6,078 research outputs found

    The role of SWAP-70 in cancer metastasis and tumor immunity

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    Cancer metastasis accounts for approximately 90% of all cancer-related deaths; however, the underlying mechanisms remain largely unknown. It has been known proteins that control F-actin dynamics are crucial for cancer metastasis. In this study, we revealed how an F-actin binding protein, Switch-associated protein 70 (SWAP-70), contributes to breast cancer metastasis. Moreover, immunotherapy is a promising approach to treat metastatic cancer cells by enhancing the function of the host immune system against cancer. Our lab has conducted extensive studies on how SWAP-70 regulates the function of several immune cell types, including dendritic cells (DCs), B cells, and mast cells. These cells have been reported to contribute to tumor immunity. Thus, we hypothesized that SWAP-70 plays a role in tumor immunity. To characterize the function of SWAP-70 in metastasis, we generated 4T1, mouse breast cancer, SWAP-70 knockout (KO) cells using Crispr/Cas9 technology. A syngeneic orthotopic model was used to recapitulate clinical disease progression, and the results showed that SWAP-70 led to significant metastasis to the lungs and bones in immunocompetent mice. Several functional assays have revealed that SWAP-70 promotes anchorage-independent growth, cell migration, invasion, and adhesion in 4T1 cells. Biophysical measurements showed that SWAP-70 contributes to cellular mechanics. To investigate how SWAP-70 in host cells affects tumor immunity, SWAP-70 deficient mice were injected with E0771 mouse breast cancer cells to study tumorigenicity. SWAP-70 deficient mice showed delayed primary tumor growth and less distant metastasis. Isolated SWAP-70−/− DCs were impaired in generating CD8 T cell responses pulsed with soluble OVA protein, but not with OVA peptide, suggesting that the antigen uptake, processing, and presentation process in SWAP-70−/− DCs may be diminished. Taken together, our findings describe the potential mechanisms by which the loss of SWAP-70 hinders cancer metastasis and provide several insights into how targeting SWAP-70 could be a potential therapeutic approach to target cancer

    Study of the excited 11^- charm and charm-strange mesons

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    We give a systematical study on the recently reported excited charm and charm-strange mesons with potential 11^- spin-parity, including the Ds1(2700)+D^*_{s1}(2700)^+, Ds1(2860)+D^*_{s1}(2860)^+, D(2600)0D^*(2600)^0, D(2650)0D^*(2650)^0, D1(2680)0D^*_1(2680)^0 and D1(2760)0D^*_1(2760)^0. The main strong decay properties are obtained by the framework of Bethe-Salpeter (BS) methods. Our results reveal that the two 11^- charm-strange mesons can be well described by the further 23 ⁣S12^3\!S_1-13 ⁣D11^3\!D_1 mixing scheme with a mixing angle of 8.73.2+3.98.7^{+3.9}_{-3.2} degrees. The predicted decay ratio B(DK)B(D K)\frac{\mathcal{B}(D^*K)}{\mathcal{B}(D~K)} for Ds1(2860)D^*_{s1}(2860) is 0.620.12+0.220.62^{+0.22}_{-0.12}.~D(2600)0D^*(2600)^0 can also be explained as the 23 ⁣S12^3\!S_1 predominant state with a mixing angle of (7.53.3+4.0)-(7.5^{+4.0}_{-3.3}) degrees. Considering the mass range, D(2650)0D^*(2650)^0 and D1(2680)0D^*_1(2680)^0 are more likely to be the 23 ⁣S12^3\!S_1 predominant states, although the total widths under both the 23 ⁣S12^3\!S_1 and 13 ⁣D11^3\!D_1 assignments have no great conflict with the current experimental data. The calculated width for LHCb D1(2760)0D^*_1(2760)^0 seems about 100 \si{MeV} larger than experimental measurement if taking it as 13 ⁣D11^3\!D_1 or 13 ⁣D11^3\!D_1 dominant state cuˉc\bar u. The comparisons with other calculations and several important decay ratios are also present. For the identification of these 11^- charm mesons, further experimental information, such as B(Dπ)B(Dπ)\frac{\mathcal{B}(D\pi)}{\mathcal{B}(D^*\pi)} are necessary.Comment: 18 pages, 3 figure

    Width-tuned magnetic order oscillation on zigzag edges of honeycomb nanoribbons

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    Quantum confinement and interference often generate exotic properties in nanostructures. One recent highlight is the experimental indication of a magnetic phase transition in zigzag-edged graphene nanoribbons at the critical ribbon width of about 7 nm [G. Z. Magda et al., Nature \textbf{514}, 608 (2014)]. Here we show theoretically that with further increase in the ribbon width, the magnetic correlation of the two edges can exhibit an intriguing oscillatory behavior between antiferromagnetic and ferromagnetic, driven by acquiring the positive coherence between the two edges to lower the free energy. The oscillation effect is readily tunable in applied magnetic fields. These novel properties suggest new experimental manifestation of the edge magnetic orders in graphene nanoribbons, and enhance the hopes of graphene-like spintronic nanodevices functioning at room temperature.Comment: 22 pages, 9 figure

    An Empirical Study of Civil Servants’ Lifelong E-Learning Continuance Intention

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    E-learning is an effective way for job-training and continuous education. In recognizing the need for civil servants to embrace the lifelong learning to sustain competitiveness, many countries around the world have created policies to develop e-learning. This study is focus on civil servants’ e-learning continuance intention and through e-learning experience to achieve lifelong learning. Based on Information system (IS) success model proposed by Seddon (1997) and adding organizational factors (Incentive, Supervisor Support, and Technical Support) to survey civil servants’ e-learning behaviour. The sample for the study was taken from the civil servants in Taiwan who have the experience of using the lifelong e-learning websites. The results also support Seddon’s IS success model. Finally, the implications and limitations of the study are discussed

    A Study on the Satisfaction of Supply Chain Management System from the View of Justice and Value

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    Due to the common, most enterprises have utilized information technology (IT) to enhance their competition and performance. Meanwhile, governments in Taiwan have encouraged enterprises to adapt e-commerce by putting policies and facilitating technology. Nevertheless, only few literatures discuss or evaluate the satisfaction of E-SCM after establishing information systems by enterprises. This research attempts to integrate three well-founded theories – Information System Success model (ISS), Organization Justice Theory and Consumer Value to develop our model. Using Structural Square Modeling (SEM) analysis performed on results of a questionnaire given to the providers of SCM who have established the E-SCM in their enterprises. The results showed that the distributive justice, procedural justice and interactive justice in the organization justice theory have a significant effect on the performance outcome in the E-SCM. It also showed that the system and service quality in the IS success model and the cost and service value in shopping value have a significant effect on the satisfaction of the E-SCM. The contribution of this study can be further research in academic and practical

    A Pilot Study of the Short Term Effectiveness and Safety of Amniotic Fluid in Severe Dry Eye Disease

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    The aim of this study was to evaluate if amniotic fluid (AF) mixed with artificial tears or soaked with a soft contact lens (SCL) as a treatment for severe dry eye disease (DED) would improve its signs or symptoms. In this retrospective pilot study 22 consecutive eyes of 11 patients with level 3 DED classified by DEWS 1 (Dry Eye WorkShop 1 2007), were included in the study between June 1 and September 30 in 2017. The study was conducted before DEWS II (Dry Eye WorkShop II 2017), which was published in October 2017. Therefore, DEWS II was not adopted for this study. Soft Contact Lens Acuvue Oasys of Plano with 8.8 base curve and 14 mm diameters by Johnson and Johnson were used to soak in FloGraft, which is an AF, for 30 minutes before placing in 12 eyes in Group 1. The contact lenses were placed in the left eye for 1 week. In Group 2, 10 eyes used 6 mL of artificial tears mixed with 0.25 mL of AF, which were applied to the eye four times a day for 1 week. No other eye medications were used. The eyes that were included had diffuse punctate staining and fast tear breaking times of <5 seconds with severe ocular symptoms (DEWS 1 level 3-4). Photos of fluorescein stain corneas before the treatment and 1 week after the treatment were used to compare the distribution of punctate staining as the objective outcomes for signs. Several questions adopted from the Ocular Surface disease Index (OSDI) about subjective symptoms before and after the treatment were asked, and documented on the chart. Improvement either in symptoms or signs or both of DED after 1 week at follow-up examination was recorded. Group 1, with SCL 46% had improvement after 1 week and Group 2, with artificial tears 50% had improvement after 1 week. Improvement means either symptom relief or comparatively decreased distribution of punctate staining on the cornea or both. No cases had inflammation, infection, irritation or blurred vision. We concluded that FloGraft as an AF can safely improve the symptoms or the signs of severe DED either as a mix with artificial tears or soaked with SCL by about 50% in this case series without evidence of irritation, inflammation or blurred vision in the short term

    Formulation of novel lipid-coated magnetic nanoparticles as the probe for in vivo imaging

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    <p>Abstract</p> <p>Background</p> <p>Application of superparamagnetic iron oxide nanoparticles (SPIOs) as the contrast agent has improved the quality of magnetic resonance (MR) imaging. Low efficiency of loading the commercially available iron oxide nanoparticles into cells and the cytotoxicity of previously formulated complexes limit their usage as the image probe. Here, we formulated new cationic lipid nanoparticles containing SPIOs feasible for <it>in vivo </it>imaging.</p> <p>Methods</p> <p>Hydrophobic SPIOs were incorporated into cationic lipid 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP) and polyethylene-glycol-2000-1,2-distearyl-3-sn-phosphatidylethanolamine (PEG-DSPE) based micelles by self-assembly procedure to form lipid-coated SPIOs (L-SPIOs). Trace amount of Rhodamine-dioleoyl-phosphatidylethanolamine (Rhodamine-DOPE) was added as a fluorescent indicator. Particle size and zeta potential of L-SPIOs were determined by Dynamic Light Scattering (DLS) and Laser Doppler Velocimetry (LDV), respectively. HeLa, PC-3 and Neuro-2a cells were tested for loading efficiency and cytotoxicity of L-SPIOs using fluorescent microscopy, Prussian blue staining and flow cytometry. L-SPIO-loaded CT-26 cells were tested for <it>in vivo </it>MR imaging.</p> <p>Results</p> <p>The novel formulation generates L-SPIOs particle with the average size of 46 nm. We showed efficient cellular uptake of these L-SPIOs with cationic surface charge into HeLa, PC-3 and Neuro-2a cells. The L-SPIO-loaded cells exhibited similar growth potential as compared to unloaded cells, and could be sorted by a magnet stand over ten-day duration. Furthermore, when SPIO-loaded CT-26 tumor cells were injected into Balb/c mice, the growth status of these tumor cells could be monitored using optical and MR images.</p> <p>Conclusion</p> <p>We have developed a novel cationic lipid-based nanoparticle of SPIOs with high loading efficiency, low cytotoxicity and long-term imaging signals. The results suggested these newly formulated non-toxic lipid-coated magnetic nanoparticles as a versatile image probe for cell tracking.</p
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