ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside

Tyrosine Kinase Inhibitors (TKI) have significantly changed the landscape of current cancer therapy. Understanding of mechanisms of aberrant TK signaling and strategies to inhibit TKs in cancer, further promote the development of novel agents

Inhibition of Serine Protease Activity Protects Against High Fat Diet-Induced Inflammation and Insulin Resistance.

Recent evidence suggests that enhanced protease-mediated inflammation may promote insulin resistance and result in diabetes. This study tested the hypothesis that serine protease plays a pivotal role in type 2 diabetes, and inhibition of serine protease activity prevents hyperglycemia in diabetic animals by modulating insulin signaling pathway. We conducted a single-center, cross-sectional study with 30 healthy controls and 57 patients with type 2 diabetes to compare plasma protease activities and inflammation marker between groups. Correlations of plasma total and serine protease activities with variables were calculated. In an in-vivo study, LDLR-/- mice were divided into normal chow diet, high-fat diet (HFD), and HFD with selective serine protease inhibition groups to examine the differences of obesity, blood glucose level, insulin resistance and serine protease activity among groups. Compared with controls, diabetic patients had significantly increased plasma total protease, serine protease activities, and also elevated inflammatory cytokines. Plasma serine protease activity was positively correlated with body mass index, hemoglobin A1c, homeostasis model assessment-insulin resistance index (HOMA-IR), tumor necrosis factor-α, and negatively with adiponectin concentration. In the animal study, administration of HFD progressively increased body weight, fasting glucose level, HOMA-IR, and upregulated serine protease activity. Furthermore, in-vivo serine protease inhibition significantly suppressed systemic inflammation, reduced fasting glucose level, and improved insulin resistance, and these effects probably mediated by modulating insulin receptor and cytokine expression in visceral adipose tissue. Our findings support the serine protease may play an important role in type 2 diabetes and suggest a rationale for a therapeutic strategy targeting serine protease for clinical prevention of type 2 diabetes

Arbitrage, Covered Interest Parity and Cointegration Analysis on the NTD/USD Forex Market Revisited

This study applies interest parity theory including Covered Interest Parity (CIP) to examine the 30-, 60-.90-, and 180-day maturities for the NTD/USD foreign exchange (FX) market. In the empirical unit root tests, we find that NTD/USD forward premium and interest rate spread present I(0) property. Empirical results are provided that interest rate differential appears stationary component; imply the stable relationship between Taiwan and USA on monetary policy. Using Taylor (1989)'s covered interest arbitrage model, the empirical results exhibit the absence of excess profit opportunities on New Taiwan Dollar (NTD) or US Dollar (USD) returns. Additionally, theoretical innovation approach of the cost-of-carry model is considered to evaluate the arbitrage opportunities in FX study. Accordingly, the covered interest parity condition generally continue to hold that almost zero-arbitrage results support FX market efficiency although the Federal Reserve implemented several rounds of quantitative easing after the peak of the 2008 financial crisis. Ultimately, Taiwanese FX market emerges to have been little affected by the increased crisis risks during the turbulent times because of the its limited development and market integration. Keywords: Covered Interest Parity, Market Integration, Granger Causality Tests, Cost-of-Carry model JEL Classifications: G1, G12, F3

Ontology-based Fuzzy Markup Language Agent for Student and Robot Co-Learning

An intelligent robot agent based on domain ontology, machine learning mechanism, and Fuzzy Markup Language (FML) for students and robot co-learning is presented in this paper. The machine-human co-learning model is established to help various students learn the mathematical concepts based on their learning ability and performance. Meanwhile, the robot acts as a teacher's assistant to co-learn with children in the class. The FML-based knowledge base and rule base are embedded in the robot so that the teachers can get feedback from the robot on whether students make progress or not. Next, we inferred students' learning performance based on learning content's difficulty and students' ability, concentration level, as well as teamwork sprit in the class. Experimental results show that learning with the robot is helpful for disadvantaged and below-basic children. Moreover, the accuracy of the intelligent FML-based agent for student learning is increased after machine learning mechanism.Comment: This paper is submitted to IEEE WCCI 2018 Conference for revie

Metastatic Biomarkers in Synovial Sarcoma

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma (STS) that typically occurs in the extremities near a joint. Metastatic disease is common and usually occurs in the lungs and lymph nodes. Surgical management is the mainstay of treatment with chemotherapy and radiation typically used as adjuvant treatment. Although chemotherapy has a positive impact on survival, the prognosis is poor if metastatic disease occurs. The biology of sarcoma invasion and metastasis remain poorly understood. Chromosomal translocation with fusion of the SYT and SSX genes has been described and is currently used as a diagnostic marker, although the full impact of the fusion is unknown. Multiple biomarkers have been found to be associated with SS and are currently under investigation regarding their pathways and mechanisms of action. Further research is needed in order to develop better diagnostic screening tools and understanding of tumor behavior. Development of targeted therapies that reduce metastatic events in SS, would dramatically improve patient prognosis

Formation of amyloid fibrils from β-amylase

AbstractFibril formation has been considered a significant feature of amyloid proteins. However, it has been proposed that fibril formation is a common property of many proteins under appropriate conditions. We studied the fibril formation of β-amylase, a non-amyloid protein rich in α-helical structure, because the secondary structure of β-amylase is similar to that of prions. With the conditions for the fibril formation of prions, β-amylase proteins were converted into amyloid fibrils. The features of β-amylase proteins and fibrils are compared to prion proteins and fibrils. Furthermore, the cause of neurotoxicity in amyloid diseases is discussed.Structured summary of protein interactionsBeta-Amylase and Beta-Amylase bind by fluorescence technology (View Interaction: 1, 2) MoPrP and MoPrP bind by circular dichroism (View interaction) MoPrP and MoPrP bind by transmission electron microscopy (View interaction) Beta-Amylase and Beta-Amylase bind by circular dichroism (View interaction) MoPrP and MoPrP bind by fluorescence technology (View Interaction: 1, 2) Beta-Amylase and Beta-Amylase bind by transmission electron microscopy (View interaction

High level of miR-196b at newly diagnosed pediatric acute myeloid leukemia predicts a poor outcome

Differential expression of microRNAs (miRNAs) has been implicated in leukemogenesis. We investigate the ex- pression pattern of miR-196b. Using quantitative real-time PCR (qRT-PCR), we detected the expression of miR- 196b and its correlated genes (SMC1A/MLH1) in initial pediatric AML. A significant association was observed between overexpression of miR-196b and inferior overall survival of pediatric AML (Log Rank P<0.0001). AML M4/5 subtype, high white blood cell (WBC) count at presentation, MLL rearrangement, or FLT3-ITD mutation at diagnosis and non-remission group after the first induction chemotherapy possessed higher miR-196b expression. Furthermore, a positive relationship was found between the expression of miR-196b and SMC1A/MLH1 (Spear- man’s r=0.37 and 0.44, P=0.001 and <0.0001, respectively). Taken together, these findings suggest that differen- tially high expression of miR-196b in diagnostic marrow samples of pediatric AML is associated with unfavorable outcome, and miR-196b potentially can be a novel biomarker for the diagnosis, prognosis and treatment in pediatric AML

Experimental Investigation on Thermoelectric Chiller Driven by Solar Cell

This paper presents experimental explorations on cooling performance of thermoelectric chillers being driven by solar cells, as well as comparison results to the performance being driven by fixed direct current. Solar energy is clear and limitless and can be collected by solar cells. We use solar cells to drive thermoelectric chillers, where the cold side is connected to the water tank. It is found that 250 mL of water can be cooled from 18.5°C to 13°C, where the corresponding coefficient of performance (COP) is changed between 0.55 and 1.05, when solar insolation is changed between 450 W/m2 and 1000 W/m2. The experimental results demonstrate that the thermoelectric chiller driven by solar cell is feasible and effective for energy saving issues

Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy