Novel vitamin K
3 analogues were synthesized and evaluated for their anticancer activity. Compound
6,
9,
10,
11,
14, and (
±)
15 demonstrated a strong inhibitory activity against the tumor cells of ...A-549, Hep G2, MCF7, MES-SA, MES-SA/Dx5, MKN45, SW-480, and TW-039. Compound (
±)
15 displayed potent tumor cell cytotoxicity, and compound
14 selectively affected MCF7, even though it did not influence normal cells Detroit551 and WI-38. Compound (
±)
15 inhibited MES-SA and MES-SA/Dx5, and this specific result shows that compound (
±)
15 may become a good anticancer drug candidate.
Novel vitamin K
3 analogues were synthesized and evaluated for their anticancer activity.
A series of benzothiazolium compounds were identified as novel classes of inhibitors of nitric oxide production in a cell culture system. They exhibited approximately 1600 folds potency with IC(50) ...at approximately 50nM to several microM as compared to IC(50) 88.4microM of l-NMMA, a known inhibitor of nitric oxide synthase. The mechanistic studies suggest that decreased iNOS protein synthesis and mRNA transcription, at least in part, were related to the inhibitory activity of effective benzothiazolium compounds. The correlation of in vivo and in vitro activities using mouse paw edema model was also demonstrated.
Novel vitamin K(3) analogues were synthesized and evaluated for their anticancer activity. Compound 6, 9, 10, 11, 14, and (+/-)15 demonstrated a strong inhibitory activity against the tumor cells of ...A-549, Hep G2, MCF7, MES-SA, MES-SA/Dx5, MKN45, SW-480, and TW-039. Compound (+/-)15 displayed potent tumor cell cytotoxicity, and compound 14 selectively affected MCF7, even though it did not influence normal cells Detroit551 and WI-38. Compound (+/-)15 inhibited MES-SA and MES-SA/Dx5, and this specific result shows that compound (+/-)15 may become a good anticancer drug candidate.
碩士
國立成功大學
政治經濟學研究所
96
With nation’s fast growing economy, Chinese Enterprises have been aggressively starting the “transnational Mergers and Acquisitions” activities under the galbalization megatrend ...over the past years. And those large Chinese state-owned enterprises have been the main role of executing the transnational Mergers and Acquisitions among all Chinese Enterprises. However, Chinese state-owned enterprises always affiliate with the Chinese government. Therefore, the Chinese state-owned enterprises’ transnational Mergers and Acquisitions activities reveal that the Chinese central government has great influence on those Chinese state-owned enterprises’ transnational M & As activities.
This research accentuates the Chinese central government’s main influence on Chinese state-owned enterprises’ transnational M & As activities. With the “State-Centered Approach”, This research focuses on analyzing how the Chinese central government use it’s “autonomy” and “capacity” to impel the Chinese state-owned ente
碩士
國立臺灣大學
生化科技學系
105
Genomic instability refers to an increased tendency of alterations in the genome during cell cycle progression, and likely contributes to the development of many cancers. To ...faithfully transmit genetic information to the progeny, efficient DNA repair pathways are required for the maintenance of genomic stability. Ikbkap gene encodes IKAP/Elp1, which functions as a scaffold subunit of the Elongator complex (Elp1-6). The Elongator complex was initially described as an RNA polymerase II-associated transcription elongation factor, but it has been shown later to be involved in a variety of cellular functions through regulation of histone acetylation and tRNA modification. A previous study has shown that Ikbkap regulates meiotic synapsis, double strand break (DSB) repair and recombination during male meiotic progression. Downregulation of DNA repair-related genes was observed in Ikbkap deficient testes, suggesting that Ikbkap plays a crucial role in DNA damage response (DDR) in germ cells. To investigate whether Ikbkap maintains genomic stability in somatic cells, we deleted Ikbkap in mouse embryonic fibroblasts (MEFs). Comet assays show that Ikbkap-/- MEFs are hypersensitive to DNA damage, like -irradiation. Ikbkap-/- MEFs exhibited a proliferative impediment in response to -irradiation. In addition, a significant accumulation of chromosomal abnormalities, including breaks was observed in Ikbkap-/- MEFs compared to controls. Although apoptotic rate was unaffected in Ikbkap-/- MEFs one day post -irradiation, these data shows that IKAP function is essential for the ability to survive DNA damage, and implicating IKAP in repair in U-2 OS cells. Furthermore, we revealed that Ikbkap is required for DNA repair by homologous recombination (HR), but not non-homologous end joining (NHEJ) using U-2 OS cell lines harbouring a green fluorescent protein reporter for DSB repair. These finding define a function of Ikbkap in DNA repair. Further investigation will be focused on the underlying DNA repair mechanisms.
Purpose
To investigate deep reinforcement learning (DRL) based on historical treatment plans for developing automated radiation adaptation protocols for nonsmall cell lung cancer (NSCLC) patients ...that aim to maximize tumor local control at reduced rates of radiation pneumonitis grade 2 (RP2).
Methods
In a retrospective population of 114 NSCLC patients who received radiotherapy, a three‐component neural networks framework was developed for deep reinforcement learning (DRL) of dose fractionation adaptation. Large‐scale patient characteristics included clinical, genetic, and imaging radiomics features in addition to tumor and lung dosimetric variables. First, a generative adversarial network (GAN) was employed to learn patient population characteristics necessary for DRL training from a relatively limited sample size. Second, a radiotherapy artificial environment (RAE) was reconstructed by a deep neural network (DNN) utilizing both original and synthetic data (by GAN) to estimate the transition probabilities for adaptation of personalized radiotherapy patients’ treatment courses. Third, a deep Q‐network (DQN) was applied to the RAE for choosing the optimal dose in a response‐adapted treatment setting. This multicomponent reinforcement learning approach was benchmarked against real clinical decisions that were applied in an adaptive dose escalation clinical protocol. In which, 34 patients were treated based on avid PET signal in the tumor and constrained by a 17.2% normal tissue complication probability (NTCP) limit for RP2. The uncomplicated cure probability (P+) was used as a baseline reward function in the DRL.
Results
Taking our adaptive dose escalation protocol as a blueprint for the proposed DRL (GAN + RAE + DQN) architecture, we obtained an automated dose adaptation estimate for use at ∼2/3 of the way into the radiotherapy treatment course. By letting the DQN component freely control the estimated adaptive dose per fraction (ranging from 1–5 Gy), the DRL automatically favored dose escalation/de‐escalation between 1.5 and 3.8 Gy, a range similar to that used in the clinical protocol. The same DQN yielded two patterns of dose escalation for the 34 test patients, but with different reward variants. First, using the baseline P+ reward function, individual adaptive fraction doses of the DQN had similar tendencies to the clinical data with an RMSE = 0.76 Gy; but adaptations suggested by the DQN were generally lower in magnitude (less aggressive). Second, by adjusting the P+ reward function with higher emphasis on mitigating local failure, better matching of doses between the DQN and the clinical protocol was achieved with an RMSE = 0.5 Gy. Moreover, the decisions selected by the DQN seemed to have better concordance with patients eventual outcomes. In comparison, the traditional temporal difference (TD) algorithm for reinforcement learning yielded an RMSE = 3.3 Gy due to numerical instabilities and lack of sufficient learning.
Conclusion
We demonstrated that automated dose adaptation by DRL is a feasible and a promising approach for achieving similar results to those chosen by clinicians. The process may require customization of the reward function if individual cases were to be considered. However, development of this framework into a fully credible autonomous system for clinical decision support would require further validation on larger multi‐institutional datasets.
We report unusual photophysical properties observed on two newly designed 3-hydroxychromone derivatives exhibiting the excited-state intramolecular proton transfer (ESIPT) reaction. The efficiency of ...ESIPT reaction is greatly enhanced upon excitation with high energy quanta to S
(
> 1) levels in low-polarity solvents. Based on detailed analyses of excitation and emission spectra as well as time-resolved emission kinetics we derive that conditions, in which this phenomenon contradicting Kasha's rule is observed, are quite different from that for observation of anti-Kasha emission.
Abstract
The industrialization of quantum dot light-emitting diodes (QLEDs) requires the use of less hazardous cadmium-free quantum dots, among which ZnSe-based blue and InP-based green and red ...quantum dots have received considerable attention. In comparison, the development of InP-based green QLEDs is lagging behind. Here, we prepare green InP/ZnSe/ZnS quantum dots with a diameter of 8.6 nm. We then modify the InP quantum dot emitting layer by passivation with various alkyl diamines and zinc halides, which decreases electron mobility and enhances hole transport. This, together with optimizing the electron transport layer, leads to green 545 nm InP QLEDs with a maximum quantum efficiency (EQE) of 16.3% and a current efficiency 57.5 cd/A. EQE approaches the theoretical limit of InP quantum dots, with an emission quantum yield of 86%.
Photoluminescent gold nanodots (Au NDs) are prepared via etching and codeposition of hybridized ligands, an antimicrobial peptide (surfactin; SFT), and 1‐dodecanethiol (DT), on gold nanoparticles ...(≈3.2 nm). As‐prepared ultrasmall SFT/DT–Au NDs (size ≈2.5 nm) are a highly efficient antimicrobial agent. The photoluminescence properties and stability as well as the antimicrobial activity of SFT/DT–Au NDs are highly dependent on the density of SFT on Au NDs. Relative to SFT, SFT/DT–Au NDs exhibit greater antimicrobial activity, not only to nonmultidrug‐resistant bacteria but also to the multidrug‐resistant bacteria. The minimal inhibitory concentration values of SFT/DT–Au NDs are much lower (>80‐fold) than that of SFT. The antimicrobial activity of SFT/DT–Au NDs is mainly due to the synergistic effect of SFT and DT–Au NDs on the disruption of the bacterial membrane. In vitro cytotoxicity and hemolysis analyses have revealed superior biocompatibility of SFT/DT–Au NDs than that of SFT. Moreover, in vivo methicillin‐resistant S. aureus–infected wound healing studies in rats show faster healing, better epithelialization, and are more efficient in the production of collagen fibers when SFT/DT–Au NDs are used as a dressing material. This study suggests that the SFT/DT–Au NDs are a promising antimicrobial candidate for preclinical applications in treating wounds and skin infections.
Surfactin, an antimicrobial lipopeptide, when self‐assembled on photoluminescent gold nanodots (Au NDs) exhibits an >80‐fold improvement in its antimicrobial activity against multidrug‐resistant bacteria. Antibacterial wound‐healing assays further reveal that the surfactin–Au ND hybrid material is superior to that of surfactin alone on a bacteria‐infected flesh wound in rats.
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