Breast Cancer Diagnosis Using a Microfluidic Multiplexed Immunohistochemistry Platform

BACKGROUND: Biomarkers play a key role in risk assessment, assessing treatment response, and detecting recurrence and the investigation of multiple biomarkers may also prove useful in accurate prediction and prognosis of cancers. Immunohistochemistry (IHC) has been a major diagnostic tool to identify therapeutic biomarkers and to subclassify breast cancer patients. However, there is no suitable IHC platform for multiplex assay toward personalized cancer therapy. Here, we report a microfluidics-based multiplexed IHC (MMIHC) platform that significantly improves IHC performance in reduction of time and tissue consumption, quantification, consistency, sensitivity, specificity and cost-effectiveness. METHODOLOGY/PRINCIPAL FINDINGS: By creating a simple and robust interface between the device and human breast tissue samples, we not only applied conventional thin-section tissues into on-chip without any additional modification process, but also attained perfect fluid control for various solutions, without any leakage, bubble formation, or cross-contamination. Four biomarkers, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR) and Ki-67, were examined simultaneously on breast cancer cells and human breast cancer tissues. The MMIHC method improved immunoreaction, reducing time and reagent consumption. Moreover, it showed the availability of semi-quantitative analysis by comparing Western blot. Concordance study proved strong consensus between conventional whole-section analysis and MMIHC (n = 105, lowest Kendall's coefficient of concordance, 0.90). To demonstrate the suitability of MMIHC for scarce samples, it was also applied successfully to tissues from needle biopsies. CONCLUSIONS/SIGNIFICANCE: The microfluidic system, for the first time, was successfully applied to human clinical tissue samples and histopathological diagnosis was realized for breast cancers. Our results showing substantial agreement indicate that several cancer-related proteins can be simultaneously investigated on a single tumor section, giving clear advantages and technical advances over standard immunohistochemical method. This novel concept will enable histopathological diagnosis using numerous specific biomarkers at a time even for small-sized specimens, thus facilitating the individualization of cancer therapy

Valuation of marginal CO2 abatement options for electric power plants in Korea

The electricity generation sector in Korea is under pressure to mitigate greenhouse gases as directed by the Kyoto Protocol. The principal compliance options for power companies under the cap-and-trade include the application of direct CO2 emission abatement and the procurement of emission allowances. The objective of this paper is to provide an analytical framework for assessing the cost-effectiveness of these options. We attempt to derive the marginal abatement cost for CO2 using the output distance function and analyze the relative advantages of emission allowance procurement option as compared to direct abatement option. Real-option approach is adopted to incorporate emission allowance price uncertainty. Empirical result shows the marginal abatement cost with an average of [euro]14.04/ton CO2 for fossil-fueled power plants and confirms the existence of substantial cost heterogeneity among plants which is sufficient to achieve trading gains in allowance market. The comparison of two options enables us to identify the optimal position of the compliance for each plant. Sensitivity analyses are also presented with regard to several key parameters including the initial allowance prices and interest rate. The result of this paper may help Korean power plants to prepare for upcoming regulations targeted toward the reduction of domestic greenhouse gases.CO2 marginal abatement cost Emission allowance Real option

Prediction of Flexural Capacity of RC Beams Strengthened in Flexure with FRP Fabric and Cementitious Matrix

This paper presents both experimental and analytical research results for predicting the flexural capacity of reinforced concrete (RC) beams strengthened in flexure with fabric reinforced cementitious matrix (FRCM). In order to assess the efficiency of the FRCM-strengthening method, six beams were strengthened in flexure with FRCM composite having different amounts and layers of FRP fabric and were tested under four-point loading. From test results, it was confirmed that the slippage between the FRP fabric and matrix occurs at a high strain level, and all of the FRCM-strengthened beams failed by the debonding of the FRCM. Additionally, a new bond strength model for FRCM considering the slippage between fabric and matrix was proposed, using a test database to predict the strengthening performance of the FRCM composite. The prediction of the proposed bond strength model agreed well with the debonding loads of the test database

Shear Strengthening Performance of Hybrid FRP-FRCM

The effectiveness of a hybrid fiber reinforced polymer- (FRP-) fabric reinforced cementitious matrix (FRCM) for shear strengthening was investigated though an experimental study. FRP materials of FRCM are usually fabricated in the form of a fabric to enhance the bond strength between the FRP material and the cementitious matrix. The hybrid FRP fabric used in this study consisted of carbon FRP (CFRP) and glass FRP (GFRP) in warp and weft directions, respectively. A total of 11 beams were fabricated and 8 beams among them were strengthened in shear with externally bonded hybrid FRP-FRCM. The number of plies, the bond types, and the spacing of the hybrid FRP fabric were considered as experimental variables. Additionally, a shear capacity model for a FRCM shear strengthened beam was proposed. The values predicted by the proposed model were compared with those by the ACI 549 code and test results. It was confirmed from the comparison that the proposed model predicted the shear strengthening performance of the hybrid FRP-FRCM more reliably than the ACI 549 code did

Applicability of a Combined DAF-MF Process to Respond to Changes in Reservoir Water Quality through a Two-Year Pilot Plant Operation

The optimal operating conditions of a combined dissolved air flotation (DAF)-microfiltration (MF) process to respond to changes in raw water quality were investigated by operating a pilot plant for two years. Without DAF pre-treatment (i.e., MF alone), MF operated stably with a transmembrane pressure (TMP) increase of 0.24 kPa/d when the turbidity of raw water was low and stable (max. 13.4 NTU). However, as the raw water quality deteriorated (max. 76.9 NTU), the rate of TMP increase reached 43.5 kPa/d. When DAF pre-treatment was applied (i.e., the combined DAF-MF process), the MF process operated somewhat stably; however, the rate of TMP increase was relatively high (i.e., 0.64 kPa/d). Residual coagulants and small flocs were not efficiently separated by the DAF process, exacerbating membrane fouling. Based on the particle count analysis of the DAF effluent, the DAF process was optimised based on the coagulant dose and hydraulic loading rate. After optimisation, the rate of TMP increase for the MF process stabilised at 0.17 kPa/d. This study demonstrates that the combined DAF-MF process responded well to substantial changes in raw water quality. In addition, it was suggested that the DAF process must be optimised to avoid excessive membrane fouling

Disruption of IL-18 signaling via engineered IL-18BP biologics alleviates experimental cholestatic liver disease

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis around intrahepatic and extrahepatic bile ducts leading to severe hepatic cirrhosis and high mortality. Although there is an urgent clinical unmet need for PSC, no effective medical therapy has been developed to delay the disease progression until today. IL-18 binding protein (IL-18BP) is well-known to be a natural negative feedback regulator for IL-18, and we have developed a recombinant long-acting IL-18BP referred to as APB-R3 as a therapeutic agent to treat IL-18-related inflammatory diseases. Here, we aimed to study whether disrupted IL-18 signaling by APB-R3 treatment can inhibit PSC injuries in the experimental DDC diet-induced PSC rodent model. First, we found that the amounts of free IL-18 are augmented under PSC condition with increased expression of biliary IL-18 receptors. Administration of APB-R3 effectively attenuated key diagnostic parameters of PSC such as plasma ALP and GGT levels as well as bile acids levels. We also observed that blockade of IL-18 suppressed ductular reactive and proliferative phenotypes of cholangiocytes. Additionally, APB-R3 significantly ameliorated DDC diet-induced periductal fibrosis and transcriptional expressions of pro-fibrotic marker genes. Enhanced senescence associated secretory phenotype (SASP) markers in cholestatic liver disease were diminished by APB-R3 treatment. Our findings clearly demonstrate that the administration of IL-18BP biologics, APB-R3, effectively alleviates DDC diet-induced biliary injuries in rodent PSC model, implying APB-R3 can be a promising therapeutic reagent which warrants clinical human trials as new therapeutic options