All countries regulate CO
2
emissions, triggering similar evolution on powertrain at a similar pace all over the planet. Engine irregularities are more severe due to downsizing and uptorquing. ...Torsional filtration targets are also challenging powertrain performance. This drives powertrain market and more efficient torque transfer system. Conventional filtration solutions such as clutch/dampers and DMF have their own limitations. For the past few years the addtion of centrifugal pendulum absorber meets the required filtration target. The vehicle architecture and type of damper accompanying pendulum absorber contribute to the dynamic stability and performance. In this study, we have shown the behaviors of DMF pendulum in rear wheel driveline with six speed manual transmission. Normally the performance of a pendulum in high engine speed range is not so efficient compare to lower speed range. This study mainly focuses on variations on design parameters of pendulum, which enables better filtration in high speed range.
In anticancer therapy, combination therapy has been suggested as an alternative to the insufficient therapeutic efficacy of single therapy. Among combination therapies, combination chemo- and ...photodynamic therapy are actively investigated. However, photodynamic therapy shows a limitation in the penetration depth of the laser. Therefore, sonodynamic therapy (SDT), using ultrasound instead of a laser as a trigger, is an upcoming strategy for deep tumors. Additionally, free drugs are easily degraded by enzymes, have difficulty in reaching the target site, and show side effects after systemic administration; therefore, the development of drug delivery systems is desirable for sufficient drug efficacy for combination therapy. However, nanocarriers, such as microbubbles, and albumin nanoparticles, are unstable in the body and show low drug-loading efficiency. Here, we propose polylactide (PLA)-poly (ethylene glycol) (PEG) polymersomes (PLs) with a high drug loading rate of doxorubicin (DOX) and verteporfin (VP) for effective combination therapy in both in vitro and in vivo experiments. The cellular uptake efficiency and cytotoxicity test results of VP-DOX-PLs were higher than that of single therapy. Moreover, in vivo biodistribution showed the accumulation of the VP-DOX-PLs in tumor regions. Therefore, VP-DOX-PLs showed more effective anticancer efficacy than either single therapy in vivo. These results suggest that the combination therapy of SDT and chemotherapy could show novel anticancer effects using VP-DOX-PLs.
Ultrasound imaging, one of the common diagnosis techniques, is frequently used since it is safe, cost-efficient technique and real-time imaging can be conducted. However, various organs and tissues ...reflect ultrasonic waves, which leads to difficulty in imaging small biomolecules and to a low spatial resolution for deep-tissue images. As such, there have been significant advances in photonics and optical molecular probes in recent years, and photoacoustic (PA) tomography (PAT) has emerged as a promising modality that can overcome the limitations of ultrasound. PAT relies on the photoacoustic effect, which is the conversion of absorbed optical energy into acoustic energy. Since fewer biomolecules exhibit the photoacoustic effect compared to the scattering or reflection of ultrasound, PAT can be employed to generate high-resolution images. PAT also has a number of other advantages when compared to conventional biomedical imaging modalities such as optical tomography, ultrasound imaging, computed tomography, positron emission tomography and magnetic resonance imaging. This review provides a general overview of the contrast agents used for PAT, including organic, inorganic and hybrid contrast agents, and describes their application. This review also identifies limitations of current PAT contrast agents and suggests future research directions for their development.
Lipid-coated microbubbles are widely used as an ultrasound contrast agent, as well as drug delivery carriers. However, the two main limitations in ultrasound diagnosis and drug delivery using ...microbubbles are the short half-life in the blood system, and the difficulty of surface modification of microbubbles for active targeting. The exosome, a type of extracellular vesicle, has a preferentially targeting ability for its original cell. In this study, exosome-fused microbubbles (Exo-MBs) were developed by embedding the exosome membrane proteins into microbubbles. As a result, the stability of Exo-MBs is improved over the conventional microbubbles. On the same principle that under the exposure of ultrasound, microbubbles are cavitated and self-assembled into nano-sized particles, and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles (Exo-NPs). The Exo-NPs showed favorable targeting properties to their original cells. A photosensitizer, chlorin e6, was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier. Much higher therapeutic efficacy of photodynamic therapy was confirmed, followed by cancer immunotherapy from immunogenic cell death. We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.
Exosomes, which are released from all cells and take part in cell-to-cell communication, have been utilized as drug delivery vehicles in many recent studies. Immunotherapy is an emerging technology ...which uses patients' innate immune systems. In immunotherapy, immune cells are stimulated through antibodies, the other immune cells and genetic modifications for the purposes of, for instance, cancer therapy. In this study, tumor-derived re-assembled exosome (R-Exo) was simultaneously utilized as both a drug delivery carrier and an immunostimulatory agent. A chlorin e6 photosensitizer was loaded into tumor-derived exosomes during exosomal re-assembly. After this modification, R-Exo retains its original average size and has the same membrane proteins, which allows for targeting of tumor cells. Chlorin e6-loaded R-Exo (Ce6-R-Exo) can be visualized by photoacoustic imaging and can efficiently generate reactive oxygen species inside tumor cells under laser irradiation. In addition, Ce6-R-Exo increased the release of cytokines from immune cells, which indicates that these modified exosomes can be used as an immunotherapeutic agent. In conclusion, we developed a novel strategy that enables photoacoustic imaging-guided photodynamic and immune-combination therapy for the treatment of cancer with tumor-derived Ce6-R-Exo.
Display omitted
Topology Synthesis for Low Power Cascaded Crossbar Switches Jang, Yongho; Kim, Jungsoo; Kyung, Chong-Min
IEEE transactions on computer-aided design of integrated circuits and systems,
2010-Dec., 2010-12-00, 20101201, Letnik:
29, Številka:
12
Journal Article
Recenzirano
Crossbar switch network has an increasing impact on such critical measures as throughput, latency, area, and power consumption of complex system-on-chip as technology scales to deep submicrometer. ...With high clock frequency crossbar switch network design, global wire delay and pipeline registers inserted for throughput are important because they affect area, frequency, and power consumption of the chip. The traffic congestion is also a very important factor because it leads to the lowering of throughput of the crossbar switch network. In this paper, we present a topology synthesis method for the low-power cascaded crossbar switch network satisfying the given bandwidth, latency, frequency, and area constraints. Unlike previous papers, our paper considers wire delay, traffic congestion, and pipeline register insertion at the same time. Experimental results show that the topologies optimized for power consumption for a given clock frequency consume less power than existing methods by up to 38.04%.
Nanotechnology-based combination therapies, especially chemo-gene therapy, have been spotlighted as promising alternatives for cancer therapy. However, only a small amount of systemically ...administered nanomedicines reach the tumor site by the enhanced permeability and retention (EPR) effect, resulting in the limited therapeutic efficacy. Furthermore, the design of ideal drug delivery system for chemo-gene therapy has been impeded by the chemical and physical differences between nucleic acids and chemotherapeutics. Herein, we report a precisely designed nanocomplex which exhibits a focused ultrasound (FU)-responsive release and enhanced accumulation of released therapeutics to tumor site. After the nanocomplex composed of siRNA nanoparticles (siRNA-NP) and chemotherapeutics-loaded microbubbles was systemically injected, the nanocomplex was collapsed around the tumor tissue by FU exposure, and both siRNA-NP and chemotherapeutics were penetrated the dense extracellular matrix (ECM) of tumor site, leading to the enhanced chemo-gene therapeutic efficacy. The two-in-one nanocomplex is expected as a promising platform for combination therapy that can enhance the therapeutic efficiency of combination drugs at the cell and/or tissue levels with high drug loading ratio.
The multifunctional nanocomplex facilitates enhanced penetration/accumulation of siRNA-NP and Paclitaxel by focused ultrasound (FU) triggering. Additionally, FU-triggered effect enable the extracellular matrix to loosen, resulting in excellent chemo-gene therapeutic efficacy. Display omitted
Recently, combination therapy has received much attention because of its highly therapeutic effect in various types of cancers. In particular, chemo-photodynamic combination therapy has been ...considered as an outstanding strategy. However, an abnormal increase in tumor angiogenesis caused by reactive oxygen species (ROS) generated during photodynamic therapy (PDT) has been reported. In this study, the complex of doxorubicin (DOX)-encapsulating anti-angiogenic small interfering RNA (siRNA) nanoparticle and chlorin e6 (Ce6)-encapsulating microbubble has been developed to suppress tumor angiogenesis. The first compartment, doxorubicin-encapsulating siRNA nanoparticle, was electrostatically coated using two biocompatible polymers to prevent the damage of genetic materials. The other part, Ce6-encapsulating microbubble, serves as an ultrasound-triggered local delivery system as well as a drug carrier. Both the in vitro and in vivo experimental results demonstrate successful inhibition of angiogenesis with a minimized damage of siRNAs caused by ROS as well as improved therapeutic effect by chemo-photodynamic-gene triple combination therapy using ultrasound-triggered local delivery.
Doxorubicin-encapsulating anti-VEGF siRNA nanoparticle-Ce6-loaded microbubbles complex, DOX-siVEGF-NPs/Ce6-MBs, can simultaneously deliver the drug, photosensitizer and genetic material through sonoporation effect using external ultrasound irradiation. Chemo-photodynamic combination therapy significantly improved therapeutic effect. The genetic materials, anti-VEGF siRNA, placed separately with photosensitizer to avoid degradation by ROS, inhibit angiogenesis from side-effect of PDT. Display omitted
Metastasis is the leading cause of cancer-related deaths. A number of chemotherapeutic and early diagnosis strategies, including nanomedicine, have been developed to target metastatic tumor cells. ...However, simultaneous inhibition and imaging of metastasis is yet to be fully achieved.
To overcome this limitation, we have developed human serum albumin-based nanoparticles (tHSA-NPs) with photoacoustic imaging capability, which target carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6). CEACAM6 is highly expressed in metastatic anoikis-resistant tumor cells.
, the CEACAM6-targeting tHSA-NPs efficiently targeted CEACAM6-overexpressing metastatic anoikis-resistant tumor cells.
, CEACAM6-targeting tHSA-NPs administered intravenously to BALB/c nude mice efficiently inhibited lung metastasis in circulating anoikis-resistant tumor cells compared to the controls. In addition, anoikis-resistant tumor cells can be successfully detected by photoacoustic imaging, both
and
using the intrinsic indocyanine green-binding affinity of albumin.
In summary, the CEACAM6-targeting albumin-based nanoparticles allowed the delivery of drugs and photoacoustic imaging to metastatic anoikis-resistant tumor cells
and
. Based on the expression of CEACAM6 in a variety of tumors, CEACAM6-targeting nanomedicine might be used to target various types of metastatic tumor cells.
Photoacoustic (PA) imaging has attracted much attention as a new biomedical imaging modality due to its ultrasonic spatial resolution, optical contrast resolution, and deeper imaging depth than other ...optical imaging modalities. Exogenous PA contrast agents have been developed, with high optical absorbance at a desired wavelength, to improve their imaging sensitivity over background signal produced from endogenous nontargeted absorbers. However, the current approaches to PA imaging are based on a nonoptimal detection of PA signal, due to the fact that the PA signal contains a broad range of frequency components, whereas an ultrasound transducer is only capable of receiving signals within a certain frequency range. As a result, much of the signal generated by PA contrast agent is lost when received by an ultrasound transducer. In this study, we propose a new concept for PA contrast enhancement. This method uses chromophore-embedded microbubbles as selective resonance frequency amplifiers; only the PA signal energy within a desired spectral bandwidth can be selectively increased by adjusting the microbubble size. Therefore, the efficiency of the signal reception by an ultrasound transducer can be improved when the operating frequency of the transducer is similar to the amplified spectral bandwidth, thus allowing for more sensitive PA imaging. This new concept was validated using a porphyrin-phospholipid microbubble (p-MB) in vitro and in vivo experiments, which showed that the p-MBs increased the PA signals up to 40.94 times, compared with the PA signals from the freely dispersed porphyrin-embedded liposomes (i.e., porphysomes).
PDF
