and biophysical findings previously reported in the literature, including the chemistry of hydrocarbon hydroxylation, regeneration of the catalyst for multiple turnovers, and the mechanism of aborting non-productive cycles to ensure kinetic competence.
Communications Biology, 2020
2D classification plays a pivotal role in analyzing single particle cryo-electron microscopy imag... more 2D classification plays a pivotal role in analyzing single particle cryo-electron microscopy images. Here, we introduce a simple and loss-less pre-processor that incorporates a fast dimension-reduction (2SDR) de-noiser to enhance 2D classification. By implementing this 2SDR pre-processor prior to a representative classification algorithm like RELION and ISAC, we compare the performances with and without the pre-processor. Tests on multiple cryo-EM experimental datasets show the pre-processor can make classification faster, improve yield of good particles and increase the number of class-average images to generate better initial models. Testing on the nanodisc-embedded TRPV1 dataset with high heterogeneity using a 3D reconstruction workflow with an initial model from class-average images highlights the pre-processor improves the final resolution to 2.82 Å, close to 0.9 Nyquist. Those findings and analyses suggest the 2SDR pre-processor, of minimal cost, is widely applicable for boost...
AIP Advances, 2020
The spatial resolution of x-ray free-electron laser (XFEL) coherent diffraction imaging is curren... more The spatial resolution of x-ray free-electron laser (XFEL) coherent diffraction imaging is currently limited by the fluence of XFELs. Here, we clarify this issue by systematically studying the diffraction with a SPring-8 angstrom compact free electron laser XFEL on gold nanoparticles of size from 10 nm to 80 nm in water solution. The coherent x-ray diffraction patterns obtained from single XFEL pulses were quantitatively analyzed using a small-angle x-ray scattering scheme along with computer simulations. The results show that the detectability of Au nanoparticles can be described by a “master curve” as a function of total electron density, particle size, and x-ray fluence. The difficulty in detecting a small particle under the current XFEL fluence, however, could be largely eliminated by the image enhancement effect through interference from a strong scattering nanoparticle nearby. We investigate this image enhancement effect by quantitatively analyzing the two-particle scattering ...
Phytomedicine, 2020
Background: More than 80% of advanced prostate cancer (PCa) cases have bone metastasis, with a 5-... more Background: More than 80% of advanced prostate cancer (PCa) cases have bone metastasis, with a 5-year survival rate of 25%. Previously, we reported that GRT, a standardized, pharmaceutical-grade aspalathin-rich extract (12.78 g aspalathin/100 g extract), prepared from green rooibos produced from the leaves and fine stems of Aspalathus linearis, inhibits the proliferation of PCa cells, meriting this investigation to determine if GRT can suppress the migration and invasion of castration-resistant prostate cancer (CRPC) cells. Purpose: In the present study, we investigated whether GRT extract can interfere with the migration and invasion of human CRPC cells. Methods: Transwell assays were used to explore the effects of GRT on the migration and invasion of CRPC cells. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism(s). Results: Treatment with 25-100 μg/ml GRT suppressed the migration and invasion of LNCaP C4-2B and 22Rv1 CRPC cells. MWA and Western blot analysis indicated that GRT treatment suppressed the protein level of yesassociated protein (YAP), macrophage stimulating 1 protein (MST1), phospho-MST1/phospho-MST2 T183/ T180, and paxillin, but increased the abundance of E-cadherin. Over-expression of YAP rescued the suppressive effects of GRT on migration and invasion of CRPC cells. Treatment with the major flavonoid of GRT-the Cglucosyl dihydrochalcone, aspalathin-at a concentration of 75-100 μg/ml also reduced the migration and invasion of CRPC cells, and the inhibition was partially rescued by YAP over-expression. Conclusions: GRT treatment suppresses the migration and invasion of CRPC cells via inhibition of YAP signaling and paxillin.
Phytomedicine, 2019
Background: Androgen ablation therapy is the primary treatment for metastatic prostate cancer (PC... more Background: Androgen ablation therapy is the primary treatment for metastatic prostate cancer (PCa). However, the majority of PCa patients receiving the androgen deprivation therapy develop recurrent castration-resistant prostate cancer (CRPC) within two years. Chemotherapies show little effect on prolonging survival of CRPC patients and new treatments are needed. Previous studies reported that the extracts from rooibos (Aspalathus linearis) exhibit chemopreventive properties in some cancer models, including skin, liver and oesophagus cancers in animals. We therefore investigate if extracts from rooibos can suppress the proliferation of CRPC cells. Purpose: We investigated whether an aspalathin-rich green rooibos extract (GRT TM ; 12.78 g aspalathin/100 g extract) demonstrates anti-cancer activity against CRPC cells. Methods: High performance liquid chromatography (HPLC) was used to profile the major flavonoids in GRT. Hoechst-dye proliferation assay, 3,4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) viability assay and flow cytometry assay were used to explore the effects of GRT on the proliferation and cell cycle progression of CRPC cells. Comet assay was used to survey whether GRT induces apoptosis in CRPC cells. LNCaP 104-R1 xenograft nude mice model was used to determine the inhibitory effect of GRT on CRPC tumors in vivo. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism. Results: GRT contained aspalathin as the most abundant flavonoid. GRT suppressed the proliferation and survival of LNCaP 104-R1, LNCaP FGC and PC-3 PCa cells. Flow cytometry analysis showed that GRT decreased the population of PCa cells in S phase but increased the cell population in G2/M phase. Comet assay confirmed that GRT induced apoptosis in LNCaP 104-R1 cells. Gavage of 400 mg/kg GRT suppressed LNCaP 104-R1 xenografts in castrated nude mice. MWA and Western blot analysis indicated that GRT treatment suppressed Akt1, phospho-Akt Ser473, Cdc2, Bcl-2, TRAF4 and Aven, but increased activated Caspase 3, cytochrome c, and p27 Kip1. Overexpression of Akt rescued the suppressive effects of GRT on CRPC cells. Co-treatment of GRT with Bcl-2 inhibitor ABT-737, PI3K inhibitor LY294002 and Akt inhibitor GSK 690693 exhibited additive inhibitory effect on proliferation of CRPC cells. Conclusions: GRT suppresses the proliferation of CRPC cells via inhibition of Akt signaling.
Phytomedicine, 2019
Demethoxycurcumin sensitizes the response of non-small cell lung cancer to cisplatin through down... more Demethoxycurcumin sensitizes the response of non-small cell lung cancer to cisplatin through downregulation of TP and ERCC1-related pathways, Phytomedicine (2018), doi:
Nanoscale, Jan 8, 2018
Using the excellent performances of a SACLA (RIKEN/HARIMA, Japan) X-ray free electron laser (X-FE... more Using the excellent performances of a SACLA (RIKEN/HARIMA, Japan) X-ray free electron laser (X-FEL), coherent diffraction imaging (CDI) was used to detect individual liposome particles in water, with or without inserted doxorubicin nanorods. This was possible because of the electron density differences between the carrier, the liposome, and the drug. The result is important since liposome nanocarriers at present dominate drug delivery systems. In spite of the low cross-section of the original ingredients, the diffracted intensity of drug-free liposomes was sufficient for spatial reconstruction yielding quantitative structural information. For particles containing doxorubicin, the structural parameters of the nanorods could be extracted from CDI. Furthermore, the measurement of the electron density of the solution enclosed in each liposome provides direct evidence of the incorporation of ammonium sulphate into the nanorods. Overall, ours is an important test for extending the X-FEL a...
ISPRS International Journal of Geo-Information, 2017
Smartphones have become indispensable in our daily lives. Their various embedded sensors have ins... more Smartphones have become indispensable in our daily lives. Their various embedded sensors have inspired innovations in mobile applications-especially for indoor navigation. However, the accuracy, reliability and generalizability of navigation all continue to struggle in environments lacking a Global Navigation Satellite System (GNSS). Pedestrian Dead Reckoning (PDR) is a popular method for indoor pedestrian navigation. Unfortunately, due to its fundamental principles, even a small navigation error will amplify itself, step by step, generally leading to the need for supplementary resources to maintain navigation accuracy. Virtually all mobile devices and most robots contain a basic camera sensor, which has led to the popularity of image-based localization, and vice versa. However, all of the image-based localization requires continuous images for uninterrupted positioning. Furthermore, the solutions provided by either image-based localization or a PDR are usually in a relative coordinate system. Therefore, this research proposes a system, which uses space resection-aided PDR with geo-referenced images of a previously mapped environment to enable seamless navigation and solve the shortcomings of PDR and image-based localization, and evaluates the performance of space resection with different assumptions using a smartphone. The indoor mobile mapping system (IMMS) is used for the effective production of geo-referenced images. The preliminary results indicate that the proposed algorithm is suitable for universal pedestrian indoor navigation, achieving the accuracy required for commercial applications.
Nucleic Acids Research, 2017
Splicing is initiated by a productive interaction between the pre-mRNA and the U1 snRNP, in which... more Splicing is initiated by a productive interaction between the pre-mRNA and the U1 snRNP, in which a short RNA duplex is established between the 5 splice site of a pre-mRNA and the 5 end of the U1 snRNA. A long-standing puzzle has been why the AU dincucleotide at the 5-end of the U1 snRNA is highly conserved, despite the absence of an apparent role in the formation of the duplex. To explore this conundrum, we varied this AU dinucleotide into all possible permutations and analyzed the resulting molecular consequences. This led to the unexpected findings that the AU dinucleotide dictates the optimal binding of cap-binding complex (CBC) to the 5 end of the nascent U1 snRNA, which ultimately influences the utilization of U1 snRNP in splicing. Our data also provide a structural interpretation as to why the AU dinucleotide is conserved during evolution.
2010 11th International Conference on Electronic Packaging Technology & High Density Packaging, 2010
A novel solar microsensor with microelectromechanical system (MEMS)-based packaging for improving... more A novel solar microsensor with microelectromechanical system (MEMS)-based packaging for improving solar tracking efficiency was proposed and a functional solar power sensing array was also developed. Solar energy as a renewable energy source in the world is the most important issue. The microsensor with different shapes of masks as light inlet was fabricated on silicon wafers to provide variable attenuation
In this paper, we propose an analytical framework for cooperative dual-hop relaying over in-door ... more In this paper, we propose an analytical framework for cooperative dual-hop relaying over in-door composite fading environments. We focus on overcoming the limitations of non-closed form problems of log-normal statistics and simplifying the tremendous complication of former frameworks. The approximated expressions combined outage and bit-error-rate (BER) probability are derived and analyzed in terms of a variety of log-normal standard deviations and the diversity order against the cooperative relaying signal-to-noise (SNR) mean power. As a consequence, we refine a specific analysis framework using the generality of these linear closed-form expressions. The analytical results demonstrated that our proposed framework will provide a simple and effective approach for evaluating the impact of the shadowing effects, cooperative diversity gain and determining the cooperation power constraint.
Lecture Notes in Computer Science
For a programmable I/O device controller, the allocation of device parameters on I/O registers af... more For a programmable I/O device controller, the allocation of device parameters on I/O registers affects the code size and execution time of its associated I/O device driver. In traditional design flow, the development of device drivers can not begin until the allocation is fixed. This paper presents a new design methodology that allows a designer to seek an allocation that reduces the software or hardware cost concurrently with developing device drivers. The software cost means the code size or execution time and the hardware cost the number of I/O registers. The exact allocation with the minimum cost under constraints is formulated as zero-one integer linear programming problem. Heuristic algorithms based on iterative refinement are also proposed. The proposed design methodology was implemented in C language. Compared with current industrial designs, the approach can obtain design alternatives that reduce both software and hardware costs. Furthermore, the experimental results also investigate design spaces for various application features. It turns out that the HW/SW codesign approach is favorable in development of embedded systems.
Proceedings of the 15th ACM Great Lakes symposium on VLSI, 2005
This work presents a new HW/SW codesign approach for programmable controllers (ICs or IPs) managi... more This work presents a new HW/SW codesign approach for programmable controllers (ICs or IPs) managing IO devices. A novel cost function is defined to evaluate a device driver's performance and formulate its exact minimization as a zero-one integer linear programming problem. The cost function is used to explore the design trade-off between the code performance of a device driver and
Proceedings of the Design Automation & Test in Europe Conference, 2006
The allocation of device variables on I/O registers affects the code size and performance of an I... more The allocation of device variables on I/O registers affects the code size and performance of an I/O device driver. This work seeks the allocation with the minimal software or hardware cost in a hardware/software codesign environment. The problems of exact minimization under constraints are formulated as zero-one integer linear programming problems. Heuristic algorithms based on iterative refinement are also proposed. The proposed design methodology was implemented in C language. Compared with industrial designs, the system can obtain design alternatives that reduce both software and hardware costs.
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Papers by Shih Hsin Huang