Seamless SIP multimedia session transfer on IPv6 network via device switching

Due to significant popularity of Location-based Services and Multimedia communication over mobile devices, there are many researches has been conducted to extend the features of location tracking and make it cost-effective to users. It becomes necessary for the users to have seamless communication with automated switching of software applications. This paper focuses on the performance of indoor location tracking system on IPv6 Network Island with multiple real time applications that has location assisted transfer for mobile users. RSSI (Received Signal Strength Indicator) mechanism has been used to locate the moving nodes. The developed location tracking server is having dynamic and centralized MySQL database management system. SIP (Session Initial Protocols) user agent has been used to deploy intercommunicating of multimedia data for instance; video and audio conference, text messaging among the moving nodes and user can transfer the seamlessly transfer the session to their nearest mobile node which will be determined by the Location Server. This paper is going to discuss about the seamless performance of SIP during the session transference. The developed project is cost-effective and precisely conducive for the industries or any indoor organization. The prototype of the project has been successfully developed and has been tested as well. The results show the seamless connectivity of the multimedia application during device switching

A novel intraperitoneal metastatic xenograft mouse model for survival outcome assessment of esophageal adenocarcinoma

Esophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States. The 5-year survival rate of EAC is below 20% and most patients present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Improvement of EAC patient outcome requires well-characterized animal models in which to evaluate novel therapeutics. In this study we aimed to establish a peritoneal dissemination xenograft mouse model of EAC that would support survival outcome analyses. To find the best candidate cell line from 7 human EAC cell lines of different origin named ESO26, OE33, ESO51, SK-GT-2, OE19, OACM5.1C and Flo-1 were injected intraperitoneally/subcutaneously into SCID mice. The peritoneal/xenograft tumor formation and mouse survival were compared among different groups. All cell lines injected subcutaneously formed tumors within 3 months at variable rates. All cell lines except OACM5.1C formed intraperitoneal tumors within 3 months at variable rates. Median animal survival with peritoneal dissemination was 108 days for ESO26 cells (5X106), 65 days for OE33 cells (5X106), 88 days for ESO51 cells (5X106), 76 days for SK-GT-2 cells (5X106), 55 days for OE19 cells (5X106), 45 days for OE19 cells (10X106) and 82 days for Flo-1 cells (5X106). Interestingly, only in the OE19 model all mice (7/7 for 5X106 and 5/5 for10X106) developed bloody ascites with liver metastasis after intraperitoneal injection. The median survival time of these animals was the shortest (45 days for 10X106 cells). In addition, median survival was significantly increased after paclitaxel treatment compared with the control group (57 days versus 45 days, p = 0.0034) along with a significant decrease of the relative subcutaneous tumor volume (p = 0.00011). Thus peritoneal dissemination mouse xenograft model for survival outcome assessment after intraperitoneal injection of OE19 cells will be very useful for the evaluation of cancer therapeutics

Therapeutic targeting of hypoxia and hypoxia inducible factor 1 with acriflavine in experimental esophageal adenocarcinoma

Background: Hypoxia or insufficient tissue oxygenation contributes to cancer aggressiveness and poor clinical prognosis. Typically, cancer cell lines are used in two-dimensional (2D) cultures for screening of anticancer agents, and they do not represent the hypoxic tumor microenvironment. In this study, we established a novel three dimensional (3D) spheroid co-culture model of esophageal adenocarcinoma (EAC). We then observed treatment response of chemo and hypoxia-targeting therapies in 2D, 3D and in vivo models of experimental EAC. Methods: EAC 3D spheroids were generated from co-culturing human EAC and fibroblast cell lines. NanoCulture® plates and dishes were used for 3D spheroid cultures. Hypoxic status was detected by adding hypoxia probe LOX-1 and fluorescent microscopy. Paclitaxel (PT), carboplatin (CP) and nanoparticle albumin-bound paclitaxel (NPT) were used as chemotherapeutic agents, whereas acriflavine was used as hypoxia-targeting agent. In vitro cell growth was detected by WST-1 assay, in vivo tumor growth was detected by measuring subcutaneous xenografts, apoptosis was detected by cleaved caspase 3/PARP expressions, and hypoxia-targeting was detected by HIF-1α expression. Results: 3D culture was more resistant to antiproliferative effect of chemotherapeutic agents PT, CP, NPT over 2D monolayer culture. Contrary to that, hypoxia-targeting agent acriflavine showed stronger antiproliferative effects in 3D culture than in 2D culture. We observed strong expression of hypoxia inducible factor-1α (HIF-1α) in 3D culture with no expression of HIF-1α in 2D culture, and acriflavine treatment completely abolished the HIF-1α expression in 3D culture. We also observed hypoxia inside the 3D culture spheroids, but not in cells grown in 2D culture. In addition, acriflavine showed significant in vivo antitumor efficacy both as monotherapy and in combination with NPT. Conclusion: Thus 3D cultures may be better than 2D cultures in simulating the important in vivo tumor characteristic of hypoxia, and HIF-targeting therapy acriflavine could be a novel treatment strategy for EAC.&nbsp

Targeting the Warburg Effect to Overcome Lapatinib Resistance in Esophageal Adenocarcinoma

Background: Esophageal adenocarcinoma (EAC) is known to overexpress HER2. Lapatinib, a dual tyrosine kinase inhibitor blocking HER1 and HER2 pathways fails to improve patient survival. The molecular mechanisms of this lapatinib resistance remain largely unclear. Therefore, we explored the role of the glycolytic enzyme pyruvate kinase M2 (PKM2), a key regulator of the Warburg effect, in the lapatinib resistance mechanism of EAC cells. Methods: First we established a lapatinib-resistant OE19 (LPR-OE19) cell line from OE19 EAC cells and characterized it. We then investigated the comparative cell growth inhibition and apoptotic effects of the HER2 inhibitor lapatinib and the PKM2 inhibitor shikonin, either alone or in combinations, with and without knockdown of PKM2 by siRNAs. In vitro cell growth was detected by WST-1 assay, protein expressions were detected by western blot analysis and ActivSignal assay, gene expressions were detected by qRT-PCR, cell migration capability was detected by wound scratch assay, and lactate production was detected by a lactate assay kit. To identify whether PKM2 interacts with HSP40 protein, co-immunofluorescence and immunofluorescence microscopy were used to detect their sub-cellular localization in LPR-OE19 cells. Results: Lapatinib resistant LPR-OE19 cells showed downregulation of HSP40, both at protein and mRNA levels, whereas it showed upregulation of PKM2 only at the protein level. LPR-OE19 cells showed significantly reduced sensitivity to lapatinib induced cell growth inhibition, apoptosis, and decreased cell migration compared to parent OE19 cells. Interestingly, augmented cell growth inhibition, apoptosis, and decreased cell migration were observed in LPR-OE19 cells compared to parent OE19 cells when lapatinib was combined with shikonin. More interestingly, knockdown of PKM2 in LPR-OE19 cells abolished the reduced sensitivity of lapatinib induced cell growth inhibition and also abolished the augmented cell growth inhibition response when lapatinib and shikonin were combined. Moreover, LPR-OE19 cells showed enhanced lactate production compared to parent OE19 cells, while PKM2 knockdown in LPR-OE19 cells caused decreased lactate production. Interestingly, PKM2 and HSP40 co-localize with each other in the cell nucleus suggesting that PKM2 binds to the molecular chaperone HSP40. Conclusions: These data suggest that combination therapy with HER2 inhibitor lapatinib and glycolytic inhibitor shikonin could be a novel treatment strategy for specific EAC

Targeting the Warburg effect to overcome lapatinib resistance in esophageal adenocarcinoma

Background: Esophageal adenocarcinoma (EAC) overexpresses HER2. Lapatinib, a dual tyrosine kinase inhibitor blocking HER1 and HER2 pathways failed to improve patient survival. Molecular mechanisms of this lapatinib resistance are still unclear. We therefore explored the role of glycolytic enzyme pyruvate kinase M2 (PKM2), a key regulator of the Warburg effect in the lapatinib resistance mechanism of EAC cells. Methods: First we established a lapatinibresistant OE19 (LPR-OE19) cell line from OE19 EAC cells. We then investigated the comparative cell growth inhibition, apoptotic and lactate production effects of HER2 inhibitor lapatinib and PKM2 inhibitor shikonin either alone or in combinations, both in OE19 and LPR-OE19 cells with and without knockdown of PKM2 and HSP40 by siRNAs. Results: Lapatinib resistant LPR-OE19 cells showed downregulation of HSP40 both at protein and mRNA levels, but showed upregulation of PKM2 only at the protein level. LPR-OE19 cells showed significantly reduced sensitivity to lapatinib induced cell growth inhibition, apoptosis and decreased cell migration compared to parent OE19 cells. Interestingly, augmented cell growth inhibition, apoptosis and decreased cell migration were observed in LPR-OE19 cells compared to parent OE19 cells when lapatinib was combined with shikonin. Knockdown of PKM2 in LPR-OE19 cells abolished the reduced sensitivity of lapatinib induced cell growth inhibition, and also abolished augmented cell growth inhibition response when lapatinib and shikonin were combined. Contrary to that, knockdown of HSP40 in OE19 cells enhanced PKM2 expression leading to significantly reduced sensitivity to lapatinib induced growth inhibition with augmented growth inhibition when lapatinib and shikonin were combined. Moreover, LPR-OE19 cells showed enhanced lactate production compared to parent OE19. Interestingly, PKM2 and HSP40 co-localize with each other in the cell nucleus suggesting that PKM2 binds to molecular chaperone HSP40. Conclusions: These data suggest that targeting HSP40PKM2 interaction could be an innovative therapeutic approach to overcome lapatinib resistance in EAC

TRIM31: A Protein With an Oncogenic Role in Esophageal Adenocarcinoma

Background: Esophageal adenocarcinoma (EAC) is a major cancer in the United States with increasing incidence. It is an aggressive cancer involving columnar-type cells different from the normal esophageal (NE) squamous cells. This metaplasia often involves an intermediary morphology called Barrett’s esophagus (BE), which occurs from repeated acid exposure of the esophagus from gastroesophageal reflux disease (GERD). GERD leading to BE is a common pre-occurrence in EAC patients, but the mechanism remains obscure. To explore the mechanism and its components, we compared gene expression in BE and EAC cells with normal cells and discovered the overexpression of TRIM31 in the pathogenic cells. Although previous studies have shown oncogenic potential of TRIM31 in some cancers, its role in EAC is yet to be understood. Methods: RNA sequencing and transcriptomic profiling were performed on human NE, BE, and EAC epithelial tissue samples. TRIM31 expression in NE cell line (Het-1A) and EAC cell lines (OE19, Flo-1, OE33, SK-GT-2, and OACM5.1C) were identified by Western blot. The Het-1A cell line, after exposure to acidic pH and bile acid, was assessed for variable TRIM31 expression. Cell viability analysis of NE and EAC cell lines after exposure to acidic pH and bile acids was observed by WST-1 assay. Results: RNA sequencing, transcriptomic profiling, and western blot revealed overexpression of TRIM31 in BE and EAC epithelium. Exposure of Het-1A cells to bile acids in acidic pH changed the cell morphology with enhanced expression of TRIM31. WST-1 revealed that EAC cells were more resistant to acidic pH and bile acid exposure. Conclusions and potential impact: Our data suggests that increased TRIM31 expression correlates with esophageal epithelium resistance when exposed to bile acids and acidic pH. Consequently, TRIM31 may be a key player in the metaplasia of GERD-induced EAC development and may be an innovative therapeutic target and marker for EAC

Targeted therapy in esophageal cancer

Esophageal cancer consists of two distinct histological types, esophageal squamous cell-carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Esophageal carcinoma is a grave malignancy with regards to prognosis and mortality. ESCC remains the dominant histological type of esophageal cancer worldwide, with about 90 percent of all cases worldwide. However, EAC is now much more common in the United States and the Western World, and represents one of the fastest growing cancers there. Despite significant progress in multimodality treatment options, the overall prognosis remains poor, and 5-year survival rates for all-comers are still below 20 percent. Although esophageal cancer initially responds well to systemic therapy, most patients recur and eventually die from their disease. Therefore, new treatment options are urgently needed. The combination of traditional systemic therapy with new biologicals and/or targeted agents is one of these new treatment options. Some of these agents are already approved, while others are currently undergoing clinical trials. These targeted therapies have emerged as an important tool for the treatment of many different cancer types, including esophageal cancer. Herein, we review the recent literature and ongoing clinical trials in esophageal cancer targeted therapies, and discuss the different targeted pathways. Currently, most esophageal cancer patients are still treated with a combination of chemotherapies like taxanes (paclitaxel, docetaxel), platinums (carboplatin, cisplatin), anthracyclines (doxorubicin, epirubicin) or pyrimidine analogs (5-fluorouracil). Future treatment strategies should be based on the molecular features of each patient’s individual tumor, and should include biologicals/targeted agents tailored to these specific findings

Formulation of hybrid 3D image segmentation algorithm based partial differential equation

Segmentation is an important tool for analysis and understanding of most images encountered in science and engineering. One of the best segmentation methods that can perform 3D segmentation is the level-set method which has its mathematical foundation in partial differential equation (PDE). Owing to its complex nature, it exhibits a level of unacceptable sluggishness on implementation hence a need to hasten up the process by hybridizing it with a faster region-based segmentation method which is inherently a logical approach to segmentation pivoted on thresholding but not as good in segmentation as the former. This work presents a mathematical hybrid of the two methods that is hoped to produce a better segmentation result

Fiber based practical QKD system

A method to estimate parameters of the decoy state method based on one decoy state protocol for both BB84 and SARG04 has been presented. This method has given different lower bound of the fraction of single-photon counts (y1), the fraction of two-photon counts (y2), the upper bound QBER of single -photon pulses (e1), the upper bound QBER of two-photon pulses (e2), and the lower bound of key generation rate for both BB84 and SARG04. The fiber based QKD systems also have been simulated using the proposed method for BB84 and SARG04. The numerical simulation has shown that the fiber based QKD systems using the proposed method for BB84 are able to achieve both a higher secret key rate and greater secure distance than that of SARG04

Performance Analysis of Location Tracking System for Multiple Levels

Location tracking in an indoor environment is possible with various techniques based on mechanical, acoustical, ultrasonic, optical, infrared, inertial or radio signal measurements. Global Positioning System (GPS) is one of famous tracking system as a feasible and effective outdoor tracking system. Nowadays, location tracking information and visualization of 3D graphics either in outdoor or indoor environment had been presented as one of research issues. Traditional tracking system with 2D-image standard presents only few and dull information to users. In addition 2D localization only supports one level platform (i.e. horizontally). Thus, the 3D location tracking system had been developed to support multilevel network. In this paper we developed a real-time indoor tracking system with 3D locations which are able to provide more useful location tracking information to user using radio signals. This system had been developed for multiple levels building.  For this project we used the existing Wireless Local Area Network (WLANs) attached devices called the access point (AP) to the edge of the wired network. Nodes communicate with the AP using a wireless network adapter similar in function to a traditional Ethernet adapter. The signal from the nodes or the APs that using WLAN can be read or calculated using Received Signal Strength Indication (RSSI) due to its low-cost solutions. Besides that, the system operates in the IPv6 network to provide more reliable system. The localization algorithm use is triangulation method which is suitable for indoor environment. In this paper we present the results of the 3D location tracking for one level as well as two level building. The results are comparing in terms of experimental and calculated