Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including vasodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases (NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interestingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting the etiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and has been associated with tumour grade, proliferation rate and expression of important signaling components associated with cancer development such as the oestrogen receptor. It appears that high levels of NOS expression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumor cells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxically therefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic properties. Increased NO-generation in a cell may select mutant p53 cells and contribute to tumour angiogenesis by upregulating VEGF. In addition, NO may modulate tumour DNA repair mechanisms by upregulating p53, poly(ADP-ribose) polymerase (PARP) and the DNA-dependent protein kinase (DNA-PK). An understanding at the molecular level of the role of NO in cancer will have profound therapeutic implications for the diagnosis and treatment of disease.
A lamella-forming poly(ethylene oxide)-b-polystyrene (PEO-b-PS) diblock copolymer has been blended with a low molecular weight polystyrene (PS) homopolymer to form a miscible polymer blend. The PEO volume fraction is 0.32, and the order-disorder transition temperature (T ODT) of this blend is 175 °C. Therefore, the PEO blocks form nanocylinders surrounded by a PS matrix below the TODT. Since the glass transition temperature of the PS is 64 °C and the PEO crystal melting occurs at ∼50 °C, the PEO-block crystallization takes place in a two-dimensionally confined glassy environment. The cylinder diameter is determined to be 13.7 nm, based on small-angle X-ray scattering (SAXS) and transmission electron microscopy results. Using simultaneous two-dimensional SAXS and wide-angle X-ray scattering techniques, the crystal orientation (the c-axes of the PEO crystals) within the nanocylinders is found to change simply depending upon the crystallization temperature (T c). At very low Tc (<-30 °C), PEO crystals are randomly oriented within the confined cylinders. Starting at Tc ) -30 °C, the crystal orientation changes to be inclined with respect to the cylinder axis, a ˆ. The tilt angle from a ˆcontinuously increases with increasing Tc, and finally it becomes 90°when Tc g 2 °C. Crystallographic analysis indicates that the crystal c-axis orientation at each Tc corresponds to a uniform crystal orientation.
Purpose: We aimed to evaluate the value of deep learning on positron emission tomography with computed tomography (PET/CT)-based radiomics for individual induction chemotherapy (IC) in advanced nasopharyngeal carcinoma (NPC). Experimental Design: We constructed radiomics signatures and nomogram for predicting disease-free survival (DFS) based on the extracted features from PET and CT images in a training set (n ¼ 470), and then validated it on a test set (n ¼ 237). Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis were applied to evaluate the discriminatory ability of radiomics nomogram, and compare radiomics signatures with plasma Epstein-Barr virus (EBV) DNA. Results: A total of 18 features were selected to construct CT-based and PET-based signatures, which were significantly associated with DFS (P < 0.001). Using these signatures , we proposed a radiomics nomogram with a C-index of 0.754 [95% confidence interval (95% CI), 0.709-0.800] in the training set and 0.722 (95% CI, 0.652-0.792) in the test set. Consequently, 206 (29.1%) patients were stratified as high-risk group and the other 501 (70.9%) as low-risk group by the radiomics nomogram, and the corresponding 5-year DFS rates were 50.1% and 87.6%, respectively (P < 0.0001). High-risk patients could benefit from IC while the low-risk could not. Moreover, radiomics nomogram performed significantly better than the EBV DNA-based model (C-index: 0.754 vs. 0.675 in the training set and 0.722 vs. 0.671 in the test set) in risk stratification and guiding IC. Conclusions: Deep learning PET/CT-based radiomics could serve as a reliable and powerful tool for prognosis prediction and may act as a potential indicator for individual IC in advanced NPC.
Morphology, thermal and rheological properties of polymer-organoclay composites prepared by melt-blending of polystyrene (PS), poly(methyl methacrylate) (PMMA), and PS/PMMA blends with Cloisite organoclays were examined by transmission electron microscopy, small-angle X-ray scattering, secondary ion mass spectroscopy, differential scanning calorimetry, and rheological techniques. Organoclay particles were finely dispersed and predominantly delaminated in PMMA-clay composites, whereas organoclays formed micrometer-sized aggregates in PS-clay composites. In PS/PMMA blends, the majority of clay particles was concentrated in the PMMA phase and in the interfacial region between PS and PMMA. Although incompatible PS/PMMA blends remained phaseseparated after being melt-blended with organoclays, the addition of organoclays resulted in a drastic reduction in the average microdomain sizes (from 1-1.5 m to ca. 300 -500 nm), indicating that organoclays partially compatibilized the immiscible PS/PMMA blends. The effect of surfactant (di-methyl di-octadecyl-ammonia chloride), used in the preparation of organoclays, on the PS/PMMA miscibility was also investigated. The free surfactant was more compatible with PMMA than with PS; the surfactant was concentrated in PMMA and in the interfacial region of the blends. The microdomain size reduction resulting from the addition of organoclays was definitely more significant than that caused by adding the same amount of free surfactant without clay. The effect of organoclays on the rheological properties was insignificant in all tested systems, suggesting weak interactions between the clay particles and the polymer matrix. In the PS system, PMMA, and organoclay the extent of clay exfoliation and the resultant properties are controlled by the compatibility between the polymer matrix and the surfactant rather than by interactions between the polymer and the clay surface.
Crystallization temperature (Tc)-dependent crystal orientations within nanoconfined lamellae have been studied in a self-assembled poly(ethylene oxide)-block-polystyrene (PEO-b-PS) diblock copolymer. The copolymer possesses number-average molecular weights of M h n PEO ) 8.7K and M h n PS ) 9.2K, and it forms a microphase-separated lamellar structure in the melt. It has been found that the PEO crystal (the c axis) orientations are determined by only varying the Tc. 1 Based on real-time simultaneous twodimensional (2D) small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS) experiments, the formation of crystal orientation is found in an early stage of PEO crystallization confined between the PS lamellae. To understand whether the crystal orientation is determined during the primary nucleation or crystal growth step, specifically designed self-seeded crystallization experiments are carried out using 2D SAXS and WAXS techniques. Experimental results suggest that primary nuclei (self-seeds) do not possess specific orientation with respect to the PS lamellar surface normal, disregarding the history of crystal orientation in the samples generated before the self-seeding process. It is found that the initial stage of crystal growth determines the final crystal orientation in the nanoconfined lamellae. Studies of the correlation lengths (apparent crystallite sizes) along both [120] directions of the PEO crystals with various crystal orientations indicate that the PEO crystals formed in nanoconfined lamellae undergo a change from a one-dimensional to a two-dimensional growth with increasing T c.
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