There is a growing demand for using non-destructive geophysical techniques to internally image dam condition and facilitate the early detection of anomalous phenomena. Near surface geophysical ...techniques have advanced significantly in the last few decades, and can play a significant role in the siting, construction, and operational safety and sustainable management of dams. Application of engineering geophysics in site characterization during feasibility investigation phase is already part of the standard of practice. This paper introduces newer applications of engineering geophysics during construction phase, dam safety assessment, and sustainable management, including quality control of compacted soils, investigation of abnormal leakage in an earth dam, evaluation of an aged concrete dam, geophysical health monitoring for a newly-constructed dam, and monitoring of sediment transport for sediment management. The applications were presented with more emphases on the needs of dam engineering and adapting appropriate geophysical methods to make assessment more effective and consequential. The collage of these case studies is to broaden the view of how geophysical methods can be applied to a dam project throughout a dam's life cycle and strengthen the linkage between geophysical surveillance and engineering significance at all stages.
•Various new applications of engineering geophysics on dams in Taiwan are introduced from a life cycle perspective.•The needs of dam engineering are emphasized and how to adapt appropriate geophysical methods accordingly are demonstrated.•More quantitative engineering interpretation and process monitoring are proposed at various stages of dam engineering.•Extending the application of geophysics from planning phase to construction phase and sustainable management, are discussed.
Aims
Sodium‐glucose cotransporter 2 inhibitors (SGLT‐2is) have been demonstrated to be associated with cancer cell mechanisms. However, whether they increase the risk of cancer remains unclear. Thus, ...this study aimed to determine the association between SGLT‐2i use and the incidence of cancer in patients with diabetes mellitus (DM) in Taiwan.
Materials and Methods
This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT‐2is during 2016–2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP‐4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use.
Results
After controlling for relevant variables, the SGLT‐2i cohort (aHR = 0.90, 95% CI = 0.87–0.93) had a significantly lower risk of developing cancer than the DPP‐4i cohort, particularly when the SGLT‐2i was dapagliflozin (aHR = 0.91, 95% CI = 0.87–0.95) or empagliflozin (aHR = 0.90, 95% CI = 0.86–0.94). Regarding cancer type, the SGLT‐2i cohort's risk of cancer was significantly lower than that of the DPP‐4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer.
Conclusions
SGLT‐2i use was associated with a significantly lower risk of cancer than DPP‐4i use.
An excellent thermally activated delayed fluorescence (TADF) emitter requires a sophisticated molecular design strategy to incorporate structural features to simultaneously achieve high ...photoluminescence quantum yield (PLQY) and high horizontal emission dipole ratio (Θ//). This work reports the uses of heteroarenes and dicarbonitrile benzenes to design four new acceptors PymCN, PyoCN, PmmCN, and PmoCN, which are linked to a common donor dimethylacridine (DMAC) for making new TADF emitters. The emission wavelength, ΔEST, krisc, kr, and the resulting PLQY of the target TADF emitters are governed by the combined natures of the heteroaryl bridges (Py vs Pm) and the CN‐substituted patterns (o‐CN vs m‐CN). The photophysical and device characteristics reveal the best acceptor to be PyoCN, which is further coupled with spiroacridine to afford a new emitter SpiroAC‐PyoCN with an enhanced PLQY of 100% compared to that (91%) of the DMAC‐based counterpart DMAC‐PyoCN. Furthermore, linking PyoCN with spiro‐bisacridine (SBAC) gives an A–D–A‐configured TADF emitter SBAC‐PyoCN with both enhanced PLQY (100%) and Θ// (90%). The device employing SBAC‐PyoCN as emitter renders a maximum external quantum efficiency up to 36.1% owing to its unity PLQY and superior light out‐coupling efficiency. This rational molecular design strategy provides a feasible means to achieve an excellent TADF emitter design.
A rational strategy for designing thermally activated delayed fluorescence emitter is reported, using dimethylacridine as a common donor to select the acceptor PyoCN that comprises pyridine and ortho‐dicarbonitrile benezene. PyoCN links to rigid donors spiroacridine and spiro‐bisacridine, leading to high photoluminescence quantum yield and high horizontal emission dipole ratio. The best device accomplishes a maximum external quantum efficiency up to 36.1%.
Galangin, a member of the flavonol compounds of the flavonoids, could exert anti-inflammatory effects in various cell types. It has been used for the treatment of arthritis, airway inflammation, ...stroke, and cognitive impairment. Thrombin, one of the regulators of matrix metalloproteinase (MMPs), has been known as a vital factor of physiological and pathological processes, including cell migration, the blood⁻brain barrier breakdown, brain edema formation, neuroinflammation, and neuronal death. MMP-9 especially may contribute to neurodegenerative diseases. However, the effect of galangin in combating thrombin-induced MMP-9 expression is not well understood in neurons. Therefore, we attempted to explore the molecular mechanisms by which galangin inhibited MMP-9 expression and cell migration induced by thrombin in SK-N-SH cells (a human neuroblastoma cell line). Gelatin zymography, western blot, real-time PCR, and cell migration assay were used to elucidate the inhibitory effects of galangin on the thrmbin-mediated responses. The results showed that galangin markedly attenuated the thrombin-stimulated phosphorylation of proto-oncogene tyrosine-protein kinase (c-Src), proline-rich tyrosine kinase 2 (Pyk2), protein kinase C (PKC)α/β/δ, protein kinase B (Akt), mammalian target of rapamycin (mTOR), p42/p44 mitogen-activated protein kinase (MAPK), Jun amino-terminal kinases (JNK)1/2, p38 MAPK, forkhead box protein O1 (FoxO1), p65, and c-Jun and suppressed MMP-9 expression and cell migration in SK-N-SH cells. Our results concluded that galangin blocked the thrombin-induced MMP-9 expression in SK-N-SH cells via inhibiting c-Src, Pyk2, PKCα/βII/δ, Akt, mTOR, p42/p44 MAPK, JNK1/2, p38 MAPK, FoxO1, c-Jun, and p65 phosphorylation and ultimately attenuated cell migration. Therefore, galangin may be a potential candidate for the management of brain inflammatory diseases.
Neuroinflammation is a landmark of neuroinflammatory and neurodegenerative diseases. Matrix metalloproteinase (MMP)-9, one member of MMPs, has been shown to contribute to the pathology of these brain ...diseases. Several experimental models have demonstrated that lipopolysaccharide (LPS) exerts a pathological role through Toll-like receptors (TLRs) in neuroinflammation and neurodegeneration. However, the mechanisms underlying LPS-induced MMP-9 expression in rat brain astrocytes (RBA-1) are not completely understood. Here, we applied pharmacological inhibitors and siRNA transfection to assess the levels of MMP-9 protein, mRNA, and promoter activity, as well as protein kinase phosphorylation in RBA-1 cells triggered by LPS. We found that LPS-induced expression of pro-form MMP-9 and cell migration were mediated through TLR4, proto-oncogene tyrosine-protein kinase (c-Src), proline-rich tyrosine kinase 2 (Pyk2), platelet-derived growth factor receptor (PDGFR), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), p38 mitogen-activated protein kinase (MAPK), and Jun amino-terminal kinase (JNK)1/2 signaling molecules in RBA-1 cells. In addition, LPS-stimulated binding of c-Jun to the MMP-9 promoter was confirmed by chromatin immunoprecipitation (ChIP) assay, which was blocked by pretreatment with c-Src inhibitor II, PF431396, AG1296, LY294002, Akt inhibitor VIII, p38 MAP kinase inhibitor VIII, SP600125, and tanshinone IIA. These results suggest that in RBA-1 cells, LPS activates a TLR4/c-Src/Pyk2/PDGFR/PI3K/Akt/p38 MAPK and JNK1/2 pathway, which in turn triggers activator protein 1 (AP-1) activation and ultimately induces MMP-9 expression and cell migration.
A series of compounds containing arylamine and 1,2‐diphenyl‐1H‐benzdimidazole moieties are developed as ambipolar, blue‐emitting materials with tunable blue‐emitting wavelengths, tunable ambipolar ...carrier‐transport properties and tunable triplet energy gaps. These compounds possess several novel properties: (1) they emit in the blue region with high quantum yields; (2) they have high morphological stability and thermal stability; (3) they are capable of ambipolar carrier transport; (4) they possess tunable triplet energy gaps, suitable as hosts for yellow‐orange to green phosphors. The electron and hole mobilities of these compounds lie in the range of 0.68–144 × 10−6 and 0.34–147 × 10−6 cm2 V−1 s−1, respectively. High‐performance, single‐layer, blue‐emitting, fluorescent organic light‐emitting diodes (OLEDs) are achieved with these ambipolar materials. High‐performance, single‐layer, phosphorescent OLEDs with yellow‐orange to green emission are also been demonstrated using these ambipolar materials, which have different triplet energy gaps as the host for yellow‐orange‐emitting to green‐emitting iridium complexes. When these ambipolar, blue‐emitting materials are lightly doped with a yellow‐orange‐emitting iridium complex, white organic light‐emitting diodes (WOLEDs) can be achieved, as well by the use of the incomplete energy transfer between the host and the dopant.
High‐performance, single‐layer, blue, fluorescent OLEDs based on ambipolartransport compounds containing arylamine and 1,2‐diphenyl‐1H‐benzdimidazole moieties are described. High‐performance yellow‐orange and green, single‐layer, phosphorescent OLEDs are also possible by using these materials as the host for phosphorescent dopants. White OLEDs can also be achieved.
Carbon quantum dots (CQDs) are emerging novel nanomaterials with a wide range of applications and high biocompatibility. However, there is a lack of in-depth research on whether CQDs can cause acute ...or long-term adverse reactions in aquatic organisms. In this study, two different types of CQDs prepared by ammonia citrate and spermidine, namely CQD
and CQD
, were used to evaluate their biocompatibilities. In the fish embryo acute toxicity test (FET), the LD50 of CQD
and CQD
was about 500 and 100 ppm. During the stage of eleutheroembryo, the LD50 decreased to 340 and 55 ppm, respectively. However, both CQDs were quickly eliminated from embryo and eleutheroembryo, indicating a lack of bioaccumulation. Long-term accumulation of CQDs was also performed in this study, and adult zebrafish showed no adverse effects in 12 weeks. In addition, there was no difference in the hatchability and deformity rates of offspring produced by adult zebrafish, regardless of whether they were fed CQDs or not. The results showed that both CQD
and CQD
have low toxicity and bioaccumulation to zebrafish. Moreover, the toxicity assay developed in this study provides a comprehensive platform to assess the impacts of CQDs on aquatic organisms in the future.
Scour is a major threat to bridge safety, especially in harsh fluvial environments. Real-time monitoring of bridge scour is still very limited due to the lack of robust and economic scour monitoring ...device. Time domain reflectometry (TDR) is an emerging waveguide-based technique holding great promise to develop more durable scour monitoring devices. This study presents new types of TDR sensing waveguides in forms of either sensing rod or sensing wire, taking into account of the measurement range, durability, and ease of field installation. The sensing rod is composed of a hollow grooved steel rod paired up with a metal strip on the insulating groove, while the sensing wire consists of two steel strands with one of them coated with an insulating jacket. The measurement sensitivity is inevitably sacrificed when other properties such as the measurement range, field durability, and installation easiness are enhanced. Factors affecting the measurement sensitivity were identified and experimentally evaluated for better arranging the waveguide conductors. A data reduction method for scour-depth estimation without the need for identifying the sediment/water reflection and a two-step calibration procedure for rating propagation velocities were proposed to work with the new types of TDR sensing waveguides. Both the calibration procedure and the data reduction method were experimentally validated. The test results indicated that the new TDR sensing waveguide provides accurate scour depth measurements regardless of the sacrificed sensitivity. The insulating coating of the new TDR sensing waveguide was also demonstrated to be effective in extending the measurement range up to at least 15 m.
Loss of tumor suppressor activity and upregulation of oncogenic pathways simultaneously contribute to tumorigenesis. Expression of the tumor suppressor, GCIP (Grap2‐ and cyclin D1‐interacting ...protein), is usually reduced or lost in advanced cancers, as seen in both mouse tumor models and human cancer patients. However, no previous study has examined how cancer cells down‐regulate GCIP expression. In this study, we first validate the tumor suppressive function of GCIP using clinical gastric cancer tissues and online database analysis. We then reveal a novel mechanism whereby MEK2 directly interacts with and phosphorylates GCIP at its Ser313 and Ser356 residues to promote the turnover of GCIP by ubiquitin‐mediated proteasomal degradation. We also reveal that decreased GCIP stability enhances cell proliferation and promotes cancer cell migration and invasion. Taken together, these findings provide a more comprehensive view of GCIP in tumorigenesis and suggest that the oncogenic MEK/ERK signaling pathway negatively regulates the protein level of GCIP to promote cell proliferation and migration.
Tumor cells have long been observed to share several biological characteristics with normal stem/progenitor cells; however, the oncogenic mechanisms underlying the lung stem/progenitor cell signaling ...remain elusive. Here, we report that SOX2, a self‐renewal factor in lung stem/progenitor cells, is highly expressed in a subclass of lung cancer cells, the proliferation, survival, and chemoresistance of which are dependent on SOX2 signaling. Overexpression of SOX2 promotes oncogenic phenotypes in lung cancer cells; knockdown of SOX2 attenuated cell proliferation. We observed that SOX2 increased the expression of epidermal growth factor receptor (EGFR), and EGFR activation further upregulated SOX2 levels, forming a positive feedback loop. SOX2 expression promoted chemoresistance, and silencing of SOX2 perturbed mitochondrial function, causing marked apoptosis and autophagy. SOX2 induced BCL2L1, the ectopic expression of which rescued the effects of SOX2 silencing on apoptosis, autophagy, and mitochondrial function. SOX2 promoted tumor formation, along with increased cell proliferation in a xenograft mouse model. SOX2 expression is associated with poor prognosis in lung cancer patients; moreover, SOX2, EGFR, and BCL2L1 expression levels were significantly correlated in lung tumors. Our findings support the emerging role of SOX2 in cell proliferation and survival by eliciting oncogenic EGFR and BCL2L1 signaling with potential applications as a prognosis marker and a therapeutic target in lung cancer. Stem Cells 2013;31:2607–2619
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