Mechatronics and Remote Driving Control of the Drive-by-Wire for a Go Kart.

This research mainly aims at the construction of the novel acceleration pedal, the brake pedal and the steering system by mechanical designs and mechatronics technologies, an approach of which is rarely seen in Taiwan. Three highlights can be addressed: 1. The original steering parts were removed with the fault tolerance design being implemented so that the basic steering function can still remain in case of the function failure of the control system. 2. A larger steering angle of the front wheels in response to a specific rotated angle of the steering wheel is devised when cornering or parking at low speed in interest of drivability, while a smaller one is designed at high speed in favor of driving stability. 3. The operating patterns of the throttle, brake, and steering wheel can be customized in accordance with various driving environments and drivers' requirements using the self-developed software. The implementation of a steer-by-wire system in the remote driving control for a go kart is described in this study. The mechatronic system is designed in order to support the conversion from human driving to autonomous driving for the go kart in the future. The go kart, using machine vision, is wirelessly controlled in the WiFi frequency bands. The steer-by-wire system was initially modeled as a standalone system for one wheel and subsequently developed into its complete form, including front wheel steering components, acceleration components, brake components, a microcontroller, drive circuit and digital to analog converter. The control output section delivers the commands to the subsystem controllers, relays and converters. The remote driving control of the go kart is activated when proper commands are sent by the vehicle control unit (VCU). All simulation and experiment results demonstrated that the control strategies of duel motors and the VCU control were successfully optimized. The feasibility study and performance evaluation of Taiwan's go karts will be conducted as an extension of this study in the near future.

A multifunctional nanocarrier for efficient TRAIL-based gene therapy against hepatocellular carcinoma with desmoplasia in mice.

The anticancer efficacy of TNF-related apoptosis-inducing ligand (TRAIL)-based therapy is limited because of systemic toxicity, poor bioavailability, and development of TRAIL resistance. We developed a tumor-targeted LCPP (lipid/calcium/phosphate/protamine) nanoparticle (NP) to deliver TRAIL plasmid DNA (pDNA) into hepatocellular carcinoma (HCC) cells in a mouse model of HCC. TRAIL pDNA was encapsulated in a pH stimuli-responsive calcium phosphate (CaP) core, and protamine was added to facilitate nuclear delivery of pDNA. In addition, intracellular release of Ca2+ from the CaP core overcame TRAIL resistance by calcium influx-dependent DR5 up-regulation. TRAIL expression also attenuated fibrosis in liver tissues surrounding HCCs by reverting activated hepatic stellate cells (HSCs) to a quiescent state or by directly inducing apoptosis in activated HSCs. CONCLUSION: TRAIL pDNA delivered by HCC-targeted LCPP NPs in combination with conventional sorafenib treatment attenuated HCC progression as well as liver fibrosis. Overall, our study presents an effective TRAIL-based cancer therapy that could be developed for clinical applications. (Hepatology 2018;67:899-913).

Advancement and applications of peptide phage display technology in biomedical science.

Combinatorial phage library is a powerful research tool for high-throughput screening of protein interactions. Of all available molecular display techniques, phage display has proven to be the most popular approach. Screening phage-displayed random peptide libraries is an effective means of identifying peptides that can bind target molecules and regulate their function. Phage-displayed peptide libraries can be used for (i) B-cell and T-cell epitope mapping, (ii) selection of bioactive peptides bound to receptors or proteins, disease-specific antigen mimics, peptides bound to non-protein targets, cell-specific peptides, or organ-specific peptides, and (iii) development of peptide-mediated drug delivery systems and other applications. Targeting peptides identified using phage display technology may be useful for basic research and translational medicine. In this review article, we summarize the latest technological advancements in the application of phage-displayed peptide libraries to applied biomedical sciences.

Optimization of steering control to improve the energy consumption of internal combustion engine vehicles.

This study aims at developing a vehicle dynamic simulator using combined CarSim and MATLAB/Simulink software packages loaded with the performance curves and characteristics of an internal combustion engine to optimize the effects of steering control on the energy consumption of an internal combustion engine vehicle. The simulator consists of modules for the engine, transmission, vehicle dynamic load, energy management strategy, and driving patterns. The goal of this research is to develop an advanced Steer By Wire (SBW) system. As the vehicle is turning, the repeatable turning or oversteer might occur due to several factors: 1. The path is narrow or the road curvature is high; 2. The insufficient designs of turning radius; 3. The driver's choice for turning paths; 4. Human operation factor (slow or fast operating steering wheel that the vehicle is unable to follow the route). Hence, under various steering sensitivity, vehicle speed, and turning radius, we searched the optimal operation parameters globally that the vehicle might save the maximal energy under the safety concerns. The results will be provided as the reference for the drivers or directly be integrated for the SBW under the semi-automatic driving mode. The results of optimal steering control show that: as the turning radius is 40m and vehicle speed is 70 km/h, the maximal energy consumption improvement is 42.72%. If the optimal vehicle speed is considered, the improvement can be even larger. The vehicle model was built based on the real vehicle parameters which can further be employed for the real transportation system.

PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization.

Cancer cell migration plays a crucial role during the metastatic process. Reversible tyrosine phosphorylation by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) have been implicated in the regulation of cancer cell migration and invasion. However, the underlying mechanisms have not been fully elucidated. Here, we show that depletion of the FERM and PDZ domain-containing protein tyrosine phosphatase PTPN3 enhances lung cancer cell migration/invasion and metastasis by promoting actin filament assembly and focal adhesion dynamics. We further identified Src and DAAM1 (dishevelled associated activator of morphogenesis 1) as interactors of PTPN3. DAAM1 is a formin-like protein involved in the regulation of actin cytoskeletal remodeling. PTPN3 inhibits Src activity and Src-mediated phosphorylation of Tyr652 on DAAM1. The tyrosine phosphorylation of DAAM1 is essential for DAAM1 homodimer formation and actin polymerization. Ectopic expression of a DAAM1 phosphodeficient mutant inhibited F-actin assembly and suppressed lung cancer cell migration and invasion. Our findings reveal a novel mechanism by which reversible tyrosine phosphorylation of DAAM1 by Src and PTPN3 regulates actin dynamics and lung cancer invasiveness.

Hepatocellular carcinoma-targeted nanoparticles for cancer therapy.

Nanocarriers, such as liposomes, have the potential to increase the payload of chemotherapeutic drugs while decreasing toxicity to non-target tissues; such advantageous properties can be further enhanced through surface conjugation of nanocarriers with targeting moieties. We previously reported that SP94 peptides, identified by phage display, exhibited higher binding affinity to human hepatocellular carcinoma (HCC) than to hepatocytes and other normal cells. Here, we confirm the tumor-targeting properties of SP94 peptide by near-infrared fluorescence imaging. Non-targeted PEGylated liposomal doxorubicin (LD) and SP94­conjugated PEGylated liposomal doxorubicin (SP94­LD) were compared by assessing pharmacokinetics, tissue distribution, and antitumor efficacy in xenograft-bearing mice, in order to investigate the effectiveness of SP94­mediated targeting for cancer therapy. SP94­LD demonstrated a significant increase in drug accumulation in tumors, while its plasma residence time was the same as its non-targeted equivalent. Consistent with this result, conjugation of targeting peptide SP94 enhances the therapeutic efficacy of liposomal doxorubicin in mouse models with hepatocellular carcinoma xenografts. Furthermore, combination targeted therapy exhibited a significant enhancement against orthotopic tumor growth, and markedly extended the survival of mice compared with all other treatments. Our study shows that SP94­mediated targeting enhances antitumor efficacy by improving tumor pharmacokinetics and tissue distribution, allowing large amounts of antitumor drugs to accumulate in tumors.

α-Enolase-binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer.

Colorectal cancer is one of the most commonly diagnosed cancers and a leading cause of cancer mortality worldwide. Current treatment for colorectal cancer results in only limited success, and more effective therapeutic approaches are thus urgently needed. The development of new methods for early detection and effective treatments for cancer is contingent on the identification of biomarkers on the surface of cancer cells, as well as isolation of tumor-specific ligands with high binding affinity to such biomarkers. In vitro biopanning of a phage-displayed peptide library was used to identify specific peptides binding to human colorectal carcinoma cells. The targeting peptide pHCT74 showed the greatest potential for drug delivery in both in vitro and in vivo studies. The use of biotinylated peptides combined with an affinity trapping method and liquid chromatography-tandem mass spectrometry identified the target protein for the pHCT74 peptide as α-enolase. In animal model studies, combined pHCT74-conjugated liposomal doxorubicin (pHCT74-LD) and pHCT74-conjugated liposomal vinorelbine (pHCT74-sLV) therapy exhibited an enhanced antitumor effect and markedly extended the survival of mice with human colorectal cancer in subcutaneous and orthotopic models. Our findings indicate that α-enolase-targeted lipid nanoparticles have great potential for application in targeted drug delivery systems for colorectal cancer therapy.

A novel peptide enhances therapeutic efficacy of liposomal anti-cancer drugs in mice models of human lung cancer.

Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy.