Protopine Inhibits Heterotypic Celladhesion In Mda-Mb-231 Cells Through Down-Regulation Of Multi-Adhesive Factors

Background: A Chinese herb Corydalis yanhusuo W.T. Wang that showed anticancer and anti-angiogenesis effects in our previous studies was presented for further studies. In the present study, we studied the anticancer proliferation and adhesion effects of five alkaloids which were isolated from Corydalis yanhusuo.Materials and Methods: MTT dose response curves, cell migration assay, cell invasion assay, as well as three types of cell adhesive assay were performed on MDA-MB-231 human breast cancer cells. The mechanism of the compounds on inhibiting heterotypic cell adhesion were further explored by determining the expression of epidermal growth factor receptor (EGFR), Intercellular adhesion molecule 1 (ICAM-1), αv-integrin, β1- integrin and β5- integrin by western blotting assay.Results: In five tested alkaloids, only protopine exhibited anti-adhesive and anti-invasion effects in MDA-MB-231 cells, which contributed to the anti-metastasis effect of Corydalis yanhusuo. The results showed that after treatment with protopine for 90 min, the expression of EGFR, ICAM-1, αv-integrin, β1- integrin and β5- integrin were remarkably reduced.Conclusion: The present results suggest that protopine seems to inhibit the heterotypic cell adhesion between MDA-MB-231 cells, and human umbilical vein endothelial cells by changing the expression of adhesive factors.Keywords: Corydalis yanhusuo, Protopine, Adhesion, Breast cancer, Integrin

Evaluation of minimum residual pressure as design criterion for South African water distribution systems

The South African civil engineering fraternity has grown to accept 24 m as the design criterion for minimum residual pressure in water distribution systems. However, the theoretical peak demand in many systems has increased beyond the point where minimum residual pressure exceeds 24 m – at least according to hydraulic models. Additions of customers to existing supply systems have led to increased peak flows with time, often without infrastructure upgrades to internal reticulation. Increased flows imply reduced pressures. This is not necessarily a concern: peak flow conditions rarely occur in a supply system and also, customer complaints often act as a first sign of ‘low pressures’. No complaints imply ‘no low pressures’. The researchers analysed hydraulic models for 14 different towns in 5 municipal areas of South Africa, including 2 large metros,to identify the minimum residual pressures currently expected. The results include almost 55 000 model nodes and show that about 20% of the nodes in the distribution systems analysed have pressures of below 24 m, while pressures of below 14 m are not uncommon. Whether this relatively common occurrence of low pressures under modelled peak demand is found in practice is not known at this stage. A new guideline for minimum residual pressure based on previous criteria and results from this study is presented, noting that a physical lower limit of about 10 m water pressure is specified in home appliance specifications

Partially linear censored quantile regression

Censored regression quantile (CRQ) methods provide a powerful and flexible approach to the analysis of censored survival data when standard linear models are felt to be appropriate. In many cases however, greater flexibility is desired to go beyond the usual multiple regression paradigm. One area of common interest is that of partially linear models: one (or more) of the explanatory covariates are assumed to act on the response through a non-linear function. Here the CRQ approach of Portnoy (J Am Stat Assoc 98:1001–1012, 2003) is extended to this partially linear setting. Basic consistency results are presented. A simulation experiment and unemployment example justify the value of the partially linear approach over methods based on the Cox proportional hazards model and on methods not permitting nonlinearity

Crude oil risk forecasting : new evidence from multiscale analysis approach

Fluctuations in the crude oil price allied to risk have increased significantly over the last decade frequently varying at different risk levels. Although existing models partially predict such variations, so far, they have been unable to predict oil prices accurately in this highly volatile market. The development of an effective, predictive model has therefore become a prime objective of research in this field. Our approach, albeit based in part on previous research, develops an original methodology, in that we have created a risk forecasting model with the ability to predict oil price fluctuations caused by changes in both fundamental and transient risk factors. We achieve this by disintegrating the multi-scale risk-structure of the crude oil market using Variational Mode Decomposition. Normal and transient risk factors are then extracted from the crude oil price using Variational Mode Decomposition and modelled separately using the Quantile Regression Neural Network (QRNN) model. Both risk factors are integrated and ensembled to produce the risk estimates. We then apply our proposed risk forecasting model to predicting future downside risk level in three major crude oil markets, namely the West Taxes Intermediate (WTI), the Brent Market, and the OPEC market. The results demonstrate that our model has the ability to capture downside risk estimates with significantly improved precision, thus reducing estimation errors and increasing forecasting reliability

Tetrazine Carbon Nanotubes for Pretargeted In Vivo "Click-to-Release" Bioorthogonal Tumour Imaging.

The bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) cleavage reaction between tetrazine and trans-cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single-walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO-caged molecule was used to deliver active effector molecules. To optimize a turn-on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near-infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real-time, non-invasive tumour visualization with a high target-to-background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine-functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off-site activation of fluorophore/drug

Bayesian hydrograph separation in a minimally gauged alpine volcanic watershed in central Chile

This study examines the question of how much information one can extract from a tracer-based hydrograph separation in a remote and minimally gaged alpine catchment in Chile. We combine PCA-based endmember mixing analysis to identify the sources of flow contribution to the Diguillín River with a hierarchical Bayesian mixing model to integrate spatial and temporal variability in endmember concentration and quantify the source contributions to streamflow over time. The PCA-analysis shows that precipitation isotopes do not vary by elevation (e.g. snow and rainfall had identical signatures) but vary significantly by season, and that a third endmember is necessary to bound streamflow variability at the basin outlet, which was not captured by our field sampling. One of the main advantages of Bayesian methods is the quasi-machine learning capabilities, where we treated the third endmember as a parameter from which the mixing model could both estimate proportional contributions as well as posterior estimates for the tracer concentrations. The two tracer, three endmember hydrograph separation revealed groundwater to be the largest and precipitation (rain and snow) to be the smallest contributor, on average, to streamflow with the third unknown endmember contributing around 40% of streamflow during the Winter wet season. We hypothesize that interflow is occurring as the third endmember in the Alto Diguillín subwatershed, based on inferred tracer values and the presence of alluvium atop impermeable bedrock along certain reaches. More work is necessary to observe and sample these flowpaths, which was not possible during this study. The results of this work have implications for water resource management, since groundwater sustains the majority of streamflow in the Diguillín, and climate change will impact the timing and quantity of baseflow and interflow. Overall, we demonstrate the utility of combining PCA with Bayesian statistical modeling and inference to extract maximum information from a limited field dataset in a remote alpine catchment. The findings of this work can guide future water management in the Diguillín, but also provide clear questions for future research

Study on the serum oxidative stress status in silicosis patients

To determine whether oxidative-stress damage play an important role in the mechanism of silicosis, the oxidative stress parameters were investigated in silicosis patients and controls group. 128 silicosis patients and 130 healthy controls were included. The serum superoxide dismutase (SOD) activity and the levels of malonyldialdehyde (MDA) and glutathione (GSH) were analyzed. The levels of GSH and MDA in silicosis patients were significantly higher than those of the controls group. SOD activity was higher in the silicosis group than that in the controls (p < 0.05) except for III stage. None of the 3 variables examined were associated with the age among both the controls and silicosis patients. The GSH level and SOD activity significantly declined over a prolonged disease period, while MDA levels remained largely unaffected by the disease duration. These results confirmed the role of oxidative stress in the mechanism of silicosis. Therefore, effective antioxidant therapy for inhibiting oxidative stress may be a therapeutic option in silicosis.Key words: Silica, silicosis, superoxide dismutase, glutathione, malondialdehyde

Accumulation-mode aerosol number concentrations in the Arctic during the ARCTAS aircraft campaign: Long-range transport of polluted and clean air from the Asian continent

We evaluate the impact of transport from midlatitudes on aerosol number concentrations in the accumulation mode (light-scattering particles (LSP) with diameters >180 nm) in the Arctic during the Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) campaign. We focus on transport from the Asian continent. We find marked contrasts in the number concentration (NLSP), transport efficiency (TE N-LSP, the fraction transported from sources to the Arctic), size distribution, and the chemical composition of aerosols between air parcels from anthropogenic sources in East Asia (Asian AN) and biomass burning sources in Russia and Kazakhstan (Russian BB). Asian AN air had lower NLSP and TEN-LSP (25 cm-3 and 18% in spring and 6.2 cm-3 and 3.0% in summer) than Russian BB air (280 cm-3 and 97% in spring and 36 cm-3 and 7.6% in summer) due to more efficient wet scavenging during transport from East Asia. Russian BB in this spring is the most important source of accumulation-mode aerosols over the Arctic, and BB emissions are found to be the primary source of aerosols within all the data in spring during ARCTAS. On the other hand, the contribution of Asian AN transport had a negligible effect on the accumulation-mode aerosol number concentration in the Arctic during ARCTAS. Compared with background air, NLSP was 2.3-4.7 times greater for Russian BB air but 2.4-2.6 times less for Asian AN air in both spring and summer. This result shows that the transport of Asian AN air decreases aerosol number concentrations in the Arctic, despite the large emissions of aerosols in East Asia. The very low aerosol number concentrations in Asian AN air were caused by wet removal during vertical transport in association with warm conveyor belts (WCBs). Therefore, this cleansing effect will be prominent for air transported via WCBs from other midlatitude regions and seasons. The inflow of clean midlatitude air can potentially have an important impact on accumulation-mode aerosol number concentrations in the Arctic. Copyright 2011 by the American Geophysical Union

Cortical oscillatory dysrhythmias in visual snow syndrome: a magnetoencephalography study

Visual Snow refers to the persistent visual experience of static in the whole visual field of both eyes. It is often reported by patients with migraine and co-occurs with conditions like tinnitus and tremor. The underlying pathophysiology of the condition is poorly understood. Previously we hypothesised, that visual snow syndrome may be characterised by disruptions to rhythmical activity within the visual system. To test this, data from 18 patients diagnosed with visual snow syndrome, and 16 matched controls, were acquired using magnetoencephalography. Participants were presented with visual grating stimuli, known to elicit decreases in alpha-band (8-13Hz) power and increases in gamma-band power (40-70Hz). Data were mapped to source-space using a beamformer. Across both groups, decreased alpha power and increased gamma power localised to early visual cortex. Data from the primary visual cortex were compared between groups. No differences were found in either alpha or gamma peak frequency or the magnitude of alpha power, p>0.05. However, compared with controls, our visual snow syndrome cohort displayed significantly increased primary visual cortex gamma power, p=0.035. This new electromagnetic finding concurs with previous functional MRI and PET findings suggesting that in visual snow syndrome, the visual cortex is hyper-excitable. The coupling of alpha-phase to gamma amplitude within the primary visual cortex was also quantified. Compared with controls, the visual snow syndrome group had significantly reduced alpha-gamma phase-amplitude coupling, p<0.05, indicating a potential excitation-inhibition imbalance in visual snow syndrome, as well as a potential disruption to top-down “noise-cancellation” mechanisms. Overall, these results suggest that rhythmical brain activity in primary visual cortex is both hyperexcitable and disorganised in visual snow syndrome, consistent with this being a condition of thalamocortical dysrhythmia