The Possibility of Precise Positioning in the Urban Area

A third civil frequency at 1176.45MHz will be added to the GPS system.QZSS (Quasi Zenith Satellite System) proposed by Japan will also have thenew signal. This new frequency and the advent of QZSS will greatly enhancethe accuracy, reliability and robustness of civilian GPS receivers. One of theseenhancements is that it is possible to determine the GPS phase ambiguitiesmore or less instantaneously. This performance will have a tremendous impacton navigation. In this paper, the possibility of precise positioning in the urbanarea is examined from a point of instantaneous ambiguity resolution.A typical QZSS constellation, a third civil frequency andambiguity_estimation for triple-frequency data is discussed. The simulator forprecise positioning includes multipath effect which has been developed is alsodiscussed. To reflect multipath effect, the following points are considered:Building reflection, building diffraction, ground reflection, antenna pattern, andcorrelator selection. It is confirmed that a third civil frequency could make itmuch easier to resolve ambiguities more quickly and the advent of QZSS helpsto increase visible satellites in the urban area (Asian area). Although nextgeneration satellite positioning system doesn’t provide perfect navigation,improved performance could be realized

Reliable Positioning and Journey Planning for Intelligent Transport Systems

Safety and reliability of intelligent transport systems applications require positioning accuracy at the sub-meter level with availability and integrity above 99%. At present, no single positioning sensor can meet these requirements in particular in the urban environment. Possible sensors that can be used for this task are first reviewed. Next, a suggested integrated system of low-cost real-time kinematic (RTK) GNSS, inertial measurement units (IMU) and vehicle odometer is discussed. To ensure positioning integrity, a method for fault detection in GNSS observations and computation of the protection levels (PL) that bound the position errors at a pre-set risk probability of the integrated sensors are presented. A case study is performed for demonstration. Moreover, to save energy, reduce pollution, and to improve the economy of the trip, proper journey planning is required. A new approach is introduced using 3D city models to predict the route with the best positioning integrity, availability and precision for route selection among different possible routes. The practical demonstration shows that effectiveness of this method. Finally, the potential of using the next generation SBAS for ITS applications was tested using kinematic tests carried out in various environments characterized by different levels of sky-visibility that may affect observations from GNSS

Verification of GNSS Multipath and Positioning in Urban Areas Using 3D maps

The reflections and diffractions of global navigation satellite system (GNSS) signals from buildings may produce large measurement errors. Detecting non-line-of-sight signals using 3D maps is a means to detect and exclude satellites with large measurement errors. However, the true position is typically needed for using 3D maps. In this study, we verify the assumption that an approximate user position can be used when using 3D maps. We found that the correct fixed position of real-time kinematic GNSS (RTK-GNSS) could be achieved when approximate positions for RTK-GNSS assisted by 3D maps were within 5-15 m from the true position

Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model

Objective: STAT3 plays a vital role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment and is reported to be a critical mediator of the oncogenic effects of EGFR mutations. STAT3 activation is mediated through JAK family kinases. We investigated the effect of the JAK1/2 inhibitor AZD1480 on lung tumors induced by an activating EGFR mutation. Materials and methods: Three EGFR tyrosine kinase inhibitor-resistant cell lines (RPC-9, PC-9/Van-R and PC-9/ER3) established from PC-9 harboring an EGFR exon19 deletion mutation were used. Growth inhibition was measured using an MIT assay. Effects of AZD1480 were also evaluated in the xenograft model and in the EGFR transgenic mice model. Protein expressions were assessed by immunoblotting and immunohistochemistry. Group differences were compared using Student's t-test. To evaluate the efficacy of AZD1480 on survival, AZD1480 or vehicle was administered orally from 7 weeks of age of the transgenic mice. Overall survival curves were calculated using the Kaplan-Meier method. Results: The sensitivities of resistant and parent cells to AZD1480 were similar in vitro. AZD1480 (30 or 50 mg/kg/day, per os) reduced angiogenesis and revealed significant tumor regression in a mouse xenograft model: Subsequently, the transgenic mice were treated with AZD1480 (30 mg/kg/day) or vehicle alone. The numbers of lung tumors (long axis exceeding 1 mm) in the AZD1480-treated group and control group were 0.37 +/- 0.18 and 2.25 +/- 0.53 (p <0.001), respectively. AZD1480 treatment suppressed pSTAT3, pJAK1, pJAK2 and angiogenesis. The median survival time in the AZD1480-treated group (217 days) was significantly greater than that in the control group (106 days) (log-rank test, p <0.0001). Conclusion: AZD1480 may be effective against lung tumors driven by an activating EGER mutation

Afatinib Prolongs Survival Compared with Gefitinib in an Epidermal Growth Factor Receptor-Driven Lung Cancer Model

An irreversible ErbB family blocker is expected to inhibit tumors with activating epidermal growth factor receptor (EGFR) mutations more strongly than reversible EGFR tyrosine kinase inhibitors and to overcome acquired resistance to the T790M secondary mutation. Eleven-week-old transgenic mice with Egfr exon 19 deletion mutation were treated with afatinib, gefitinib, or vehicle for 4 weeks. All mice were sacrificed at 15 weeks of age, and the number of superficial left lung tumors with a long axis exceeding 1 mm was counted. The afatinib-treated group had significantly fewer tumors than the vehicle group (P < 0.01) and tended to have fewer tumors than the gefitinib-treated group (P = 0.06). Pathologically, gefitinib-treated mice had clearer, more nodular tumors than afatinib-treated mice. Immunoblotting showed that afatinib suppressed not only pEGFR but also pHER2, and induced apoptosis for longer periods than gefitinib. Subsequently, when each drug was administered 5 days per week until death, afatinib significantly enhanced mouse survival compared with gefitinib (median survival time: 456 days vs. 376.5 days; log-rank test, P < 0.01). Finally, the combination of afatinib with bevacizumab was found to be superior to either drug alone in exon 19 deletion/T790M and L858R/T790M xenograft tumors. Overall, afatinib was more potent than gefitinib in tumors harboring an exon 19 deletion mutation, and the combination of afatinib with bevacizumab efficiently suppressed tumors harboring the T790M secondary mutation

Maintaining real-time precise point positioning during outages of orbit and clock corrections

The precise point positioning (PPP) is a popular positioning technique that is dependent on the use of precise orbits and clock corrections. One serious problem for real-time PPP applications such as natural hazard early warning systems and hydrographic surveying is when a sudden communication break takes place resulting in a discontinuity in receiving these orbit and clock corrections for a period that may extend from a few minutes to hours. A method is presented to maintain real-time PPP with 3D accuracy less than a decimeter when such a break takes place. We focus on the open-access International GNSS Service (IGS) real-time service (RTS) products and propose predicting the precise orbit and clock corrections as time series. For a short corrections outage of a few minutes, we predict the IGS-RTS orbits using a high-order polynomial, and for longer outages up to 3 h, the most recent IGS ultra-rapid orbits are used. The IGS-RTS clock corrections are predicted using a second-order polynomial and sinusoidal terms. The model parameters are estimated sequentially using a sliding time window such that they are available when needed. The prediction model of the clock correction is built based on the analysis of their properties, including their temporal behavior and stability. Evaluation of the proposed method in static and kinematic testing shows that positioning precision of less than 10 cm can be maintained for up to 2 h after the break. When PPP re-initialization is needed during the break, the solution convergence time increases; however, positioning precision remains less than a decimeter after convergence

Subpopulation of small-cell lung cancer cells expressing CD133 and CD87 show resistance to chemotherapy

Tumors are presumed to contain a small population of cancer stem cells (CSCs) that initiate tumor growth and promote tumor spreading. Multidrug resistance in CSCs is thought to allow the tumor to evade conventional therapy. This study focused on expression of CD133 and CD87 because CD133 is a putative marker of CSCs in some cancers including lung, and CD87 is associated with a stem-cell-like property in small-cell lung cancer (SCLC). Six SCLC cell lines were used. The expression levels of CD133 and CD87 were analyzed by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry. CD133+/- and CD87+/- cells were isolated by flow cytometry. The drug sensitivities were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Non-obese diabetic/severe combined immunodeficiency mice were used for the tumor formation assay. SBC-7 cells showed the highest expression levels of both CD133 and CD87 among the cell lines. CD133-/CD87-, CD133+/CD87-, and CD133-/CD87+ cells were isolated from SBC-7 cells; however, CD133+/CD87+ cells could not be obtained. Both CD133+/CD87- and CD133-/CD87+ subpopulations showed a higher resistance to etoposide and paclitaxel and greater re-populating ability than the CD133-/CD87- subpopulation. CD133+/CD87- cells contained more G0 quiescent cells than CD133-/CD87- cells. By contrast, CD133-/CD87- cells showed the highest tumorigenic potential. In conclusion, both CD133 and CD87 proved to be inadequate markers for CSCs; however, they might be beneficial for predicting resistance to chemotherapy. (Cancer Sci 2013; 104: 7884

Identification of targetable kinases in idiopathic pulmonary fibrosis

Background Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). Methods Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). Results Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. Conclusions We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF

Effects of (−)-epigallocatechin-3-gallate on EGFR- or Fusion Gene-driven Lung Cancer Cells

(−)-Epigallocatechin-3-gallate (EGCG) has been shown to bind to several receptors including epidermal growth factor receptor (EGFR). EGFR tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK) inhibitors are effective for non-small cell lung cancers harboring activating EGFR mutations and ALK or c-ros oncogene 1 (ROS1) fusion genes, respectively. We investigated the effects of EGCG on EGFR- or fusion gene-driven lung cancer cells such as PC-9, RPC-9, H1975, H2228 and HCC78. The five cell lines had similar sensitivity to EGCG. Phosphorylated (p)EGFR, pAkt and pErk in PC-9, RPC-9 and H1975 cells were suppressed by EGCG (50 or 100 μM). EGCG also inhibited pALK in H2228, pROS1 in HCC78, and pErk and pAkt in both cell lines. All the xenograft tumors established using the 5 cell lines in EGCG-treated groups were significantly smaller than the tumors in the vehicle-treated groups. The numbers of tumor blood vessels of xenograft tissues in EGCG-treated mice were significantly lower than those in vehicle-treated mice. In conclusion, EGCG may be effective for EGFR-driven lung tumors irrespective of the presence of T790M, and for ALK or ROS1 fusion gene-driven lung tumors