| 1. |
- Su, Linjia, et al.
(författare)
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GRP75-driven, cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca2+ nanoparticles underlies distinct gene therapy effect in ovarian cancer
- 2022
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Ingår i: Journal of Nanobiotechnology. - : Springer Nature. - 1477-3155. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Practice of tumor-targeted suicide gene therapy is hampered by unsafe and low efficient delivery of plasmid DNA (pDNA). Using HIV-Tat-derived peptide (Tat) to non-covalently form Tat/pDNA complexes advances the delivery performance. However, this innovative approach is still limited by intracellular delivery efficiency and cell-cycle status. In this study, Tat/pDNA complexes were further condensed into smaller, nontoxic nanoparticles by Ca2+ addition. Formulated Tat/pDNA-Ca2+ nanoparticles mainly use macropinocytosis for intercellular delivery, and their macropinocytic uptake was persisted in mitosis (M-) phase and highly activated in DNA synthesis (S-) phase of cell-cycle. Over-expression or phosphorylation of a mitochondrial chaperone, 75-kDa glucose-regulated protein (GRP75), promoted monopolar spindle kinase 1 (MPS1)-controlled centrosome duplication and cell-cycle progress, but also driven cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca2+ nanoparticles. Further in vivo molecular imaging based on DF (Fluc-eGFP)-TF (RFP-Rluc-HSV-ttk) system showed that Tat/pDNA-Ca2+ nanoparticles exhibited highly suicide gene therapy efficiency in mouse model xenografted with human ovarian cancer. Furthermore, arresting cell-cycle at S-phase markedly enhanced delivery performance of Tat/pDNA-Ca2+ nanoparticles, whereas targeting GRP75 reduced their macropinocytic delivery. More importantly, in vivo targeting GRP75 combined with cell-cycle or macropinocytosis inhibitors exhibited distinct suicide gene therapy efficiency. In summary, our data highlight that mitochondrial chaperone GRP75 moonlights as a biphasic driver underlying cell-cycle-dependent macropinocytosis of Tat/pDNA-Ca2+ nanoparticles in ovarian cancer.
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| 2. |
- Wang, Yiran, et al.
(författare)
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Repeatability of Epithelium Thickness Measured by an AS-OCT in Different Grades of Keratoconus and Compared to AS-OCT/Placido Topography
- 2024
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Ingår i: American Journal of Ophthalmology. - 0002-9394. ; 265, s. 213-223
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare agreement of corneal epithelium thickness (ET) between AS-OCT system (RTVue, Optovue) and AS-OCT/Placido topographer (MS-39, CSO) in eyes with different stages of keratoconus (KC), and to assess the repeatability of RTVue AS-OCT. DESIGN: Prospective reliability analysis. METHODS: KC eyes were classified into forme fruste KC (FFKC), mild, moderate, and severe KC. Agreement was evaluated with Bland–Altman plots and 95% limits of agreement (LoA). The repeatability of RTVue was assessed via within-subject standard deviation (Sw), test–retest variability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC). RESULTS: A total of 119 KC eyes were enrolled, with 21 being FFKC, 26 mild, 39 moderate, and 34 severe. The 95% LoA ranged between −5.9 and 4.8 µm for center epithelium thickness (CET), between −5.7 and 8.2 µm for thinnest epithelium thickness (TET). At 1-mm measuring points, the 95% LoA of superior, inferior, nasal, and temporal were −4.2 to 4.7 µm, −5.2 to 6.0 µm, −7.9 to 10.2 µm, and −11.2 to 6.0 µm. At 3-mm measuring points, the corresponding values were −2.8 to 9.3 µm, −2.0 to 13.0 µm, −4.6 to 9.6 µm, and −6.3 to 9.7 µm, indicating that the 2 instruments were not interchangeable without adjustment. Despite that the repeatability of RTVue measurements in KC patients were acceptable, repeatability decreased gradually with the peripheralization of the measurement points. CONCLUSIONS: The 2 OCT-based devices, RTVue and MS-39, do not provide interchangeable measurements of epithelium thickness in KC patients. Repeatability decreases in cases of more severe KC, emphasizing the importance of grading before clinical examination to avoid diagnostic errors.
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| 3. |
- Yuan, Shichen, et al.
(författare)
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Balancing Charge Injection via a Tailor-Made Electron-Transporting Material for High Performance Blue Perovskite QLEDs
- 2023
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Ingår i: ACS Energy Letters. - : AMER CHEMICAL SOC. - 2380-8195. ; 8:1, s. 818-826
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Tidskriftsartikel (refereegranskat)abstract
- One of the great challenges in perovskite quantum dot light-emitting diodes (Pe-QLEDs) is the unbalanced charge injection that significantly hinders the device performance and stability. Herein, we tailor-made a high mobility electron-transporting material (ETM), named B2, to balance the carrier injection in blue Pe-QLEDs. B2 with a tailored asymmetric anthracenyl structure exhibits a promising electron mobility of 2.7 x 10(-4) cm(2)center dot V-1 center dot s(-1), which is almost 20 times higher than the commonly used ETM-TPBi (1.1 x 10(-5) cm(2)center dot V-1 center dot s(-1)). Subsequently, sky blue (490 nm) Pe-QLED with B2 as the ETM presented a remarkably high external quantum efficiency (EQE) of 13.17% and a low turn-on voltage of 2.2 V, which is much better than that of the TPBi-based device (EQE of 8.31% and Vturn-on of 3.2 V). In addition, B2 also demonstrated a universal application in green and deep blue Pe-QLEDs. This work provides an important guidance to rational design of high electron mobility ETMs for high-performance LEDs.
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| 4. |
- Cai, Shengyun, et al.
(författare)
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Photo-stable substituted dihydroindolo[2,3-b]carbazole-based organic dyes : tuning the photovoltaic properties by optimizing the pi structure for panchromatic DSSCs
- 2014
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 70:43, s. 8122-8128
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Tidskriftsartikel (refereegranskat)abstract
- Three dihydroindolo[2,3-b]carbazole (DDC) donor based organic dyes (DDC6-DDC8) with long conjugated systems were successfully synthesized and characterized by optical, electrochemical, computational analysis, and photovoltaic methods. It was found that the elongated pi system as well as the high molar extinction coefficients (4.2-5.3 M-1 cm(-1)) sufficiently reinforced the light harvesting ability with the IPCE response of one dye DDC8 extended to 850 nm, which resulted in large J(sc) of these dyes based devices (high as 16.41 mA cm(-2)). The attached alkyl chains suppress the dark current to some extent, resulting the DDC6 and DDC7 devices in high V-oc, while DDC8 displayed low V-oc, because BTD in DDC8 could attract the iodine ion, which could accelerate the charge recombination. Among the three dyes, DDC7 displayed the best performance with an eta value 6.53% under 4 mu m thick scattering layer (condition 1+1), which was boosted to 7.49% under 8 mu m thick scattering layer (condition 1+2). The photo-stability measurements indicated that all the three dyes are fairly photo-stable.
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| 5. |
- Hu, Han, et al.
(författare)
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Severe Traffic Crash Speaks : Safety Facts From Mountain Roads in China
- 2013
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Ingår i: Proceedings of the 16th International Conference Road Safety on Four Continents. - Linköping : Statens väg- och transportforskningsinstitut.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- objective to build up a systematic mountain road safety enhancement technology, this study analyses severe traffic crashes from 2006 to 2010 occurred on an inter-regional mountain arterial road network in south China. In order to digest these crash data collected from local traffic police stations, the authors conduct the in-depth crash analysis from the aspect of human, vehicle, road, and management. By developing the definition sets for crash deterministic causing factors judging system, the deterministic causes of severe accidents on mountain roads in China are deeply investigated. Results of our analysis indicate that human factor does weigh the most in the occurrence of the severe crashes; main crash types on mountain roads are running-off road, headon collision, overturned; Almost 76% severe crashes occurred on slope/curve combination sites; and freight car shall be given more attentions in reducing the severe accidents.
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| 6. |
- Hu, Jingmei, et al.
(författare)
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Speed Control Effect Study on Optical Illusion Deceleration Markings
- 2013
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Ingår i: Proceedings of the 16th International Conference Road Safety on Four Continents. - Linköping : Statens väg- och transportforskningsinstitut.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The optical illusion deceleration marking is one of the commonly used speed control measures. In this research, the authors analyzed operating speed and trajectory of motor vehicle at intersection where optical illusion deceleration marking is installed. Quantitative and qualitative evaluation on effect of optical illusion deceleration marking is conducted. Results showed that optical illusion deceleration marking would help to reduce operating speed and average speed by 5-10km/h, to regulate motorcycle driver behavior, and to reduce speed difference, so that driving safety is ensured. Optical illusion deceleration marking is suitable for accident prone road sections on two-lane highways which main vehicle types are passenger car and motorcycle.
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| 7. |
- Keyu, Guo, et al.
(författare)
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A Phase-Domain Model of Dual Three-Phase Segmented Powered Linear PMSM for Hardware-assisted Real-Time Simulation
- 2022
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Ingår i: IEEE Transactions on Industry Applications. - 0093-9994 .- 1939-9367. ; 58:4, s. 4511-4521
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a Hardware-assisted real-time simulation phase-domain (PD) model of a dual three-phase segmented powered linear permanent magnet synchronous machine (SP-LPMSM) used in electromagnetic launch is established. The model is able to consider the end-effect, saturation effect, coupling effect and open-phase fault conditions, which are specially occurs in the segmented structure in SP-LPMSM. The unbalanced inductances and saturation effect caused by the segmented structure are investigated and a simplified look-up table for inductances is introduced. Additionally, to accurately evaluate the coupling effect, the permanent magnet (PM) flux linkage is decoupled into the product of unit PM flux linkage and coupling coefficient. In order to avoid the numerical impulse caused by the derivative in the progress of calculating back-EMF, sigmoid function is adopted to express the coupling coefficient. Meanwhile, to make the PD-model compatible with the open-circuit fault conditions, incidence matrices and current constraint matrices are introduced to unify the PD-models with different winding connection types and open circuit faults into one general form. The PD-Model realized in Field-Programmable Gate Arrays (FPGA) based hardware is validated in comparison with finite element analysis results.
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| 8. |
- Li, Jinhai, et al.
(författare)
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Effects of Roadway Segment Alignments and Locations on Rural Two-Lane Highway Crash Rates
- 2013
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Ingår i: Proceedings of the 16th International Conference Road Safety on Four Continents. - Linköping : Statens väg- och transportforskningsinstitut.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper investigates the effects of road segment alignment and location on rural two-lane highway crash rates by taking the mileage of segment types into consideration. Roadway segments are classified and redefined according to the segment alignment and location. The definitions of crash rates in terms of segment alignment and location are presented respectively. The study gathers crash data and the roadway geometric information of rural two-lane highways in southwest of China and crash rates of each segment type are proposed by utilizing the proposed definitions. The result indicates that gentle-slope & sharp-curve segments and intersections tend to have extremely higher crash rates than the other types of segments.
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| 9. |
- Liu, Anbu, et al.
(författare)
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DDR1/2 enhance KIT activation and imatinib resistance of primary and secondary KIT mutants in gastrointestinal stromal tumors
- 2024
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Ingår i: Molecular Carcinogenesis. - 0899-1987. ; 63:1, s. 75-93
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal stromal tumors (GISTs) are predominantly initiated by KIT mutations. In this study, we observed that discoidin domain receptors 1 and 2 (DDR1 and DDR2) exhibited high expression in GISTs, were associated with KIT, and enhanced the activation of both wild-type KIT and primary KIT mutants. Inhibition of DDR1/2 led to a reduction in the activation of KIT and its downstream signaling molecules, ultimately impairing GIST cell survival and proliferation in vitro. Consequently, treatment of mice carrying germline KIT/V558A mutation with DDR1/2 inhibitor significantly impeded tumor growth, and the combined use of DDR1/2 inhibitor and imatinib, the first-line targeted therapeutic agent for GISTs, markedly enhanced tumor growth suppression. In addition, DDR1/2 inhibition resulted in decreased KIT expression, while KIT inhibition led to upregulation of DDR1/2 expression in GISTs. The presence of DDR1/2 also decreased the sensitivity of wild-type KIT or primary KIT mutants to imatinib, indicating a possible role for DDR1/2 in promoting GIST survival during KIT-targeted therapy. The development of drug-resistant secondary KIT mutations is a primary factor contributing to GIST recurrence following targeted therapy. Similar to primary KIT mutants, DDR1/2 can associate with and enhance the activation of secondary KIT mutants, further diminishing their sensitivity to imatinib. In summary, our data demonstrate that DDR1/2 contribute to KIT activation in GISTs and strengthen resistance to imatinib for both primary and secondary KIT mutants, providing a rationale for further exploration of DDR1/2 targeting in GIST treatment.
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| 10. |
- Ning, Rui, et al.
(författare)
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Assessing progression limits in different grades of keratoconus from a novel perspective : precision of measurements of the corneal epithelium
- 2024
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Ingår i: Eye and Vision. - 2326-0254. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: To assess repeatability and reproducibility of corneal epithelium thickness (ET) measured by a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in keratoconus (KC) population at different stages, as well as to determine the progression limits for evaluating KC progression. Methods: A total of 149 eyes were enrolled in this study, with 29 eyes in the forme fruste keratoconus (FFKC) group, 34 eyes in the mild KC group, 40 eyes in the moderate KC group, and 46 eyes in the severe KC group. Employing the within-subject standard deviation (Sw), test-retest variability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) to evaluate intraoperator repeatability and interoperator reproducibility. Results: The repeatability and reproducibility of MS-39 in patients with KC were acceptable, according to ICC values ranging from 0.732 to 0.954. However, patients with more severe KC and progressive peripheralization of the measurement points had higher TRTs but a thinning trend. The current study tended to set the cut-off values of mild KC, moderate KC, and severe KC to 4.9 µm, 5.2 µm, and 7.4 µm for thinnest epithelium thickness (TET). When differences between follow-ups are higher than those values, progression of the disease is possible. As for center epithelium thickness (CET), cut-off values for mild KC, moderate KC, and severe KC should be 2.8 µm, 4.4 µm, and 5.3 µm. This might be useful in the follow-up and diagnosis of keratoconus. Conclusions: This study demonstrated that the precision of MS-39 was reduced in measuring more severe KC patients and more peripheral corneal points. In determining disease progression, values should be differentiated between disease-related real changes and measurement inaccuracies. Due to the large difference in ET measured by MS-39 between various stages of disease progression, it is necessary to accurately grade KC patients to avoid errors in KC clinical decision-making.
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