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Sample records for advanced nsclc methods

  1. Clinicopathologic Features of Advanced Squamous NSCLC.

    PubMed

    Socinski, Mark A; Obasaju, Coleman; Gandara, David; Hirsch, Fred R; Bonomi, Philip; Bunn, Paul; Kim, Edward S; Langer, Corey J; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Spigel, David R; Stinchcombe, Thomas E; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-09-01

    Lung cancer remains the leading cause of cancer-related death worldwide. NSCLC accounts for more than 85% of all lung cancers, and the prognosis for advanced-stage disease is typically poor. In recent years, the importance of histologic subtypes of NSCLC has been recognized, and the distinction between squamous and other NSCLC histologic subtypes is now critical to patient management. Squamous cell lung cancer (sqCLC) represents approximately 25% to 30% of NSCLC. The prognosis for patients with advanced NSCLC is poorer for those with sqCLC than for those with adenocarcinoma. This is partly due to a number of clinical characteristics that distinguish sqCLC from other NSCLC histologic subtypes, such as smoking history, comorbid diseases, age, and molecular profile. Together, these factors make sqCLC an especially challenging disease to manage. Herein, we review some of the key clinicopathologic features of sqCLC. Understanding these features to optimally address many of the unique therapeutic challenges of this disease is likely to be central to ultimately improving outcomes for patients with squamous NSCLC. PMID:27296106

  2. RAGE Genetic Polymorphisms Are Associated with Risk, Chemotherapy Response and Prognosis in Patients with Advanced NSCLC

    PubMed Central

    Hua, Feng; Wang, Bin; Mao, Wei; Feng, Xueren

    2012-01-01

    Aim To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE) and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC). Method This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, −429T/C, −374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. Results All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. Conclusion The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC. PMID:23071492

  3. Percutaneous CT-guided microwave ablation as maintenance after first-line treatment for patients with advanced NSCLC

    PubMed Central

    Ni, Xiang; Han, Jun-Qing; Ye, Xin; Wei, Zhi-Gang

    2015-01-01

    Background Systemic therapy is recommended for advanced non-small-cell lung cancer (NSCLC). However, conventional first-line treatment has generated a plateau in response rate of 25% to 35%. Few studies have shown patients benefit from microwave ablation (MWA) in combination with radiotherapy and chemotherapy. This study aims to evaluate safety and efficacy of percutaneous computed tomography-guided MWA as maintenance after first-line treatment for patients with advanced NSCLC. Methods Patients with histologically verified NSCLC stage IIIB or IV between January 2010 and March 2014 were involved. After completion of first-line treatment with partial response or stable disease, 35 patients with 39 tumors underwent 39 MWA procedures. Complications, progression-free survival (PFS), overall survival (OS), and correlated predictors were analyzed. Results During a median follow-up of 17.7 months and 10.8 months after initial MWA, local efficacy was 87.2%, median MWA-related local control time was 10.6 months, and tumor size was the only predictor (P=0.002). Median MWA-related PFS, MWA-related OS, PFS, and OS were 5.4, 10.6, 11.8 and 17.7 months, respectively. Local efficacy was significantly correlated with MWA-related PFS (P=0.003), MWA-related OS (P=0.000), and OS (P=0.001). There were no procedure-specific deaths. Total incidence of major complications was 12.8%, including pneumothorax resolved by closed pleural drainage and pneumonia controlled by antibiotics in a short time. Conclusion This study concluded two points, including: 1) patients benefited from MWA as maintenance both in local control and survival; 2) as maintenance MWA was superior to conventional maintenance therapy with improved survival and well-tolerated complications. Therefore, MWA was a safe and effective maintenance after first-line treatment in patients with advanced NSCLC. PMID:26604789

  4. EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10)

    PubMed Central

    Vázquez, Sergio; Casal, Joaquín; Afonso Afonso, Francisco Javier; Fírvida, José Luis; Santomé, Lucía; Barón, Francisco; Lázaro, Martín; Pena, Carolina; Amenedo, Margarita; Abdulkader, Ihab; González-Arenas, Carmen; Fachal, Laura; Vega, Ana

    2016-01-01

    Purpose This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. Patients and methods All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. Results Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8–15.3) months and 17.8 (95% confidence interval: 13.9–21.6) months, respectively, in patients carrying sensitizing mutations. Conclusion The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC. PMID:26893581

  5. Pilot study of radiofrequency hyperthermia in combination with gefitinib in gefitinib‐effective patients with advanced NSCLC

    PubMed Central

    Qin, Yijia; Sun, Yu; Liu, Yongmei; Luo, Yiqiao

    2016-01-01

    Background Non‐small‐cell lung cancer (NSCLC) is the leading cause of death from cancer in China. Gefitinib is effective for patients with positive epidermal growth factor receptor gene mutation; however, acquired drug resistance counteracts the duration response. Hyperthermia is widely clinically applied in the treatment of solid tumors. This pilot study was designed to evaluate the feasibility of the combination of gefitinib and hyperthermia. Methods Patients newly diagnosed with advanced NSCLC were screened. Eleven patients who responded to first‐line gefitinib treatment were enrolled in the study. Along with 250 mg gefitinib daily, local radiofrequency hyperthermia was administered twice a week until tumor progression was observed. The serum, heat shock protein (HSP)70, was also frequently detected during the course. Results The most common toxicity included skin rash (81.8%) and abnormal liver function (45.5%) when treated with gefitinib, and fatty scleroma (36.4%) was observed when combined with hyperthermia. Grade 3 side effects (skin rash) occurred in only one patient. Median progression‐free survival was 22 months (95% confidence interval [CI]: 12.95–31.05 months) and median overall survival was 26 months (95% CI: 22.81–29.19 months). Serum HSP70 concentration increased and maintained a significantly high level compared with the baseline before hyperthermia administration. Conclusions The novel therapy of gefitinib combined with radiofrequency hyperthermia is safe and effective for advanced NSCLC patients. Whether an improvement in therapeutic efficacy is associated with the elevation of serum HSP70 concentration requires further study.

  6. Prediction models for platinum-based chemotherapy response and toxicity in advanced NSCLC patients.

    PubMed

    Yin, Ji-Ye; Li, Xi; Li, Xiang-Ping; Xiao, Ling; Zheng, Wei; Chen, Juan; Mao, Chen-Xue; Fang, Chao; Cui, Jia-Jia; Guo, Cheng-Xian; Zhang, Wei; Gao, Yang; Zhang, Chun-Fang; Chen, Zi-Hua; Zhou, Hui; Zhou, Hong-Hao; Liu, Zhao-Qian

    2016-07-10

    In this study, we aimed to establish a platinum-based chemotherapy response and toxicity prediction model in advanced non-small cell lung cancer (NSCLC) patients. 416 single nucleotide polymorphisms (SNPs) in 185 genes were genotyped, and their association with drug response and toxicity were estimated using logistic regression. Nine data mining techniques were employed to establish the prediction model; the sensitivity, specificity, overall accuracy and receiver operating characteristic (ROC) curve were used to assess the models' performance. Finally, selected models were validated in an independent cohort. The models established by naïve Bayesian algorithm had the best performance. The response prediction model achieved a sensitivity of 0.90 and a specificity of 0.47 with the ROC area under curve (AUC) of 0.80. The overall toxicity prediction model achieved a sensitivity of 0.86 and a specificity of 0.46 with the ROC AUC of 0.73. The hematological toxicity prediction model achieved a sensitivity of 0.89 and a specificity of 0.39 with the ROC AUC of 0.76. The gastrointestinal toxicity prediction model achieved a sensitivity of 0.93 and a specificity of 0.35 with the ROC AUC of 0.80. In conclusion, we provided platinum-based chemotherapy response and toxicity prediction models for advanced NSCLC patients. PMID:27126360

  7. High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib.

    PubMed

    Fiala, Ondrej; Pesek, Milos; Finek, Jindrich; Topolcan, Ondrej; Racek, Jaroslav; Minarik, Marek; Benesova, Lucie; Bortlicek, Zbynek; Poprach, Alexandr; Buchler, Tomas

    2015-12-01

    Erlotinib is a low molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally advanced or metastatic-stage non-small cell lung cancer (NSCLC). Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low. Aside from activating EGFR mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib. We retrospectively analyzed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using an immunoturbidimetric method. High baseline levels of CRP (≥10 mg/l) were measured in 387 (65 %) patients, and normal levels (<10 mg/l) were measured in 208 (35 %) patients. The median progression-free survival (PFS) and overall survival (OS) for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p < 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that CRP was significantly associated with PFS and also with OS (hazard ratio (HR) = 1.57, p < 0.001, and HR = 1.63, p < 0.001, respectively). In conclusion, the results of the conducted retrospective study suggest that high baseline level of CRP was independently associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. CRP is a commonly used biomarker which is simple and easy to detect, and thus, it is feasible for the use in the routine clinical practice. PMID:26088452

  8. A serum microRNA signature as a prognostic factor for patients with advanced NSCLC and its association with tissue microRNA expression profiles

    PubMed Central

    GUO, JING; MENG, RUI; YIN, ZHONGYUAN; LI, PENGCHENG; ZHOU, RUI; ZHANG, SHENG; DONG, XIAORONG; LIU, LI; WU, GANG

    2016-01-01

    The aim of the present study was to detect microRNA (miRNA) signatures in advanced non-small cell lung cancer (NSCLC), and to study the association between miRNA expression levels in serum and tissue. A cohort of patients who had previously been diagnosed with advanced NSCLC was enrolled in the present study. miRNAs associated with prognosis, which had previously been detected in early stage NSCLC samples, were measured in the serum of the patient groups using a cross-validation method. In addition, serum miRNAs associated with progression-free survival (PFS) were detected in paired fresh tissue samples, in order to analyze the correlation between serum and tissue expression levels. A risk-score analysis was used to develop a four-miRNA signature to predict PFS. miR-1, miR-30d, miR-221 and miR-486 were identified as having a significant correlation with PFS in advanced NSCLC. miR-221 and miR-486 exhibited significant positive correlations between serum and tissue expression. Furthermore, overexpression of miR-221 and reduced expression of miR-486 increased cell proliferation, migration and invasion in vitro. In conclusion, the miRNA signature identified in the present study may be considered an independent prognostic factor of PFS in advanced NSCLC. In addition, the expression levels of miR-221 and miR-486 were significantly correlated between serum and tissue. miR-221 was identified as an oncogenic risk factor, whereas miR-486 exerted protective effects against cancer cell proliferation, migration and invasion. PMID:27081922

  9. The efficacy and safety of immunotherapy in patients with advanced NSCLC: a systematic review and meta-analysis

    PubMed Central

    Zhou, Liang; Wang, Xi-Ling; Deng, Qing-Long; Du, Yan-Qiu; Zhao, Nai-Qing

    2016-01-01

    Immunotherapy is a novel treatment for advanced non-small cell lung cancer (NSCLC) patients. Immunotherapy includes two main broad classes of therapeutic vaccines and immune checkpoint inhibitors, as well as cytokines, biological response modifiers and cellular therapy. The present systematic review and meta-analysis aims to evaluate the efficacy and safety of different classes of immunotherapy in patients with advanced NSCLC. Literature search was done on Medline, Embase and Cochrane Library. The primary endpoints were overall survival (OS) and grade ≥3 adverse events. Twenty randomized controlled trials were finally identified in our study. Efficacy analysis indicated an improvement of OS in advanced NSCLC patients after treating by therapeutic vaccines and immune checkpoint inhibitors, but not for other immunomodulators. Safety analysis showed that immunotherapy was well-tolerated. All kinds of grade ≥3 adverse events were similar between experimental group and control group except that neutropenia and thrombocytopenia had a higher incidence in patients received vaccines. In conclusion, immunotherapy is a promising treatment for advanced NSCLC patients. Our findings will be further confirmed and supplemented by several phase II and phase III RCTs which are going to complete in near future. PMID:27558285

  10. The efficacy and safety of immunotherapy in patients with advanced NSCLC: a systematic review and meta-analysis.

    PubMed

    Zhou, Liang; Wang, Xi-Ling; Deng, Qing-Long; Du, Yan-Qiu; Zhao, Nai-Qing

    2016-01-01

    Immunotherapy is a novel treatment for advanced non-small cell lung cancer (NSCLC) patients. Immunotherapy includes two main broad classes of therapeutic vaccines and immune checkpoint inhibitors, as well as cytokines, biological response modifiers and cellular therapy. The present systematic review and meta-analysis aims to evaluate the efficacy and safety of different classes of immunotherapy in patients with advanced NSCLC. Literature search was done on Medline, Embase and Cochrane Library. The primary endpoints were overall survival (OS) and grade ≥3 adverse events. Twenty randomized controlled trials were finally identified in our study. Efficacy analysis indicated an improvement of OS in advanced NSCLC patients after treating by therapeutic vaccines and immune checkpoint inhibitors, but not for other immunomodulators. Safety analysis showed that immunotherapy was well-tolerated. All kinds of grade ≥3 adverse events were similar between experimental group and control group except that neutropenia and thrombocytopenia had a higher incidence in patients received vaccines. In conclusion, immunotherapy is a promising treatment for advanced NSCLC patients. Our findings will be further confirmed and supplemented by several phase II and phase III RCTs which are going to complete in near future. PMID:27558285

  11. A Screening Method for the ALK Fusion Gene in NSCLC.

    PubMed

    Murakami, Yoshiko; Mitsudomi, Tetsuya; Yatabe, Yasushi

    2012-01-01

    Lung cancer research has recently made significant progress in understanding the molecular pathogenesis of lung cancer and in developing treatments for it. Such achievements are directly utilized in clinical practice. Indeed, the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (ALK) fusion gene was first described in non-small cell lung cancer in 2007, and a molecularly targeted drug against the fusion was approved in 2011. However, lung cancer with the ALK fusion constitutes only a small fraction of lung cancers; therefore, efficient patient selection is crucial for successful treatment using the ALK inhibitor. Currently, RT-PCR, fluorescent in situ hybridization (FISH), and immunohistochemistry are commonly used to detect the ALK fusion. Although FISH is currently the gold standard technique, there are no perfect methods for detecting these genetic alterations. In this article, we discuss the advantages and disadvantages of each method and the possible criteria for selecting patients who are more likely to have the ALK fusion. If we can successfully screen patients, then ALK inhibitor treatment will be the best example of personalized therapy in terms of selecting patients with an uncommon genotype from a larger group with the same tumor phenotype. In other words, the personalized therapy may offer a new challenge for current clinical oncology. PMID:22655265

  12. A Screening Method for the ALK Fusion Gene in NSCLC

    PubMed Central

    Murakami, Yoshiko; Mitsudomi, Tetsuya; Yatabe, Yasushi

    2012-01-01

    Lung cancer research has recently made significant progress in understanding the molecular pathogenesis of lung cancer and in developing treatments for it. Such achievements are directly utilized in clinical practice. Indeed, the echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (ALK) fusion gene was first described in non-small cell lung cancer in 2007, and a molecularly targeted drug against the fusion was approved in 2011. However, lung cancer with the ALK fusion constitutes only a small fraction of lung cancers; therefore, efficient patient selection is crucial for successful treatment using the ALK inhibitor. Currently, RT-PCR, fluorescent in situ hybridization (FISH), and immunohistochemistry are commonly used to detect the ALK fusion. Although FISH is currently the gold standard technique, there are no perfect methods for detecting these genetic alterations. In this article, we discuss the advantages and disadvantages of each method and the possible criteria for selecting patients who are more likely to have the ALK fusion. If we can successfully screen patients, then ALK inhibitor treatment will be the best example of personalized therapy in terms of selecting patients with an uncommon genotype from a larger group with the same tumor phenotype. In other words, the personalized therapy may offer a new challenge for current clinical oncology. PMID:22655265

  13. Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

    PubMed Central

    Bansal, Pranshu; Osman, Diaa; Gan, Gregory N.; Simon, George R.; Boumber, Yanis

    2016-01-01

    Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). With the discovery of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2), RET, and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding. PMID:27200298

  14. The Efficacy of Bevacizumab Compared with Other Targeted Drugs for Patients with Advanced NSCLC: A Meta-Analysis from 30 Randomized Controlled Clinical Trials

    PubMed Central

    Zhu, Min; Liu, Tianshu; Zhao, Naiqing

    2013-01-01

    Background The extent of the benefit of bevacizumab combined with chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) is still unclear. We performed this meta-analysis to compare the efficacy of bevacizumab with other commonly used targeted drugs for different patients with advanced NSCLC. Methods We searched PubMed, Cochrane Library, EMBASE and abstracts from the proceedings of the American Society of Clinical Oncology (ASCO), and identified 30 randomized controlled clinical trials published within 1999 to 2011 for meta-analysis. Results The outcomes of treatment efficacy included response rate, PFS and OS. Comparing bevacizumab (15 mg/kg) with chemotherapy to standard chemotherapy alone, for chemotherapy-naïve patients, the pooled OR of response rate was 2.741(95%CI: 2.046, 3.672), the pooled HR for disease progression was 0.645 (95%CI: 0.561, 0.743), and the pooled HR for death was 0.790 (95%CI: 0.674, 0.926), respectively. In addition, the adjusted HR for previously-treated patients was 0.680 (95%CI: 0.492, 0.942) comparing bevacizumab combined with chemotherapy to standard chemotherapy alone. Conclusions Bevacizumab accompanied by chemotherapy was found to significantly improve patients' response rate, progression free survival (PFS), and overall survival (OS) among chemotherapy-naïve patients compared to other targeted drugs in the treatment of non-small cell lung carcinoma (NSCLC). PMID:23614008

  15. Recent advances in epigenomics in NSCLC: real-time detection and therapeutic implications.

    PubMed

    Di Paolo, Antonello; Del Re, Marzia; Petrini, Iacopo; Altavilla, Giuseppe; Danesi, Romano

    2016-08-01

    NSCLC is an aggressive disease with one of the poorer prognosis among cancers. The disappointing response to chemotherapy drives the search for genetic biomarkers aimed at both attaining an earlier diagnosis and choosing the most appropriate chemotherapy. In this scenario, epigenomic markers, such as DNA methylation, histone acetylation and the expression of noncoding RNAs, have been demonstrated to be reliable for the stratification of NSCLC patients. Newest techniques with increased sensitivity and the isolation of nucleic acids from plasma may allow an early diagnosis and then monitoring the efficacy over time. However, prospective confirmatory studies are still lacking. This article presents an overview of the epigenetic markers evaluated in NSCLC and discusses the role of their real-time detection in the clinical management of the disease. PMID:27479016

  16. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy: Result from 3 clinical trials of advanced NSCLC by 1 institution.

    PubMed

    He, Xiaobo; Zhang, Yang; Ma, Yuxiang; Zhou, Ting; Zhang, Jianwei; Hong, Shaodong; Sheng, Jin; Zhang, Zhonghan; Yang, Yunpeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

    2016-08-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC.A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed. The response evaluation criteria in solid tumors (RECIST) were used to identify responders, who had complete response (CR) or partial responses (PR) and nonresponders who had stable disease (SD) or progressive disease (PD). Receiver operating characteristics (ROC) analysis was used to find the optimal tumor shrinkage as an indicator for tumor therapeutic outcome. Univariate and multivariate Cox regression analyses were performed to compare the progression-free survival (PFS) and overall survival (OS) between responders and nonresponders stratified based on radiologic criteria.Among the 88 NSCLC patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46 responders (≤8.32%) and 42 nonresponders (≥8.32%). Univariate and multivariate Cox regression analyses indicated that (1) the responders (≤8.32%) and nonresponders (≥ -8.32%) were significantly different in median PFS (13.40 vs 1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) -8.32% in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11, 95% CI, 3.75 to 17.51, P < 0.001) and OS (HR, 2.36, 95

  17. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy

    PubMed Central

    He, Xiaobo; Zhang, Yang; Ma, Yuxiang; Zhou, Ting; Zhang, Jianwei; Hong, Shaodong; Sheng, Jin; Zhang, Zhonghan; Yang, Yunpeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

    2016-01-01

    Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC. A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed. The response evaluation criteria in solid tumors (RECIST) were used to identify responders, who had complete response (CR) or partial responses (PR) and nonresponders who had stable disease (SD) or progressive disease (PD). Receiver operating characteristics (ROC) analysis was used to find the optimal tumor shrinkage as an indicator for tumor therapeutic outcome. Univariate and multivariate Cox regression analyses were performed to compare the progression-free survival (PFS) and overall survival (OS) between responders and nonresponders stratified based on radiologic criteria. Among the 88 NSCLC patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46 responders (≤8.32%) and 42 nonresponders (≥8.32%). Univariate and multivariate Cox regression analyses indicated that (1) the responders (≤8.32%) and nonresponders (≥ −8.32%) were significantly different in median PFS (13.40 vs 1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) –8.32% in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11, 95% CI, 3.75 to 17.51, P < 0.001) and OS

  18. Novel EGFR mutation specific antibodies for NSCLC: Immunohistochemistry as a possible screening method for EGFR mutations

    PubMed Central

    Kato, Yasufumi; Peled, Nir; Wynes, Murry W.; Yoshida, Koichi; Pardo, Marta; Mascaux, Celine; Ohira, Tatsuo; Tsuboi, Masahiro; Matsubayashi, Jun; Nagao, Toshitaka; Ikeda, Norihiko; Hirsch, Fred R.

    2010-01-01

    Background Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) predict better outcome to EGFR tyrosine kinase inhibitors (TKIs). The most common mutations are exon 19 deletions (most frequently E746-A750) and L858R point mutation in exon 21. Here, we evaluated the accuracy of novel EGFR mutation specific antibodies in a Japanese cohort with NSCLC and compared to direct DNA sequencing and clinical outcome. Materials and methods Immunohistochemistry (IHC) using antibodies specific for the E746-A750 and L858R mutations in EGFR was performed on tissue microarrays of tumors from 70 gefitinib treated NSCLC patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21. Results DNA sequencing showed EGFR mutations in 41 patients (58.6%), and exon 19 deletions in 18 patients (25.7%), 61% (11/18) had a deletion in the range of E746-A750) and 12 (17.1%) had exon 21 mutations (L858R). IHC showed, for the E746-A750 and L858R mutations, sensitivity (81.8% and 75%), specificity (100%, 96.6%), PPV (100%, 81.8%) and NPV (96.7%, 94.9%). Analysis for objective response rates (ORR) and survival were not correlated to IHC staining, although the combined staining showed non-significant trends towards better overall survival for patients with EGFR mutations. Conclusions The mutation specific IHC antibodies have high sensitivity and specificity for pre-defined EFGR mutations and may be suitable for screening for these pre-defined mutations. However, negative IHC results require further mutation analyses prior to excluding EGFR-targeted therapy. PMID:20697298

  19. Down-regulation of miR-503 expression predicate advanced mythological features and poor prognosis in patients with NSCLC

    PubMed Central

    Liu, Lei; Qu, Weiqing; Zhong, Zhaokun

    2015-01-01

    Objective: We aimed to explore what impact miR-503 has on the prognosis of patients with non-small cell lung cancer (NSCLC). Methods: Cancer and matched non-malignant lung tissue specimens were collected from 109 patients who underwent surgery in Tanisha Hospital from Jun 2006 to July 2013. Overall survival (OS) curves were analyzed using the Lapland-Meier method, and the differences were examined using log-rank tests. Cox proportional- hazards regression analysis was applied in order to estimate univariate and multivariate hazard ratios for OS. Results: The relative expression of miR-503 in NSCLC tissues (0.366 ± 0.130) was significantly lower than that in matched noncancerous lung tissues (1.667 ± 1.047, P < 0.01). Statistically significant association was observed between miR-503 expression and lymphatic invasion (P = 0.005), distant metastasis (P = 0.002), TNM stage (P = 0.008), and tumor grade (P = 0.043). Lapland Meier analysis clearly illustrated that the patients with the lower expression of miR-503 had a worse outcome compared to patients with higher miR-503 expression (P = 0.004). Furthermore, multivariate analysis revealed that miR-503 expression level was an independent prognostic factor for overall survival (HR = 3.992, 95% CI: 2.276-9.872; P = 0.018) in NSCLC. Conclusion: In patients with NSCLC, low miR-503 expression is an independent prognostic factor. PMID:26191272

  20. The impact of histological types on the efficacy of angiogenesis inhibitors in the treatment of advanced NSCLC: a meta-analysis of randomized controlled trials

    PubMed Central

    Zhang, Jian; Liu, Jie; Chen, Huiguo; Wu, Weibin; Li, Xiaojun; Wu, Yonghui; Zhang, Kai; Gu, Lijia

    2015-01-01

    Purpose We aimed at assessing the overall efficacy of angiogenesis inhibitor (AI)-containing regimens in the treatment of advanced non-small-cell lung cancer (NSCLC) according to histological types. Methods Studies from PubMed and Web of Science, and abstracts presented at American Society of Clinical Oncology (ASCO) meeting up to October 31, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials (RCTs) evaluating AIs in advanced NSCLC with survival data according to patients’ histologies. The endpoints were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 10,035 patients with advanced NSCLC from 13 RCTs were identified for analysis. The pooled results demonstrated that AI-containing regimens significantly improved the PFS (HR, 0.84, 95% confidence interval (CI): 0.78–0.91, P<0.001) and OS (HR, 0.92, 95% CI: 0.85–0.99, P=0.017) in lung adenocarcinoma when compared to non-AI-containing regimens. Additionally, there was a significantly improved PFS (HR, 0.87, 95% CI: 0.77–0.98, P=0.027) for AI-containing regimens in squamous cell lung carcinoma, but it did not translated into OS benefit (HR, 1.02, 95% CI: 0.92–1.15, P=0.68). For NSCLC patients with other histological types, the use of AIs did not significantly improve PFS (HR, 0.90, 95% CI: 0.75–1.09, P=0.27) and OS (HR, 0.90, 95% CI: 0.76–1.08, P=0.19). Conclusion The findings of this study suggest that the addition of AIs to the treatment therapies for patients with lung adenocarcinoma offers improved survival benefits. Prospective clinical trials investigating the role of AIs in this setting are recommended. PMID:26366091

  1. Specific Safety Profile of Bevacizumab in Asian Patients With Advanced NSCLC

    PubMed Central

    Chen, Zhenguang; Zhong, Beilong; Lun, Xueping; Lai, Yingrong; Bella, Amos Ela; Yang, Weilin; Wu, Jiabin

    2015-01-01

    Abstract Randomized studies have obtained varying findings regarding the benefits and toxicities of bevacizumab in the treatment of nonsmall cell lung cancer (NSCLC). It is unclear whether the discrepancies among trials are due to ethnic/racial differences. We therefore performed a meta-analysis of all published, randomized, controlled clinical trials involving bevacizumab in patients with NSCLC to assess its effectiveness and safety in Asian and non-Asian populations. Results from the phase II JO19907 trial, the phase III AVAiL and ECOG 4599 trials, and the phase IV SAiL trials were used to calculate the benefits and toxicities of bevacizumab in Asian and non-Asian patients. Combined statistical estimates, including hazard ratios and odds ratios, were calculated using fixed-effects and random-effects models. A total of 4308 patients were evaluated. Combining bevacizumab with different chemotherapy regimens resulted in similar objective response rates, overall survival, and progression-free survival in Asian and non-Asian populations. Disease control rates, however, were only reported in Asian populations. The rates of severe bleeding (relative risk [RR], 2.17; P = 0.02) and thromboembolism (RR, 3.65; P < 0.0001) were significantly higher, while the rate of severe proteinuria was significantly lower (RR, 0.43; P < 0.0001), in non-Asian than in Asian populations. The rates of severe hypertension (P = 0.71) and hemoptysis (P = 0.66) were similar in Asian and non-Asian populations. Bevacizumab combined with chemotherapy for first-line NSCLC treatment showed similar benefits in Asian and non-Asian populations, but had specific safety profiles in each.

  2. F-18-FDG-PET Confined Radiotherapy of Locally Advanced NSCLC With Concomitant Chemotherapy: Results of the PET-PLAN Pilot Trial

    SciTech Connect

    Fleckenstein, Jochen; Hellwig, Dirk; Kremp, Stephanie; Grgic, Aleksandar; Groeschel, Andreas; Kirsch, Carl-Martin; Nestle, Ursula; Ruebe, Christian

    2011-11-15

    Purpose: The integration of fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the process of radiotherapy (RT) planning of locally advanced non-small-cell lung cancer (NSCLC) may improve diagnostic accuracy and minimize interobserver variability compared with target volume definition solely based on computed tomography. Furthermore, irradiating only FDG-PET-positive findings and omitting elective nodal regions may allow dose escalation by treating smaller volumes. The aim of this prospective pilot trial was to evaluate the therapeutic safety of FDG-PET-based RT treatment planning with an autocontour-derived delineation of the primary tumor. Methods and Materials: Eligible patients had Stages II-III inoperable NSCLC, and simultaneous, platinum-based radiochemotherapy was indicated. FDG-PET and computed tomography acquisitions in RT treatment planning position were coregistered. The clinical target volume (CTV) included the FDG-PET-defined primary tumor, which was autodelineated with a source-to-background algorithm, plus FDG-PET-positive lymph node stations. Limited by dose restrictions for normal tissues, prescribed total doses were in the range of 66.6 to 73.8 Gy. The primary endpoint was the rate of out-of-field isolated nodal recurrences (INR). Results: As per intent to treat, 32 patients received radiochemotherapy. In 15 of these patients, dose escalation above 66.6 Gy was achieved. No Grade 4 toxicities occurred. After a median follow-up time of 27.2 months, the estimated median survival time was 19.3 months. During the observation period, one INR was observed in 23 evaluable patients. Conclusions: FDG-PET-confined target volume definition in radiochemotherapy of NSCLC, based on a contrast-oriented source-to-background algorithm, was associated with a low risk of INR. It might provide improved tumor control because of dose escalation.

  3. CEA serum level as early predictive marker of outcome during EGFR-TKI therapy in advanced NSCLC patients.

    PubMed

    Facchinetti, Francesco; Aldigeri, Raffaella; Aloe, Rosalia; Bortesi, Beatrice; Ardizzoni, Andrea; Tiseo, Marcello

    2015-08-01

    Considering the role of carcinoembryonic antigen (CEA) serum levels as potential useful predictive marker during chemotherapy treatment, we studied its applicability in advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). Our retrospective cohort consists of 79 patients (33 EGFR mutated and 46 EGFR wild type or unknown) affected by advanced NSCLC, for whom CEA serum values at the beginning of TKI therapy and after the first month of treatment were available, regardless of treatment line. Baseline CEA value, percentage of CEA reduction after 1 month, and percentage of patients with ≥20 % CEA decrease after 1 month (CEA response) were correlated with disease control rate (DCR), progression-free (PFS), and overall (OS) survival, according to EGFR mutational status. Median baseline CEA levels were significantly higher in EGFR mutated (40.9 ng/ml; interquartile range (IQR) 8.9-197.6) than in wild-type cases (6.2 ng/ml; IQR 2.8-12.8; p = 0.003). Both percentage reduction in CEA levels (-10.7 vs. +13.4 %) and percentage of cases with CEA response (42 vs. 20 %) were significantly higher in mutated vs. wild-type/unknown patients (p = 0.007 and p = 0.027, respectively). In wild-type/unknown patients, CEA response was significantly correlated with DCR (p = 0.001) and resulted as a significant predictor of PFS both in univariate (p = 0.002) and in multivariate analyses (hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.11-0.66; p = 0.004); only a trend was found for OS prediction (p = 0.082). In EGFR-mutated group, CEA reduction did not show any correlation either with PFS or OS. CEA response after 1 month of EGFR-TKI therapy could be a useful marker, worthy to further studies, as early predictor of treatment outcome in EGFR wild-type/unknown unselected NSCLC cases for which no molecular predictor is yet available. PMID:25731731

  4. A Phase II Study of Modulated-Capecitabine and Docetaxel in Chemonaive Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)

    PubMed Central

    Bertino, Erin M.; Bekaii-Saab, Tanios; Fernandez, Soledad; Diasio, Robert B.; Karim, Nagla A.; Otterson, Gregory A.; Villalona-Calero, Miguel A.

    2012-01-01

    Introduction This phase II single-arm trial of docetaxel and capecitabine in previously untreated non-small cell lung cancer (NSCLC) patients was designed to evaluate response rate of this regimen based on promising efficacy data from phase II testing in pre-treated NSCLC patients. The trial also evaluated the correlation between peripheral blood dihydropyrimidine dehydrogenase (DPD) expression and efficacy/toxicity. Methods Patients with advanced NSCLC (metastatic, including malignant pleural effusion) without prior chemotherapy were enrolled. Baseline DPD screening was performed; patients with baseline DPD level < 0.07 nmol/min/mg protein were considered ineligible for the study. Treatment included a 28-day cycle of docetaxel 36 mg/m2 days 1, 8, 15 and capecitabine 1250 mg/m2/day in divided doses on days 5–18. Overall response rate (RR) was the primary endpoint with a target RR of 50%. Correlative studies included evaluation of DPD activity levels in peripheral blood and correlation with clinical responses. Results Twenty-eight patients received 86 cycles of treatment (median 3 cycles) and were evaluable for response. The RR was 18% (5 patients); RR did not meet the pre-specified efficacy endpoint and the trial was stopped. 14 patients had stable disease (SD - 50%) and 4 pts had SD > 12 weeks. Median time to progression was 3.3 months (95% CI 1.5 – 4.6 months). Median overall survival was 10.5 months (95% CI: 3.2 – 15 months). Main toxicities included fatigue, stomatitis and leukopenia. DPD levels ranged from 0.06 to 0.26 nmol/min/mg. The majority of responders (4/5) had DPD levels ≤ 0.1 nmol/min/mg. Most of the responders (4/5) experienced grade 3 toxicities including leukopenia, dehydration, fatigue, and diarrhea. None of the patients (0/4) with higher DPD levels (>0.2 nmol/min/mg) had a response. Conclusion The response rate for the regimen did not demonstrate sufficient activity and further study of this regimen in this setting is not indicated

  5. Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules

    PubMed Central

    Sutiman, Natalia; Zhang, Zhenxian; Tan, Eng Huat; Ang, Mei Kim; Tan, Shao-Weng Daniel; Toh, Chee Keong; Ng, Quan Sing; Chowbay, Balram; Lim, Wan-Teck

    2016-01-01

    Purpose This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV) and metronomic (MSV) dosing schedules in patients with advanced non-small cell lung cancer (NSCLC). Methods This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16) and at 100 mg/week in the MSV group (N = 14). Erlotinib was administered orally daily. Results The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13%) and hyponatremia (N = 1; 6%) in the CSV group, and neutropenia (N = 5; 36%) in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group. Conclusions Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups. Trial Registration ClinicalTrials.gov NCT00702182 PMID:27135612

  6. A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.

    PubMed

    Planchard, David; Yokoi, Takashi; McCleod, Michael J; Fischer, Jürgen R; Kim, Young-Chul; Ballas, Marc; Shi, Kelvin; Soria, Jean-Charles

    2016-05-01

    Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing. PMID:27265743

  7. Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance.

    PubMed

    Zheng, D; Ye, X; Zhang, M Z; Sun, Y; Wang, J Y; Ni, J; Zhang, H P; Zhang, L; Luo, J; Zhang, J; Tang, L; Su, B; Chen, G; Zhu, G; Gu, Y; Xu, J F

    2016-01-01

    EGFR T790M mutation occurs in half of non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI (TKI) resistance, based on tumor re-biopsies using an invasive clinical procedure. Here, we dynamically monitored T790M mutation in circulating tumor DNA (ctDNA) using serial plasma samples from NSCLC patients receiving TKI through Droplet Digital PCR (ddPCR) method and the associations between overall survival (OS) starting from initial TKI treatment and the T790M ctDNA status detected in plasma were analyzed. Among 318 patients, 117 who acquired TKI resistance were eligible for the analysis. T790M ctDNA was detected in the plasma of 55/117 (47%) patients. Almost half of the T790M ctDNA positive patients were identified at a median time of 2.2 months prior to clinically progressive disease (PD). Furthermore, within the patients receiving TKI treatment at 2(nd) line or later, the T790M ctDNA positive group had significantly shorter OS than the negative group (median OS: 26.9 months versus NA, P = 0.0489). Our study demonstrates the feasibility of monitoring EGFR mutation dynamics in serial plasma samples from NSCLC patients receiving TKI therapy. T790M ctDNA can be detected in plasma before and after PD as a poor prognostic factor. PMID:26867973

  8. Time-to-Progression of NSCLC from Early to Advanced Stages: An Analysis of data from SEER Registry and a Single Institute

    PubMed Central

    Yuan, Ping; Cao, Jin Lin; Rustam, Azmat; Zhang, Chong; Yuan, Xiao Shuai; Bao, Fei Chao; Lv, Wang; Hu, Jian

    2016-01-01

    The average time required for cancers to progress through stages can be reflected in the average age of the patients diagnosed at each stage of disease. To estimate the time it takes for non-small-cell lung cancer (NSCLC) to progress through different tumor, node and metastasis (TNM) stages and sizes, we compared the mean adjusted age of 45904 NSCLC patients with different stages and tumor sizes from Surveillance, Epidemiology and End Results (SEER) cancer registry database and our institute. Multiple-linear-regression models for age were generated adjusting for various factors. Caucasian, African-American and Asian patients with stage IA cancers were on average 0.8, 1.0 and 1.38 adjusted years younger, respectively, than those with stage IIIB cancers (p < 0.001). And these with T1a cancers were on average 0.84, 0.92 and 1.21 adjusted years younger, respectively, than patients with T3 cancers (p < 0.001). Patients with tumors measuring larger than 8 cm in diameter were on average 0.85 adjusted years older than these with tumors smaller than 1 cm (p < 0.001), with Caucasian demonstrating the shortest age span (0.79 years, P < 0.001). In conclusion, the time-to-progression of NSCLC from early to advanced stages varied among ethnicities, Caucasian patients demonstrating a more rapid progression nature of tumor than their African-American and Asian counterparts. PMID:27346236

  9. Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

    PubMed

    Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

    2016-06-01

    Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost

  10. Approval summary: pemetrexed maintenance therapy of advanced/metastatic nonsquamous, non-small cell lung cancer (NSCLC).

    PubMed

    Cohen, Martin H; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    On July 2, 2009, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta® Injection; Eli Lilly and Company, Indianapolis, IN) for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy. A double-blind study of pemetrexed plus best supportive care versus placebo plus best supportive care was conducted. Pemetrexed, 500 mg/m(2) i.v., was administered every 21 days until disease progression. Folic acid, vitamin B(12), and a corticosteroid were given to all study patients. There were 663 randomized patients (pemetrexed, 441; placebo, 222). Treatments were well balanced with respect to baseline disease characteristics and stratification factors. The median overall survival (OS) time for intent-to-treat (ITT) patients was 13.4 months for patients receiving pemetrexed and 10.6 months for those receiving placebo (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95; p = .012). Median OS times were 15.5 months versus 10.3 months for patients with nonsquamous histologies receiving pemetrexed and placebo, respectively (HR, 0.70; 95% CI, 0.56-0.88). The median OS time in patients with squamous histology receiving pemetrexed was 9.9 months, versus 10.8 months for those receiving placebo (HR, 1.07; 95% CI, 0.77-1.50). A significantly longer progression-free survival interval for both the ITT and nonsquamous patient populations receiving pemetrexed maintenance therapy was also observed. The most common (>5%) adverse reactions in patients receiving pemetrexed were hematologic toxicity, an increase in hepatic enzymes, fatigue, gastrointestinal toxicity, sensory neuropathy, and skin rash. PMID:21148615

  11. Optimised Pre-Analytical Methods Improve KRAS Mutation Detection in Circulating Tumour DNA (ctDNA) from Patients with Non-Small Cell Lung Cancer (NSCLC)

    PubMed Central

    Sherwood, James L.; Corcoran, Claire; Brown, Helen; Sharpe, Alan D.; Musilova, Milena; Kohlmann, Alexander

    2016-01-01

    Introduction Non-invasive mutation testing using circulating tumour DNA (ctDNA) is an attractive premise. This could enable patients without available tumour sample to access more treatment options. Materials & Methods Peripheral blood and matched tumours were analysed from 45 NSCLC patients. We investigated the impact of pre-analytical variables on DNA yield and/or KRAS mutation detection: sample collection tube type, incubation time, centrifugation steps, plasma input volume and DNA extraction kits. Results 2 hr incubation time and double plasma centrifugation (2000 x g) reduced overall DNA yield resulting in lowered levels of contaminating genomic DNA (gDNA). Reduced “contamination” and increased KRAS mutation detection was observed using cell-free DNA Blood Collection Tubes (cfDNA BCT) (Streck), after 72 hrs following blood draw compared to EDTA tubes. Plasma input volume and use of different DNA extraction kits impacted DNA yield. Conclusion This study demonstrated that successful ctDNA recovery for mutation detection in NSCLC is dependent on pre-analytical steps. Development of standardised methods for the detection of KRAS mutations from ctDNA specimens is recommended to minimise the impact of pre-analytical steps on mutation detection rates. Where rapid sample processing is not possible the use of cfDNA BCT tubes would be advantageous. PMID:26918901

  12. Quantification of Cell-Free mSHOX2 Plasma DNA for Therapy Monitoring in Advanced Stage Non-Small Cell (NSCLC) and Small-Cell Lung Cancer (SCLC) Patients

    PubMed Central

    Schmidt, Bernd; Beyer, Julia; Dietrich, Dimo; Bork, Ines; Liebenberg, Volker; Fleischhacker, Michael

    2015-01-01

    Purpose Most patients suffering from advanced lung cancer die within a few months. To exploit new therapy regimens we need better methods for the assessment of a therapy response. Material and Methods In a pilot study we prospectively enrolled 36 patients with advanced NSCLC and SCLC (34 stage IV, 2 stage IIIB) of whom 34 received standard platinum-based chemo/radiotherapy and two were treated with a tyrosine kinase inhibitor. We measured the levels of extracellular methylated SHOX2 DNA (mSHOX2) in plasma before and during therapy until re-staging. The mSHOX2 analysis was blinded with respect to the clinical data making it an observational study. Results According to the re-staging of 31 first-line patients, 19 patients were classified as non-responders while 12 patients were in the responder group. We observed a tight correlation between radiological data and the change of plasma mSHOX2 level as the equivalent for a therapy response. A ROC analysis showed a high discriminatory power for both patient groups already one week after therapy start (AUC 0.844). Additionally, a Kaplan-Meier and Cox Proportional Hazards analyses revealed a strong relationship between survival and plasma mSHOX2 value p≤0.001 (hazard ratio 11.08) providing some evidence for mSHOX2 also being a predictive marker. Conclusion The longitudinal measurement of extracellular plasma mSHOX2 DNA yields information about the response to cytotoxic treatment and allows an early assessment of treatment response for lung cancer patients. If confirmed in a larger study this would be a valuable tool for selecting and guiding a cytotoxic treatment. PMID:25675432

  13. Multiple Marker Detection in Peripheral Blood for NSCLC Diagnosis

    PubMed Central

    Ulivi, Paola; Mercatali, Laura; Casoni, Gian-Luca; Scarpi, Emanuela; Bucchi, Lauro; Silvestrini, Rosella; Sanna, Stefano; Monteverde, Marco; Amadori, Dino; Poletti, Venerino; Zoli, Wainer

    2013-01-01

    Background Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC). Methods 100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method. Results Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p = 0.0002 and p = 0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15–11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75–13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71–4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01–1.33; p = 0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI = 0.90–0.97, with sensitivity and specificity over 90%. Conclusions Free circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer. PMID:23468981

  14. Role of Gemcitabine and Pemetrexed as Maintenance Therapy in Advanced NSCLC: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Feng, Xuqin; Wen, Shimin; Fu, Xi; Guo, Cuihua; He, Wenwu

    2016-01-01

    Background Gemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies. This systematic review and meta-analysis were conducted to assess the role of gemcitabine and pemetrexed in the maintenance treatment of non-small-cell lung carcinoma (NSCLC). Methods We performed a literature search using PubMed, EMBASE and Cochrane library databases from their inceptions to September 16, 2015. We also searched the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) databases from 2008 to 2015. Two authors independently extracted the data. The Cochrane Collaboration’s risk of bias graph was used to assess the risk of bias. The GRADE system was used to assess the grading of evidence, and a meta-analysis was conducted using Stata 11.0 software. Results Eleven randomized controlled trial (RCT) studies were collected. Ten studies were included in the meta-analysis and divided into the following 4 groups: gemcitabine vs. best supportive care (BSC)/observation, pemetrexed vs. BSC/placebo, pemetrexed + bevacizumab vs. bevacizumab and pemetrexed vs. bevacizumab. Gemcitabine exhibited significantly improved progression-free survival (PFS) compared with BSC (hazard ratio (HR) = 0.62, p = 0.000). Pemetrexed exhibited significantly improved PFS (HR = 0.54, p = 0.000) and OS (HR = 0.75, p = 0.000) compared with BSC. Pemetrexed + bevacizumab almost exhibited significantly improved PFS (HR = 0.71, p = 0.051) compared with bevacizumab. Pemetrexed exhibited no improvement in PFS or overall survival (OS) compared with bevacizumab. Regarding the grade, the GRADE system indicated that the gemcitabine group was "MODERATE", the pemetrexed group was "HIGH", and both the pemetrexed + bevacizumab vs. bevacizumab groups and pemetrexed vs. B groups were "LOW". Conclusions Gemcitabine or pemetrexed compared

  15. Prospective Validation Obtained in a Similar Group of Patients and with Similar High Throughput Biological Tests Failed to Confirm Signatures for Prediction of Response to Chemotherapy and Survival in Advanced NSCLC: A Prospective Study from the European Lung Cancer Working Party

    PubMed Central

    Berghmans, Thierry; Ameye, Lieveke; Lafitte, Jean-Jacques; Colinet, Benoît; Cortot, Alexis; CsToth, Ingrid; Holbrechts, Stéphane; Lecomte, Jacques; Mascaux, Céline; Meert, Anne-Pascale; Paesmans, Marianne; Richez, Michel; Scherpereel, Arnaud; Tulippe, Christian; Willems, Luc; Dernies, Tiffany; Leclercq, Nathalie; Sculier, Jean-Paul

    2014-01-01

    Aim: Cisplatin doublets are standard 1st line treatment for advanced non-small cell lung cancer (NSCLC), without accurate predictor for response and survival, but important toxicity. Our aims were to identify predictive (for response) and prognostic (for survival) biological signatures in patients with NSCLC using messenger RNAs (mRNA) and miRNA expression. Methods: Patients with pathologically proven untreated NSCLC, receiving 1st line cisplatin–vinorelbine and with an assessable lesion were eligible. A bronchial biopsy was lysed into Tripure Isolation Reagent on ice, snap frozen, and stored at −80°C. mRNA expression was analyzed using microarrays Agilent Technologies. miRNA expression was assessed using TaqMan Low Density Arrays (756 human miR panel, Applied Biosystems). Validation was performed by RT-PCR on the selected genes. Survival was measured from the registration date and response assessed by WHO criteria. Results: Biopsies for transcriptomic analyses were obtained from 60 consecutive patients. No statistically significant differences were observed according to the main clinical characteristics, response rate (43 vs. 41%) or survival (median 25 vs. 29 months) between derivation and validation sets. In the derivation set (n = 38 patients), two mRNA and one miRNA predictive signatures for response were obtained. One mRNA and one miRNA prognostic signatures were derived from the first set, allowing an adequate distinction of patients with good and poor overall and progression-free survivals. None of these signatures could be validated in the validation set (n = 22 patients). Conclusion: In this prospective study with advanced NSCLC treated with cisplatin–vinorelbine, we were able to derive with high throughput techniques predictive and prognostic signatures based on transcriptomic analyses. However, these results could not be reproduced in an independent validation set. The role of miRNA and mRNA as predictive or prognostic factors remains a

  16. Liquid Biopsies in the Screening of Oncogenic Mutations in NSCLC and its Application in Targeted Therapy.

    PubMed

    Tang, Jason H; Chia, David

    2015-01-01

    Non-small cell lung cancer (NSCLC) still dominates cancer-related deaths in America. Despite this, new discoveries and advancements in technology are helping with the detection and treatment of NSCLC. The discovery of circulating tumor DNA in blood and other biofluids is essential for the creation of a DNA biomarker. Limitations in technology and sequencing have stunted assay development, but with recent advancements in the next-generation sequencing, droplet digital PCR, and EFIRM, the detection of mutations in biofluids has become possible with reasonable sensitivity and specificity. These methods have been applied to the detection of mutations in NSCLC by measuring the levels of circulating tumor DNA. ALK fusion genes along with mutations in EGFR and KRAS have been shown to correlate to tumor size and metastasis. These methods allow for noninvasive, affordable, and efficient diagnoses of oncogenic mutations that overcome the issues of traditional biopsies. These issues include tumor heterogeneity and early detection of cancers with asymptomatic early stages. Early detection and treatment remain the best way to ensure survival. This review aims to describe these new technologies along with their application in mutation detection in NSCLC in order to proactively utilize targeted anticancer therapy. PMID:27279235

  17. Association of CD44 Gene Polymorphism with Survival of NSCLC and Risk of Bone Metastasis

    PubMed Central

    Liu, Yaosheng; Qing, Haifeng; Su, Xiuyun; Wang, Cheng; Li, Zhuo; Liu, Shubin

    2015-01-01

    Background Previous studies have reported CD44 expression influenced the development and progression of tumors. The aim of this study was to investigate whether single-nucleotide polymorphisms (SNPs) of the CD44 gene are associated with survival of non-small cell lung cancer (NSCLC) and occurrence rate of bone metastasis. Material/Methods A total of 234 patients with NSCLC between 2003 and 2010 were enrolled in this study and 468 healthy persons were used as controls. Two polymorphisms, rs13347 and rs187115, in the CD44 gene were genotyped using DNA from blood lymphocytes. For statistical analysis we used the chi-square test, Fisher’s exact test, Kaplan-Meier method, and log-rank test. Results CD44 gene rs13347 polymorphism was not associated with NSCLC risk. For rs187115, the association with NSCLC risk was observed (P<0.001). Allele G carriers had significantly higher occurrence rates of bone metastasis (OR=0.4, 95%CI: 0.20–0.64, P<0.001) and more advanced tumor stage (OR=2.6, 95%CI: 1.50–4.45, P=0.001) compared to carriers of allele A. The survival rates for patients with AA genotype were significantly higher than for patients with the AG+GG genotypes (P<0.001). In multivariate analysis of survival in NSCLC patients, significant predictors were CD44 gene (AG+GG) (RR=0.48, 95%CI: 0.34–0.68, P<0.001), tumor stage (RR=0.45, 95%CI: 0. 0.31–0.65, P<0.001), and bone metastasis (RR=1.52, 95%CI: 1.05–2.21, P=0.027). Conclusions CD44 gene rs187115 polymorphism is a potential predictive marker of survival in NSCLC patients, and is significantly correlated with bone metastasis and tumor stage. PMID:26356590

  18. Comparison of treatment costs of grade 3/4 adverse events associated with erlotinib or pemetrexed maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) in Germany, France, Italy, and Spain.

    PubMed

    Banz, Kurt; Bischoff, Helge; Brunner, Matthias; Chouaid, Christos; de Castro Carpeño, Javier; de Marinis, Filippo; Grossi, Francesco; Vergnenègre, Alain; Walzer, Stefan

    2011-12-01

    Objective of this indirect economic comparison was to estimate and compare management costs of grade 3/4 adverse events (AEs) reported for first-line erlotinib or pemetrexed maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC). The economic analysis was performed for Germany, France, Italy and Spain. Types and incidences of reported grade 3/4 AEs observed with erlotinib or pemetrexed maintenance therapy were retrieved from two recently published placebo-controlled trials. Country-specific estimates on standard treatment algorithms and incremental medical resource utilization associated with each of the reported grade 3/4 AEs have been obtained from clinical oncologists practicing in the four countries and co-authoring this article. The resource use items were subsequently assigned country-specific tariffs to estimate total per-patients costs associated with the AE profiles of the two compared maintenance regimens. For the economic analysis a customized economic spreadsheet model was employed. Our comparison shows lower total average per-patient AE management costs for erlotinib than for pemetrexed maintenance therapy in all four studied countries. Total estimated cost savings per patient in favour of erlotinib amount to € 121, € 237, € 106, and € 119 for Germany, France, Italy and Spain, respectively. These AE cost savings for erlotinib when compared to pemetrexed represent a decrease by 80%, 71%, 94%, and 82%, respectively. The study also discovered considerable differences in AE management costs across countries which are primarily due to differences in clinician's estimates of hospitalization referral rates. Erlotinib maintenance therapy in patients with advanced NSCLC causes lower AE management costs than pemetrexed maintenance therapy indicating a potentially superior tolerability profile. PMID:21592611

  19. Differences in the efficacy of S-1 monotherapy according to histological type in pretreated patients with advanced non-small cell lung cancer

    PubMed Central

    Hisamatsu, Yasushi; Murakami, Haruyasu; Akamatsu, Hiroaki; Kimura, Madoka; Mori, Keita; Imai, Hisao; Ono, Akira; Shukuya, Takehito; Taira, Tetsuhiko; Kenmotsu, Hirotsugu; Naito, Tateaki; Endo, Masahiro; Nakajima, Takashi; Takahashi, Toshiaki; Yamamoto, Nobuyuki

    2014-01-01

    Background S-1 is a novel antimetabolic agent that inhibits thymidylate synthase. The expression of thymidylate synthase is higher in squamous (Sq) non-small cell lung cancer (NSCLC) than in non-Sq NSCLC. The aim of this retrospective study was to assess the efficacy of S-1 monotherapy for advanced NSCLC according to the histological subtype. Methods We reviewed the clinical records of patients with advanced NSCLC treated with S-1 monotherapy as second- or third-line therapy between May 2005 and July 2012 at the Shizuoka Cancer Center. Results A total of 71 patients were included in this retrospective study. Patient characteristics were similar in the Sq NSCLC (n = 15) and non-Sq NSCLC (n = 56) groups, except with regard to gender and smoking status. The overall response rates were 0% (95% confidence interval [CI] 0–17%) for Sq NSCLC and 11% (95% CI 3–19%) for non-Sq NSCLC (P = 0.33). For Sq NSCLC and non-Sq NSCLC, the median progression-free survival times were 2.1 and 2.8 months (P = 0.02), respectively, and the median overall survival times were 6.1 and 10.1 months (P = 0.01), respectively. Conclusion S-1 monotherapy may be more effective in patients with non-Sq NSCLC than in those with Sq NSCLC. PMID:26766988

  20. Advanced probabilistic method of development

    NASA Technical Reports Server (NTRS)

    Wirsching, P. H.

    1987-01-01

    Advanced structural reliability methods are utilized on the Probabilistic Structural Analysis Methods (PSAM) project to provide a tool for analysis and design of space propulsion system hardware. The role of the effort at the University of Arizona is to provide reliability technology support to this project. PSAM computer programs will provide a design tool for analyzing uncertainty associated with thermal and mechanical loading, material behavior, geometry, and the analysis methods used. Specifically, reliability methods are employed to perform sensitivity analyses, to establish the distribution of a critical response variable (e.g., stress, deflection), to perform reliability assessment, and ultimately to produce a design which will minimize cost and/or weight. Uncertainties in the design factors of space propulsion hardware are described by probability models constructed using statistical analysis of data. Statistical methods are employed to produce a probability model, i.e., a statistical synthesis or summary of each design variable in a format suitable for reliability analysis and ultimately, design decisions.

  1. Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC

    PubMed Central

    Gupta, Ravi; Fischer, Kari R.; Choi, Hyejin; El Rayes, Tina; Ryu, Seongho; Nasar, Abu; Spinelli, Cathy F.; Andrews, Weston; Elemento, Olivier; Nolan, Daniel; Stiles, Brendon; Rafii, Shahin; Narula, Navneet; Davuluri, Ramana; Altorki, Nasser K.; Mittal, Vivek

    2015-01-01

    Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor “activated/reprogrammed” stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value. PMID:26046767

  2. Personalized Therapy of Non-small Cell Lung Cancer (NSCLC).

    PubMed

    Gadgeel, Shirish M

    2016-01-01

    Lung cancer remains the most common cause of cancer related deaths in both men and women in the United States and non-small cell lung cancer (NSCLC) accounts for over 85 % of all lung cancers. Survival of these patients has not significantly altered in over 30 years. This chapter initially discusses the clinical presentation of lung cancer patients. Most patients diagnosed with lung cancer due to symptoms have advanced stage cancer. Once diagnosed, lung cancer patients need imaging studies to assess the stage of the disease before decisions regarding therapy are finalized. The most important prognostic factors are stage of the disease and performance status and these factors also determine therapy. The chapter subsequently discusses management of each stage of the disease and the impact of several pathologic, clinical factors in personalizing therapy for each individual patient. Transition from chemotherapy for every patient to a more personalized approach based on histology and molecular markers has occurred in the management of advanced stage NSCLC. It is expected that such a personalized approach will extend to all stages of NSCLC and will likely improve the outcomes of all NSCLC patients. PMID:26703806

  3. Peripheral Blood miR-328 Expression as a Potential Biomarker for the Early Diagnosis of NSCLC

    PubMed Central

    Ulivi, Paola; Foschi, Giovanni; Mengozzi, Marta; Scarpi, Emanuela; Silvestrini, Rosella; Amadori, Dino; Zoli, Wainer

    2013-01-01

    Lung cancer is often diagnosed at an advanced stage, with subsequently poor prognosis. There are no biomarkers available to facilitate early diagnosis or to discriminate between benign and malignant nodules. MicroRNAs (miRNAs) are stable molecules that can be found and measured in peripheral blood, thus representing potential diagnostic biomarkers. We evaluated 100 individuals comprising 86 patients with predominantly early-stage non-small cell lung cancer (NSCLC) and 24 healthy donors. RNA was extracted from peripheral blood samples and the expression of a panel of miRNAs was analyzed by Real-Time PCR method. Expression levels of miR-328, miR-18a, miR-339 and miR-140 were significantly higher in NSCLC patients than in healthy donors (p < 0.05). In particular, miR-328 showed good diagnostic accuracy in discriminating between patients with early NSCLC and healthy donors (AUC ROC 0.82, 95% CI 0.72–0.92), with 70% sensitivity and 83% specificity at the best relative expression cut-off of 300. Moreover, miR-339 was a good discriminant between healthy donors and late-stage NSCLC patients (AUC ROC 0.79, 95% CI 0.68–0.91). In conclusion, miR-328 represents a potential diagnostic biomarker of NSCLC, especially for the identification of early-stage tumors. Its role in discriminating between benign and malignant nodules detected by spiral CT warrants further investigation. PMID:23681013

  4. Advanced accelerator methods: The cyclotrino

    SciTech Connect

    Welch, J.J.; Bertsche, K.J.; Friedman, P.G.; Morris, D.E.; Muller, R.A.

    1987-04-01

    Several new and unusual, advanced techniques in the small cyclotron are described. The cyclotron is run at low energy, using negative ions and at high harmonics. Electrostatic focusing is used exclusively. The ion source and injection system is in the center, which unfortunately does not provide enough current, but the new system design should solve this problem. An electrostatic extractor that runs at low voltage, under 5 kV, and a microchannel plate detector which is able to discriminate low energy ions from the /sup 14/C are used. The resolution is sufficient for /sup 14/C dating and a higher intensity source should allow dating of a milligram size sample of 30,000 year old material with less than 10% uncertainty.

  5. Advanced reliability methods - A review

    NASA Astrophysics Data System (ADS)

    Forsyth, David S.

    2016-02-01

    There are a number of challenges to the current practices for Probability of Detection (POD) assessment. Some Nondestructive Testing (NDT) methods, especially those that are image-based, may not provide a simple relationship between a scalar NDT response and a damage size. Some damage types are not easily characterized by a single scalar metric. Other sensing paradigms, such as structural health monitoring, could theoretically replace NDT but require a POD estimate. And the cost of performing large empirical studies to estimate POD can be prohibitive. The response of the research community has been to develop new methods that can be used to generate the same information, POD, in a form that can be used by engineering designers. This paper will highlight approaches to image-based data and complex defects, Model Assisted POD estimation, and Bayesian methods for combining information. This paper will also review the relationship of the POD estimate, confidence bounds, tolerance bounds, and risk assessment.

  6. Pazopanib diminishes non-small cell lung cancer (NSCLC) growth and metastases in vivo

    PubMed Central

    Zhao, Honglin; Yang, Fan; Shen, Wang; Wang, Yuli; Li, Xuebing; You, Jiacong; Zhou, Qinghua

    2015-01-01

    Background Anti-angiogenesis has been demonstrated to have a critical role in lung cancer pathogenesis. Here, we characterized the effect of the small-molecule angiogenesis inhibitor pazopanib on non-small cell lung cancer (NSCLC) cells. Methods NSCLC cells were tested for viability and migration after incubation with varying concentrations of pazopanib. Further, the phosphorylation status of extracellular signal-regulated kinase, protein kinase B, and MEK were assessed in vitro. For in vivo testing, mice grafted with NSCLC cell lines L9981 and A549 were treated orally with pazopanib. Results Pazopanib inhibits signaling pathways in tumor cells, thus blocking NSCLC cell growth and migration in vitro and inducing tumor cell arrest at G0/G1 phase. We show that pazopanib could inhibit tumor cell growth, decrease metastases, and prolong survival in two mouse xenograft models of human NSCLC. Conclusion These preclinical studies of pazopanib show the possibility of clinical application and, ultimately, improvement in patient outcome. PMID:26273349

  7. Advanced Fine Particulate Characterization Methods

    SciTech Connect

    Steven Benson; Lingbu Kong; Alexander Azenkeng; Jason Laumb; Robert Jensen; Edwin Olson; Jill MacKenzie; A.M. Rokanuzzaman

    2007-01-31

    The characterization and control of emissions from combustion sources are of significant importance in improving local and regional air quality. Such emissions include fine particulate matter, organic carbon compounds, and NO{sub x} and SO{sub 2} gases, along with mercury and other toxic metals. This project involved four activities including Further Development of Analytical Techniques for PM{sub 10} and PM{sub 2.5} Characterization and Source Apportionment and Management, Organic Carbonaceous Particulate and Metal Speciation for Source Apportionment Studies, Quantum Modeling, and High-Potassium Carbon Production with Biomass-Coal Blending. The key accomplishments included the development of improved automated methods to characterize the inorganic and organic components particulate matter. The methods involved the use of scanning electron microscopy and x-ray microanalysis for the inorganic fraction and a combination of extractive methods combined with near-edge x-ray absorption fine structure to characterize the organic fraction. These methods have direction application for source apportionment studies of PM because they provide detailed inorganic analysis along with total organic and elemental carbon (OC/EC) quantification. Quantum modeling using density functional theory (DFT) calculations was used to further elucidate a recently developed mechanistic model for mercury speciation in coal combustion systems and interactions on activated carbon. Reaction energies, enthalpies, free energies and binding energies of Hg species to the prototype molecules were derived from the data obtained in these calculations. Bimolecular rate constants for the various elementary steps in the mechanism have been estimated using the hard-sphere collision theory approximation, and the results seem to indicate that extremely fast kinetics could be involved in these surface reactions. Activated carbon was produced from a blend of lignite coal from the Center Mine in North Dakota and

  8. Recent advances in lattice Boltzmann methods

    SciTech Connect

    Chen, S.; Doolen, G.D.; He, X.; Nie, X.; Zhang, R.

    1998-12-31

    In this paper, the authors briefly present the basic principles of lattice Boltzmann method and summarize recent advances of the method, including the application of the lattice Boltzmann method for fluid flows in MEMS and simulation of the multiphase mixing and turbulence.

  9. MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: a prospective case–control study

    PubMed Central

    Razzak, R.; Bédard, E.L.R.; Kim, J.O.; Gazala, S.; Guo, L.; Ghosh, S.; Joy, A.; Nijjar, T.; Wong, E.; Roa, W.H.

    2016-01-01

    Background Non-small-cell lung cancer (nsclc) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. Micrornas (mirnas) are a class of short, noncoding rna molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting nsclc. We investigated the stage-specific nsclc detection potential of an efficient panel of 3 mirnas (mir-21, mir-210, mir-372) using a single sputum sample. Methods A single spontaneously expectorated sputum sample was prospectively collected from 21 early nsclc (≤stage ii) patients, 22 advanced nsclc (≥stage iii) patients, and 10 control subjects. Mirna expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis. Results Mean tumour size (±95% confidence interval) in the early and advanced nsclc patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced nsclc cases respectively. In comparing the early nsclc group with the control group, the mirna panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced nsclc group, the mirna panel detected nsclc with a sensitivity and specificity of 64% and 100% respectively. Conclusions A sputum mir-21, mir-210, and mir-372 expression profile might provide a sensitive and highly specific means for detecting nsclc. Sputum mirna analysis demonstrates promise as a potential complementary screening tool. PMID:27122989

  10. Nintedanib in NSCLC: evidence to date and place in therapy

    PubMed Central

    Bronte, Giuseppe; Passiglia, Francesco; Galvano, Antonio; Barraco, Nadia; Listì, Angela; Castiglia, Marta; Rizzo, Sergio; Fiorentino, Eugenio; Bazan, Viviana; Russo, Antonio

    2016-01-01

    The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both preclinical and clinical phase I and II trials; however, its approval for the use in clinical practice has been possible because of the positive results of the LUME-Lung 1 trial (nintedanib + docetaxel versus docetaxel alone) in terms of progression-free survival and overall survival, and a manageable tolerability profile. Therefore, the good results seen in the clinical trials with nintedanib in the second-line setting for NSCLC patients with adenocarcinoma subtype are encouraging enough to recommend it in clinical practice. PMID:27239237

  11. Three emerging new drugs for NSCLC: pemetrexed, bortezomib, and cetuximab.

    PubMed

    Dubey, Sarita; Schiller, Joan H

    2005-04-01

    Despite advances made in cytotoxic chemotherapy, the prognosis for patients with non-small cell lung cancer (NSCLC) continues to be poor. New, more effective drugs must be identified and developed to improve the outcome of these patients. Three drugs with promising activity in NSCLC are pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com), bortezomib (Velcade; Millennium Pharmaceuticals, Inc., Cambridge, MA, http://www.mlnm.com), and cetuximab (Erbitux; ImClone Systems, Inc., New York, NY, http://www.imclone.com). Pemetrexed inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase, enzymes necessary for purine and pyrimidine synthesis, thus causing cell-cycle arrest in the S phase. Bortezomib, a proteasome inhibitor, interferes with the cytosolic protein degradation machinery, namely the ubiquitin-proteasome complex, causing breakdown of cell-cycle regulators and cell-cycle arrest. Cetuximab is a chimeric mouse-human antibody that inhibits ligand-dependent activation of the epidermal growth factor receptor, resulting in receptor internalization and inhibition of downstream pathways that, in turn, causes cell growth and progression. All three drugs are approved for different tumor types, and studies defining their role in NSCLC are under way. PMID:15821248

  12. Advanced analysis methods in particle physics

    SciTech Connect

    Bhat, Pushpalatha C.; /Fermilab

    2010-10-01

    Each generation of high energy physics experiments is grander in scale than the previous - more powerful, more complex and more demanding in terms of data handling and analysis. The spectacular performance of the Tevatron and the beginning of operations of the Large Hadron Collider, have placed us at the threshold of a new era in particle physics. The discovery of the Higgs boson or another agent of electroweak symmetry breaking and evidence of new physics may be just around the corner. The greatest challenge in these pursuits is to extract the extremely rare signals, if any, from huge backgrounds arising from known physics processes. The use of advanced analysis techniques is crucial in achieving this goal. In this review, I discuss the concepts of optimal analysis, some important advanced analysis methods and a few examples. The judicious use of these advanced methods should enable new discoveries and produce results with better precision, robustness and clarity.

  13. Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application

    PubMed Central

    Sacco, Paola Claudia; Sgambato, Assunta; Casaluce, Francesca; Rossi, Antonio; Gridelli, Cesare

    2015-01-01

    The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC. Unfortunately, drug resistance develops after initial benefit through a variety of mechanisms. Novel generation EGFR and ALK inhibitors are currently in advanced clinical development and are producing encouraging results in patients with acquired resistance to previous generation agents. The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations or ALK rearrangements is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC. PMID:26327924

  14. Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application.

    PubMed

    Maione, Paolo; Sacco, Paola Claudia; Sgambato, Assunta; Casaluce, Francesca; Rossi, Antonio; Gridelli, Cesare

    2015-09-01

    The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC. Unfortunately, drug resistance develops after initial benefit through a variety of mechanisms. Novel generation EGFR and ALK inhibitors are currently in advanced clinical development and are producing encouraging results in patients with acquired resistance to previous generation agents. The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations or ALK rearrangements is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC. PMID:26327924

  15. Cost estimating methods for advanced space systems

    NASA Technical Reports Server (NTRS)

    Cyr, Kelley

    1988-01-01

    The development of parametric cost estimating methods for advanced space systems in the conceptual design phase is discussed. The process of identifying variables which drive cost and the relationship between weight and cost are discussed. A theoretical model of cost is developed and tested using a historical data base of research and development projects.

  16. What Is the Best Way to Contour Lung Tumors on PET Scans? Multiobserver Validation of a Gradient-Based Method Using a NSCLC Digital PET Phantom

    SciTech Connect

    Werner-Wasik, Maria; Nelson, Arden D.; Choi, Walter; Arai, Yoshio; Faulhaber, Peter F.; Kang, Patrick; Almeida, Fabio D.; Xiao, Ying; Ohri, Nitin; Brockway, Kristin D.; Piper, Jonathan W.; Nelson, Aaron S.

    2012-03-01

    Purpose: To evaluate the accuracy and consistency of a gradient-based positron emission tomography (PET) segmentation method, GRADIENT, compared with manual (MANUAL) and constant threshold (THRESHOLD) methods. Methods and Materials: Contouring accuracy was evaluated with sphere phantoms and clinically realistic Monte Carlo PET phantoms of the thorax. The sphere phantoms were 10-37 mm in diameter and were acquired at five institutions emulating clinical conditions. One institution also acquired a sphere phantom with multiple source-to-background ratios of 2:1, 5:1, 10:1, 20:1, and 70:1. One observer segmented (contoured) each sphere with GRADIENT and THRESHOLD from 25% to 50% at 5% increments. Subsequently, seven physicians segmented 31 lesions (7-264 mL) from 25 digital thorax phantoms using GRADIENT, THRESHOLD, and MANUAL. Results: For spheres <20 mm in diameter, GRADIENT was the most accurate with a mean absolute % error in diameter of 8.15% (10.2% SD) compared with 49.2% (51.1% SD) for 45% THRESHOLD (p < 0.005). For larger spheres, the methods were statistically equivalent. For varying source-to-background ratios, GRADIENT was the most accurate for spheres >20 mm (p < 0.065) and <20 mm (p < 0.015). For digital thorax phantoms, GRADIENT was the most accurate (p < 0.01), with a mean absolute % error in volume of 10.99% (11.9% SD), followed by 25% THRESHOLD at 17.5% (29.4% SD), and MANUAL at 19.5% (17.2% SD). GRADIENT had the least systematic bias, with a mean % error in volume of -0.05% (16.2% SD) compared with 25% THRESHOLD at -2.1% (34.2% SD) and MANUAL at -16.3% (20.2% SD; p value <0.01). Interobserver variability was reduced using GRADIENT compared with both 25% THRESHOLD and MANUAL (p value <0.01, Levene's test). Conclusion: GRADIENT was the most accurate and consistent technique for target volume contouring. GRADIENT was also the most robust for varying imaging conditions. GRADIENT has the potential to play an important role for tumor delineation in

  17. Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

    PubMed Central

    De Grève, Jacques; Van Meerbeeck, Jan; Vansteenkiste, Johan F.; Decoster, Lore; Meert, Anne-Pascale; Vuylsteke, Peter; Focan, Christian; Canon, Jean-Luc; Humblet, Yves; Berchem, Guy; Colinet, Benoit; Galdermans, Danny; Bosquée, Lionel; Vermeij, Joanna; Dewaele, Alex; Geers, Caroline; Schallier, Denis; Teugels, Erik

    2016-01-01

    Introduction Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor. Methods Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease. Results Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung. Conclusion The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed. Trial Registration ClinicalTrials.gov NCT00339586 PMID:27032107

  18. Advanced Bayesian Method for Planetary Surface Navigation

    NASA Technical Reports Server (NTRS)

    Center, Julian

    2015-01-01

    Autonomous Exploration, Inc., has developed an advanced Bayesian statistical inference method that leverages current computing technology to produce a highly accurate surface navigation system. The method combines dense stereo vision and high-speed optical flow to implement visual odometry (VO) to track faster rover movements. The Bayesian VO technique improves performance by using all image information rather than corner features only. The method determines what can be learned from each image pixel and weighs the information accordingly. This capability improves performance in shadowed areas that yield only low-contrast images. The error characteristics of the visual processing are complementary to those of a low-cost inertial measurement unit (IMU), so the combination of the two capabilities provides highly accurate navigation. The method increases NASA mission productivity by enabling faster rover speed and accuracy. On Earth, the technology will permit operation of robots and autonomous vehicles in areas where the Global Positioning System (GPS) is degraded or unavailable.

  19. Advanced Analysis Methods in High Energy Physics

    SciTech Connect

    Pushpalatha C. Bhat

    2001-10-03

    During the coming decade, high energy physics experiments at the Fermilab Tevatron and around the globe will use very sophisticated equipment to record unprecedented amounts of data in the hope of making major discoveries that may unravel some of Nature's deepest mysteries. The discovery of the Higgs boson and signals of new physics may be around the corner. The use of advanced analysis techniques will be crucial in achieving these goals. The author discusses some of the novel methods of analysis that could prove to be particularly valuable for finding evidence of any new physics, for improving precision measurements and for exploring parameter spaces of theoretical models.

  20. Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation

    PubMed Central

    Groenendijk, Floris H; Mellema, Wouter W; van der Burg, Eline; Schut, Eva; Hauptmann, Michael; Horlings, Hugo M; Willems, Stefan M; van den Heuvel, Michel M; Jonkers, Jos; Smit, Egbert F; Bernards, René

    2015-01-01

    The multikinase inhibitor sorafenib is under clinical investigation for the treatment of many solid tumors, but in most cases, the molecular target responsible for the clinical effect is unknown. Furthermore, enhancing the effectiveness of sorafenib using combination strategies is a major clinical challenge. Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2. We further show in a phase II clinical trial in KRAS mutant advanced non-small cell lung cancer (NSCLC) with single agent sorafenib an improved disease control rate in patients using the antidiabetic drug metformin. Consistent with this, sorafenib and metformin act synergistically in inhibiting cellular proliferation in NSCLC in vitro and in vivo. A synergistic effect of both drugs is also seen on phosphorylation of the AMPKα activation site. Our results provide a rationale for the synergistic antiproliferative effects, given that AMPK inhibits downstream mTOR signaling. These data suggest that the combination of sorafenib with AMPK activators could have beneficial effects on tumor regression by AMPK pathway activation. The combination of metformin or other AMPK activators and sorafenib could be tested in prospective clinical trials. PMID:25080865

  1. Emerging treatments and combinations in the management of NSCLC: clinical potential of nintedanib

    PubMed Central

    Reck, Martin; Mellemgaard, Anders

    2015-01-01

    There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy. PMID:26170616

  2. Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases.

    PubMed

    Dudnik, Elizabeth; Yust-Katz, Shlomit; Nechushtan, Hovav; Goldstein, Daniel A; Zer, Alona; Flex, Dov; Siegal, Tali; Peled, Nir

    2016-08-01

    Central nervous system (CNS) metastases occur in 30% of patients with advanced non-small cell lung cancer (NSCLC). Localized treatments targeting CNS metastases result in delays in systemic therapy administration and are associated with neurocognitive impairment. Nivolumab is an immune check-point inhibitor that is approved as a second-line treatment of NSCLC. Data regarding the intracranial activity of nivolumab is lacking. We retrospectively reviewed the efficacy and safety of nivolumab in five patients with advanced NSCLC and new/progressing intracranial metastases. Intracranial response was assessed by magnetic resonance imaging (MRI) using mRECIST v. 1.1 criteria. All patients had parenchymal brain metastases; two patients had leptomeningeal carcinomatosis diagnosed according to radiological criteria. All patients were asymptomatic and did not require corticosteroids or immediate local therapy. We observed one complete and one partial response in the brain. Stabilization of leptomeningeal carcinomatosis for 10 weeks was achieved in one additional patient. Two patients progressed in the CNS. Time-to-response comprised 5 weeks and 9 weeks; both responses are still ongoing at the time of the report (24+ and 28+ weeks since start of treatment). Systemic responses and intracranial responses were largely concordant. No treatment-related or CNS metastases-related grade≥3 adverse events were observed. Nivolumab might have intracranial activity and favorable safety profile in patients with CNS metastases secondary to NSCLC. Nivolumab CNS activity warrants further evaluation. PMID:27393516

  3. 7 CFR 27.92 - Method of payment; advance deposit.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Method of payment; advance deposit. 27.92 Section 27... Micronaire § 27.92 Method of payment; advance deposit. Any payment or advance deposit under this subpart...,” and may not be made in cash except in cases where the total payment or deposit does not exceed...

  4. Effect of ABCG2/BCRP Expression on Efflux and Uptake of Gefitinib in NSCLC Cell Lines

    PubMed Central

    Galetti, Maricla; Petronini, Pier Giorgio; Fumarola, Claudia; Cretella, Daniele; La Monica, Silvia; Bonelli, Mara; Cavazzoni, Andrea; Saccani, Francesca; Caffarra, Cristina; Andreoli, Roberta; Mutti, Antonio; Tiseo, Marcello; Ardizzoni, Andrea; Alfieri, Roberta R.

    2015-01-01

    Background BCRP/ABCG2 emerged as an important multidrug resistance protein, because it confers resistance to several classes of cancer chemotherapeutic agents and to a number of novel molecularly-targeted therapeutics such as tyrosine kinase inhibitors. Gefitinib is an orally active, selective EGFR tyrosine kinase inhibitor used in the treatment of patients with advanced non small cell lung cancer (NSCLC) carrying activating EGFR mutations. Membrane transporters may affect the distribution and accumulation of gefitinib in tumour cells; in particular a reduced intracellular level of the drug may result from poor uptake, enhanced efflux or increased metabolism. Aim The present study, performed in a panel of NSCLC cell lines expressing different ABCG2 plasma membrane levels, was designed to investigate the effect of the efflux transporter ABCG2 on intracellular gefitinib accumulation, by dissecting the contribution of uptake and efflux processes. Methods and Results Our findings indicate that gefitinib, in lung cancer cells, inhibits ABCG2 activity, as previously reported. In addition, we suggest that ABCG2 silencing or overexpression affects intracellular gefitinib content by modulating the uptake rather than the efflux. Similarly, overexpression of ABCG2 affected the expression of a number of drug transporters, altering the functional activities of nutrient and drug transport systems, in particular inhibiting MPP, glucose and glutamine uptake. Conclusions Therefore, we conclude that gefitinib is an inhibitor but not a substrate for ABCG2 and that ABCG2 overexpression may modulate the expression and activity of other transporters involved in the uptake of different substrates into the cells. PMID:26536031

  5. Downregulation of the long non-coding RNA TUSC7 promotes NSCLC cell proliferation and correlates with poor prognosis

    PubMed Central

    Wang, Zhongwei; Jin, Yingying; Ren, Hongtao; Ma, Xiulong; Wang, Baofeng; Wang, Yali

    2016-01-01

    Background: Emerging evidence indicated that dysregulated long non-coding RNAs (lncRNAs) was implicated in the tumorigenesis and progression. LncRNA TUSC7 was involved in various malignancies. However, the role of TUSC7 in human non-small-cell lung cancer (NSCLC) remains unclear. Methods: Expression of TUSC7 was analyzed in 112 cases of NSCLC tissues and six lung cancer cell lines by quantitative real-time PCR (qRT-PCR). Then the correlation of TUSC7 expression with clinicopathological features and prognosis was aslo studied. Furthermore, overexpression of TUSC7 was performed and its role in tumor progression was explored. Results: The expression level of TUSC7 was lower in NSCLC tissues and lung cancer cells compared with their normal counterparts. Lower expression of TUSC7 in NSCLC tissues was associated with larger tumor size and higher TNM stage. Patients with lower TUSC7 expression had worse overall survival compared with the high expression cases. Univariate and multivariate analyses suggested that low expression of TUSC7 was an independent poor prognostic indicator for NSCLC patients. Moreover, upregulation of TUSC7 expression could inhibit proliferation of lung cancer cell in vitro. Conclusions: Our results suggested that TUSC7 was a potential biomarker for NSCLC prognosis, and the dysregulation of TUSC7 may play an important role in the NSCLC progression. PMID:27158360

  6. Advanced electromagnetic methods for aerospace vehicles

    NASA Astrophysics Data System (ADS)

    Balanis, Constantine A.; Sun, Weimin; El-Sharawy, El-Budawy; Aberle, James T.; Birtcher, Craig R.; Peng, Jian; Tirkas, Panayiotis A.; Kokotoff, David; Zavosh, Frank

    1993-06-01

    The Advanced Helicopter Electromagnetics (AHE) Industrial Associates Program has continuously progressed with its research effort focused on subjects identified and recommended by the Advisory Task Force of the program. The research activities in this reporting period have been steered toward practical helicopter electromagnetic problems, such as HF antenna problems and antenna efficiencies, recommended by the AHE members at the annual conference held at Arizona State University on 28-29 Oct. 1992 and the last biannual meeting held at the Boeing Helicopter on 19-20 May 1993. The main topics addressed include the following: Composite Materials and Antenna Technology. The research work on each topic is closely tied with the AHE Consortium members' interests. Significant progress in each subject is reported. Special attention in the area of Composite Materials has been given to the following: modeling of material discontinuity and their effects on towel-bar antenna patterns; guidelines for composite material modeling by using the Green's function approach in the NEC code; measurements of towel-bar antennas grounded with a partially material-coated plate; development of 3-D volume mesh generator for modeling thick and volumetric dielectrics by using FD-TD method; FDTD modeling of horn antennas with composite E-plane walls; and antenna efficiency analysis for a horn antenna loaded with composite dielectric materials.

  7. Advanced continuous cultivation methods for systems microbiology.

    PubMed

    Adamberg, Kaarel; Valgepea, Kaspar; Vilu, Raivo

    2015-09-01

    Increasing the throughput of systems biology-based experimental characterization of in silico-designed strains has great potential for accelerating the development of cell factories. For this, analysis of metabolism in the steady state is essential as only this enables the unequivocal definition of the physiological state of cells, which is needed for the complete description and in silico reconstruction of their phenotypes. In this review, we show that for a systems microbiology approach, high-resolution characterization of metabolism in the steady state--growth space analysis (GSA)--can be achieved by using advanced continuous cultivation methods termed changestats. In changestats, an environmental parameter is continuously changed at a constant rate within one experiment whilst maintaining cells in the physiological steady state similar to chemostats. This increases the resolution and throughput of GSA compared with chemostats, and, moreover, enables following of the dynamics of metabolism and detection of metabolic switch-points and optimal growth conditions. We also describe the concept, challenge and necessary criteria of the systematic analysis of steady-state metabolism. Finally, we propose that such systematic characterization of the steady-state growth space of cells using changestats has value not only for fundamental studies of metabolism, but also for systems biology-based metabolic engineering of cell factories. PMID:26220303

  8. Advanced electromagnetic methods for aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Balanis, Constantine A.; Sun, Weimin; El-Sharawy, El-Budawy; Aberle, James T.; Birtcher, Craig R.; Peng, Jian; Tirkas, Panayiotis A.; Andrew, William V.; Kokotoff, David; Zavosh, Frank

    1993-01-01

    The Advanced Helicopter Electromagnetics (AHE) Industrial Associates Program has fruitfully completed its fourth year. Under the support of the AHE members and the joint effort of the research team, new and significant progress has been achieved in the year. Following the recommendations by the Advisory Task Force, the research effort is placed on more practical helicopter electromagnetic problems, such as HF antennas, composite materials, and antenna efficiencies. In this annual report, the main topics to be addressed include composite materials and antenna technology. The research work on each topic has been driven by the AHE consortium members' interests and needs. The remarkable achievements and progresses in each subject is reported respectively in individual sections of the report. The work in the area of composite materials includes: modeling of low conductivity composite materials by using Green's function approach; guidelines for composite material modeling by using the Green's function approach in the NEC code; development of 3-D volume mesh generator for modeling thick and volumetric dielectrics by using FD-TD method; modeling antenna elements mounted on a composite Comanche tail stabilizer; and antenna pattern control and efficiency estimate for a horn antenna loaded with composite dielectric materials.

  9. Advanced electromagnetic methods for aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Balanis, Constantine A.; Sun, Weimin; El-Sharawy, El-Budawy; Aberle, James T.; Birtcher, Craig R.; Peng, Jian; Tirkas, Panayiotis A.; Kokotoff, David; Zavosh, Frank

    1993-01-01

    The Advanced Helicopter Electromagnetics (AHE) Industrial Associates Program has continuously progressed with its research effort focused on subjects identified and recommended by the Advisory Task Force of the program. The research activities in this reporting period have been steered toward practical helicopter electromagnetic problems, such as HF antenna problems and antenna efficiencies, recommended by the AHE members at the annual conference held at Arizona State University on 28-29 Oct. 1992 and the last biannual meeting held at the Boeing Helicopter on 19-20 May 1993. The main topics addressed include the following: Composite Materials and Antenna Technology. The research work on each topic is closely tied with the AHE Consortium members' interests. Significant progress in each subject is reported. Special attention in the area of Composite Materials has been given to the following: modeling of material discontinuity and their effects on towel-bar antenna patterns; guidelines for composite material modeling by using the Green's function approach in the NEC code; measurements of towel-bar antennas grounded with a partially material-coated plate; development of 3-D volume mesh generator for modeling thick and volumetric dielectrics by using FD-TD method; FDTD modeling of horn antennas with composite E-plane walls; and antenna efficiency analysis for a horn antenna loaded with composite dielectric materials.

  10. Why Video? How Technology Advances Method

    ERIC Educational Resources Information Center

    Downing, Martin J., Jr.

    2008-01-01

    This paper reports on the use of video to enhance qualitative research. Advances in technology have improved our ability to capture lived experiences through visual means. I reflect on my previous work with individuals living with HIV/AIDS, the results of which are described in another paper, to evaluate the effectiveness of video as a medium that…

  11. A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives

    PubMed Central

    Russo, Alessandro; Franchina, Tindara; Rita Ricciardi, Giuseppina Rosaria; Picone, Antonio; Ferraro, Giuseppa; Zanghì, Mariangela; Toscano, Giuseppe; Giordano, Antonio; Adamo, Vincenzo

    2015-01-01

    The discovery of Epidermal Growth Factor Receptor (EGFR) mutations in Non Small Cell Lung Cancer (NSCLC) launched the era of personalized medicine in advanced NSCLC, leading to a dramatic shift in the therapeutic landscape of this disease. After ten years from the individuation of activating mutations in the tyrosine kinase domain of the EGFR in NSCLC patients responding to the EGFR tyrosine kinase inhibitor (TKI) Gefitinib, several progresses have been done and first line treatment with EGFR TKIs is a firmly established option in advanced EGFR-mutated NSCLC patients. During the last decade, different EGFR TKIs have been developed and three inhibitors have been approved so far in these selected patients. However, despite great breakthroughs have been made, treatment of these molecularly selected patients poses novel therapeutic challenges, such as emerging of acquired resistance, brain metastases development or the need to translate these treatments in earlier clinical settings, such as adjuvant therapy. The aim of this paper is to provide a comprehensive review of the major progresses reported so far in the EGFR inhibition in this molecularly-selected subgroup of NSCLC patients, from the early successes with first generation EGFR TKIs, Erlotinib and Gefitinib, to the novel irreversible and mutant-selective inhibitors and ultimately the emerging challenges that we, in the next future, are called to deal with. PMID:26308162

  12. Method and apparatus for advancing tethers

    DOEpatents

    Zollinger, W. Thor

    1998-01-01

    A tether puller for advancing a tether through a channel may include a bellows assembly having a leading end fixedly attached to the tether at a first position and a trailing end fixedly attached to the tether at a second position so that the leading and trailing ends of the bellows assembly are located a substantially fixed distance apart. The bellows assembly includes a plurality of independently inflatable elements each of which may be separately inflated to an extended position and deflated to a retracted position. Each of the independently inflatable elements expands radially and axially upon inflation. An inflation system connected to the independently inflatable elements inflates and deflates selected ones of the independently inflatable elements to cause the bellows assembly to apply a tractive force to the tether and advance it in the channel.

  13. Method and apparatus for advancing tethers

    DOEpatents

    Zollinger, W.T.

    1998-06-02

    A tether puller for advancing a tether through a channel may include a bellows assembly having a leading end fixedly attached to the tether at a first position and a trailing end fixedly attached to the tether at a second position so that the leading and trailing ends of the bellows assembly are located a substantially fixed distance apart. The bellows assembly includes a plurality of independently inflatable elements each of which may be separately inflated to an extended position and deflated to a retracted position. Each of the independently inflatable elements expands radially and axially upon inflation. An inflation system connected to the independently inflatable elements inflates and deflates selected ones of the independently inflatable elements to cause the bellows assembly to apply a tractive force to the tether and advance it in the channel. 9 figs.

  14. Controlling template erosion with advanced cleaning methods

    NASA Astrophysics Data System (ADS)

    Singh, SherJang; Yu, Zhaoning; Wähler, Tobias; Kurataka, Nobuo; Gauzner, Gene; Wang, Hongying; Yang, Henry; Hsu, Yautzong; Lee, Kim; Kuo, David; Dress, Peter

    2012-03-01

    We studied the erosion and feature stability of fused silica patterns under different template cleaning conditions. The conventional SPM cleaning is compared with an advanced non-acid process. Spectroscopic ellipsometry optical critical dimension (SE-OCD) measurements were used to characterize the changes in pattern profile with good sensitivity. This study confirmed the erosion of the silica patterns in the traditional acid-based SPM cleaning mixture (H2SO4+H2O2) at a rate of ~0.1nm per cleaning cycle. The advanced non-acid clean process however only showed CD shift of ~0.01nm per clean. Contamination removal & pattern integrity of sensitive 20nm features under MegaSonic assisted cleaning is also demonstrated.

  15. Advanced electromagnetic methods for aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Balanis, Constantine A.; Sun, Weimin; El-Sharawy, El-Budawy; Aberle, James T.; Birtcher, Craig R.; Peng, Jian; Tirkas, Panayiotis A.

    1992-01-01

    The Advanced Helicopter Electromagnetics (AHE) Industrial Associates Program continues its research on variety of main topics identified and recommended by the Advisory Task Force of the program. The research activities center on issues that advance technology related to helicopter electromagnetics. While most of the topics are a continuation of previous works, special effort has been focused on some of the areas due to recommendations from the last annual conference. The main topics addressed in this report are: composite materials, and antenna technology. The area of composite materials continues getting special attention in this period. The research has focused on: (1) measurements of the electrical properties of low-conductivity materials; (2) modeling of material discontinuity and their effects on the scattering patterns; (3) preliminary analysis on interaction of electromagnetic fields with multi-layered graphite fiberglass plates; and (4) finite difference time domain (FDTD) modeling of fields penetration through composite panels of a helicopter.

  16. NATO PILOT STUDY ON ADVANCED CANCER RISK ASSESSMENT METHODS

    EPA Science Inventory

    NCEA scientists are participating in a study of advanced cancer risk assessment methods, conducted under the auspices of NATO's Committee on the Challenges of Modern Society. The product will be a book of case studies that illustrate advanced cancer risk assessment methods, avail...

  17. Advanced methods of structural and trajectory analysis for transport aircraft

    NASA Technical Reports Server (NTRS)

    Ardema, Mark D.

    1995-01-01

    This report summarizes the efforts in two areas: (1) development of advanced methods of structural weight estimation, and (2) development of advanced methods of trajectory optimization. The majority of the effort was spent in the structural weight area. A draft of 'Analytical Fuselage and Wing Weight Estimation of Transport Aircraft', resulting from this research, is included as an appendix.

  18. Progress of EGFR-TKI and ALK/ROS1 inhibitors in advanced non-small cell lung cancer

    PubMed Central

    Ge, Liangqing; Shi, Ruizheng

    2015-01-01

    To discuss the mechanism and clinical application of EGFR-TKI and ALK/ROS1 inhibitors in non-small cell lung cancer (NSCLC), we reviewed recent available data mainly from PubMed. We found that chemotherapy, progression-free survival (PFS), objective response rate (ORR), and quality of life of patients with advanced NSCLC can be greatly improved in these drugs medication compared with conventional chemotherapy. Though many questions like resistance to EGFR-TKI and ALK/ROS1 inhibitors exist, molecular targeted therapy is an important therapeutic method for the management of NSCLC. The role of molecule targeted therapy in the initiation and development of NSCLC deserves further study. PMID:26379824

  19. Advanced electromagnetic methods for aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Balanis, Constantine A.; El-Sharawy, El-Budawy; Hashemi-Yeganeh, Shahrokh; Aberle, James T.; Birtcher, Craig R.

    1991-01-01

    The Advanced Helicopter Electromagnetics is centered on issues that advance technology related to helicopter electromagnetics. Progress was made on three major topics: composite materials; precipitation static corona discharge; and antenna technology. In composite materials, the research has focused on the measurements of their electrical properties, and the modeling of material discontinuities and their effect on the radiation pattern of antennas mounted on or near material surfaces. The electrical properties were used to model antenna performance when mounted on composite materials. Since helicopter platforms include several antenna systems at VHF and UHF bands, measuring techniques are being explored that can be used to measure the properties at these bands. The effort on corona discharge and precipitation static was directed toward the development of a new two dimensional Voltage Finite Difference Time Domain computer program. Results indicate the feasibility of using potentials for simulating electromagnetic problems in the cases where potentials become primary sources. In antenna technology the focus was on Polarization Diverse Conformal Microstrip Antennas, Cavity Backed Slot Antennas, and Varactor Tuned Circular Patch Antennas. Numerical codes were developed for the analysis of two probe fed rectangular and circular microstrip patch antennas fed by resistive and reactive power divider networks.

  20. Advanced particulate matter control apparatus and methods

    DOEpatents

    Miller, Stanley J.; Zhuang, Ye; Almlie, Jay C.

    2012-01-10

    Apparatus and methods for collection and removal of particulate matter, including fine particulate matter, from a gas stream, comprising a unique combination of high collection efficiency and ultralow pressure drop across the filter. The apparatus and method utilize simultaneous electrostatic precipitation and membrane filtration of a particular pore size, wherein electrostatic collection and filtration occur on the same surface.

  1. ERβ localization influenced outcomes of EGFR-TKI treatment in NSCLC patients with EGFR mutations

    PubMed Central

    Wang, Zhijie; Li, Zhenxiang; Ding, Xiaosheng; Shen, Zhirong; Liu, Zhentao; An, Tongtong; Duan, Jianchun; Zhong, Jia; Wu, Meina; Zhao, Jun; Zhuo, Minglei; Wang, Yuyan; Wang, Shuhang; Sun, Yu; Bai, Hua; Wang, Jie

    2015-01-01

    Effects of estrogen receptorβ (ERβ) localization on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) are unknown. First, we analyzed the relationship between ERβ localization determined by immunohistochemistry and EGFR-TKI outcomes in 184 patients with advanced NSCLC and found that ERβ expression localized in the cytoplasm and/or nucleus. The frequency of cytoplasmic ERβ (c-ERβ) and nuclear ERβ (n-ERβ) co-expression was 12% (22/184). C-ERβ and n-ERβ co-expression was correlated with poor median progression-free survival compared to patients without co-expression. In subsequent in vitro experiments, PC9 cells transfected with ERβ isoform1 (ERβ1, strong expression of both c-ERβ and n-ERβ) were more resistant to gefitinib than PC9 cells transfected with ERβ isoform2 or 5 (ERβ2 or ERβ5, strong expression of ERβ in cytoplasm but not nucleus). Resistance was identified due to interactions between ERβ1 and other isoforms, and mediated by activation of non-genomic pathways. Moreover, gefitinib resistance was reversed by a combination treatment with gefitinib and fulvestrant, both in cell lines and in one NSCLC patient. These results suggested that c-ERβ and n-ERβ co-expression was a potential molecular indicator of EGFR-TKI resistance, which might be overcome by combining EGFR-TKI and ER antagonist. PMID:26096604

  2. ERβ localization influenced outcomes of EGFR-TKI treatment in NSCLC patients with EGFR mutations.

    PubMed

    Wang, Zhijie; Li, Zhenxiang; Ding, Xiaosheng; Shen, Zhirong; Liu, Zhentao; An, Tongtong; Duan, Jianchun; Zhong, Jia; Wu, Meina; Zhao, Jun; Zhuo, Minglei; Wang, Yuyan; Wang, Shuhang; Sun, Yu; Bai, Hua; Wang, Jie

    2015-01-01

    Effects of estrogen receptorβ (ERβ) localization on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) are unknown. First, we analyzed the relationship between ERβ localization determined by immunohistochemistry and EGFR-TKI outcomes in 184 patients with advanced NSCLC and found that ERβ expression localized in the cytoplasm and/or nucleus. The frequency of cytoplasmic ERβ (c-ERβ) and nuclear ERβ (n-ERβ) co-expression was 12% (22/184). C-ERβ and n-ERβ co-expression was correlated with poor median progression-free survival compared to patients without co-expression. In subsequent in vitro experiments, PC9 cells transfected with ERβ isoform1 (ERβ1, strong expression of both c-ERβ and n-ERβ) were more resistant to gefitinib than PC9 cells transfected with ERβ isoform2 or 5 (ERβ2 or ERβ5, strong expression of ERβ in cytoplasm but not nucleus). Resistance was identified due to interactions between ERβ1 and other isoforms, and mediated by activation of non-genomic pathways. Moreover, gefitinib resistance was reversed by a combination treatment with gefitinib and fulvestrant, both in cell lines and in one NSCLC patient. These results suggested that c-ERβ and n-ERβ co-expression was a potential molecular indicator of EGFR-TKI resistance, which might be overcome by combining EGFR-TKI and ER antagonist. PMID:26096604

  3. Intercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations.

    PubMed

    Zwitter, Matjaz; Rajer, Mirjana; Stanic, Karmen; Vrankar, Martina; Doma, Andrej; Cuderman, Anka; Grmek, Marko; Kern, Izidor; Kovac, Viljem

    2016-08-01

    Among attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5 - 15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2-3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3  months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted. PMID:27261103

  4. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

    PubMed Central

    Dietel, Manfred; Bubendorf, Lukas; Dingemans, Anne-Marie C; Dooms, Christophe; Elmberger, Göran; García, Rosa Calero; Kerr, Keith M; Lim, Eric; López-Ríos, Fernando; Thunnissen, Erik; Van Schil, Paul E; von Laffert, Maximilian

    2016-01-01

    Background There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC. Methods Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to include all relevant aspects concerning NSCLC diagnosis. After careful consideration, the following topics were selected and each was reviewed by the experts: surgical resection and sampling; biopsy procedures for analysis; preanalytical and other variables affecting quality of tissue; tissue conservation; testing procedures for epidermal growth factor receptor, anaplastic lymphoma kinase and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) in lung tissue and cytological specimens; as well as standardised reporting and quality control (QC). Finally, an optimal workflow was described. Results Suggested optimal procedures and workflows are discussed in detail. The broad consensus was that the complex workflow presented can only be executed effectively by an interdisciplinary approach using a well-trained team. Conclusions To optimise diagnosis and treatment of patients with NSCLC, it is essential to establish SOPs that are adaptable to the local situation. In addition, a continuous QC system and a local multidisciplinary tumour-type-oriented board are essential. PMID:26530085

  5. Advanced spectral methods for climatic time series

    USGS Publications Warehouse

    Ghil, M.; Allen, M.R.; Dettinger, M.D.; Ide, K.; Kondrashov, D.; Mann, M.E.; Robertson, A.W.; Saunders, A.; Tian, Y.; Varadi, F.; Yiou, P.

    2002-01-01

    The analysis of univariate or multivariate time series provides crucial information to describe, understand, and predict climatic variability. The discovery and implementation of a number of novel methods for extracting useful information from time series has recently revitalized this classical field of study. Considerable progress has also been made in interpreting the information so obtained in terms of dynamical systems theory. In this review we describe the connections between time series analysis and nonlinear dynamics, discuss signal- to-noise enhancement, and present some of the novel methods for spectral analysis. The various steps, as well as the advantages and disadvantages of these methods, are illustrated by their application to an important climatic time series, the Southern Oscillation Index. This index captures major features of interannual climate variability and is used extensively in its prediction. Regional and global sea surface temperature data sets are used to illustrate multivariate spectral methods. Open questions and further prospects conclude the review.

  6. Advanced verification methods for OVI security ink

    NASA Astrophysics Data System (ADS)

    Coombs, Paul G.; McCaffery, Shaun F.; Markantes, Tom

    2006-02-01

    OVI security ink +, incorporating OVP security pigment* microflakes, enjoys a history of effective document protection. This security feature provides not only first-line recognition by the person on the street, but also facilitates machine-readability. This paper explores the evolution of OVI reader technology from proof-of-concept to miniaturization. Three different instruments have been built to advance the technology of OVI machine verification. A bench-top unit has been constructed which allows users to automatically verify a multitude of different banknotes and OVI images. In addition, high speed modules were fabricated and tested in a state of the art banknote sorting machine. Both units demonstrate the ability of modern optical components to illuminate and collect light reflected from the interference platelets within OVI ink. Electronic hardware and software convert and process the optical information in milliseconds to accurately determine the authenticity of the security feature. Most recently, OVI ink verification hardware has been miniaturized and simplified providing yet another platform for counterfeit protection. These latest devices provide a tool for store clerks and bank tellers to unambiguously determine the validity of banknotes in the time period it takes the cash drawer to be opened.

  7. Indentation Methods in Advanced Materials Research Introduction

    SciTech Connect

    Pharr, George Mathews; Cheng, Yang-Tse; Hutchings, Ian; Sakai, Mototsugu; Moody, Neville; Sundararajan, G.; Swain, Michael V.

    2009-01-01

    Since its commercialization early in the 20th century, indentation testing has played a key role in the development of new materials and understanding their mechanical behavior. Progr3ess in the field has relied on a close marriage between research in the mechanical behavior of materials and contact mechanics. The seminal work of Hertz laid the foundations for bringing these two together, with his contributions still widely utilized today in examining elastic behavior and the physics of fracture. Later, the pioneering work of Tabor, as published in his classic text 'The Hardness of Metals', exapdned this understanding to address the complexities of plasticity. Enormous progress in the field has been achieved in the last decade, made possible both by advances in instrumentation, for example, load and depth-sensing indentation and scanning electron microscopy (SEM) and transmission electron microscopy (TEM) based in situ testing, as well as improved modeling capabilities that use computationally intensive techniques such as finite element analysis and molecular dynamics simulation. The purpose of this special focus issue is to present recent state of the art developments in the field.

  8. Advances in methods for deepwater TLP installations

    SciTech Connect

    Wybro, P.G.

    1995-10-01

    This paper describes a method suitable for installing deepwater TLP structures in water depths beyond 3,000 ft. An overview is presented of previous TLP installation, wherein an evaluation is made of the various methods and their suitability to deepwater applications. A novel method for installation of deepwater TLP`s is described. This method of installation is most suitable for deepwater and/or large TLP structures, but can also be used in moderate water depth as well. The tendon installation method utilizes the so-called Platform Arrestor Concept (PAC), wherein tendon sections are transported by barges to site, and assembled vertically using a dynamically position crane vessel. The tendons are transferred to the platform where they are hung off until there are a full complement of tendons. The hull lock off operation is performed on all tendons simultaneously, avoiding dangerous platform resonant behavior. The installation calls for relatively simple installation equipment, and also enables the use of simple tendon tie-off equipment, such as a single piece nut.

  9. Advanced reliability method for fatigue analysis

    NASA Technical Reports Server (NTRS)

    Wu, Y.-T.; Wirsching, P. H.

    1984-01-01

    When design factors are considered as random variables and the failure condition cannot be expressed by a closed form algebraic inequality, computations of risk (or probability of failure) may become extremely difficult or very inefficient. This study suggests using a simple and easily constructed second degree polynomial to approximate the complicated limit state in the neighborhood of the design point; a computer analysis relates the design variables at selected points. Then a fast probability integration technique (i.e., the Rackwitz-Fiessler algorithm) can be used to estimate risk. The capability of the proposed method is demonstrated in an example of a low cycle fatigue problem for which a computer analysis is required to perform local strain analysis to relate the design variables. A comparison of the performance of this method is made with a far more costly Monte Carlo solution. Agreement of the proposed method with Monte Carlo is considered to be good.

  10. Transonic wing analysis using advanced computational methods

    NASA Technical Reports Server (NTRS)

    Henne, P. A.; Hicks, R. M.

    1978-01-01

    This paper discusses the application of three-dimensional computational transonic flow methods to several different types of transport wing designs. The purpose of these applications is to evaluate the basic accuracy and limitations associated with such numerical methods. The use of such computational methods for practical engineering problems can only be justified after favorable evaluations are completed. The paper summarizes a study of both the small-disturbance and the full potential technique for computing three-dimensional transonic flows. Computed three-dimensional results are compared to both experimental measurements and theoretical results. Comparisons are made not only of pressure distributions but also of lift and drag forces. Transonic drag rise characteristics are compared. Three-dimensional pressure distributions and aerodynamic forces, computed from the full potential solution, compare reasonably well with experimental results for a wide range of configurations and flow conditions.

  11. Advanced method for making vitreous waste forms

    SciTech Connect

    Pope, J.M.; Harrison, D.E.

    1980-01-01

    A process is described for making waste glass that circumvents the problems of dissolving nuclear waste in molten glass at high temperatures. Because the reactive mixing process is independent of the inherent viscosity of the melt, any glass composition can be prepared with equal facility. Separation of the mixing and melting operations permits novel glass fabrication methods to be employed.

  12. Advancing-layers method for generation of unstructured viscous grids

    NASA Technical Reports Server (NTRS)

    Pirzadeh, Shahyar

    1993-01-01

    A novel approach for generating highly stretched grids which is based on a modified advancing-front technique and benefits from the generality, flexibility, and grid quality of the conventional advancing-front-based Euler grid generators is presented. The method is self-sufficient for the insertion of grid points in the boundary layer and beyond. Since it is based on a totally unstructured grid strategy, the method alleviates the difficulties stemming from the structural limitations of the prismatic techniques.

  13. Advanced Electromagnetic Methods for Aerospace Vehicles

    NASA Technical Reports Server (NTRS)

    Balanis, Constantine A.; Polycarpou, Anastasis; Birtcher, Craig R.; Georgakopoulos, Stavros; Han, Dong-Ho; Ballas, Gerasimos

    1999-01-01

    The imminent destructive threats of Lightning on helicopters and other airborne systems has always been a topic of great interest to this research grant. Previously, the lightning induced currents on the surface of the fuselage and its interior were predicted using the finite-difference time-domain (FDTD) method as well as the NEC code. The limitations of both methods, as applied to lightning, were identified and extensively discussed in the last meeting. After a thorough investigation of the capabilities of the FDTD, it was decided to incorporate into the numerical method a subcell model to accurately represent current diffusion through conducting materials of high conductivity and finite thickness. Because of the complexity of the model, its validity will be first tested for a one-dimensional FDTD problem. Although results are not available yet, the theory and formulation of the subcell model are presented and discussed here to a certain degree. Besides lightning induced currents in the interior of an aircraft, penetration of electromagnetic fields through apertures (e.g., windows and cracks) could also be devastating for the navigation equipment, electronics, and communications systems in general. The main focus of this study is understanding and quantifying field penetration through apertures. The simulation is done using the FDTD method and the predictions are compared with measurements and moment method solutions obtained from the NASA Langley Research Center. Cavity-backed slot (CBS) antennas or slot antennas in general have many applications in aircraft-satellite type of communications. These can be flushmounted on the surface of the fuselage and, therefore, they retain the aerodynamic shape of the aircraft. In the past, input impedance and radiation patterns of CBS antennas were computed using a hybrid FEM/MoM code. The analysis is now extended to coupling between two identical slot antennas mounted on the same structure. The predictions are performed

  14. ANGPTL4 Correlates with NSCLC Progression and Regulates Epithelial-Mesenchymal Transition via ERK Pathway.

    PubMed

    Zhu, Xiaoming; Guo, Xiaobin; Wu, Sen; Wei, Li

    2016-08-01

    Purpose Lung cancer remains the leading cause of cancer deaths with intricate mechanisms. In the present study, we evaluated the clinical significance and biological role of ANGPTL4 in non-small cell lung cancer (NSCLC), the most common lung cancer subtype. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for examining the mRNA level of ANGPTL4 in NSCLC tissues and adjacent non-tumor tissues, NSCLC cell lines, and the immortalized human bronchial epithelial cell line HBE, respectively. A tissue microarray was used for analyzing the relationship between ANGPTL4 expression and the clinicopathological parameters of NSCLC patients. Commercial lentivirus expressing shRNAs was used for silencing ANGPTL4. Cell Counting Kit-8 (CCK-8) was employed for evaluating the cell proliferation ability and transwell with or without matrigel was used for cell migration and invasion assay. Results As the result, ANGPTL4 was over-expressed in NSCLC tissues compared with benign lung tissues. Silencing ANGPTL4 expression strongly inhibited the proliferation, migration, and invasion of A549 and H520 cells, which was in accordance with the increase of epithelial marker E-cadherin and decrease of mesenchymal marker vimentin. By screening the ERK, AKT, EGFR, and STAT3 pathways, we found that cell growth, migration, and invasion arrest induced by loss of ANGPTL4 expression was partially attributable to down-regulation of ERK signaling. Conclusion These results suggested that ANGPTL4 was essential for proliferation and metastasis of lung cancer cells and might serve as a novel target for the treatment of lung cancer. PMID:27166634

  15. Cost estimating methods for advanced space systems

    NASA Technical Reports Server (NTRS)

    Cyr, Kelley

    1988-01-01

    Parametric cost estimating methods for space systems in the conceptual design phase are developed. The approach is to identify variables that drive cost such as weight, quantity, development culture, design inheritance, and time. The relationship between weight and cost is examined in detail. A theoretical model of cost is developed and tested statistically against a historical data base of major research and development programs. It is concluded that the technique presented is sound, but that it must be refined in order to produce acceptable cost estimates.

  16. Advances in organometallic synthesis with mechanochemical methods.

    PubMed

    Rightmire, Nicholas R; Hanusa, Timothy P

    2016-02-14

    Solvent-based syntheses have long been normative in all areas of chemistry, although mechanochemical methods (specifically grinding and milling) have been used to good effect for decades in organic, and to a lesser but growing extent, inorganic coordination chemistry. Organometallic synthesis, in contrast, represents a relatively underdeveloped area for mechanochemical research, and the potential benefits are considerable. From access to new classes of unsolvated complexes, to control over stoichiometries that have not been observed in solution routes, mechanochemical (or 'M-chem') approaches have much to offer the synthetic chemist. It has already become clear that removing the solvent from an organometallic reaction can change reaction pathways considerably, so that prediction of the outcome is not always straightforward. This Perspective reviews recent developments in the field, and describes equipment that can be used in organometallic synthesis. Synthetic chemists are encouraged to add mechanochemical methods to their repertoire in the search for new and highly reactive metal complexes and novel types of organometallic transformations. PMID:26763151

  17. Advancements in Research Synthesis Methods: From a Methodologically Inclusive Perspective

    ERIC Educational Resources Information Center

    Suri, Harsh; Clarke, David

    2009-01-01

    The dominant literature on research synthesis methods has positivist and neo-positivist origins. In recent years, the landscape of research synthesis methods has changed rapidly to become inclusive. This article highlights methodologically inclusive advancements in research synthesis methods. Attention is drawn to insights from interpretive,…

  18. Advances in LC: bioanalytical method transfer.

    PubMed

    Wright, Patricia; Wright, Adrian

    2016-09-01

    There are three main reasons for transferring from an existing bioanalytical assay to an alternative chromatographic method: speed, cost and sensitivity. These represent a challenge to the analyst in that there is an interplay between these three considerations and one factor is often improved at the expense of another. These three factors act as drivers to encourage technology development and support its uptake. The more recently introduced chromatographic technologies may show significant improvements against one of more of these factors relative to conventional 4.6-mm id reversed-phase HPLC. In this article, some of these new chromatographic approaches will be considered in terms of what they can offer the bioanalysts. PMID:27491842

  19. Current methods and advances in bone densitometry

    NASA Technical Reports Server (NTRS)

    Guglielmi, G.; Gluer, C. C.; Majumdar, S.; Blunt, B. A.; Genant, H. K.

    1995-01-01

    Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include single and dual photon absorptiometry (SPA and DPA), single and dual X-ray absorptiometry (SXA and DXA) and quantitative computed tomography (QCT). While differing in anatomic sites measured and in their estimates of precision, accuracy, and fracture discrimination, all of these methods provide clinically useful measurements of skeletal status. It is the intent of this review to discuss the pros and cons of these techniques and to present the new applications of ultrasound (US) and magnetic resonance (MRI) in the detection and management of osteoporosis.

  20. Current methods and advances in bone densitometry.

    PubMed

    Guglielmi, G; Gluer, C C; Majumdar, S; Blunt, B A; Genant, H K

    1995-01-01

    Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include single and dual photon absorptiometry (SPA and DPA), single and dual X-ray absorptiometry (SXA and DXA) and quantitative computed tomography (QCT). While differing in anatomic sites measured and in their estimates of precision, accuracy, and fracture discrimination, all of these methods provide clinically useful measurements of skeletal status. It is the intent of this review to discuss the pros and cons of these techniques and to present the new applications of ultrasound (US) and magnetic resonance (MRI) in the detection and management of osteoporosis. PMID:11539928

  1. Advanced Fuzzy Potential Field Method for Mobile Robot Obstacle Avoidance

    PubMed Central

    Park, Jong-Wook; Kwak, Hwan-Joo; Kang, Young-Chang; Kim, Dong W.

    2016-01-01

    An advanced fuzzy potential field method for mobile robot obstacle avoidance is proposed. The potential field method primarily deals with the repulsive forces surrounding obstacles, while fuzzy control logic focuses on fuzzy rules that handle linguistic variables and describe the knowledge of experts. The design of a fuzzy controller—advanced fuzzy potential field method (AFPFM)—that models and enhances the conventional potential field method is proposed and discussed. This study also examines the rule-explosion problem of conventional fuzzy logic and assesses the performance of our proposed AFPFM through simulations carried out using a mobile robot. PMID:27123001

  2. Advanced Fuzzy Potential Field Method for Mobile Robot Obstacle Avoidance.

    PubMed

    Park, Jong-Wook; Kwak, Hwan-Joo; Kang, Young-Chang; Kim, Dong W

    2016-01-01

    An advanced fuzzy potential field method for mobile robot obstacle avoidance is proposed. The potential field method primarily deals with the repulsive forces surrounding obstacles, while fuzzy control logic focuses on fuzzy rules that handle linguistic variables and describe the knowledge of experts. The design of a fuzzy controller--advanced fuzzy potential field method (AFPFM)--that models and enhances the conventional potential field method is proposed and discussed. This study also examines the rule-explosion problem of conventional fuzzy logic and assesses the performance of our proposed AFPFM through simulations carried out using a mobile robot. PMID:27123001

  3. Advanced electromagnetic methods for aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Balanis, Constantine A.; Choi, Jachoon; El-Sharawy, El-Budawy; Hashemi-Yeganeh, Shahrokh; Birtcher, Craig R.

    1990-01-01

    High- and low-frequency methods to analyze various radiation elements located on aerospace vehicles with combinations of conducting, nonconducting, and energy absorbing surfaces and interfaces. The focus was on developing fundamental concepts, techniques, and algorithms which would remove some of the present limitations in predicting radiation characteristics of antennas on complex aerospace vehicles. In order to accomplish this, the following subjects were examined: (1) the development of techniques for rigorous analysis of surface discontinuities of metallic and nonmetallic surfaces using the equivalent surface impedance concept and Green's function; (2) the effects of anisotropic material on antenna radiation patterns through the use of an equivalent surface impedance concept which is incorporated into the existing numerical electromagnetics computer codes; and (3) the fundamental concepts of precipitation static (P-Static), such as formulations and analytical models. A computer code was used to model the P-Static process on a simple structure. Measurement techniques were also developed to characterized the electrical properties at microwave frequencies. Samples of typical materials used in airframes were tested and the results are included.

  4. Cost estimating methods for advanced space systems

    NASA Technical Reports Server (NTRS)

    Cyr, Kelley

    1994-01-01

    NASA is responsible for developing much of the nation's future space technology. Cost estimates for new programs are required early in the planning process so that decisions can be made accurately. Because of the long lead times required to develop space hardware, the cost estimates are frequently required 10 to 15 years before the program delivers hardware. The system design in conceptual phases of a program is usually only vaguely defined and the technology used is so often state-of-the-art or beyond. These factors combine to make cost estimating for conceptual programs very challenging. This paper describes an effort to develop parametric cost estimating methods for space systems in the conceptual design phase. The approach is to identify variables that drive cost such as weight, quantity, development culture, design inheritance and time. The nature of the relationships between the driver variables and cost will be discussed. In particular, the relationship between weight and cost will be examined in detail. A theoretical model of cost will be developed and tested statistically against a historical database of major research and development projects.

  5. Unstructured viscous grid generation by advancing-front method

    NASA Technical Reports Server (NTRS)

    Pirzadeh, Shahyar

    1993-01-01

    A new method of generating unstructured triangular/tetrahedral grids with high-aspect-ratio cells is proposed. The method is based on new grid-marching strategy referred to as 'advancing-layers' for construction of highly stretched cells in the boundary layer and the conventional advancing-front technique for generation of regular, equilateral cells in the inviscid-flow region. Unlike the existing semi-structured viscous grid generation techniques, the new procedure relies on a totally unstructured advancing-front grid strategy resulting in a substantially enhanced grid flexibility and efficiency. The method is conceptually simple but powerful, capable of producing high quality viscous grids for complex configurations with ease. A number of two-dimensional, triangular grids are presented to demonstrate the methodology. The basic elements of the method, however, have been primarily designed with three-dimensional problems in mind, making it extendible for tetrahedral, viscous grid generation.

  6. Advanced Ablative Insulators and Methods of Making Them

    NASA Technical Reports Server (NTRS)

    Congdon, William M.

    2005-01-01

    Advanced ablative (more specifically, charring) materials that provide temporary protection against high temperatures, and advanced methods of designing and manufacturing insulators based on these materials, are undergoing development. These materials and methods were conceived in an effort to replace the traditional thermal-protection systems (TPSs) of re-entry spacecraft with robust, lightweight, better-performing TPSs that can be designed and manufactured more rapidly and at lower cost. These materials and methods could also be used to make improved TPSs for general aerospace, military, and industrial applications.

  7. Strategy to Promote Active Learning of an Advanced Research Method

    ERIC Educational Resources Information Center

    McDermott, Hilary J.; Dovey, Terence M.

    2013-01-01

    Research methods courses aim to equip students with the knowledge and skills required for research yet seldom include practical aspects of assessment. This reflective practitioner report describes and evaluates an innovative approach to teaching and assessing advanced qualitative research methods to final-year psychology undergraduate students. An…

  8. Challenges and Opportunities for Cancer Vaccines in the Current NSCLC Clinical Scenario

    PubMed Central

    Rodriguez, Pedro C; Sanchez, Belinda

    2013-01-01

    This review is aimed to focus on NSCLC as an emerging and promising model for active immunotherapy and the challenges for its inclusion in the current clinical scenario. Cancer vaccines for NSCLC have been focused as a therapeutic option based on the identification of a tumor hallmark and the active immunization with the related molecules that triggers cellular and/or humoral responses that consequently destroy or delay the rate of malignant progression. This therapeutic intervention in an established disease state has been aimed to impact into prolonging patient´s survival with ethically accepted quality of life. Understanding of relationship between structure and function in cancer vaccines is essential to interpret their opportunities to impact into prolonging survival and increasing quality of life in cancer patients. It is widely accepted that the failure of the cancer vaccines in the NSCLC scenario is related with its introduction in the advanced disease stages and poor performance status of the patients due to the combination of the tumor induced immunosuppression with the immune senescence. Despite first, second and emerging third line of onco-specific treatments the life expectancy for NSCLC patients diagnosed at advanced stages is surrounding the 12 months of median survival and in facts the today real circumstances are extremely demanding for the success inclusion of cancer vaccines as therapeutic choice in the clinical scenario. The kinetics of the active immunizations encompasses a sequential cascade of clinical endpoints: starting by the activation of the immune system, followed by the antitumor response and finalizing with the consequential impact on patients’ overall survival. Today this cascade of clinical endpoints is the backbone for active immunization assessment and moreover the concept of cancer vaccines, applied in the NSCLC setting, is just evolving as a complex therapeutic strategy, in which the opportunities for cancer vaccines start

  9. A panel of promoter methylation markers for invasive and noninvasive early detection of NSCLC using a quantum dots-based FRET approach.

    PubMed

    Ma, Yunfei; Bai, Yanan; Mao, Hailei; Hong, Qunying; Yang, Dawei; Zhang, Honglian; Liu, Fangming; Wu, Zhenhua; Jin, Qinghui; Zhou, Hongbo; Cao, Jian; Zhao, Jianlong; Zhong, Xinhua; Mao, Hongju

    2016-11-15

    Non-small-cell lung cancer (NSCLC) leads to a significant proportion of cancer-related deaths, and early detection of NSCLC can significantly increase cancer survival rates. A promising approach has been studied to exploit DNA methylation, which is closely correlated to early cancer diagnosis. Herein, in order to realize the early detection of NSCLC, we utilized the developed quantum dots-based (QDs-based) fluorescence resonance energy transfer (FRET) nanosensor technique to analyze the promoter methylation in early stage NSCLC tissue samples and noninvasive bronchial brushing specimens. Using this method, the methylation levels can be quantitatively determined by measuring the signal amplification during FRET. A panel of three tumor suppressor genes (PCDHGB6, HOXA9 and RASSF1A) was assessed in 50 paired early stage NSCLC and their adjacent nontumorous tissue (NT) samples, and 50 early stage NSCLC bronchial brushing and normal specimens. The combined detection was able to identify not only tissue samples but noninvasive bronchial brushing specimens from control cases with a high degree of sensitivity of 92% (AUC=0.977, P<0.001) and 80% (AUC=0.907, P<0.001) respectively, indicating the versatility of promoter expression in invasive and noninvasive NSCLC samples. Therefore this approach can be used to sensitively analyze the methylation levels of cancer-related genes, which might be a potential tool for noninvasive early clinical diagnosis of cancers. PMID:27240011

  10. A Primer In Advanced Fatigue Life Prediction Methods

    NASA Technical Reports Server (NTRS)

    Halford, Gary R.

    2000-01-01

    Metal fatigue has plagued structural components for centuries, and it remains a critical durability issue in today's aerospace hardware. This is true despite vastly improved and advanced materials, increased mechanistic understanding, and development of accurate structural analysis and advanced fatigue life prediction tools. Each advance is quickly taken advantage of to produce safer, more reliable more cost effective, and better performing products. In other words, as the envelop is expanded, components are then designed to operate just as close to the newly expanded envelop as they were to the initial one. The problem is perennial. The economic importance of addressing structural durability issues early in the design process is emphasized. Tradeoffs with performance, cost, and legislated restrictions are pointed out. Several aspects of structural durability of advanced systems, advanced materials and advanced fatigue life prediction methods are presented. Specific items include the basic elements of durability analysis, conventional designs, barriers to be overcome for advanced systems, high-temperature life prediction for both creep-fatigue and thermomechanical fatigue, mean stress effects, multiaxial stress-strain states, and cumulative fatigue damage accumulation assessment.

  11. Advanced surface paneling method for subsonic and supersonic flow

    NASA Technical Reports Server (NTRS)

    Erickson, L. L.; Johnson, F. T.; Ehlers, F. E.

    1976-01-01

    Numerical results illustrating the capabilities of an advanced aerodynamic surface paneling method are presented. The method is applicable to both subsonic and supersonic flow, as represented by linearized potential flow theory. The method is based on linearly varying sources and quadratically varying doublets which are distributed over flat or curved panels. These panels are applied to the true surface geometry of arbitrarily shaped three dimensional aerodynamic configurations.

  12. Advanced stress analysis methods applicable to turbine engine structures

    NASA Technical Reports Server (NTRS)

    Pian, T. H. H.

    1985-01-01

    Advanced stress analysis methods applicable to turbine engine structures are investigated. Constructions of special elements which containing traction-free circular boundaries are investigated. New versions of mixed variational principle and version of hybrid stress elements are formulated. A method is established for suppression of kinematic deformation modes. semiLoof plate and shell elements are constructed by assumed stress hybrid method. An elastic-plastic analysis is conducted by viscoplasticity theory using the mechanical subelement model.

  13. Integrative Discovery of Epigenetically Derepressed Cancer Testis Antigens in NSCLC

    PubMed Central

    Glazer, Chad A.; Smith, Ian M.; Ochs, Michael F.; Begum, Shahnaz; Westra, William; Chang, Steven S.; Sun, Wenyue; Bhan, Sheetal; Khan, Zubair; Ahrendt, Steven; Califano, Joseph A.

    2009-01-01

    Background Cancer/testis antigens (CTAs) were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small cell lung cancer (NSCLC) whose transcription is driven by promoter demethylation. Methodology/Principal Findings Our screening approach found 290 significant genes from the over 47,000 transcripts incorporated in the Affymetrix Human Genome U133 Plus 2.0 expression array. Of the top 55 candidates, 10 showed both differential overexpression and promoter region hypomethylation in NSCLC. Surprisingly, 6 of the 10 genes discovered by this approach were CTAs. Using a separate cohort of primary tumor and normal tissue, we validated NSCLC promoter hypomethylation and increased expression by quantitative RT-PCR for all 10 genes. We noted significant, coordinated coexpression of multiple target genes, as well as coordinated promoter demethylation, in a large set of individual tumors that was associated with the SCC subtype of NSCLC. In addition, we identified 2 novel target genes that exhibited growth-promoting effects in multiple cell lines. Conclusions/Significance Coordinated promoter demethylation in NSCLC is associated with aberrant expression of CTAs and potential, novel candidate protooncogenes that can be identified using integrative discovery techniques. These findings have significant implications for discovery of novel CTAs and CT antigen directed immunotherapy. PMID:19997593

  14. Vandetanib: An overview of its clinical development in NSCLC and other tumors.

    PubMed

    Morabito, A; Piccirillo, M C; Costanzo, R; Sandomenico, C; Carillio, G; Daniele, G; Giordano, P; Bryce, J; Carotenuto, P; La Rocca, A; Di Maio, M; Normanno, N; Rocco, G; Perrone, F

    2010-09-01

    Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), epidermal growth factor receptor (EGFR) and Ret tyrosine kinases involved in tumor growth, progression and angiogenesis. Phase I studies indicated that the recommended dose of vandetanib as a single agent is 300 mg/day. Rash, diarrhea, hypertension and asymptomatic Q-Tc prolongation were the most common adverse events. Four randomized phase III clinical trials evaluated the efficacy of vandetanib in non-small cell lung cancer (NSCLC) in combination with docetaxel (ZODIAC), pemetrexed (ZEAL) or as a single agent (ZEST and ZEPHYR). Only the ZODIAC trial met its primary endpoint (progression-free survival [PFS]), while no study showed an advantage in overall survival with vandetanib. No significant antitumor activity has been observed in small cell lung cancer, advanced ovarian, colorectal, breast, prostate cancer and multiple myeloma. In advanced metastatic medullary thyroid cancer, one randomized phase III clinical trial has demonstrated that vandetanib can significantly improve response rate, PFS and time to worsening of pain. Several key questions remain to be addressed regarding the identification of clinical or molecular biomarkers predictive of response, the choice of the optimal dose or schedule of vandetanib and the safety of long-term administration. The results of ongoing trials in untreated patients with advanced NSCLC and other tumors should better define the optimal clinical application of vandetanib. PMID:20967300

  15. Updating advances on recombinant human endostatin combined with radiotherapy for non-small cell lung cancer with brain metastasis

    PubMed Central

    Qiao, Yun

    2012-01-01

    Brain metastases (BM) heavily affects the prognosis of advanced non-small cell lung cancer (NSCLC). Although whole-brain radiotherapy remains the mainstream therapy for BM caused by NSCLC, the effectiveness is unsatisfactory. Endostar, a recombinant human endostatin (RHES), has shown certain therapeutic effect on advanced NSCLC. This article reviews the feasibility of Endostar combined with radiotherapy in the treatment of BM caused by NSCLC. PMID:25806159

  16. METHODS ADVANCEMENT FOR MILK ANALYSIS: THE MAMA STUDY

    EPA Science Inventory

    The Methods Advancement for Milk Analysis (MAMA) study was designed by US EPA and CDC investigators to provide data to support the technological and study design needs of the proposed National Children=s Study (NCS). The NCS is a multi-Agency-sponsored study, authorized under the...

  17. Advanced boundary layer transition measurement methods for flight applications

    NASA Technical Reports Server (NTRS)

    Holmes, B. J.; Croom, C. C.; Gail, P. D.; Manuel, G. S.; Carraway, D. L.

    1986-01-01

    In modern laminar flow flight research, it is important to understand the specific cause(s) of laminar to turbulent boundary-layer transition. Such information is crucial to the exploration of the limits of practical application of laminar flow for drag reduction on aircraft. The transition modes of interest in current flight investigations include the viscous Tollmien-Schlichting instability, the inflectional instability at laminar separation, and the crossflow inflectional instability, as well as others. This paper presents the results to date of research on advanced devices and methods used for the study of laminar boundary-layer transition phenomena in the flight environment. Recent advancements in the development of arrayed hot-film devices and of a new flow visualization method are discussed. Arrayed hot-film devices have been designed to detect the presence of laminar separation, and of crossflow vorticity. The advanced flow visualization method utilizes color changes in liquid-crystal coatings to detect boundary-layer transition at high altitude flight conditions. Flight and wind tunnel data are presented to illustrate the design and operation of these advanced methods. These new research tools provide information on disturbance growth and transition mode which is essential to furthering our understanding of practical design limits for applications of laminar flow technology.

  18. Combine therapy of gefitinib and fulvestrant enhances antitumor effects on NSCLC cell lines with acquired resistance to gefitinib.

    PubMed

    Xu, Ruitong; Shen, Hua; Guo, Renhua; Sun, Jing; Gao, Wen; Shu, Yongqian

    2012-07-01

    Gefitinib, an EGFR receptor tyrosine kinase inhibitor, is approved for clinical use in the treatment of non-small cell lung cancer (NSCLC), but the emergence of mutations resistant to these inhibitors, such as T790M, has become a clinical problem. According to statistics, female patients, the presence of adenocarcinoma or non-smokers experienced a higher response rate. This may be involved in interaction between the estrogen receptor (ER) and the epidermal growth factor receptor (EGFR). To test whether inhibition of the ER signaling pathway affects the antitumor effect of gefitinib, gefitinib and an ER antagonist, fulvestrant, were administered to NSCLC cell lines with acquired resistance to gefitinib. Compared with treatment of either fulvestrant or gefitinib alone, drug combination obviously decreased proliferation of H1976, H1650 and PC-9 cells coming from adenocarcinoma. Rapid activations of EGFR pathway by E2β were observed in H1975 cells with T790M mutation. Additionally, EGFR and ERs expression were down-regulated respectively in response to estrogen and EGF but up-regulated in response to fulvestrant and gefitinib in vitro. These results suggest that there is a functional cross-signaling between the EGFR/ER pathways in NSCLC with acquired resistance to gefitinib, possibly providing rationale for combining gefitinib with anti-estrogen therapy for advanced NSCLC treatment. PMID:22560634

  19. Domain Decomposition By the Advancing-Partition Method

    NASA Technical Reports Server (NTRS)

    Pirzadeh, Shahyar Z.

    2008-01-01

    A new method of domain decomposition has been developed for generating unstructured grids in subdomains either sequentially or using multiple computers in parallel. Domain decomposition is a crucial and challenging step for parallel grid generation. Prior methods are generally based on auxiliary, complex, and computationally intensive operations for defining partition interfaces and usually produce grids of lower quality than those generated in single domains. The new technique, referred to as "Advancing Partition," is based on the Advancing-Front method, which partitions a domain as part of the volume mesh generation in a consistent and "natural" way. The benefits of this approach are: 1) the process of domain decomposition is highly automated, 2) partitioning of domain does not compromise the quality of the generated grids, and 3) the computational overhead for domain decomposition is minimal. The new method has been implemented in NASA's unstructured grid generation code VGRID.

  20. Angiogenesis inhibitors rechallenge in patients with advanced non-small-cell lung cancer: a pooled analysis of randomized controlled trials

    PubMed Central

    Zhao, Lingdi; Li, Wei; Zhang, Huiying; Hou, Nan; Guo, Lanwei; Gao, Quanli

    2015-01-01

    Purpose Data on the role of angiogenesis inhibitors (AIs) rechallenge in the treatment of advanced non-small-cell lung cancer (NSCLC) patients who previously received bevacizumab remain limited. We aim to investigate the efficacy of AIs in the treatment of advanced NSCLC in this setting. Methods Studies from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology meeting up to December 1, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating AIs in advanced NSCLC, with survival data on patients who previously received bevacizumab. The end points were overall survival and progression-free survival. Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 452 patients with advanced NSCLC who previously received bevacizumab were identified for analysis. The meta-analysis results demonstrated that AI rechallenge significantly improved progression-free survival (hazard ratio: 0.72, 95% confidence interval: 0.58–0.89, P=0.002) when compared to non-AI containing regimens. Additionally, a nonsignificant improvement in overall survival was also observed in advanced NSCLC in this setting (hazard ratio: 0.82, 95% confidence interval: 0.65–1.03, P=0.087). Similar results were also observed in subgroup analysis according to treatment regimens. Conclusion The findings of this study suggest that NSCLC patients who relapsed after a first-line bevacizumab-containing chemotherapy obtain improved clinical benefits from AI rechallenge. Prospective clinical trials investigating the role of AI rechallenge in this setting are recommended. PMID:26491352

  1. Advanced propulsion for LEO-Moon transport. 1: A method for evaluating advanced propulsion performance

    NASA Technical Reports Server (NTRS)

    Stern, Martin O.

    1992-01-01

    This report describes a study to evaluate the benefits of advanced propulsion technologies for transporting materials between low Earth orbit and the Moon. A relatively conventional reference transportation system, and several other systems, each of which includes one advanced technology component, are compared in terms of how well they perform a chosen mission objective. The evaluation method is based on a pairwise life-cycle cost comparison of each of the advanced systems with the reference system. Somewhat novel and economically important features of the procedure are the inclusion not only of mass payback ratios based on Earth launch costs, but also of repair and capital acquisition costs, and of adjustments in the latter to reflect the technological maturity of the advanced technologies. The required input information is developed by panels of experts. The overall scope and approach of the study are presented in the introduction. The bulk of the paper describes the evaluation method; the reference system and an advanced transportation system, including a spinning tether in an eccentric Earth orbit, are used to illustrate it.

  2. Advances and future directions of research on spectral methods

    NASA Technical Reports Server (NTRS)

    Patera, A. T.

    1986-01-01

    Recent advances in spectral methods are briefly reviewed and characterized with respect to their convergence and computational complexity. Classical finite element and spectral approaches are then compared, and spectral element (or p-type finite element) approximations are introduced. The method is applied to the full Navier-Stokes equations, and examples are given of the application of the technique to several transitional flows. Future directions of research in the field are outlined.

  3. Advances in subtyping methods of foodborne disease pathogens.

    PubMed

    Boxrud, Dave

    2010-04-01

    Current subtyping methods for the detection of foodborne disease outbreaks have limitations that reduce their use by public health laboratories. Recent advances in subtyping of foodborne disease pathogens utilize techniques that identify nucleic acid polymorphisms. Recent methods of nucleic acid characterization such as microarrays and mass spectrometry (MS) may provide improvements such as increasing speed and data portability while decreasing labor compared to current methods. This article discusses multiple-locus variable-number tandem-repeat analysis, single-nucleotide polymorphisms, nucleic acid sequencing, whole genome sequencing, variable absent or present loci, microarrays and MS as potential subtyping methods to enhance our ability to detect foodborne disease outbreaks. PMID:20299203

  4. An advanced probabilistic structural analysis method for implicit performance functions

    NASA Technical Reports Server (NTRS)

    Wu, Y.-T.; Millwater, H. R.; Cruse, T. A.

    1989-01-01

    In probabilistic structural analysis, the performance or response functions usually are implicitly defined and must be solved by numerical analysis methods such as finite element methods. In such cases, the most commonly used probabilistic analysis tool is the mean-based, second-moment method which provides only the first two statistical moments. This paper presents a generalized advanced mean value (AMV) method which is capable of establishing the distributions to provide additional information for reliability design. The method requires slightly more computations than the second-moment method but is highly efficient relative to the other alternative methods. In particular, the examples show that the AMV method can be used to solve problems involving non-monotonic functions that result in truncated distributions.

  5. PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

    PubMed Central

    Natoli, Clara; Rizzo, Sergio; Galvano, Antonio; Listì, Angela; Cicero, Giuseppe; Rolfo, Christian; Santini, Daniele; Russo, Antonio

    2016-01-01

    Background Clinical trials of immune checkpoints modulators, including both programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have recently shown promising activity and tolerable toxicity in pre-treated NSCLC patients. However the predictive role of PD-L1 expression is still controversial. This pooled analysis aims to clarify the association of clinical objective responses to anti PD-1/PD-L1 monoclonal antibodies (MoAbs) and tumor PD-L1 expression in pre-treated NSCLC patients. Methods Data from published studies, that evaluated efficacy and safety of PD-1/PD-L1 inhibitors in pre-treated NSCLC patients, stratified by tumor PD-L1 expression status (immunohistochemistry, cut-off point 1%), were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the Overall Response Rate (ORR) (as evaluated by Response Evaluation Criteria in Solid Tumors, version 1.1), according to PD-L1 expression status. Results A total of seven studies, with 914 patients, were eligible. Pooled analysis showed that patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had a significantly higher ORR, compared to patients with PD-L1 negative tumors (OR: 2.44; 95% CIs: 1.61-3.68). Conclusions PD-L1 tumor over-expression seems to be associated with higher clinical activity of anti PD-1/PD-L1 MoAbs, in pre-treated NSCLC patients, suggesting a potential role of PD-L1 expression, IHC cut-off point 1%, as predictive biomarker for the selection of patients to treat with immune-checkpoint inhibitors. PMID:26918451

  6. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients.

    PubMed

    Chen, Xi; Wan, Jin; Liu, Jiankun; Xie, Wei; Diao, Xinwei; Xu, Jianping; Zhu, Bo; Chen, Zhengtang

    2010-09-01

    The presence of IL-17-positive cells is observed in a variety of inflammatory associated cancers and IL-17 has been found to be involved in angiogenesis. The aim of this study is to determine the prognostic significance of IL-17 in NSCLC patients and to examine the correlation between IL-17 expression and lymphatic vessel density in NSCLC tissues. The expression of IL-17 was measured by immunohistochemistry in 52 paraffin-embedded tissues with non-small cell lung cancer. The chi(2) test was used to analyze the correlation between IL-17 expression and clinical parameters and lymphatic vessel density (LVD). The Kaplan-Meier method, univariate and multivariate regression analysis was used to analyze the correlation between IL-17 expression and overall survival and disease-free survival. High expression of IL-17 was observed in 25 of 52 lung cancer patients and was associated with smoking status, TNM stage, LVD, overall survival and disease-free survival. Univariate and multivariate analysis showed that IL-17 was an independent prognostic factor for overall survival and disease-free survival. Our results indicate that IL-17 may play a role in the metastasis of lung cancer by promoting lymphangiogenesis. IL-17 expression is an independent prognostic factor in both overall and disease-free survival in NSCLC. PMID:20022135

  7. PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups

    PubMed Central

    Schmidt, Lars Henning; Kümmel, Andreas; Görlich, Dennis; Mohr, Michael; Bröckling, Sebastian; Mikesch, Jan Henrik; Grünewald, Inga; Marra, Alessandro; Schultheis, Anne M.; Wardelmann, Eva; Müller-Tidow, Carsten; Spieker, Tilmann; Schliemann, Christoph; Berdel, Wolfgang E.

    2015-01-01

    Background Immunotherapy can become a crucial therapeutic option to improve prognosis for lung cancer patients. First clinical trials with therapies targeting the programmed cell death receptor PD-1 and its ligand PD-L1 have shown promising results in several solid tumors. However, in lung cancer the diagnostic, prognostic and predictive value of these immunologic factors remains unclear. Method The impact of both factors was evaluated in a study collective of 321 clinically well-annotated patients with non-small lung cancer (NSCLC) using immunohistochemistry. Results PD-1 expression by tumor infiltrating lymphocytes (TILs) was found in 22%, whereas tumor cell associated PD-L1 expression was observed in 24% of the NSCLC tumors. In Fisher’s exact test a positive correlation was found for PD-L1 and Bcl-xl protein expression (p = 0.013). Interestingly, PD-L1 expression on tumor cells was associated with improved overall survival in pulmonary squamous cell carcinomas (SCC, p = 0.042, log rank test), with adjuvant therapy (p = 0.017), with increased tumor size (pT2-4, p = 0.039) and with positive lymph node status (pN1-3, p = 0.010). These observations were confirmed by multivariate cox regression models. Conclusion One major finding of our study is the identification of a prognostic implication of PD-L1 in subsets of NSCLC patients with pulmonary SCC, with increased tumor size, with a positive lymph node status and NSCLC patients who received adjuvant therapies. This study provides first data for immune-context related risk stratification of NSCLC patients. Further studies are necessary both to confirm this observation and to evaluate the predictive value of PD-1 and PD-L1 in NSCLC in the context of PD-1 inhibition. PMID:26313362

  8. Fracture Toughness in Advanced Monolithic Ceramics - SEPB Versus SEVENB Methods

    NASA Technical Reports Server (NTRS)

    Choi, S. R.; Gyekenyesi, J. P.

    2005-01-01

    Fracture toughness of a total of 13 advanced monolithic ceramics including silicon nitrides, silicon carbide, aluminas, and glass ceramic was determined at ambient temperature by using both single edge precracked beam (SEPB) and single edge v-notched beam (SEVNB) methods. Relatively good agreement in fracture toughness between the two methods was observed for advanced ceramics with flat R-curves; whereas, poor agreement in fracture toughness was seen for materials with rising R-curves. The discrepancy in fracture toughness between the two methods was due to stable crack growth with crack closure forces acting in the wake region of cracks even in SEVNB test specimens. The effect of discrepancy in fracture toughness was analyzed in terms of microstructural feature (grain size and shape), toughening exponent, and stable crack growth determined using back-face strain gaging.

  9. Advanced stress analysis methods applicable to turbine engine structures

    NASA Technical Reports Server (NTRS)

    Pian, Theodore H. H.

    1991-01-01

    The following tasks on the study of advanced stress analysis methods applicable to turbine engine structures are described: (1) constructions of special elements which contain traction-free circular boundaries; (2) formulation of new version of mixed variational principles and new version of hybrid stress elements; (3) establishment of methods for suppression of kinematic deformation modes; (4) construction of semiLoof plate and shell elements by assumed stress hybrid method; and (5) elastic-plastic analysis by viscoplasticity theory using the mechanical subelement model.

  10. Advanced preservation methods and nutrient retention in fruits and vegetables.

    PubMed

    Barrett, Diane M; Lloyd, Beate

    2012-01-15

    Despite the recommendations of international health organizations and scientific research carried out around the world, consumers do not take in sufficient quantities of healthy fruit and vegetable products. The use of new, 'advanced' preservation methods creates a unique opportunity for food manufacturers to retain nutrient content similar to that found in fresh fruits and vegetables. This review presents a summary of the published literature regarding the potential of high-pressure and microwave preservation, the most studied of the 'advanced' processes, to retain the natural vitamin A, B, C, phenolic, mineral and fiber content in fruits and vegetables at the time of harvest. Comparisons are made with more traditional preservation methods that utilize thermal processing. Case studies on specific commodities which have received the most attention are highlighted; these include apples, carrots, oranges, tomatoes and spinach. In addition to summarizing the literature, the review includes a discussion of postharvest losses in general and factors affecting nutrient losses in fruits and vegetables. Recommendations are made for future research required to evaluate these advanced process methods. PMID:22102258

  11. Diagnostic value of Cyfra21-1, SCC and CEA for differentiation of early-stage NSCLC from benign lung disease.

    PubMed

    Chen, Feng; Wang, Xiu-Ying; Han, Xiao-Hong; Wang, Hai; Qi, Jun

    2015-01-01

    Non-small cell lung cancer (NSCLC), which account for the most of lung carcinoma, is sometimes difficult to differentiate from benign lung diseases presented with nodular shadow in imaging scan. There is a need to find another non-invasive way to diagnosis early-stage NSCLC. To examine the potential diagnostic value of SCC, CFYRA 21-1 and CEA for the differentiation of early-stage NCSCL from benign lung diseases, we analyzed serum levels of tumor markers in 278 patients, including 248 patients with NSCLC and 30 patients with benign lung diseases. These benign lung diseases were presented with evidence of a high likelihood of having lung cancer. After surgical operation, diagnosis of lung cancer and benign lung disease were confirmed by histological examination. Preoperative tumor marker levels were quantified. Mann-Whitney U test was used to compare median levels of SCC, CFYRA 21-1 and CEA between the benign group and lung cancer group. Analysis of variance results were used for differences between different clinical stages of NSCLC. ROC was used to evaluate the diagnostic value of tumor markers. The median levels of Cyfra21-1, SCC and CEA were much higher in NSCLC than those in benign lung diseases. And we found that the mean levels of tumor marker were higher in advanced stage of NSCLC. The combination of tumor markers resulted in a higher sensitivity (91.3%) and a lower specificity (86.7%). In conclusion, the combination of positive SCC, positive CEA and positive Cyfra21-1 appear to be helpful in distinguishing early-stage NSCLC from benign lung disease which presented with suspicious pulmonary masses. PMID:26379938

  12. Diagnostic value of Cyfra21-1, SCC and CEA for differentiation of early-stage NSCLC from benign lung disease

    PubMed Central

    Chen, Feng; Wang, Xiu-Ying; Han, Xiao-Hong; Wang, Hai; Qi, Jun

    2015-01-01

    Non-small cell lung cancer (NSCLC), which account for the most of lung carcinoma, is sometimes difficult to differentiate from benign lung diseases presented with nodular shadow in imaging scan. There is a need to find another non-invasive way to diagnosis early-stage NSCLC. To examine the potential diagnostic value of SCC, CFYRA 21-1 and CEA for the differentiation of early-stage NCSCL from benign lung diseases, we analyzed serum levels of tumor markers in 278 patients, including 248 patients with NSCLC and 30 patients with benign lung diseases. These benign lung diseases were presented with evidence of a high likelihood of having lung cancer. After surgical operation, diagnosis of lung cancer and benign lung disease were confirmed by histological examination. Preoperative tumor marker levels were quantified. Mann-Whitney U test was used to compare median levels of SCC, CFYRA 21-1 and CEA between the benign group and lung cancer group. Analysis of variance results were used for differences between different clinical stages of NSCLC. ROC was used to evaluate the diagnostic value of tumor markers. The median levels of Cyfra21-1, SCC and CEA were much higher in NSCLC than those in benign lung diseases. And we found that the mean levels of tumor marker were higher in advanced stage of NSCLC. The combination of tumor markers resulted in a higher sensitivity (91.3%) and a lower specificity (86.7%). In conclusion, the combination of positive SCC, positive CEA and positive Cyfra21-1 appear to be helpful in distinguishing early-stage NSCLC from benign lung disease which presented with suspicious pulmonary masses. PMID:26379938

  13. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC

    PubMed Central

    Besse, Benjamin; Charrier, Mélinda; Lapierre, Valérie; Dansin, Eric; Lantz, Olivier; Planchard, David; Le Chevalier, Thierry; Livartoski, Alain; Barlesi, Fabrice; Laplanche, Agnès; Ploix, Stéphanie; Vimond, Nadège; Peguillet, Isabelle; Théry, Clotilde; Lacroix, Ludovic; Zoernig, Inka; Dhodapkar, Kavita; Dhodapkar, Madhav; Viaud, Sophie; Soria, Jean-Charles; Reiners, Katrin S.; Pogge von Strandmann, Elke; Vély, Frédéric; Rusakiewicz, Sylvie; Eggermont, Alexander; Pitt, Jonathan M.; Zitvogel, Laurence; Chaput, Nathalie

    2016-01-01

    ABSTRACT Dendritic cell-derived exosomes (Dex) are small extracellular vesicles secreted by viable dendritic cells. In the two phase-I trials that we conducted using the first generation of Dex (IFN-γ-free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN-γ-Dex) was manufactured with the aim of boosting NK and T cell immune responses. We carried out a phase II clinical trial testing the clinical benefit of IFN-γ-Dex loaded with MHC class I- and class II-restricted cancer antigens as maintenance immunotherapy after induction chemotherapy in patients bearing inoperable non-small cell lung cancer (NSCLC) without tumor progression. The primary endpoint was to observe at least 50% of patients with progression-free survival (PFS) at 4 mo after chemotherapy cessation. Twenty-two patients received IFN-γ-Dex. One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo. Seven patients (32%) experienced stabilization of >4 mo. The primary endpoint was not reached. An increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. Importantly, MHC class II expression levels of the final IFN-γ-Dex product correlated with expression levels of the NKp30 ligand BAG6 on Dex, and with NKp30-dependent NK functions, the latter being associated with longer progression-free survival. This phase II trial confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC. PMID:27141373

  14. Near Infrared Photoimmunotherapy in the Treatment of Pleural Disseminated NSCLC: Preclinical Experience

    PubMed Central

    Sato, Kazuhide; Nagaya, Tadanobu; Choyke, Peter L.; Kobayashi, Hisataka

    2015-01-01

    Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet is difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of pleural disseminated non-small cell lung carcinoma (NSCLC). In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180). Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease. In conclusion, NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC in mice. Thus, NIR-PIT is a promising therapy for pleural disseminated tumors. PMID:25897335

  15. Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

    PubMed Central

    2012-01-01

    Background The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib. PMID:23234355

  16. Advanced reactor physics methods for heterogeneous reactor cores

    NASA Astrophysics Data System (ADS)

    Thompson, Steven A.

    To maintain the economic viability of nuclear power the industry has begun to emphasize maximizing the efficiency and output of existing nuclear power plants by using longer fuel cycles, stretch power uprates, shorter outage lengths, mixed-oxide (MOX) fuel and more aggressive operating strategies. In order to accommodate these changes, while still satisfying the peaking factor and power envelope requirements necessary to maintain safe operation, more complexity in commercial core designs have been implemented, such as an increase in the number of sub-batches and an increase in the use of both discrete and integral burnable poisons. A consequence of the increased complexity of core designs, as well as the use of MOX fuel, is an increase in the neutronic heterogeneity of the core. Such heterogeneous cores introduce challenges for the current methods that are used for reactor analysis. New methods must be developed to address these deficiencies while still maintaining the computational efficiency of existing reactor analysis methods. In this thesis, advanced core design methodologies are developed to be able to adequately analyze the highly heterogeneous core designs which are currently in use in commercial power reactors. These methodological improvements are being pursued with the goal of not sacrificing the computational efficiency which core designers require. More specifically, the PSU nodal code NEM is being updated to include an SP3 solution option, an advanced transverse leakage option, and a semi-analytical NEM solution option.

  17. EGFR-TKI resistance in NSCLC patients: mechanisms and strategies

    PubMed Central

    Lin, Yuxin; Wang, Xian; Jin, Hongchuan

    2014-01-01

    The epidermal growth factor receptor (EGFR) is a kind of receptor tyrosine kinase (RTK) that plays a critical role in the initiation and development of malignant tumors via modulating downstream signaling pathways. In non-small cell lung cancer (NSCLC), the activating mutations located in the tyrosine kinase domains of EGFR have been demonstrated in multiple researches as the “Achilles’ heel” of this deadly disease since they could be well-targeted by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, it’s still too early to celebrate since the first-generation EGFR-TKIs such as gefitinib and erlotinib have only achieved limited clinical benefits and acquired resistance to this kind of drugs occurred inevitably in almost all the NSCLC patients. In order to make the most of EGFR-TKIs and develop more effective regimens for the NSCLC patients, researchers majoring in different aspects start a battle against EGFR-TKI resistance. Challenging as it is, we still progress stably and step firmly toward the final victory. This review will summarize the major mechanisms of acquired resistance to EGFR-TKIs, and then discuss the development of rationally designed molecular target drugs in accordance with each mechanism, in the hope of shedding light on the great achievements we have obtained and tough obstacles we have to overcome in the battle against this deadly disease. PMID:25232485

  18. Glutaminase 1 inhibition reduces thymidine synthesis in NSCLC.

    PubMed

    Lee, Jae-Seon; Kang, Joon H; Lee, Seon-Hyeong; Lee, Chang-Hun; Son, Jaekyoung; Kim, Soo-Youl

    2016-08-26

    We found that non-small cell lung cancer (NSCLC) is remarkably sensitive to the regulation of glutamine supply by testing the metabolic dependency of 11 cancer cell lines against regulation of glycolysis, autophagy, fatty acid synthesis, and glutamine supply. Glutamine is known as a key supplement of cancer cell growth that is converted to α-ketoglutarate for anabolic biogenesis via glutamate by glutaminase 1 (GLS1). GLS1 inhibition using 10 μM of bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) showed about 50% cell growth arrest by SRB assay. By testing the synergistic effects of conventional therapeutics, BPTES combined with 5-fluorouracil (5-FU), an irreversible inhibitor of thymidylate synthase, significant effects were observed on cell growth arrest in NSCLC. We found that GLS1 inhibition using BPTES reduced metabolic intermediates including thymidine and carbamoyl phosphate. Reduction of thymidine and carbamoyl-phosphate synthesis by BPTES treatment exacerbated pyrimidine supply by combination with 5-FU, which induced cell death synergistically in NSCLC. PMID:27338638

  19. Methods and Systems for Advanced Spaceport Information Management

    NASA Technical Reports Server (NTRS)

    Fussell, Ronald M. (Inventor); Ely, Donald W. (Inventor); Meier, Gary M. (Inventor); Halpin, Paul C. (Inventor); Meade, Phillip T. (Inventor); Jacobson, Craig A. (Inventor); Blackwell-Thompson, Charlie (Inventor)

    2007-01-01

    Advanced spaceport information management methods and systems are disclosed. In one embodiment, a method includes coupling a test system to the payload and transmitting one or more test signals that emulate an anticipated condition from the test system to the payload. One or more responsive signals are received from the payload into the test system and are analyzed to determine whether one or more of the responsive signals comprises an anomalous signal. At least one of the steps of transmitting, receiving, analyzing and determining includes transmitting at least one of the test signals and the responsive signals via a communications link from a payload processing facility to a remotely located facility. In one particular embodiment, the communications link is an Internet link from a payload processing facility to a remotely located facility (e.g. a launch facility, university, etc.).

  20. Methods and systems for advanced spaceport information management

    NASA Technical Reports Server (NTRS)

    Fussell, Ronald M. (Inventor); Ely, Donald W. (Inventor); Meier, Gary M. (Inventor); Halpin, Paul C. (Inventor); Meade, Phillip T. (Inventor); Jacobson, Craig A. (Inventor); Blackwell-Thompson, Charlie (Inventor)

    2007-01-01

    Advanced spaceport information management methods and systems are disclosed. In one embodiment, a method includes coupling a test system to the payload and transmitting one or more test signals that emulate an anticipated condition from the test system to the payload. One or more responsive signals are received from the payload into the test system and are analyzed to determine whether one or more of the responsive signals comprises an anomalous signal. At least one of the steps of transmitting, receiving, analyzing and determining includes transmitting at least one of the test signals and the responsive signals via a communications link from a payload processing facility to a remotely located facility. In one particular embodiment, the communications link is an Internet link from a payload processing facility to a remotely located facility (e.g. a launch facility, university, etc.).

  1. Expression of paired basic amino acid-cleaving enzyme 4 (PACE4) correlated with prognosis in non-small cell lung cancer (NSCLC) patients

    PubMed Central

    Lin, Yun-En; Wu, Qi-Nian; Lin, Xiao-Dong; Li, Guang-Qiu

    2015-01-01

    Background Paired basic amino acid-cleaving enzyme 4 (PACE4) was shown to enhance tumor cells proliferation and invasive. This study provides the first investigation of PACE4 expression in non-small cell lung cancer (NSCLC) and the correlation with clinicopathologic features, prognostic indicators of 172 cases. Methods Quantitative real-time PCR (RT-PCR) and immunofluorescence (IF) were applied to detect PACE4 expression in NSCLC and 16HBE cell lines, then 172 consecutive NSCLC and 15 normal lung tissues were studied through immunohistochemistry (IHC). The association between PACE4 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of PACE4 expression on survival. Results PACE4 expression in NSCLC were significantly higher than normal lung cell and tissues (P<0.05). PACE4 had cytoplasmic expression and was observed in 111 of the 172 (64.5%) NSCLC patients. Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P=0.007), and clinical stage (P=0.024). Multivariable analysis confirmed that PACE4 expression increased the hazard of death after adjusting for other clinicopathological factors [hazards ratio (HR): 1.584; 95% confidence interval (CI): 1.167-2.151; P<0.001]. Overall survival (OS) was significantly prolonged in PACE4 negative group when compared with PACE4 positive group (5-year survival rates, 23.1% vs. 54.5%, log-rank test, χ2=17.717, P<0.001), as was disease-free survival (DFS) (5-year survival rates, 23.4% vs. 55.4%, log-rank test, χ2=20.486, P<0.001). Conclusions Our results suggest that positive expression of PACE4 is an independent factor for NSCLC patients and it might serve as a potential prognostic biomarker for patients with NSCLC. PMID:26101640

  2. Is IMRT Superior or Inferior to 3DCRT in Radiotherapy for NSCLC? A Meta-Analysis

    PubMed Central

    Wen, Shimin; Feng, Xuqin; Fu, Xi; Liu, Yusong; Pu, Ke

    2016-01-01

    Introduction There are no adequate data to determine whether intensity-modulated radiotherapy (IMRT) is superior to three-dimensional conformal radiotherapy (3DCRT) in the treatment of non-small cell lung cancer (NSCLC). This meta-analysis was conducted to compare the clinical outcomes of IMRT and 3DCRT in the treatment of NSCLC. Methods No exclusions were made based on types of study design. We performed a literature search in PubMed, EMBASE and the Cochrane library databases from their inceptions to April 30, 2015. The overall survival (OS) and relative risk (RR) of radiation pneumonitis and radiation oesophagitis were evaluated. Two authors independently assessed the methodological quality and extracted data. Publication bias was evaluated by funnel plot using Egger’s test results. Results From the literature search, 10 retrospective studies were collected, and of those, 5 (12,896 patients) were selected for OS analysis, 4 (981 patients) were selected for radiation pneumonitis analysis, and 4 (1339 patients) were selected for radiation oesophagitis analysis. Cox multivariate proportional hazards models revealed that 3DCRT and IMRT had similar OS (HR = 0.96, P = 0.477) but that IMRT reduced the incidence of grade 2 radiation pneumonitis (RR = 0.74, P = 0.009) and increased the incidence of grade 3 radiation oesophagitis (RR = 2.47, P = 0.000). Conclusions OS of IMRT for NSCLC is not inferior to that of 3DCRT, but IMRT significantly reduces the risk of radiation pneumonitis and increases the risk of radiation oesophagitis compared to 3DCRT. PMID:27100968

  3. Does Every Necrotizing Granulomatous Inflammation Identified by NSCLC Resection Material Require Treatment?

    PubMed Central

    Yakar, Fatih; Yakar, Aysun; Büyükpınarbaşılı, Nur; Erelel, Mustafa

    2016-01-01

    Background Lung cancer and tuberculosis (TB) are two major public health problems. They can coexist or appear sequentially. In patients with TB, lung cancer risk is increased. However, vice versa is not crystal clear. In this study, we aimed to determine the development of TB in patients with resectabled non-small cell lung cancer (NSCLC) in a 2-year postoperative follow-up period. Material/Methods We conducted a retrospective cohort study at three university hospitals. Patients who had NSCLC surgery between 2009 and 2013 were included and patient records were reviewed for the presence of necrotizing granulomatous inflammation (NGI) in resected specimens. Demographic properties, tumor type, stage, location, type of surgery, tuberculosis history, and thorax CT findings were recorded. We searched for the development of tuberculosis within a 2-year period after surgery. Results A total of 1027 patient cases were reviewed, of which 48 patients had NGI. The median age was 63 years. The most common type of cancer was squamous carcinoma; and lobectomy was the preferred operation (70.8%). Cancer involvement most commonly included the right lung (61.8%) and upper lobes (47,9%). Only 11 patients had anti-TB treatment postoperatively, which was based on radiological findings. Prior tuberculosis or anti-TB history, type, stage or localization of cancer, and adjuvant/neoadjuvant therapy were not found to be related to TB treatment. None of the study population had TB during the two-year follow-up period. Treatment decisions appeared mostly related to physician experience. There was no difference in the risk of developing TB between patients with or without treatment. This finding may change the management of our patients. Conclusions Every NGI discovered in NSCLC resected material does not always require anti-TB treatment. PMID:27064420

  4. Recent advances in computational structural reliability analysis methods

    NASA Technical Reports Server (NTRS)

    Thacker, Ben H.; Wu, Y.-T.; Millwater, Harry R.; Torng, Tony Y.; Riha, David S.

    1993-01-01

    The goal of structural reliability analysis is to determine the probability that the structure will adequately perform its intended function when operating under the given environmental conditions. Thus, the notion of reliability admits the possibility of failure. Given the fact that many different modes of failure are usually possible, achievement of this goal is a formidable task, especially for large, complex structural systems. The traditional (deterministic) design methodology attempts to assure reliability by the application of safety factors and conservative assumptions. However, the safety factor approach lacks a quantitative basis in that the level of reliability is never known and usually results in overly conservative designs because of compounding conservatisms. Furthermore, problem parameters that control the reliability are not identified, nor their importance evaluated. A summary of recent advances in computational structural reliability assessment is presented. A significant level of activity in the research and development community was seen recently, much of which was directed towards the prediction of failure probabilities for single mode failures. The focus is to present some early results and demonstrations of advanced reliability methods applied to structural system problems. This includes structures that can fail as a result of multiple component failures (e.g., a redundant truss), or structural components that may fail due to multiple interacting failure modes (e.g., excessive deflection, resonate vibration, or creep rupture). From these results, some observations and recommendations are made with regard to future research needs.

  5. Advanced superposition methods for high speed turbopump vibration analysis

    NASA Technical Reports Server (NTRS)

    Nielson, C. E.; Campany, A. D.

    1981-01-01

    The small, high pressure Mark 48 liquid hydrogen turbopump was analyzed and dynamically tested to determine the cause of high speed vibration at an operating speed of 92,400 rpm. This approaches the design point operating speed of 95,000 rpm. The initial dynamic analysis in the design stage and subsequent further analysis of the rotor only dynamics failed to predict the vibration characteristics found during testing. An advanced procedure for dynamics analysis was used in this investigation. The procedure involves developing accurate dynamic models of the rotor assembly and casing assembly by finite element analysis. The dynamically instrumented assemblies are independently rap tested to verify the analytical models. The verified models are then combined by modal superposition techniques to develop a completed turbopump model where dynamic characteristics are determined. The results of the dynamic testing and analysis obtained are presented and methods of moving the high speed vibration characteristics to speeds above the operating range are recommended. Recommendations for use of these advanced dynamic analysis procedures during initial design phases are given.

  6. Exploration of Advanced Probabilistic and Stochastic Design Methods

    NASA Technical Reports Server (NTRS)

    Mavris, Dimitri N.

    2003-01-01

    The primary objective of the three year research effort was to explore advanced, non-deterministic aerospace system design methods that may have relevance to designers and analysts. The research pursued emerging areas in design methodology and leverage current fundamental research in the area of design decision-making, probabilistic modeling, and optimization. The specific focus of the three year investigation was oriented toward methods to identify and analyze emerging aircraft technologies in a consistent and complete manner, and to explore means to make optimal decisions based on this knowledge in a probabilistic environment. The research efforts were classified into two main areas. First, Task A of the grant has had the objective of conducting research into the relative merits of possible approaches that account for both multiple criteria and uncertainty in design decision-making. In particular, in the final year of research, the focus was on the comparison and contrasting between three methods researched. Specifically, these three are the Joint Probabilistic Decision-Making (JPDM) technique, Physical Programming, and Dempster-Shafer (D-S) theory. The next element of the research, as contained in Task B, was focused upon exploration of the Technology Identification, Evaluation, and Selection (TIES) methodology developed at ASDL, especially with regards to identification of research needs in the baseline method through implementation exercises. The end result of Task B was the documentation of the evolution of the method with time and a technology transfer to the sponsor regarding the method, such that an initial capability for execution could be obtained by the sponsor. Specifically, the results of year 3 efforts were the creation of a detailed tutorial for implementing the TIES method. Within the tutorial package, templates and detailed examples were created for learning and understanding the details of each step. For both research tasks, sample files and

  7. Advanced numerical methods in mesh generation and mesh adaptation

    SciTech Connect

    Lipnikov, Konstantine; Danilov, A; Vassilevski, Y; Agonzal, A

    2010-01-01

    Numerical solution of partial differential equations requires appropriate meshes, efficient solvers and robust and reliable error estimates. Generation of high-quality meshes for complex engineering models is a non-trivial task. This task is made more difficult when the mesh has to be adapted to a problem solution. This article is focused on a synergistic approach to the mesh generation and mesh adaptation, where best properties of various mesh generation methods are combined to build efficiently simplicial meshes. First, the advancing front technique (AFT) is combined with the incremental Delaunay triangulation (DT) to build an initial mesh. Second, the metric-based mesh adaptation (MBA) method is employed to improve quality of the generated mesh and/or to adapt it to a problem solution. We demonstrate with numerical experiments that combination of all three methods is required for robust meshing of complex engineering models. The key to successful mesh generation is the high-quality of the triangles in the initial front. We use a black-box technique to improve surface meshes exported from an unattainable CAD system. The initial surface mesh is refined into a shape-regular triangulation which approximates the boundary with the same accuracy as the CAD mesh. The DT method adds robustness to the AFT. The resulting mesh is topologically correct but may contain a few slivers. The MBA uses seven local operations to modify the mesh topology. It improves significantly the mesh quality. The MBA method is also used to adapt the mesh to a problem solution to minimize computational resources required for solving the problem. The MBA has a solid theoretical background. In the first two experiments, we consider the convection-diffusion and elasticity problems. We demonstrate the optimal reduction rate of the discretization error on a sequence of adaptive strongly anisotropic meshes. The key element of the MBA method is construction of a tensor metric from hierarchical edge

  8. Advanced Motion Compensation Methods for Intravital Optical Microscopy

    PubMed Central

    Vinegoni, Claudio; Lee, Sungon; Feruglio, Paolo Fumene; Weissleder, Ralph

    2013-01-01

    Intravital microscopy has emerged in the recent decade as an indispensible imaging modality for the study of the micro-dynamics of biological processes in live animals. Technical advancements in imaging techniques and hardware components, combined with the development of novel targeted probes and new mice models, have enabled us to address long-standing questions in several biology areas such as oncology, cell biology, immunology and neuroscience. As the instrument resolution has increased, physiological motion activities have become a major obstacle that prevents imaging live animals at resolutions analogue to the ones obtained in vitro. Motion compensation techniques aim at reducing this gap and can effectively increase the in vivo resolution. This paper provides a technical review of some of the latest developments in motion compensation methods, providing organ specific solutions. PMID:24273405

  9. Associations of deregulation of mir-365 and its target mRNA TTF-1 and survival in patients with NSCLC

    PubMed Central

    Sun, Ruifang; Liu, Zhigang; Ma, Gang; Lv, Weidong; Zhao, Xinliang; Lei, Guangyan; Xu, Changfu

    2015-01-01

    microRNA (mir)-365 exerts tumor suppressor function by targeting thyroid transcription factor-1 (TTF-1) in lung cancer cells. The purpose of the present study was to assess mir-365 and its target mRNA TTF-1 in lung cancer and their correlations with patients’ survival. Quantitative real-time PCR was used to examine the expression levels of mir-365 and TTF-1 in tumor tissue and its adjacent noncancerous tissue of 126 patients with non-small cell lung cancer (NSCLC). Our results showed that mir-365 was significantly decreased in tumor tissue than that in normal tissue (P=0.006), however, TTF-1 was significantly increased in tumor tissue than in normal tissue (P<0.001). Besides, significant correlations between decreased mir-365 and advanced tumor-node-metastasis (TNM) stage (P=0.001) and regional lymph node involvement (P=0.037) was observed. The similar result was also found between increased TTF-1 and TNM stage (P=0.003). Furthermore, mir-365 downregulation or TTF-1 upregulation were associated with poor outcome of patients than mir-365 upregulation or TTF-1 downregulation (for mir-365: P<0.001; for TTF-1: P=0.002). Of note, combination of decreased mir-365 and increased TTF-1 had worst overall survival (P<0.001). In conclusion, aberrant expression of mir-365/TTF-1 may be involved in the tumor development in patients with NSCLC. Moreover, mir-365 and TTF-1 could jointly predict the prognosis of patients and their combination may serve as a biomarker to predict risk of poor survival in NSCLC patients. Mir-365/TTF-1 might serve as a potential therapeutic target for clinical treatment of NSCLC. PMID:26045746

  10. Advancing MODFLOW Applying the Derived Vector Space Method

    NASA Astrophysics Data System (ADS)

    Herrera, G. S.; Herrera, I.; Lemus-García, M.; Hernandez-Garcia, G. D.

    2015-12-01

    The most effective domain decomposition methods (DDM) are non-overlapping DDMs. Recently a new approach, the DVS-framework, based on an innovative discretization method that uses a non-overlapping system of nodes (the derived-nodes), was introduced and developed by I. Herrera et al. [1, 2]. Using the DVS-approach a group of four algorithms, referred to as the 'DVS-algorithms', which fulfill the DDM-paradigm (i.e. the solution of global problems is obtained by resolution of local problems exclusively) has been derived. Such procedures are applicable to any boundary-value problem, or system of such equations, for which a standard discretization method is available and then software with a high degree of parallelization can be constructed. In a parallel talk, in this AGU Fall Meeting, Ismael Herrera will introduce the general DVS methodology. The application of the DVS-algorithms has been demonstrated in the solution of several boundary values problems of interest in Geophysics. Numerical examples for a single-equation, for the cases of symmetric, non-symmetric and indefinite problems were demonstrated before [1,2]. For these problems DVS-algorithms exhibited significantly improved numerical performance with respect to standard versions of DDM algorithms. In view of these results our research group is in the process of applying the DVS method to a widely used simulator for the first time, here we present the advances of the application of this method for the parallelization of MODFLOW. Efficiency results for a group of tests will be presented. References [1] I. Herrera, L.M. de la Cruz and A. Rosas-Medina. Non overlapping discretization methods for partial differential equations, Numer Meth Part D E, (2013). [2] Herrera, I., & Contreras Iván "An Innovative Tool for Effectively Applying Highly Parallelized Software To Problems of Elasticity". Geofísica Internacional, 2015 (In press)

  11. New advanced control methods for doubly salient permanent magnet motor

    SciTech Connect

    Blaabjerg, F.; Christensen, L.; Rasmussen, P.O.; Oestergaard, L.; Pedersen, P.

    1995-12-31

    High performance and high efficiency in adjustable speed drives are needed and new motor constructions are world wide investigated and analyzed. This paper deals with advanced control of a recently developed Doubly Salient Permanent Magnet (DSPM) motor. The construction of the DSPM motor is shown and a dynamical model of the motor is used for simulations. As supply to the DSPM motor, a power converter with a split capacitor is used to reduce the number of devices, and a basic control method for this converter is explained. This control method will cause an unequal voltage distribution across the capacitors because the motor is asymmetrical and a decrease in efficiency and a poorer dynamic performance are the results. To minimize the problems with the unequal load of the capacitors in the converter, a new charge control strategy is developed. The efficiency of the motor can also be improved by using a power minimizing scheme based on changing the turn-on and turn-off angles of the current. The two different strategies are implemented in an adjustable-speed drive, and it is concluded that both control strategies improve the performance of the drive.

  12. Angiogenesis inhibition as a therapeutic strategy in non-small cell lung cancer (NSCLC)

    PubMed Central

    Hall, Richard D.; Le, Tri M.; Haggstrom, Daniel E.

    2015-01-01

    In many cancers, including non-small cell lung cancer (NSCLC), tumor angiogenesis pathways have been identified as important therapeutic targets. Angiogenesis is essential in the process of primary tumor growth, proliferation and metastasis. One of the best characterized group of protein factors for angiogenesis include the members of the vascular endothelial growth factor (VEGF) family, consisting of VEGF-(A-D), and placenta growth factor (PIGF). Targeting tumor angiogenesis has been approached through two primary methods, monoclonal antibodies that block VEGF-vascular endothelial growth factor receptor (VEGFR) binding or small molecule tyrosine kinase inhibitors (TKIs) that inhibit the downstream VEGFR mediated signaling. Many TKIs inhibit multiple pro-angiogenic and pro-proliferative pathways such as the mitogen activated protein (MAP) kinase pathway. Bevacizumab and ramucirumab, monoclonal antibodies targeting VEGF and the VEGFR, respectively, have each led to improvements in overall survival (OS) for NSCLC when added to standard first and second line chemotherapy, respectively. Small incremental gains seen with both bevacizumab and ramucirumab may be further improved upon by incorporating novel agents and treatment strategies, and many additional trials are ongoing. PMID:26629420

  13. [F-18] FDG-PET/CT parameters as predictors of outcome in inoperable NSCLC patients

    PubMed Central

    Nappi, Antonio; Gallicchio, Rosj; Simeon, Vittorio; Nardelli, Anna; Pelagalli, Alessandra; Zupa, Angela; Vita, Giulia; Venetucci, Angela; Di Cosola, Michele; Barbato, Francesco; Storto, Giovanni

    2015-01-01

    Background We evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) in [F-18] FDG PET/CT findings in patients with inoperable non-small-cell lung cancer (NSCLC). Patients and methods. One hundred and three patients (mean age, 65.6 ± 16 years) underwent [F-18] FDG PET/CT before the chemotherapy. The SUVmax value, the MTV (cm3; 42% threshold) and the TLG (g) were registered. The patients were followed up to 18 months thereafter (range 12–55 months). Failure to respond without progression, progression and/or disease-related death constituted surrogate end-points. The optimal SUVmax, MTV and TLG cut-off to predict the patients’ outcome were estimated. PET/CT results were then related to disease outcome (progression free survival; PFS). Results The Kaplan-Meier survival analysis for SUVmax showed a significant shorter PFS in patients presenting with lower values as compared to those with higher (p < 0.05, log-rank test). MTV and TLG were not suitable for predicting PFS apart from the subset of patients with mediastinal nodal involvement. Conclusions Despite the availability of new tools for the quantitative assessment of disease activity on PET/CT, the SUVmax rather than MTV and TLG remains the only predictor for PFS in NSCLC patients. MTV holds a value only when concomitant nodal involvement occurs. PMID:26834517

  14. Volumetric CT-based segmentation of NSCLC using 3D-Slicer

    PubMed Central

    Velazquez, Emmanuel Rios; Parmar, Chintan; Jermoumi, Mohammed; Mak, Raymond H.; van Baardwijk, Angela; Fennessy, Fiona M.; Lewis, John H.; De Ruysscher, Dirk; Kikinis, Ron; Lambin, Philippe; Aerts, Hugo J. W. L.

    2013-01-01

    Accurate volumetric assessment in non-small cell lung cancer (NSCLC) is critical for adequately informing treatments. In this study we assessed the clinical relevance of a semiautomatic computed tomography (CT)-based segmentation method using the competitive region-growing based algorithm, implemented in the free and public available 3D-Slicer software platform. We compared the 3D-Slicer segmented volumes by three independent observers, who segmented the primary tumour of 20 NSCLC patients twice, to manual slice-by-slice delineations of five physicians. Furthermore, we compared all tumour contours to the macroscopic diameter of the tumour in pathology, considered as the “gold standard”. The 3D-Slicer segmented volumes demonstrated high agreement (overlap fractions > 0.90), lower volume variability (p = 0.0003) and smaller uncertainty areas (p = 0.0002), compared to manual slice-by-slice delineations. Furthermore, 3D-Slicer segmentations showed a strong correlation to pathology (r = 0.89, 95%CI, 0.81–0.94). Our results show that semiautomatic 3D-Slicer segmentations can be used for accurate contouring and are more stable than manual delineations. Therefore, 3D-Slicer can be employed as a starting point for treatment decisions or for high-throughput data mining research, such as Radiomics, where manual delineating often represent a time-consuming bottleneck. PMID:24346241

  15. Volumetric CT-based segmentation of NSCLC using 3D-Slicer.

    PubMed

    Velazquez, Emmanuel Rios; Parmar, Chintan; Jermoumi, Mohammed; Mak, Raymond H; van Baardwijk, Angela; Fennessy, Fiona M; Lewis, John H; De Ruysscher, Dirk; Kikinis, Ron; Lambin, Philippe; Aerts, Hugo J W L

    2013-01-01

    Accurate volumetric assessment in non-small cell lung cancer (NSCLC) is critical for adequately informing treatments. In this study we assessed the clinical relevance of a semiautomatic computed tomography (CT)-based segmentation method using the competitive region-growing based algorithm, implemented in the free and public available 3D-Slicer software platform. We compared the 3D-Slicer segmented volumes by three independent observers, who segmented the primary tumour of 20 NSCLC patients twice, to manual slice-by-slice delineations of five physicians. Furthermore, we compared all tumour contours to the macroscopic diameter of the tumour in pathology, considered as the "gold standard". The 3D-Slicer segmented volumes demonstrated high agreement (overlap fractions > 0.90), lower volume variability (p = 0.0003) and smaller uncertainty areas (p = 0.0002), compared to manual slice-by-slice delineations. Furthermore, 3D-Slicer segmentations showed a strong correlation to pathology (r = 0.89, 95%CI, 0.81-0.94). Our results show that semiautomatic 3D-Slicer segmentations can be used for accurate contouring and are more stable than manual delineations. Therefore, 3D-Slicer can be employed as a starting point for treatment decisions or for high-throughput data mining research, such as Radiomics, where manual delineating often represent a time-consuming bottleneck. PMID:24346241

  16. Cytotoxic Chemotherapy as First-Line Therapy for Advanced Non-Small-Cell Lung Cancer in Taiwan: Daily Practice

    PubMed Central

    Liang, Yi-Hsin; Shao, Yu-Yun; Liao, Bin-Chi; Lee, Ho-Sheng; Yang, James Chih-Hsin; Chen, Ho-Min; Chiang, Chun-Ju; Cheng, Ann-Lii; Lai, Mei-Shu

    2016-01-01

    Aim: Cytotoxic chemotherapy is the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) without specific gene alterations. This study examined the prescription pattern and the survival outcome of cytotoxic chemotherapy regimens in daily practice in Taiwan. Methods:We established a population-based cohort of patients diagnosed with advanced NSCLC between 2005 and 2009 using the databases of Taiwan Cancer Registry and National Health Insurance in Taiwan. We then analyzed chemotherapy prescriptions and the survival outcomes of patients. Results:A total of 25,008 patients with advanced NSCLC were identified, 17,443 (70.0%) of which received first-line chemotherapy and were therefore included in this study. Among them, 11,551 (66.2%) patients had adenocarcinoma and 3,292 (18.9%) patients had squamous cell carcinoma (SCC). Approximately 70% of the patients were diagnosed with NSCLC in medical centers. Platinum-based doublet chemotherapy was administered to 66.9% of the patients. Among all chemotherapy regimens, platinum with gemcitabine (33.8%) was the most common, irrespective of geographic region. The second and third most common regimens were vinorelbine alone (13.0%) and platinum with docetaxel (11.6%). The prevalence of platinum-based doublet chemotherapy regimens decreased from 71.4% in 2005 to 64.1% in 2009. Among patients with adenocarcinoma histology, those who received platinum with pemetrexed had longer OS than did patients who received other platinum-based regimens (p < 0.001). Conclusion: Our findings reaffirm that in real-world practice, treatment plans of advanced NSCLC should be drawn up according to histology type. PMID:27471567

  17. NSCLC tumor shrinkage prediction using quantitative image features.

    PubMed

    Hunter, Luke A; Chen, Yi Pei; Zhang, Lifei; Matney, Jason E; Choi, Haesun; Kry, Stephen F; Martel, Mary K; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel; Yang, Jinzhong; Court, Laurence E

    2016-04-01

    The objective of this study was to develop a quantitative image feature model to predict non-small cell lung cancer (NSCLC) volume shrinkage from pre-treatment CT images. 64 stage II-IIIB NSCLC patients with similar treatments were all imaged using the same CT scanner and protocol. For each patient, the planning gross tumor volume (GTV) was deformed onto the week 6 treatment image, and tumor shrinkage was quantified as the deformed GTV volume divided by the planning GTV volume. Geometric, intensity histogram, absolute gradient image, co-occurrence matrix, and run-length matrix image features were extracted from each planning GTV. Prediction models were generated using principal component regression with simulated annealing subset selection. Performance was quantified using the mean squared error (MSE) between the predicted and observed tumor shrinkages. Permutation tests were used to validate the results. The optimal prediction model gave a strong correlation between the observed and predicted tumor shrinkages with r=0.81 and MSE=8.60×10(-3). Compared to predictions based on the mean population shrinkage this resulted in a 2.92 fold reduction in MSE. In conclusion, this study indicated that quantitative image features extracted from existing pre-treatment CT images can successfully predict tumor shrinkage and provide additional information for clinical decisions regarding patient risk stratification, treatment, and prognosis. PMID:26878137

  18. The Minority Report: Targeting the Rare Oncogenes in NSCLC

    PubMed Central

    McCoach, Caroline E.

    2014-01-01

    Lung cancer is still responsible for the highest number of cancer deaths worldwide. Despite this fact, significant progress has been made in the treatment of non-small cell lung cancer (NSCLC). Specifically, efforts to identify and treat genetic alterations (gene mutations, gene fusions, gene amplification events, etc.) that result in oncogenic drivers are now standard of care (EGFR and ALK) or an intense area of research. The most prevalent oncogenic drivers have likely already been identified; thus, there is now a focus on subgroups of tumors with less common genetic alterations. Interestingly, as we explore these less common mutations, we are discovering that many occur across other tumor types (i.e., non-lung cancer), further justifying their study. Furthermore, many studies have demonstrated that by searching broadly for multiple genetic alterations in large subsets of patients they are able to identify potentially targetable alterations in the majority of patients. Although individually, the rare oncogenic drivers subgroups may seem to occur too infrequently to justify their exploration, the fact that the majority of patients with NSCLC harbor a potentially actionable driver mutation within their tumors and the fact that different types of cancers often have the same oncogenic driver justifies this approach. PMID:25228144

  19. miR-25 modulates NSCLC cell radio-sensitivity through directly inhibiting BTG2 expression

    SciTech Connect

    He, Zhiwei Liu, Yi Xiao, Bing Qian, Xiaosen

    2015-02-13

    A large proportion of the NSCLC patients were insensitive to radiotherapy, but the exact mechanism is still unclear. This study explored the role of miR-25 in regulating sensitivity of NSCLC cells to ionizing radiation (IR) and its downstream targets. Based on measurement in tumor samples from NSCLC patients, this study found that miR-25 expression is upregulated in both NSCLC and radio-resistant NSCLC patients compared the healthy and radio-sensitive controls. In addition, BTG expression was found negatively correlated with miR-25a expression in the both tissues and cells. By applying luciferase reporter assay, we verified two putative binding sites between miR-25 and BTG2. Therefore, BTG2 is a directly target of miR-25 in NSCLC cancer. By applying loss-and-gain function analysis in NSCLC cell lines, we demonstrated that miR-25-BTG2 axis could directly regulated BTG2 expression and affect radiotherapy sensitivity of NSCLC cells. - Highlights: • miR-25 is upregulated, while BTG2 is downregulated in radioresistant NSCLC patients. • miR-25 modulates sensitivity to radiation induced apoptosis. • miR-25 directly targets BTG2 and suppresses its expression. • miR-25 modulates sensitivity to radiotherapy through inhibiting BTG2 expression.

  20. Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy.

    PubMed

    Bartucci, M; Svensson, S; Romania, P; Dattilo, R; Patrizii, M; Signore, M; Navarra, S; Lotti, F; Biffoni, M; Pilozzi, E; Duranti, E; Martinelli, S; Rinaldo, C; Zeuner, A; Maugeri-Saccà, M; Eramo, A; De Maria, R

    2012-05-01

    Cancer stem cell (SC) chemoresistance may be responsible for the poor clinical outcome of non-small-cell lung cancer (NSCLC) patients. In order to identify the molecular events that contribute to NSCLC chemoresistance, we investigated the DNA damage response in SCs derived from NSCLC patients. We found that after exposure to chemotherapeutic drugs NSCLC-SCs undergo cell cycle arrest, thus allowing DNA damage repair and subsequent cell survival. Activation of the DNA damage checkpoint protein kinase (Chk) 1 was the earliest and most significant event detected in NSCLC-SCs treated with chemotherapy, independently of their p53 status. In contrast, a weak Chk1 activation was found in differentiated NSCLC cells, corresponding to an increased sensitivity to chemotherapeutic drugs as compared with their undifferentiated counterparts. The use of Chk1 inhibitors in combination with chemotherapy dramatically reduced NSCLC-SC survival in vitro by inducing premature cell cycle progression and mitotic catastrophe. Consistently, the co-administration of the Chk1 inhibitor AZD7762 and chemotherapy abrogated tumor growth in vivo, whereas chemotherapy alone was scarcely effective. Such increased efficacy in the combined use of Chk1 inhibitors and chemotherapy was associated with a significant reduction of NSCLC-SCs in mouse xenografts. Taken together, these observations support the clinical evaluation of Chk1 inhibitors in combination with chemotherapy for a more effective treatment of NSCLC. PMID:22117197

  1. Efficacy of targeted agents in the treatment of elderly patients with advanced non-small-cell lung cancer: a systematic review and meta-analysis

    PubMed Central

    Chen, Jianqing; Chen, Jianbo; Wu, Xiaoan; Shi, Tao; Kang, Meiling

    2016-01-01

    Purpose The efficacy of targeted agents (TAs) in the treatment of elderly patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. We aimed to assess the efficacy of TAs in the treatment of advanced NSCLC in this setting. Materials and methods Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials assessing chemotherapies with or without TAs in elderly patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS) and progression-free survival (PFS) in elderly patients with advanced NSCLC. Results A total of 4,093 elderly patients from 17 randomized controlled trials were included for analysis. The addition of TAs to chemotherapy significantly improved PFS (hazard ratio [HR] 0.85, 95% confidence interval [CI]: 0.75–0.96, P=0.01) when compared to chemotherapy alone. There was also a tendency to improve OS in the combination groups (HR 0.92, 95% CI: 0.85–1.01, P=0.064). Subgroup analysis based on treatment line indicated that TAs plus chemotherapy as first-line chemotherapy in elderly patients with advanced NSCLC significantly improved PFS (HR 0.80, 95% CI: 0.68–0.95, P=0.01) and OS (HR 0.91, 95% CI: 0.83–0.99, P=0.037), while the use of TA-containing regimens as second-line therapy in these patients did not significantly improve PFS (HR 0.91, 95% CI: 0.75–1.10, P=0.33) and OS (HR 1.04, 95% CI: 0.81–1.33, P=0.77) in comparison with chemotherapy alone. No publication bias was detected by Begg’s and Egger’s tests for OS. Conclusion The findings of this study suggest that the addition of TAs to first-line chemotherapy in elderly patients with advanced NSCLC offers an improved PFS and OS. Further trials are recommended to clearly investigate the efficacy of adding specific TAs to first-line chemotherapy for advanced NSCLC in this setting. PMID:27536143

  2. Advances in the analysis of iminocyclitols: Methods, sources and bioavailability.

    PubMed

    Amézqueta, Susana; Torres, Josep Lluís

    2016-05-01

    Iminocyclitols are chemically and metabolically stable, naturally occurring sugar mimetics. Their biological activities make them interesting and extremely promising as both drug leads and functional food ingredients. The first iminocyclitols were discovered using preparative isolation and purification methods followed by chemical characterization using nuclear magnetic resonance spectroscopy. In addition to this classical approach, gas and liquid chromatography coupled to mass spectrometry are increasingly used; they are highly sensitive techniques capable of detecting minute amounts of analytes in a broad spectrum of sources after only minimal sample preparation. These techniques have been applied to identify new iminocyclitols in plants, microorganisms and synthetic mixtures. The separation of iminocyclitol mixtures by chromatography is particularly difficult however, as the most commonly used matrices have very low selectivity for these highly hydrophilic structurally similar molecules. This review critically summarizes recent advances in the analysis of iminocyclitols from plant sources and findings regarding their quantification in dietary supplements and foodstuffs, as well as in biological fluids and organs, from bioavailability studies. PMID:26946023

  3. Underwater Photosynthesis of Submerged Plants – Recent Advances and Methods

    PubMed Central

    Pedersen, Ole; Colmer, Timothy D.; Sand-Jensen, Kaj

    2013-01-01

    We describe the general background and the recent advances in research on underwater photosynthesis of leaf segments, whole communities, and plant dominated aquatic ecosystems and present contemporary methods tailor made to quantify photosynthesis and carbon fixation under water. The majority of studies of aquatic photosynthesis have been carried out with detached leaves or thalli and this selectiveness influences the perception of the regulation of aquatic photosynthesis. We thus recommend assessing the influence of inorganic carbon and temperature on natural aquatic communities of variable density in addition to studying detached leaves in the scenarios of rising CO2 and temperature. Moreover, a growing number of researchers are interested in tolerance of terrestrial plants during flooding as torrential rains sometimes result in overland floods that inundate terrestrial plants. We propose to undertake studies to elucidate the importance of leaf acclimation of terrestrial plants to facilitate gas exchange and light utilization under water as these acclimations influence underwater photosynthesis as well as internal aeration of plant tissues during submergence. PMID:23734154

  4. Methods for integrating optical fibers with advanced aerospace materials

    NASA Astrophysics Data System (ADS)

    Poland, Stephen H.; May, Russell G.; Murphy, Kent A.; Claus, Richard O.; Tran, Tuan A.; Miller, Mark S.

    1993-07-01

    Optical fibers are attractive candidates for sensing applications in near-term smart materials and structures, due to their inherent immunity to electromagnetic interference and ground loops, their capability for distributed and multiplexed operation, and their high sensitivity and dynamic range. These same attributes also render optical fibers attractive for avionics busses for fly-by-light systems in advanced aircraft. The integration of such optical fibers with metal and composite aircraft and aerospace materials, however, remains a limiting factor in their successful use in such applications. This paper first details methods for the practical integration of optical fiber waveguides and cable assemblies onto and into materials and structures. Physical properties of the optical fiber and coatings which affect the survivability of the fiber are then considered. Mechanisms for the transfer of the strain from matrix to fiber for sensor and data bus fibers integrated with composite structural elements are evaluated for their influence on fiber survivability, in applications where strain or impact is imparted to the assembly.

  5. PRATHAM: Parallel Thermal Hydraulics Simulations using Advanced Mesoscopic Methods

    SciTech Connect

    Joshi, Abhijit S; Jain, Prashant K; Mudrich, Jaime A; Popov, Emilian L

    2012-01-01

    At the Oak Ridge National Laboratory, efforts are under way to develop a 3D, parallel LBM code called PRATHAM (PaRAllel Thermal Hydraulic simulations using Advanced Mesoscopic Methods) to demonstrate the accuracy and scalability of LBM for turbulent flow simulations in nuclear applications. The code has been developed using FORTRAN-90, and parallelized using the message passing interface MPI library. Silo library is used to compact and write the data files, and VisIt visualization software is used to post-process the simulation data in parallel. Both the single relaxation time (SRT) and multi relaxation time (MRT) LBM schemes have been implemented in PRATHAM. To capture turbulence without prohibitively increasing the grid resolution requirements, an LES approach [5] is adopted allowing large scale eddies to be numerically resolved while modeling the smaller (subgrid) eddies. In this work, a Smagorinsky model has been used, which modifies the fluid viscosity by an additional eddy viscosity depending on the magnitude of the rate-of-strain tensor. In LBM, this is achieved by locally varying the relaxation time of the fluid.

  6. Quantifying hydrate solidification front advancing using method of characteristics

    NASA Astrophysics Data System (ADS)

    You, Kehua; DiCarlo, David; Flemings, Peter B.

    2015-10-01

    We develop a one-dimensional analytical solution based on the method of characteristics to explore hydrate formation from gas injection into brine-saturated sediments within the hydrate stability zone. Our solution includes fully coupled multiphase and multicomponent flow and the associated advective transport in a homogeneous system. Our solution shows that hydrate saturation is controlled by the initial thermodynamic state of the system and changed by the gas fractional flow. Hydrate saturation in gas-rich systems can be estimated by 1-cl0/cle when Darcy flow dominates, where cl0 is the initial mass fraction of salt in brine, and cle is the mass fraction of salt in brine at three-phase (gas, liquid, and hydrate) equilibrium. Hydrate saturation is constant, gas saturation and gas flux decrease, and liquid saturation and liquid flux increase with the distance from the gas inlet to the hydrate solidification front. The total gas and liquid flux is constant from the gas inlet to the hydrate solidification front and decreases abruptly at the hydrate solidification front due to gas inclusion into the hydrate phase. The advancing velocity of the hydrate solidification front decreases with hydrate saturation at a fixed gas inflow rate. This analytical solution illuminates how hydrate is formed by gas injection (methane, CO2, ethane, propane) at both the laboratory and field scales.

  7. Electrochemical test methods for advanced battery and semiconductor technology

    NASA Astrophysics Data System (ADS)

    Hsu, Chao-Hung

    This dissertation consists of two studies. The first study was the evaluation of metallic materials for advanced lithium ion batteries and the second study was the determination of the dielectric constant k for the low-k materials. The advanced lithium ion battery is miniature for implantable medical devices and capable of being recharged from outside of the body using magnetic induction without physical connections. The stability of metallic materials employed in the lithium ion battery is one of the major safety concerns. Three types of materials---Pt-Ir alloy, Ti alloys, and stainless steels---were evaluated extensively in this study. The electrochemical characteristics of Pt-Ir alloy, Ti alloys, and stainless steels were evaluated in several types of battery electrolytes in order to determine the candidate materials for long-term use in lithium ion batteries. The dissolution behavior of these materials and the decomposition behavior of the battery electrolyte were investigated using the anodic potentiodynamic polarization (APP) technique. Lifetime prediction for metal dissolution was conducted using constant potential polarization (CPP) technique. The electrochemical impedance spectroscopy (EIS) technique was employed to investigate the metal dissolution behavior or the battery electrolyte decomposition at the open circuit potential (OCP). The scanning electron microscope (SEM) was used to observe the morphology changes after these tests. The effects of experimental factors on the corrosion behaviors of the metallic materials and stabilities of the battery electrolytes were also investigated using the 23 factorial design approach. Integration of materials having low dielectric constant k as interlayer dielectrics and/or low-resistivity conductors will partially solve the RC delay problem for the limiting performance of high-speed logic chips. The samples of JSR LKD 5109 material capped by several materials were evaluated by using EIS. The feasibility of using

  8. Development and Applications of Advanced Electronic Structure Methods

    NASA Astrophysics Data System (ADS)

    Bell, Franziska

    This dissertation contributes to three different areas in electronic structure theory. The first part of this thesis advances the fundamentals of orbital active spaces. Orbital active spaces are not only essential in multi-reference approaches, but have also become of interest in single-reference methods as they allow otherwise intractably large systems to be studied. However, despite their great importance, the optimal choice and, more importantly, their physical significance are still not fully understood. In order to address this problem, we studied the higher-order singular value decomposition (HOSVD) in the context of electronic structure methods. We were able to gain a physical understanding of the resulting orbitals and proved a connection to unrelaxed natural orbitals in the case of Moller-Plesset perturbation theory to second order (MP2). In the quest to find the optimal choice of the active space, we proposed a HOSVD for energy-weighted integrals, which yielded the fastest convergence in MP2 correlation energy for small- to medium-sized active spaces to date, and is also potentially transferable to coupled-cluster theory. In the second part, we studied monomeric and dimeric glycerol radical cations and their photo-induced dissociation in collaboration with Prof. Leone and his group. Understanding the mechanistic details involved in these processes are essential for further studies on the combustion of glycerol and carbohydrates. To our surprise, we found that in most cases, the experimentally observed appearance energies arise from the separation of product fragments from one another rather than rearrangement to products. The final chapters of this work focus on the development, assessment, and application of the spin-flip method, which is a single-reference approach, but capable of describing multi-reference problems. Systems exhibiting multi-reference character, which arises from the (near-) degeneracy of orbital energies, are amongst the most

  9. Improved survival with stereotactic ablative radiotherapy (SABR) over lobectomy for early stage non-small cell lung cancer (NSCLC): addressing the fallout of disruptive randomized data

    PubMed Central

    Kavanagh, Brian D.; Karam, Sana D.

    2015-01-01

    The gold-standard therapy for early stage non-small cell lung cancer (esNSCLC) has historically been lobectomy with mediastinal lymph node dissection. However, up to one-third of patients with esNSCLC are considered medically-inoperable due to factors such as advanced age and comorbid illnesses. The past decade has witnessed a dramatic increase in the use of high-dose conformal radiotherapy delivered over 1-5 fractions, synonymously termed stereotactic ablative radiotherapy (SABR) or stereotactic body radiation therapy (SBRT). High rates of tumor control and favorable toxicity profiles have led to the adoption of SABR as the treatment of choice for medically-inoperable patients. Limited but growing data exist using SABR for medically-operable patients who are also candidates for lobectomy. A recent pooled analysis of two multicenter prospective randomized trials, the STARS (NCT00840749) and ROSEL (NCT00687986) protocols, published by Chang and colleagues (PMID 25981812) reported improved overall survival (OS) and reduced toxicity with SABR over lobectomy for medically-operable patients with esNSCLC. In this article we review the outcomes of this analysis in the context of existing radiotherapy and surgical data for NSCLC. Further, we discuss the potential causes and implications of these provocative results, including the shifting balance between oncologic control and treatment-related mortality in comparisons of SABR and surgical resection, termed the Head Start Effect. PMID:26244136

  10. Risk of venous and arterial thromboembolic events associated with anti-VEGF agents in advanced non-small-cell lung cancer: a meta-analysis and systematic review

    PubMed Central

    Zhang, Dianbao; Zhang, Xianfen; Zhao, Chunling

    2016-01-01

    Aims To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with antivascular endothelial growth factor (VEGF) agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC) patients. Methods We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis. Data on VTEs and ATEs were extracted. The overall incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were pooled according to the heterogeneity of included trials. Results A total of 13,436 patients from 23 trials were included for analysis. Our results showed that anti-VEGF agents significantly increased the risk of developing high-grade ATEs (Peto OR: 1.44, 95% CI: 1.00–2.07, P=0.048), but not for all-grade ATEs (Peto OR: 0.94, 95% CI: 0.56–1.59, P=0.82) compared with controls. Additionally, no increased risk of all-grade and high-grade VTEs (Peto OR: 0.94, 95% CI: 0.67–1.31, P=0.71 and Peto OR: 0.95, 95% CI: 0.73–1.22, P=0.67, respectively) was observed in advanced NSCLC patients receiving anti-VEGF agents. Conclusion The use of anti-VEGF agents in advanced NSCLC patients significantly increased the risk of high-grade ATEs, but not for VTEs. Clinicians should be aware of the risk of severe ATEs with administration of these drugs in advanced NSCLC patients. PMID:27382307

  11. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

    PubMed Central

    Xiao, Huai-Qing; Tian, Rong-Hua; Zhang, Zhi-Hao; Du, Kai-Qi; Ni, Yi-Ming

    2016-01-01

    Purpose To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC) through a trial-level meta-analysis. Methods Trials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library). All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were extracted and analyzed using comprehensive meta-analysis software (version 2.0). Results A total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%), with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01) but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084) in advanced nonsquamous NSCLC patients. Conclusion Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our findings support the use of pemetrexed plus platinum doublet regimen as first-line treatment in advanced nonsquamous NSCLC patients because of its potential survival benefits. PMID:27042115

  12. Bioinformatics Methods and Tools to Advance Clinical Care

    PubMed Central

    Lecroq, T.

    2015-01-01

    Summary Objectives To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and clinical care. Method We provide a synopsis of the articles selected for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview of current and future activities in the field. As last year, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor has evaluated separately the set of 1,594 articles and the evaluation results were merged for retaining 15 articles for peer-review. Results The selection and evaluation process of this Yearbook’s section on Bioinformatics and Translational Informatics yielded four excellent articles regarding data management and genome medicine that are mainly tool-based papers. In the first article, the authors present PPISURV a tool for uncovering the role of specific genes in cancer survival outcome. The second article describes the classifier PredictSNP which combines six performing tools for predicting disease-related mutations. In the third article, by presenting a high-coverage map of the human proteome using high resolution mass spectrometry, the authors highlight the need for using mass spectrometry to complement genome annotation. The fourth article is also related to patient survival and decision support. The authors present datamining methods of large-scale datasets of past transplants. The objective is to identify chances of survival. Conclusions The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on dedicated tools and methods to advance clinical care. Indeed, there is a need for powerful tools for managing and interpreting complex, large-scale genomic and biological datasets, but also a need for user-friendly tools developed for the clinicians in their

  13. Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

    PubMed Central

    Lai, Xi-Xi; Xu, Ren-Ai; Yu-Ping, Li; Yang, Han

    2016-01-01

    Background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC). We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC. Methods Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR) and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials. Results A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55), hypertension (RR =5.34), and hemorrhagic events (RR =2.61). No statistically significant differences were found for gastrointestinal perforation (P=0.60), arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively), or fatal events (P=0.29). Conclusion The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. PMID:27143937

  14. TMPRSS4 regulates levels of integrin α5 in NSCLC through miR-205 activity to promote metastasis

    PubMed Central

    Larzabal, L; de Aberasturi, A L; Redrado, M; Rueda, P; Rodriguez, M J; Bodegas, M E; Montuenga, L M; Calvo, A

    2014-01-01

    Background: TMPRSS4 is a membrane-anchored protease involved in cell migration and invasion in different cancer types including lung cancer. TMPRSS4 expression is increased in NSCLC and its inhibition through shRNA reduces lung metastasis. However, molecular mechanisms leading to the protumorigenic regulation of TMPRSS4 in lung cancer are unknown. Methods: miR-205 was identified as an overexpressed gene upon TMPRSS4 downregulation through microarray analysis. Cell migration and invasion assays and in vivo lung primary tumour and metastasis models were used for functional analysis of miR-205 overexpression in H2170 and H441 cell lines. Luciferase assays were used to identify a new miR-205 direct target in NSCLC. Results: miR-205 overexpression promoted an epithelial phenotype with increased E-cadherin and reduced fibronectin. Furthermore, miR-205 expression caused a G0/G1 cell cycle arrest and inhibition of cell growth, migration, attachment to fibronectin, primary tumour growth and metastasis formation in vivo. Integrin α5 (a proinvasive protein) was identified as a new miR-205 direct target in NSCLC. Integrin α5 downregulation in lung cancer cells resulted in complete abrogation of cell migration, a decreased capacity to adhere to fibronectin and reduced in vivo tumour growth, compared with control cells. TMPRSS4 silencing resulted in a concomitant reduction of integrin α5 levels. Conclusion: We have demonstrated for the first time a new molecular pathway that connects TMPRSS4 and integrin α5 through miR-205 to regulate cancer cell invasion and metastasis. Our results will help designing new therapeutic strategies to inhibit this novel pathway in NSCLC. PMID:24434435

  15. ADVANCED SEISMIC BASE ISOLATION METHODS FOR MODULAR REACTORS

    SciTech Connect

    E. Blanford; E. Keldrauk; M. Laufer; M. Mieler; J. Wei; B. Stojadinovic; P.F. Peterson

    2010-09-20

    Advanced technologies for structural design and construction have the potential for major impact not only on nuclear power plant construction time and cost, but also on the design process and on the safety, security and reliability of next generation of nuclear power plants. In future Generation IV (Gen IV) reactors, structural and seismic design should be much more closely integrated with the design of nuclear and industrial safety systems, physical security systems, and international safeguards systems. Overall reliability will be increased, through the use of replaceable and modular equipment, and through design to facilitate on-line monitoring, in-service inspection, maintenance, replacement, and decommissioning. Economics will also receive high design priority, through integrated engineering efforts to optimize building arrangements to minimize building heights and footprints. Finally, the licensing approach will be transformed by becoming increasingly performance based and technology neutral, using best-estimate simulation methods with uncertainty and margin quantification. In this context, two structural engineering technologies, seismic base isolation and modular steel-plate/concrete composite structural walls, are investigated. These technologies have major potential to (1) enable standardized reactor designs to be deployed across a wider range of sites, (2) reduce the impact of uncertainties related to site-specific seismic conditions, and (3) alleviate reactor equipment qualification requirements. For Gen IV reactors the potential for deliberate crashes of large aircraft must also be considered in design. This report concludes that base-isolated structures should be decoupled from the reactor external event exclusion system. As an example, a scoping analysis is performed for a rectangular, decoupled external event shell designed as a grillage. This report also reviews modular construction technology, particularly steel-plate/concrete construction using

  16. TU-F-12A-05: Sensitivity of Textural Features to 3D Vs. 4D FDG-PET/CT Imaging in NSCLC Patients

    SciTech Connect

    Yang, F; Nyflot, M; Bowen, S; Kinahan, P; Sandison, G

    2014-06-15

    Purpose: Neighborhood Gray-level difference matrices (NGLDM) based texture parameters extracted from conventional (3D) 18F-FDG PET scans in patients with NSCLC have been previously shown to associate with response to chemoradiation and poorer patient outcome. However, the change in these parameters when utilizing respiratory-correlated (4D) FDG-PET scans has not yet been characterized for NSCLC. The Objectives: of this study was to assess the extent to which NGLDM-based texture parameters on 4D PET images vary with reference to values derived from 3D scans in NSCLC. Methods: Eight patients with newly diagnosed NSCLC treated with concomitant chemoradiotherapy were included in this study. 4D PET scans were reconstructed with OSEM-IR in 5 respiratory phase-binned images and corresponding CT data of each phase were employed for attenuation correction. NGLDM-based texture features, consisting of coarseness, contrast, busyness, complexity and strength, were evaluated for gross tumor volumes defined on 3D/4D PET scans by radiation oncologists. Variation of the obtained texture parameters over the respiratory cycle were examined with respect to values extracted from 3D scans. Results: Differences between texture parameters derived from 4D scans at different respiratory phases and those extracted from 3D scans ranged from −30% to 13% for coarseness, −12% to 40% for contrast, −5% to 50% for busyness, −7% to 38% for complexity, and −43% to 20% for strength. Furthermore, no evident correlations were observed between respiratory phase and 4D scan texture parameters. Conclusion: Results of the current study showed that NGLDM-based texture parameters varied considerably based on choice of 3D PET and 4D PET reconstruction of NSCLC patient images, indicating that standardized image acquisition and analysis protocols need to be established for clinical studies, especially multicenter clinical trials, intending to validate prognostic values of texture features for NSCLC.

  17. Prognostic and Clinicopathological Significance of Downregulated E-Cadherin Expression in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

    PubMed Central

    Xian, Lei

    2014-01-01

    Background Many studies have investigated the prognostic role of E-cadherin in patients with NSCLC; however, the result still remains inconclusive. An up-to data system review and meta-analysis was necessary to give a comprehensive evaluation of prognostic role of E-cadherin in NSCLC. Methods Eligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between E-cadherin expression detected by immunohistochemistry (IHC) and the prognosis or clinicopathological features in patients with NSCLC. Subgroup analysis according to race, percentage of reduced/negative E-cadherin expression, histological type, and sample size were also conducted. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association. Results A total of 29 studies including 4010 patients were qualified for analysis. The analysis suggested that downregulated E-cadherin expression was significant associated with unfavorable overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS) in patients with NSCLC. Subgroup analysis by race, percentage of reduced/negative E-cadherin expression, sample size also found the significant association in OS. When only the stage I NSCLC were considered, downregulated E-cadherin expression still had an unfavorable impact on OS. Additionally, downregulated E-cadherin expression was significantly associated with differentiation grade, lymphnode metastasis, vascular invasion, and TNM stage. Conclusion Downregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC. PMID:24978478

  18. Intact or broken-apart RNA: an alternative concept for ALK fusion screening in non-small cell lung cancer (NSCLC).

    PubMed

    Kotoula, Vassiliki; Bobos, Mattheos; Vassilakopoulou, Maria; Tsolaki, Eleftheria; Chrisafi, Sofia; Psyrri, Amanda; Lazaridis, George; Papadopoulou, Kyriaki; Efstratiou, Ioannis; Michail-Strantzia, Catherine; Debelenko, Larisa V; Kosmidis, Paris; Fountzilas, George

    2015-01-01

    Anaplastic lymphoma kinase (ALK) break-apart fluorescent in situ hybridization (FISH) is currently used in diagnostics for the selection of non-small cell lung cancer (NSCLC) patients to receive crizotinib. We evaluated ALK status in NSCLC with a novel ALK mRNA test based on the break-apart FISH concept, which we called break-apart transcript (BAT) test. ALK5' and ALK3' transcript patterns were established with qPCR for ALK-expressing controls including fusion-negative neuroblastomas, as well as fusion-positive anaplastic large cell lymphomas and NSCLC. The BAT test was evaluated on 271 RNA samples from routinely processed paraffin NSCLC tissues. Test results were compared with ALK FISH (n=121), immunohistochemical (IHC) analysis (n=86), and automated quantitative analysis (AQUA, n=83). On the basis of the nonoverlapping ALK BAT patterns in ALK-expressing controls (P<0.0001), 8/174 adenocarcinomas (4.6%) among 259 informative NSCLC were predicted as fusion positive. Overall concordance for paired method results was high (94.1% to 98.8%) but mainly concerned negative prediction because of the limited availability of positive-matched cases. Tumors with 100% cytoplasmic IHC staining of any intensity (n=3) were positive for AQUA, FISH, and BAT test; tumors with lower IHC positivity and different staining patterns were AQUA-negative. Upon multiple reevaluations, ALK gene status was considered as originally misinterpreted by FISH in 3/121 cases (2.5%). Tumors with >4 ALK gene copies were associated with longer overall survival upon first-line chemotherapy. In conclusion, application of the ALK BAT test on routinely processed NSCLC tissues yields the same fusion partner independent information as ALK break-apart FISH but is more robust and cost-effective. The BAT concept may be considered for the development of further drug-predictive translocation tests. PMID:25153496

  19. Processing of alnico permanent magnets by advanced directional solidification methods

    DOE PAGESBeta

    Zou, Min; Johnson, Francis; Zhang, Wanming; Zhao, Qi; Rutkowski, Stephen F.; Zhou, Lin; Kramer, Matthew J.

    2016-07-05

    Advanced directional solidification methods have been used to produce large (>15 cm length) castings of Alnico permanent magnets with highly oriented columnar microstructures. In combination with subsequent thermomagnetic and draw thermal treatment, this method was used to enable the high coercivity, high-Titanium Alnico composition of 39% Co, 29.5% Fe, 14% Ni, 7.5% Ti, 7% Al, 3% Cu (wt%) to have an intrinsic coercivity (Hci) of 2.0 kOe, a remanence (Br) of 10.2 kG, and an energy product (BH)max of 10.9 MGOe. These properties compare favorably to typical properties for the commercial Alnico 9. Directional solidification of higher Ti compositions yieldedmore » anisotropic columnar grained microstructures if high heat extraction rates through the mold surface of at least 200 kW/m2 were attained. This was achieved through the use of a thin walled (5 mm thick) high thermal conductivity SiC shell mold extracted from a molten Sn bath at a withdrawal rate of at least 200 mm/h. However, higher Ti compositions did not result in further increases in magnet performance. Images of the microstructures collected by scanning electron microscopy (SEM) reveal a majority α phase with inclusions of secondary αγ phase. Transmission electron microscopy (TEM) reveals that the α phase has a spinodally decomposed microstructure of FeCo-rich needles in a NiAl-rich matrix. In the 7.5% Ti composition the diameter distribution of the FeCo needles was bimodal with the majority having diameters of approximately 50 nm with a small fraction having diameters of approximately 10 nm. The needles formed a mosaic pattern and were elongated along one <001> crystal direction (parallel to the field used during magnetic annealing). Cu precipitates were observed between the needles. Regions of abnormal spinodal morphology appeared to correlate with secondary phase precipitates. The presence of these abnormalities did not prevent the material from displaying superior magnetic properties in the 7.5% Ti

  20. Processing of alnico permanent magnets by advanced directional solidification methods

    NASA Astrophysics Data System (ADS)

    Zou, Min; Johnson, Francis; Zhang, Wanming; Zhao, Qi; Rutkowski, Stephen F.; Zhou, Lin; Kramer, Matthew J.

    2016-12-01

    Advanced directional solidification methods have been used to produce large (>15 cm length) castings of Alnico permanent magnets with highly oriented columnar microstructures. In combination with subsequent thermomagnetic and draw thermal treatment, this method was used to enable the high coercivity, high-Titanium Alnico composition of 39% Co, 29.5% Fe, 14% Ni, 7.5% Ti, 7% Al, 3% Cu (wt%) to have an intrinsic coercivity (Hci) of 2.0 kOe, a remanence (Br) of 10.2 kG, and an energy product (BH)max of 10.9 MGOe. These properties compare favorably to typical properties for the commercial Alnico 9. Directional solidification of higher Ti compositions yielded anisotropic columnar grained microstructures if high heat extraction rates through the mold surface of at least 200 kW/m2 were attained. This was achieved through the use of a thin walled (5 mm thick) high thermal conductivity SiC shell mold extracted from a molten Sn bath at a withdrawal rate of at least 200 mm/h. However, higher Ti compositions did not result in further increases in magnet performance. Images of the microstructures collected by scanning electron microscopy (SEM) reveal a majority α phase with inclusions of secondary αγ phase. Transmission electron microscopy (TEM) reveals that the α phase has a spinodally decomposed microstructure of FeCo-rich needles in a NiAl-rich matrix. In the 7.5% Ti composition the diameter distribution of the FeCo needles was bimodal with the majority having diameters of approximately 50 nm with a small fraction having diameters of approximately 10 nm. The needles formed a mosaic pattern and were elongated along one <001> crystal direction (parallel to the field used during magnetic annealing). Cu precipitates were observed between the needles. Regions of abnormal spinodal morphology appeared to correlate with secondary phase precipitates. The presence of these abnormalities did not prevent the material from displaying superior magnetic properties in the 7.5% Ti

  1. Advanced Methods of Observing Surface Plasmon Polaritons and Magnons

    NASA Astrophysics Data System (ADS)

    Moghaddam, Abolghasem Mobaraki

    Available from UMI in association with The British Library. Requires signed TDF. The primary objectives of this thesis are the investigation of the theoretical and experimental aspects of the design and construction of advanced techniques for the excitation of surface plasmon-polaritons, surface magneto -plasmon-polaritons and surface magnons. They involve on -line observation of these phenomena and to accomplish these goals, analytical studies of the characteristic behaviour of these phenomena have been undertaken. For excitations of surface plasmon- and surface magneto-plasmon-polaritons the most robust and conventional configuration, namely Prism-Medium-Air, coupled to a novel angle scan (prism spinning) method was employed. The system to be described here can automatically measure the reflectivity of a multilayer system over a range of angles that includes the resonance angle in an Attenuated Total Reflection (ATR) experiment. The computer procedure that controls the system is quite versatile so that it allows any right-angle prism of different angle or refractive index to be utilised. It also provided probes to check for optical alignment within the system. Moreover, it performs the angular scan many times and then averages the results in order to reduce the environmental and other possible sources of noise within the system. The mechanical side of the system is unique and could eventually be adopted as a marketable piece of equipment. It consists of a turntable for holding the prism-sample assembly and a drive motor in conjunction with a servo-potentiometer whose output not only operates the turntable but also sends a signal to a computer to measure accurately its position. The interface unit enables a computer to control automatically an angular scan ATR experiment for measuring the resonance reflectivity spectrum of a multilayer system. The interface unit uses an H-bridge switch formed by four bipolar power transistor and two small signal MOSFETs to convert

  2. EGFR, KRAS, BRAF, and HER-2 molecular status in brain metastases from 77 NSCLC patients

    PubMed Central

    Villalva, Claire; Duranton-Tanneur, Valérie; Guilloteau, Karline; Burel-Vandenbos, Fanny; Wager, Michel; Doyen, Jérôme; Levillain, Pierre Marie; Fontaine, Denys; Blons, Hélène; Pedeutour, Florence; Karayan-Tapon, Lucie

    2013-01-01

    The aim of this study was to determine the frequency of EGFR, KRAS, BRAF, and HER-2 mutations in brain metastases from non-small cell lung carcinomas (BM-NSCLC). A total of 77 samples of BM-NSCLC were included and 19 samples of BM from breast, kidney, and colorectal tumors were also studied as controls. These samples were collected from patients followed between 2008 and 2011 at Poitiers and Nice University Hospitals in France. The frequencies of EGFR, KRAS, BRAF, and HER-2 mutations in BM-NSCLC were 2.6, 38.5, 0, and 0% respectively. The incidence of KRAS mutation was significantly higher in female and younger patients (P < 0.05). No mutations of the four genes were found in BM from breast or kidney. However, among six BM from colorectal tumors, we identified KRAS mutations in three cases and BRAF mutations in two other cases. This study is the largest analysis on genetic alterations in BM-NSCLC performed to date. Our results suggest a low frequency of EGFR mutations in BM-NSCLC whereas KRAS mutations are as frequent in BM-NSCLC as in primitive NSCLC. These results raise the question of the variability of the brain metastatic potential of NSCLC cells in relation to the mutation pattern. PMID:23930206

  3. PD-L1 and Tumor Infiltrating Lymphocytes as Prognostic Markers in Resected NSCLC

    PubMed Central

    Ameratunga, Malaka; Asadi, Khashayar; Lin, Xihui; Walkiewicz, Marzena; Murone, Carmel; Knight, Simon; Mitchell, Paul; Boutros, Paul; John, Thomas

    2016-01-01

    Introduction Immune checkpoint inhibition has shifted treatment paradigms in non-small cell lung cancer (NSCLC). Conflicting results have been reported regarding the immune infiltrate and programmed death-ligand 1 (PD-L1) as a prognostic marker. We correlated the immune infiltrate and PD-L1 expression with clinicopathologic characteristics in a cohort of resected NSCLC. Methods A tissue microarray was constructed using triplicate cores from consecutive resected NSCLC. Immunohistochemistry was performed for CD8, FOXP3 and PD-L1. Strong PD-L1 expression was predefined as greater than 50% tumor cell positivity. Matched nodal samples were assessed for concordance of PD-L1 expression. Results Of 522 patients, 346 were node-negative (N0), 72 N1 and 109 N2; 265 were adenocarcinomas (AC), 182 squamous cell cancers (SCC) and 75 other. Strong PD-L1 expression was found in 24% cases. In the overall cohort, PD-L1 expression was not associated with survival. In patients with N2 disease, strong PD-L1 expression was associated with significantly improved disease-free (DFS) and overall survival (OS) in multivariate analysis (HR 0.49, 95%CI 0.36–0.94, p = 0.031; HR 0.46, 95%CI 0.26–0.80, p = 0.006). In this resected cohort only 5% harboured EGFR mutations, whereas 19% harboured KRAS and 23% other. KRAS mutated tumors were more likely to highly express PD-L1 compared to EGFR (22% vs 3%). A stromal CD8 infiltrate was associated with significantly improved DFS in SCC (HR 0.70, 95%CI 0.50–0.97, p = 0.034), but not AC, whereas FOXP3 was not prognostic. Matched nodal specimens (N = 53) were highly concordant for PD-L1 expression (89%). Conclusion PD-L1 expression was not prognostic in the overall cohort. PD-L1 expression in primary tumor and matched nodal specimens were highly concordant. The observed survival benefit in N2 disease requires confirmation. PMID:27104612

  4. Application of advanced filtering methods to the determination of the interplanetary orbit of Mariner '71.

    NASA Technical Reports Server (NTRS)

    Rourke, K. H.; Jordan, J. F.

    1972-01-01

    This paper presents the results of the applications of advanced filtering methods to the determination of the interplanetary orbit of the Mariner '71 spacecraft. The advanced techniques are specific extensions of the Kalman filter. The special problems associated with applying these techniques are discussed and the particular algorithmic implementations are outlined. The advanced methods are compared against the weighted least squares filters of conventional application. The results reveal that relatively simple advanced filter configurations yield solutions superior to those of the conventional methods when applied to the Mariner '71 radio measurements.

  5. The Prognostic Value of Epigenetic Silencing of p16 Gene in NSCLC Patients: A Systematic Review and Meta-Analysis

    PubMed Central

    Lou-Qian, Zhang; Rong, Yin; Ming, Li; Xin, Yang; Feng, Jiang; Lin, Xu

    2013-01-01

    Background The prognostic significance of p16 promoter hypermethylation in patients with non-small cell lung cancer (NSCLC) is still controversial. This analysis presents pooled estimates of the association to better elucidate whether p16 methylation has a prognostic role in NSCLC. Methods Relevant studies were identified by searching PubMed, Embase and Web of Science databases until June 2012. The association of p16 methylation with both overall survival (OS) and disease-free survival (DFS) was preformed. Studies were pooled and summary hazard ratios (HR) were calculated. Subgroup analyses, sensitivity analysis and publication bias were also conducted. Results A total of 18 studies containing 2432 patients met the inclusion criteria and had sufficient survival data for quantitative aggregation. The results showed that p16 methylation was an indicator of poor prognosis in NSCLC. The HR was 1.36 (95% CI: 1.08–1.73, I2 = 56.7%) and 1.68 (95% CI: 1.12–2.52, I2 = 38.7%) for OS and DFS, respectively. Subgroup analyses were carried out. The HRs of fresh and paraffin tissue were 1.50 (95% CI: 1.11–2.01) and 1.10 (95% CI: 0.77–1.57). The pooled HR was 1.40 (95% CI: 1.02–1.92) for methylation-specific PCR (MSP) and 1.26 (95% CI: 0.87–1.82) for quantitative MSP (Q-MSP). The combined HR of the 16 studies reporting NSCLC as a whole indicated that patients with p16 hypermethylation had poor prognosis. No significant association was found when adenocarcinoma subtype pooled. When seven studies on DFS were aggregated, the HR was 1.68 (95% CI: 1.12–2.52) without significant heterogeneity. Moreover, no obvious publication bias was detected on both OS and DFS. Conclusion The meta-analysis findings support the hypothesis that p16 methylation is associated with OS and DFS in NSCLC patients. Large well-designed prospective studies are now needed to confirm the clinical utility of p16 methylation as an independent prognostic marker. PMID:23372805

  6. Advanced materials and methods for next generation spintronics

    NASA Astrophysics Data System (ADS)

    Siegel, Gene Phillip

    The modern age is filled with ever-advancing electronic devices. The contents of this dissertation continue the desire for faster, smaller, better electronics. Specifically, this dissertation addresses a field known as "spintronics", electronic devices based on an electron's spin, not just its charge. The field of spintronics originated in 1990 when Datta and Das first proposed a "spin transistor" that would function by passing a spin polarized current from a magnetic electrode into a semiconductor channel. The spins in the channel could then be manipulated by applying an electrical voltage across the gate of the device. However, it has since been found that a great amount of scattering occurs at the ferromagnet/semiconductor interface due to the large impedance mismatch that exists between the two materials. Because of this, there were three updated versions of the spintronic transistor that were proposed to improve spin injection: one that used a ferromagnetic semiconductor electrode, one that added a tunnel barrier between the ferromagnet and semiconductor, and one that utilized a ferromagnetic tunnel barrier which would act like a spin filter. It was next proposed that it may be possible to achieve a "pure spin current", or a spin current with no concurrent electric current (i.e., no net flow of electrons). One such method that was discovered is the spin Seebeck effect, which was discovered in 2008 by Uchida et al., in which a thermal gradient in a magnetic material generates a spin current which can be injected into adjacent material as a pure spin current. The first section of this dissertation addresses this spin Seebeck effect (SSE). The goal was to create such a device that both performs better than previously reported devices and is capable of operating without the aid of an external magnetic field. We were successful in this endeavor. The trick to achieving both of these goals was found to be in the roughness of the magnetic layer. A rougher magnetic

  7. Methods and Applications for Advancing Distance Education Technologies: International Issues and Solutions

    ERIC Educational Resources Information Center

    Syed, Mahbubur Rahman, Ed.

    2009-01-01

    The emerging field of advanced distance education delivers academic courses across time and distance, allowing educators and students to participate in a convenient learning method. "Methods and Applications for Advancing Distance Education Technologies: International Issues and Solutions" demonstrates communication technologies, intelligent…

  8. Precision medicine in NSCLC and pathology: how does ALK fit in the pathway?

    PubMed

    Kerr, K M; López-Ríos, F

    2016-09-01

    The evolution of personalised medicine in lung cancer has dramatically impacted diagnostic pathology. Current challenges centre on the growing demands placed on small tissue samples by molecular diagnostic techniques. In this review, expert recommendations are provided regarding successful identification of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Steps to correctly process and conserve tumour tissue during diagnostic testing are essential to ensure tissue availability. For example, storing extra tissue sections ready for molecular diagnostic steps allows faster testing and preserves tissue. Fluorescence in situ hybridisation (FISH) is commonly used to detect ALK rearrangements, with most laboratories favouring screening by immunohistochemistry followed by a confirmatory FISH assay. Reverse transcription-polymerase chain reaction can also identify ALK fusion gene mRNA transcripts but can be limited by the quality of RNA and the risk that rare fusion variants may not be captured. Next-generation sequencing (NGS) technology has recently provided an alternative method for detecting ALK rearrangements. While current experience is limited, NGS is set to become the most efficient approach as an increasing number of genetic abnormalities is required to be tested. Upfront, reflex testing for ALK gene rearrangement should become routine as ALK tyrosine kinase inhibitor therapy moves into the first-line setting. Guidelines recommend that EGFR and ALK tests are carried out in parallel on all confirmed and potential adenocarcinomas, and this is more efficient in terms of tissue usage and testing turnaround time for both of these actionable gene alterations. The practice of sequential testing is not recommended. Identification of ALK rearrangements is now essential for the diagnosis of NSCLC, underpinned by the benefits of ALK inhibitors. As scientific understanding and diagnostic technology develops, ALK testing will continue to be an

  9. Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC

    PubMed Central

    Amato, Katherine R.; Wang, Shan; Hastings, Andrew K.; Youngblood, Victoria M.; Santapuram, Pranav R.; Chen, Haiying; Cates, Justin M.; Colvin, Daniel C.; Ye, Fei; Brantley-Sieders, Dana M.; Cook, Rebecca S.; Tan, Li; Gray, Nathanael S.; Chen, Jin

    2014-01-01

    Genome-wide analyses determined previously that the receptor tyrosine kinase (RTK) EPHA2 is commonly overexpressed in non–small cell lung cancers (NSCLCs). EPHA2 overexpression is associated with poor clinical outcomes; therefore, EPHA2 may represent a promising therapeutic target for patients with NSCLC. In support of this hypothesis, here we have shown that targeted disruption of EphA2 in a murine model of aggressive Kras-mutant NSCLC impairs tumor growth. Knockdown of EPHA2 in human NSCLC cell lines reduced cell growth and viability, confirming the epithelial cell autonomous requirements for EPHA2 in NSCLCs. Targeting EPHA2 in NSCLCs decreased S6K1-mediated phosphorylation of cell death agonist BAD and induced apoptosis. Induction of EPHA2 knockdown within established NSCLC tumors in a subcutaneous murine model reduced tumor volume and induced tumor cell death. Furthermore, an ATP-competitive EPHA2 RTK inhibitor, ALW-II-41-27, reduced the number of viable NSCLC cells in a time-dependent and dose-dependent manner in vitro and induced tumor regression in human NSCLC xenografts in vivo. Collectively, these data demonstrate a role for EPHA2 in the maintenance and progression of NSCLCs and provide evidence that ALW-II-41-27 effectively inhibits EPHA2-mediated tumor growth in preclinical models of NSCLC. PMID:24713656

  10. Advanced 3D inverse method for designing turbomachine blades

    SciTech Connect

    Dang, T.

    1995-10-01

    To meet the goal of 60% plant-cycle efficiency or better set in the ATS Program for baseload utility scale power generation, several critical technologies need to be developed. One such need is the improvement of component efficiencies. This work addresses the issue of improving the performance of turbo-machine components in gas turbines through the development of an advanced three-dimensional and viscous blade design system. This technology is needed to replace some elements in current design systems that are based on outdated technology.

  11. Advanced 3D inverse method for designing turbomachine blades

    SciTech Connect

    Dang, T.

    1995-12-31

    To meet the goal of 60% plant-cycle efficiency or better set in the ATS Program for baseload utility scale power generation, several critical technologies need to be developed. One such need is the improvement of component efficiencies. This work addresses the issue of improving the performance of turbo-machine components in gas turbines through the development of an advanced three-dimensional and viscous blade design system. This technology is needed to replace some elements in current design systems that are based on outdated technology.

  12. Exercise and nutrition interventions in advanced lung cancer: a systematic review

    PubMed Central

    Payne, C.; Larkin, P.J.; McIlfatrick, S.; Dunwoody, L.; Gracey, J.H.

    2013-01-01

    In this systematic review, we sought to evaluate the effect of physical activity or nutrition interventions (or both) in adults with advanced non-small-cell lung cancer (nsclc). Methods A systematic search for relevant clinical trials was conducted in 6 electronic databases, by hand searching, and by contacting key investigators. No limits were placed on study language. Information about recruitment rates, protocol adherence, patient-reported and clinical outcome measures, and study conclusions was extracted. Methodologic quality and risk of bias in each study was assessed using validated tools. Main Results Six papers detailing five studies involving 203 participants met the inclusion criteria. Two of the studies were single-cohort physical activity studies (54 participants), and three were controlled nutrition studies (149 participants). All were conducted in an outpatient setting. None of the included studies combined physical activity with nutrition interventions. Conclusions Our systematic review suggests that exercise and nutrition interventions are not harmful and may have beneficial effects on unintentional weight loss, physical strength, and functional performance in patients with advanced nsclc. However, the observed improvements must be interpreted with caution, because findings were not consistent across the included studies. Moreover, the included studies were small and at significant risk of bias. More research is required to ascertain the optimal physical activity and nutrition interventions in advanced inoperable nsclc. Specifically, the potential benefits of combining physical activity with nutrition counselling have yet to be adequately explored in this population. PMID:23904771

  13. Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance mechanisms in EGFR mutant NSCLC: Correlation with paired tumor samples

    PubMed Central

    Ishii, Hidenobu; Azuma, Koichi; Sakai, Kazuko; Kawahara, Akihiko; Yamada, Kazuhiko; Tokito, Takaaki; Okamoto, Isamu; Nishio, Kazuto; Hoshino, Tomoaki

    2015-01-01

    As the development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has become an issue of concern, identification of the mechanisms responsible has become an urgent priority. However, for research purposes, it is not easy to obtain tumor samples from patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) that has relapsed after treatment with EGFR-TKIs. Here, using digital PCR assay as an alternative and noninvasive method, we examined plasma and tumor samples from patients with relapsed NSCLC to establish the inter-relationships existing among T790M mutation, activating EGFR mutations, HER2 amplification, and MET amplification. Paired samples of tumor and blood were obtained from a total of 18 patients with NSCLC after they had developed resistance to EGFR-TKI treatment, and the mechanisms of resistance were analyzed by digital PCR. Digital PCR analysis of T790M mutation in plasma had a sensitivity of 81.8% and specificity of 85.7%, the overall concordance between plasma and tissue samples being 83.3%. MET gene copy number gain in tumor DNA was observed by digital PCR in three patients, of whom one exhibited positivity for MET amplification by FISH, whereas no patient demonstrated MET and HER2 copy number gain in plasma DNA. Digital PCR analysis of plasma is feasible and accurate for detection of T790M mutation in NSCLC that becomes resistant to treatment with EGFR-TKIs. PMID:26334838

  14. A novel acquired ALK F1245C mutation confers resistance to crizotinib in ALK-positive NSCLC but is sensitive to ceritinib.

    PubMed

    Kodityal, Sandeep; Elvin, Julia A; Squillace, Rachel; Agarwal, Nikita; Miller, Vincent A; Ali, Siraj M; Klempner, Samuel J; Ou, Sai-Hong Ignatius

    2016-02-01

    The emergence of acquired anaplastic lymphoma kinase (ALK) resistant mutations is a common molecular mechanism underpinning disease progression during crizotinib treatment of ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients. Identifying acquired resistance mutations in ALK is paramount for tailoring future therapy with second generation ALK inhibitors and beyond. Comprehensive genomic profiling using hybrid-capture next generation sequencing has been successful in identifying acquired ALK resistance mutations. Here we described the emergence of an ALK F1245C mutation in an advanced ALK+ NSCLC patient (EML4-ALK variant 3a/b) who developed slow disease progression after a durable response to crizotinib. The patient was eventually switched to ceritinib with on-going clinical response. This is the first patient report that ALK F1245C is an acquired resistance mutation to crizotinib that can be overcome by ceritinib. PMID:26775591

  15. Advances in Probes and Methods for Clinical EPR Oximetry

    PubMed Central

    Hou, Huagang; Khan, Nadeem; Jarvis, Lesley A.; Chen, Eunice Y.; Williams, Benjamin B.; Kuppusamy, Periannan

    2015-01-01

    EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings. PMID:24729217

  16. An advanced deterministic method for spent fuel criticality safety analysis

    SciTech Connect

    DeHart, M.D.

    1998-01-01

    Over the past two decades, criticality safety analysts have come to rely to a large extent on Monte Carlo methods for criticality calculations. Monte Carlo has become popular because of its capability to model complex, non-orthogonal configurations or fissile materials, typical of real world problems. Over the last few years, however, interest in determinist transport methods has been revived, due shortcomings in the stochastic nature of Monte Carlo approaches for certain types of analyses. Specifically, deterministic methods are superior to stochastic methods for calculations requiring accurate neutron density distributions or differential fluxes. Although Monte Carlo methods are well suited for eigenvalue calculations, they lack the localized detail necessary to assess uncertainties and sensitivities important in determining a range of applicability. Monte Carlo methods are also inefficient as a transport solution for multiple pin depletion methods. Discrete ordinates methods have long been recognized as one of the most rigorous and accurate approximations used to solve the transport equation. However, until recently, geometric constraints in finite differencing schemes have made discrete ordinates methods impractical for non-orthogonal configurations such as reactor fuel assemblies. The development of an extended step characteristic (ESC) technique removes the grid structure limitations of traditional discrete ordinates methods. The NEWT computer code, a discrete ordinates code built upon the ESC formalism, is being developed as part of the SCALE code system. This paper will demonstrate the power, versatility, and applicability of NEWT as a state-of-the-art solution for current computational needs.

  17. Advanced methods of microscope control using μManager software

    PubMed Central

    Edelstein, Arthur D.; Tsuchida, Mark A.; Amodaj, Nenad; Pinkard, Henry; Vale, Ronald D.; Stuurman, Nico

    2014-01-01

    μManager is an open-source, cross-platform desktop application, to control a wide variety of motorized microscopes, scientific cameras, stages, illuminators, and other microscope accessories. Since its inception in 2005, μManager has grown to support a wide range of microscopy hardware and is now used by thousands of researchers around the world. The application provides a mature graphical user interface and offers open programming interfaces to facilitate plugins and scripts. Here, we present a guide to using some of the recently added advanced μManager features, including hardware synchronization, simultaneous use of multiple cameras, projection of patterned light onto a specimen, live slide mapping, imaging with multi-well plates, particle localization and tracking, and high-speed imaging. PMID:25606571

  18. Comparison of Advanced Distillation Control Methods, Final Technical Report

    SciTech Connect

    Dr. James B. Riggs

    2000-11-30

    Detailed dynamic simulations of three industrial distillation columns (a propylene/propane splitter, a xylene/toluene column, and a depropanizer) have been used to evaluate configuration selections for single-ended and dual-composition control, as well as to compare conventional and advanced control approaches. In addition, a simulator of a main fractionator was used to compare the control performance of conventional and advanced control. For each case considered, the controllers were tuned by using setpoint changes and tested using feed composition upsets. Proportional Integral (PI) control performance was used to evaluate the configuration selection problem. For single ended control, the energy balance configuration was found to yield the best performance. For dual composition control, nine configurations were considered. It was determined that the use of dynamic simulations is required in order to identify the optimum configuration from among the nine possible choices. The optimum configurations were used to evaluate the relative control performance of conventional PI controllers, MPC (Model Predictive Control), PMBC (Process Model-Based Control), and ANN (Artificial Neural Networks) control. It was determined that MPC works best when one product is much more important than the other, while PI was superior when both products were equally important. PMBC and ANN were not found to offer significant advantages over PI and MPC. MPC was found to outperform conventional PI control for the main fractionator. MPC was applied to three industrial columns: one at Phillips Petroleum and two at Union Carbide. In each case, MPC was found to significantly outperform PI controls. The major advantage of the MPC controller is its ability to effectively handle a complex set of constraints and control objectives.

  19. Adherence to Scientific Method while Advancing Exposure Science

    EPA Science Inventory

    Paul Lioy was simultaneously a staunch adherent to the scientific method and an innovator of new ways to conduct science, particularly related to human exposure. Current challenges to science and the application of the scientific method are presented as they relate the approaches...

  20. SEM-contour shape analysis method for advanced semiconductor devices

    NASA Astrophysics Data System (ADS)

    Toyoda, Yasutaka; Shindo, Hiroyuki; Ota, Yoshihiro; Matsuoka, Ryoichi; Hojo, Yutaka; Fuchimoto, Daisuke; Hibino, Daisuke; Sakai, Hideo

    2013-04-01

    The new measuring method that we developed executes a contour shape analysis that is based on the pattern edge information from a SEM image. This analysis helps to create a highly precise quantification of every circuit pattern shape by comparing the contour extracted from the SEM image using a CD measurement algorithm and the ideal circuit pattern. The developed method, in the next phase, can generate four shape indices by using the analysis mass measurement data. When the shape index measured using the developed method is compared the CD, the difference of the shape index and the CD is negligibly small for the quantification of the circuit pattern shape. In addition, when the 2D patterns on a FEM wafer are measured using the developed method, the tendency for shape deformations is precisely caught by the four shape indices. This new method and the evaluation results will be presented in detail in this paper.

  1. Advances in spectroscopic methods for quantifying soil carbon

    USGS Publications Warehouse

    Liebig, Mark; Franzluebbers, Alan J.; Follett, Ronald F.; Hively, W. Dean; Reeves, James B., III; McCarty, Gregory W.; Calderon, Francisco

    2012-01-01

    The gold standard for soil C determination is combustion. However, this method requires expensive consumables, is limited to the determination of the total carbon and in the number of samples which can be processed (~100/d). With increased interest in soil C sequestration, faster methods are needed. Thus, interest in methods based on diffuse reflectance spectroscopy in the visible, near-infrared or mid-infrared ranges using either proximal or remote sensing. These methods have the ability to analyze more samples (2 to 3X/d) or huge areas (imagery) and do multiple analytes simultaneously, but require calibrations relating spectral and reference data and have specific problems, i.e., remote sensing is capable of scanning entire watersheds, thus reducing the sampling needed, but is limiting to the surface layer of tilled soils and by difficulty in obtaining proper calibration reference values. The objective of this discussion is the present state of spectroscopic methods for soil C determination.

  2. The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44hi stem-like NSCLC cells.

    PubMed

    Shi, Yang; Liu, Can; Liu, Xin; Tang, Dean G; Wang, Junchen

    2014-01-01

    Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate, which is probably due to the existence of lung cancer stem cells (CSCs). CSCs in many tumors including non-small cell lung cancer (NSCLC) have been identified using adhesion molecular CD44, either individually or in combination with other marker(s). MicroRNAs (miRNAs) regulate both normal stem cells and CSCs and dysregulation of miRNAs has been implicated in tumorigenesis. Recently, miR-34a was found to be downregulated in NSCLC cells but the biological functions of miR-34a in regulating NSCLC cell behavior have not been extensively studied. Here we show that transfection of synthetic miR-34a, but not the negative control (NC) miRNA oligonucleotides (oligos) in three NSCLC cell lines, i.e., A549, H460, and H1299, inhibited their holoclone formation, clonogenic expansion, and tumor regeneration in vivo. Furthermore, the lentiviral vector-mediated overexpression of miR-34a in purified CD44hi H460 cells also inhibited tumor outgrowth. In contrast, expression of miR-34a antagomirs (i.e., antisense oligos) in the CD44lo H460 cells promoted tumor development. Our study shows that miR-34a is a negative regulator of the tumorigenic properties of NSCLC cells and CD44hi lung CSCs, and establishes a strong rationale for developing miR-34a as a novel therapeutic agent against NSCLC. PMID:24595209

  3. Preface: Special Topic Section on Advanced Electronic Structure Methods for Solids and Surfaces

    SciTech Connect

    Michaelides, Angelos; Martinez, Todd J.; Alavi, Ali; Kresse, Georg

    2015-09-14

    This Special Topic section on Advanced Electronic Structure Methods for Solids and Surfaces contains a collection of research papers that showcase recent advances in the high accuracy prediction of materials and surface properties. It provides a timely snapshot of a growing field that is of broad importance to chemistry, physics, and materials science.

  4. Integrating Advanced High School Chemistry Research with Organic Chemistry and Instrumental Methods of Analysis

    ERIC Educational Resources Information Center

    Kennedy, Brian J.

    2008-01-01

    This paper describes and discusses the unique chemistry course opportunities beyond the advanced placement-level available at a science and technology magnet high school. Students may select entry-level courses such as honors and advanced placement chemistry; they may also take electives in organic chemistry with instrumental methods of analysis;…

  5. The Saccharomyces Genome Database: Advanced Searching Methods and Data Mining.

    PubMed

    Cherry, J Michael

    2015-12-01

    At the core of the Saccharomyces Genome Database (SGD) are chromosomal features that encode a product. These include protein-coding genes and major noncoding RNA genes, such as tRNA and rRNA genes. The basic entry point into SGD is a gene or open-reading frame name that leads directly to the locus summary information page. A keyword describing function, phenotype, selective condition, or text from abstracts will also provide a door into the SGD. A DNA or protein sequence can be used to identify a gene or a chromosomal region using BLAST. Protein and DNA sequence identifiers, PubMed and NCBI IDs, author names, and function terms are also valid entry points. The information in SGD has been gathered and is maintained by a group of scientific biocurators and software developers who are devoted to providing researchers with up-to-date information from the published literature, connections to all the major research resources, and tools that allow the data to be explored. All the collected information cannot be represented or summarized for every possible question; therefore, it is necessary to be able to search the structured data in the database. This protocol describes the YeastMine tool, which provides an advanced search capability via an interactive tool. The SGD also archives results from microarray expression experiments, and a strategy designed to explore these data using the SPELL (Serial Pattern of Expression Levels Locator) tool is provided. PMID:26631124

  6. Health, wealth, and air pollution: advancing theory and methods.

    PubMed Central

    O'Neill, Marie S; Jerrett, Michael; Kawachi, Ichiro; Levy, Jonathan I; Cohen, Aaron J; Gouveia, Nelson; Wilkinson, Paul; Fletcher, Tony; Cifuentes, Luis; Schwartz, Joel

    2003-01-01

    The effects of both ambient air pollution and socioeconomic position (SEP) on health are well documented. A limited number of recent studies suggest that SEP may itself play a role in the epidemiology of disease and death associated with exposure to air pollution. Together with evidence that poor and working-class communities are often more exposed to air pollution, these studies have stimulated discussion among scientists, policy makers, and the public about the differential distribution of the health impacts from air pollution. Science and public policy would benefit from additional research that integrates the theory and practice from both air pollution and social epidemiologies to gain a better understanding of this issue. In this article we aim to promote such research by introducing readers to methodologic and conceptual approaches in the fields of air pollution and social epidemiology; by proposing theories and hypotheses about how air pollution and socioeconomic factors may interact to influence health, drawing on studies conducted worldwide; by discussing methodologic issues in the design and analysis of studies to determine whether health effects of exposure to ambient air pollution are modified by SEP; and by proposing specific steps that will advance knowledge in this field, fill information gaps, and apply research results to improve public health in collaboration with affected communities. PMID:14644658

  7. Advanced scanning methods with tracking optical coherence tomography

    PubMed Central

    Ferguson, R. Daniel; Iftimia, Nicusor V.; Ustun, Teoman; Wollstein, Gadi; Ishikawa, Hiroshi; Gabriele, Michelle L.; Dilworth, William D.; Kagemann, Larry; Schuman, Joel S.

    2013-01-01

    An upgraded optical coherence tomography system with integrated retinal tracker (TOCT) was developed. The upgraded system uses improved components to extend the tracking bandwidth, fully integrates the tracking hardware into the optical head of the clinical OCT system, and operates from a single software platform. The system was able to achieve transverse scan registration with sub-pixel accuracy (~10 μm). We demonstrate several advanced scan sequences with the TOCT, including composite scans averaged (co-added) from multiple B-scans taken consecutively and several hours apart, en face images collected by summing the A-scans of circular, line, and raster scans, and three-dimensional (3D) retinal maps of the fovea and optic disc. The new system achieves highly accurate OCT scan registration yielding composite images with significantly improved spatial resolution, increased signal-to-noise ratio, and reduced speckle while maintaining well-defined boundaries and sharp fine structure compared to single scans. Precise re-registration of multiple scans over separate imaging sessions demonstrates TOCT utility for longitudinal studies. En face images and 3D data cubes generated from these data reveal high fidelity image registration with tracking, despite scan durations of more than one minute. PMID:19498823

  8. Review: Advances in delta-subsidence research using satellite methods

    NASA Astrophysics Data System (ADS)

    Higgins, Stephanie A.

    2016-05-01

    Most of the world's major river deltas are sinking relative to local sea level. The effects of subsidence can include aquifer salinization, infrastructure damage, increased vulnerability to flooding and storm surges, and permanent inundation of low-lying land. Consequently, determining the relative importance of natural vs. anthropogenic pressures in driving delta subsidence is a topic of ongoing research. This article presents a review of knowledge with respect to delta surface-elevation loss. The field is rapidly advancing due to applications of space-based techniques: InSAR (interferometric synthetic aperture radar), GPS (global positioning system), and satellite ocean altimetry. These techniques have shed new light on a variety of subsidence processes, including tectonics, isostatic adjustment, and the spatial and temporal variability of sediment compaction. They also confirm that subsidence associated with fluid extraction can outpace sea-level rise by up to two orders of magnitude, resulting in effective sea-level rise that is one-hundred times faster than the global average rate. In coming years, space-based and airborne instruments will be critical in providing near-real-time monitoring to facilitate management decisions in sinking deltas. However, ground-based observations continue to be necessary for generating complete measurements of surface-elevation change. Numerical modeling should seek to simulate couplings between subsidence processes for greater predictive power.

  9. Advances in spectroscopic methods for quantifying soil carbon

    USGS Publications Warehouse

    Reeves, James B., III; McCarty, Gregory W.; Calderon, Francisco; Hively, W. Dean

    2012-01-01

    The current gold standard for soil carbon (C) determination is elemental C analysis using dry combustion. However, this method requires expensive consumables, is limited by the number of samples that can be processed (~100/d), and is restricted to the determination of total carbon. With increased interest in soil C sequestration, faster methods of analysis are needed, and there is growing interest in methods based on diffuse reflectance spectroscopy in the visible, near-infrared or mid-infrared spectral ranges. These spectral methods can decrease analytical requirements and speed sample processing, be applied to large landscape areas using remote sensing imagery, and be used to predict multiple analytes simultaneously. However, the methods require localized calibrations to establish the relationship between spectral data and reference analytical data, and also have additional, specific problems. For example, remote sensing is capable of scanning entire watersheds for soil carbon content but is limited to the surface layer of tilled soils and may require difficult and extensive field sampling to obtain proper localized calibration reference values. The objective of this chapter is to discuss the present state of spectroscopic methods for determination of soil carbon.

  10. The clinicopathological significance and potential drug target of E-cadherin in NSCLC.

    PubMed

    Zhong, Kaize; Chen, Weiwen; Xiao, Ning; Zhao, Jian

    2015-08-01

    Human epithelial cadherin (E-cadherin), a member of transmembrane glycoprotein family, encoded by the E-cadherin gene, plays a key role in cell-cell adhesion, adherent junction in normal epithelial tissues, contributing to tissue differentiation and homeostasis. Although previous studies indicated that inactivation of the E-cadherin is mainly induced by hypermethylation of E-cadherin gene, evidence concerning E-cadherin hypermethylation in the carcinogenesis and development of non-small cell lung carcinoma (NSCLC) remains controversial. In this study, we conducted a meta-analysis to quantitatively evaluate the effects of E-cadherin hypermethylation on the incidence and clinicopathological characteristics of NSCLC. A comprehensive search of PubMed and Embase databases was performed up to October 2014. Analyses of pooled data were performed. Odds ratios (ORs) were calculated and summarized. Our meta-analysis combining 18 published articles demonstrated that the hypermethylation frequencies in NSCLC were significantly higher than those in normal control tissues, OR = 3.55, 95 % confidence interval (CI) = 1.98-6.36, p < 0.0001. Further analysis showed that E-cadherin hypermethylation was not strongly associated with the sex or smoking status in NSCLC patients. In addition, E-cadherin hypermethylation was also not strongly associated with pathological types, differentiated status, clinical stages, or metastatic status in NSCLC patients. The results from the current study indicate that the hypermethylation frequency of E-cadherin in NSCLC is strongly associated with NSCLC incidence and it may be an early event in carcinogenesis of NSCLC. We also discussed the potential value of E-cadherin as a drug target that may bring new direction and hope for cancer treatment through gene-targeted therapy. PMID:25758052

  11. The advance of non-invasive detection methods in osteoarthritis

    NASA Astrophysics Data System (ADS)

    Dai, Jiao; Chen, Yanping

    2011-06-01

    Osteoarthritis (OA) is one of the most prevalent chronic diseases which badly affected the patients' living quality and economy. Detection and evaluation technology can provide basic information for early treatment. A variety of imaging methods in OA were reviewed, such as conventional X-ray, computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI) and near-infrared spectroscopy (NIRS). Among the existing imaging modalities, the spatial resolution of X-ray is extremely high; CT is a three-dimensional method, which has high density resolution; US as an evaluation method of knee OA discriminates lesions sensitively between normal cartilage and degenerative one; as a sensitive and nonionizing method, MRI is suitable for the detection of early OA, but the cost is too expensive for routine use; NIRS is a safe, low cost modality, and is also good at detecting early stage OA. In a word, each method has its own advantages, but NIRS is provided with broader application prospect, and it is likely to be used in clinical daily routine and become the golden standard for diagnostic detection.

  12. Advanced quantitative magnetic nondestructive evaluation methods - Theory and experiment

    NASA Technical Reports Server (NTRS)

    Barton, J. R.; Kusenberger, F. N.; Beissner, R. E.; Matzkanin, G. A.

    1979-01-01

    The paper reviews the scale of fatigue crack phenomena in relation to the size detection capabilities of nondestructive evaluation methods. An assessment of several features of fatigue in relation to the inspection of ball and roller bearings suggested the use of magnetic methods; magnetic domain phenomena including the interaction of domains and inclusions, and the influence of stress and magnetic field on domains are discussed. Experimental results indicate that simplified calculations can be used to predict many features of these results; the data predicted by analytic models which use finite element computer analysis predictions do not agree with respect to certain features. Experimental analyses obtained on rod-type fatigue specimens which show experimental magnetic measurements in relation to the crack opening displacement and volume and crack depth should provide methods for improved crack characterization in relation to fracture mechanics and life prediction.

  13. Application of advanced reliability methods to local strain fatigue analysis

    NASA Technical Reports Server (NTRS)

    Wu, T. T.; Wirsching, P. H.

    1983-01-01

    When design factors are considered as random variables and the failure condition cannot be expressed by a closed form algebraic inequality, computations of risk (or probability of failure) might become extremely difficult or very inefficient. This study suggests using a simple, and easily constructed, second degree polynomial to approximate the complicated limit state in the neighborhood of the design point; a computer analysis relates the design variables at selected points. Then a fast probability integration technique (i.e., the Rackwitz-Fiessler algorithm) can be used to estimate risk. The capability of the proposed method is demonstrated in an example of a low cycle fatigue problem for which a computer analysis is required to perform local strain analysis to relate the design variables. A comparison of the performance of this method is made with a far more costly Monte Carlo solution. Agreement of the proposed method with Monte Carlo is considered to be good.

  14. Protein Microarrays with Novel Microfluidic Methods: Current Advances

    PubMed Central

    Dixit, Chandra K.; Aguirre, Gerson R.

    2014-01-01

    Microfluidic-based micromosaic technology has allowed the pattering of recognition elements in restricted micrometer scale areas with high precision. This controlled patterning enabled the development of highly multiplexed arrays multiple analyte detection. This arraying technology was first introduced in the beginning of 2001 and holds tremendous potential to revolutionize microarray development and analyte detection. Later, several microfluidic methods were developed for microarray application. In this review we discuss these novel methods and approaches which leverage the property of microfluidic technologies to significantly improve various physical aspects of microarray technology, such as enhanced imprinting homogeneity, stability of the immobilized biomolecules, decreasing assay times, and reduction of the costs and of the bulky instrumentation.

  15. Statistical Methods Handbook for Advanced Gas Reactor Fuel Materials

    SciTech Connect

    J. J. Einerson

    2005-05-01

    Fuel materials such as kernels, coated particles, and compacts are being manufactured for experiments simulating service in the next generation of high temperature gas reactors. These must meet predefined acceptance specifications. Many tests are performed for quality assurance, and many of these correspond to criteria that must be met with specified confidence, based on random samples. This report describes the statistical methods to be used. The properties of the tests are discussed, including the risk of false acceptance, the risk of false rejection, and the assumption of normality. Methods for calculating sample sizes are also described.

  16. Origins, Methods and Advances in Qualitative Meta-Synthesis

    ERIC Educational Resources Information Center

    Nye, Elizabeth; Melendez-Torres, G. J.; Bonell, Chris

    2016-01-01

    Qualitative research is a broad term encompassing many methods. Critiques of the field of qualitative research argue that while individual studies provide rich descriptions and insights, the absence of connections drawn between studies limits their usefulness. In response, qualitative meta-synthesis serves as a design to interpret and synthesise…

  17. Native and rearranged ALK copy number and rearranged cell count in NSCLC: Implications for ALK inhibitor therapy

    PubMed Central

    Camidge, D. Ross; Skokan, Margaret; Kiatsimkul, Porntip; Helfrich, Barbara; Lu, Xian; Barón, Anna E.; Schulte, Nathan; Maxson, DeLee; Aisner, Dara L.; Franklin, Wilbur A.; Doebele, Robert C.; Varella-Garcia, Marileila

    2013-01-01

    Background Anaplastic Lymphoma Kinase positive (ALK+) non-small cell lung cancer (NSCLC) responds to ALK inhibitors. Clinically, ≥ 15% cells showing rearrangements by break-apart FISH classify tumors as positive. Increases in native and rearranged ALK copy number also occur. Methods 1426 NSCLC clinical specimens (174 ALK+ and 1252 ALK negative), and 24 ALK negative NSCLC cell lines were investigated. ALK copy number and genomic status were assessed by FISH. Results Clinical specimens with 0–9%, 10–15%, 16–30%, 31–50% and >50% of ALK+ cells were found in 79.3%, 8.5%, 1.4%, 2.7% and 8.1% of cases, respectively. Increased native ALK copy number (≥3 copies/cell in ≥40% cells) was detected in 19% of ALK+ and 62% of ALK negative tumors. In ALK negative tumors, abundant focal amplification of native ALK was rare (0.8%). Other atypical patterns occurred in ~6% of tumors. Mean native ALK copy number ranged from 2.1–6.9 in cell lines and was not correlated with crizotinib sensitivity (IC50s 0.34–2.8 uM) (r=0.279, p=0.1764). Neither native, nor rearranged ALK copy number, nor percentage cells positive correlated with extra-central nervous system progression free survivalin ALK+ patients on crizotinib. Conclusions 8.5% of cases are below the established positivity threshold by ≤5%. Further investigation of ALK by other diagnostic techniques in such cases may be warranted. Native ALK copy number increases alone are not associated with sensitivity to ALK inhibition in vitro. However, rare complex patterns of increased native ALK in patients should be studied further as atypical rearrangements contained within these may otherwise be missed. PMID:24022839

  18. Advanced discretizations and multigrid methods for liquid crystal configurations

    NASA Astrophysics Data System (ADS)

    Emerson, David B.

    Liquid crystals are substances that possess mesophases with properties intermediate between liquids and crystals. Here, we consider nematic liquid crystals, which consist of rod-like molecules whose average pointwise orientation is represented by a unit-length vector, n( x, y, z) = (n1, n 2, n3)T. In addition to their self-structuring properties, nematics are dielectrically active and birefringent. These traits continue to lead to many important applications and discoveries. Numerical simulations of liquid crystal configurations are used to suggest the presence of new physical phenomena, analyze experiments, and optimize devices. This thesis develops a constrained energy-minimization finite-element method for the efficient computation of nematic liquid crystal equilibrium configurations based on a Lagrange multiplier formulation and the Frank-Oseen free-elastic energy model. First-order optimality conditions are derived and linearized via a Newton approach, yielding a linear system of equations. Due to the nonlinear unit-length constraint, novel well-posedness theory for the variational systems, as well as error analysis, is conducted. The approach is shown to constitute a convergent and well-posed approach, absent typical simplifying assumptions. Moreover, the energy-minimization method and well-posedness theory developed for the free-elastic case are extended to include the effects of applied electric fields and flexoelectricity. In the computational algorithm, nested iteration is applied and proves highly effective at reducing computational costs. Additionally, an alternative technique is studied, where the unit-length constraint is imposed by a penalty method. The performance of the penalty and Lagrange multiplier methods is compared. Furthermore, tailored trust-region strategies are introduced to improve robustness and efficiency. While both approaches yield effective algorithms, the Lagrange multiplier method demonstrates superior accuracy per unit cost. In

  19. Advanced hydraulic fracturing methods to create in situ reactive barriers

    SciTech Connect

    Murdoch, L. |; Siegrist, B.; Meiggs, T.

    1997-12-31

    This article describes the use of hydraulic fracturing to increase permeability in geologic formations where in-situ remedial action of contaminant plumes will be performed. Several in-situ treatment strategies are discussed including the use of hydraulic fracturing to create in situ redox zones for treatment of organics and inorganics. Hydraulic fracturing methods offer a mechanism for the in-situ treatment of gently dipping layers of reactive compounds. Specialized methods using real-time monitoring and a high-energy jet during fracturing allow the form of the fracture to be influenced, such as creation of assymmetric fractures beneath potential sources (i.e. tanks, pits, buildings) that should not be penetrated by boring. Some examples of field applications of this technique such as creating fractures filled with zero-valent iron to reductively dechlorinate halogenated hydrocarbons, and the use of granular activated carbon to adsorb compounds are discussed.

  20. Advanced finite element method for nano-resonators

    NASA Astrophysics Data System (ADS)

    Zschiedrich, Lin; Burger, Sven; Kettner, Benjamin; Schmidt, Frank

    2006-02-01

    Miniaturized optical resonators with spatial dimensions of the order of the wavelength of the trapped light offer prospects for a variety of new applications like quantum processing or construction of meta-materials. Light propagation in these structures is modelled by Maxwell's equations. For a deeper numerical analysis one may compute the scattered field when the structure is illuminated or one may compute the resonances of the structure. We therefore address in this paper the electromagnetic scattering problem as well as the computation of resonances in an open system. For the simulation effcient and reliable numerical methods are required which cope with the infinite domain. We use transparent boundary conditions based on the Perfectly Matched Layer Method (PML) combined with a novel adaptive strategy to determine optimal discretization parameters like the thickness of the sponge layer or the mesh width. Further a novel iterative solver for time-harmonic Maxwell's equations is presented.

  1. Numerical modeling of spray combustion with an advanced VOF method

    NASA Technical Reports Server (NTRS)

    Chen, Yen-Sen; Shang, Huan-Min; Shih, Ming-Hsin; Liaw, Paul

    1995-01-01

    This paper summarizes the technical development and validation of a multiphase computational fluid dynamics (CFD) numerical method using the volume-of-fluid (VOF) model and a Lagrangian tracking model which can be employed to analyze general multiphase flow problems with free surface mechanism. The gas-liquid interface mass, momentum and energy conservation relationships are modeled by continuum surface mechanisms. A new solution method is developed such that the present VOF model can be applied for all-speed flow regimes. The objectives of the present study are to develop and verify the fractional volume-of-fluid cell partitioning approach into a predictor-corrector algorithm and to demonstrate the effectiveness of the present approach by simulating benchmark problems including laminar impinging jets, shear coaxial jet atomization and shear coaxial spray combustion flows.

  2. Advanced hybrid particulate collector and method of operation

    DOEpatents

    Miller, Stanley J.

    2003-04-08

    A device and method for controlling particulate air pollutants of the present invention combines filtration and electrostatic collection devices. The invention includes a chamber housing a plurality of rows of filter elements. Between the rows of filter elements are rows of high voltage discharge electrodes. Between the rows of discharge electrodes and the rows of filter elements are grounded perforated plates for creating electrostatic precipitation zones.

  3. Advanced and In Situ Analytical Methods for Solar Fuel Materials.

    PubMed

    Chan, Candace K; Tüysüz, Harun; Braun, Artur; Ranjan, Chinmoy; La Mantia, Fabio; Miller, Benjamin K; Zhang, Liuxian; Crozier, Peter A; Haber, Joel A; Gregoire, John M; Park, Hyun S; Batchellor, Adam S; Trotochaud, Lena; Boettcher, Shannon W

    2016-01-01

    In situ and operando techniques can play important roles in the development of better performing photoelectrodes, photocatalysts, and electrocatalysts by helping to elucidate crucial intermediates and mechanistic steps. The development of high throughput screening methods has also accelerated the evaluation of relevant photoelectrochemical and electrochemical properties for new solar fuel materials. In this chapter, several in situ and high throughput characterization tools are discussed in detail along with their impact on our understanding of solar fuel materials. PMID:26267386

  4. Advancements of the Hybrid Method UF6 Container Inspection System

    SciTech Connect

    Mace, Emily K.; Orton, Christopher R.; Jordan, David V.; McDonald, Benjamin S.; Smith, Leon E.

    2011-07-17

    Safeguards inspectors currently visit uranium enrichment plants to verify UF6 cylinder enrichment declarations. Measurements are performed with handheld high-resolution detectors on a limited number of cylinders taken to be representative of the plant’s cylinder inventory. These enrichment assay methods interrogate only a small fraction of the total cylinder volume, and are time-consuming and expensive to execute. Pacific Northwest National Laboratory (PNNL) is developing an automated UF6 cylinder verification station concept based on the combined collection of traditional enrichment-meter data (186 keV photons from 235U) and non-traditional, neutron-induced, high-energy gamma-ray signatures (3-8 MeV) with an array of collimated, medium-resolution scintillators. Previous work at PNNL (2010) demonstrated proof-of-principle that this hybrid method yields accurate, full-volume assay of the cylinder enrichment, reduces systematic errors when compared to several other enrichment assay methods, and provides simplified instrumentation and algorithms suitable for long-term, unattended operations. This system aims to increase the number of inspected cylinders at higher accuracy and with lower cost than when compared to inspectors with hand-held instruments. Several measurement campaigns of 30B cylinder populations and a refined MCNP model will be reported. The MCNP model consists of per-gram basis vectors for the different uranium isotopes and several fill geometries, enabling fast generation of any UF6 enrichment level and multiple configurations. The refined model was used to optimize collimator design and detector configuration for the hybrid method. In addition, a new field prototype based on model results was utilized in a set of field measurements.

  5. Advances in multifocal methods for imaging human brain activity

    NASA Astrophysics Data System (ADS)

    Carney, Thom; Ales, Justin; Klein, Stanley A.

    2006-02-01

    The typical multifocal stimulus used in visual evoked potential (VEP) studies consists of about 60 checkerboard stimulus patches each independently contrast reversed according to an m-sequence. Cross correlation of the response (EEG, MEG, ERG, or fMRI) with the m-sequence results in a series of response kernels for each response channel and each stimulus patch. In the past the number and complexity of stimulus patches has been constrained by graphics hardware, namely the use of look-up-table (LUT) animation methods. To avoid such limitations we replaced the LUTs with true color graphic sprites to present arbitrary spatial patterns. To demonstrate the utility of the method we have recorded simultaneously from 192 cortically scaled stimulus patches each of which activate about 12mm2 of cortex in area V1. Because of the sparseness of cortical folding, very small stimulus patches and robust estimation of dipole source orientation, the method opens a new window on precise spatio-temporal mapping of early visual areas. The use of sprites also enables multiplexing stimuli such that at each patch location multiple stimuli can be presented. We have presented patterns with different orientations (or spatial frequencies) at the same patch locations but independently temporally modulated, effectively doubling the number of stimulus patches, to explore cell population interactions at the same cortical locus. We have also measured nonlinear responses to adjacent pairs of patches, thereby getting an edge response that doubles the spatial sampling density to about 1.8 mm on cortex.

  6. Recent advances in sample preparation techniques for effective bioanalytical methods.

    PubMed

    Kole, Prashant Laxman; Venkatesh, Gantala; Kotecha, Jignesh; Sheshala, Ravi

    2011-01-01

    This paper reviews the recent developments in bioanalysis sample preparation techniques and gives an update on basic principles, theory, applications and possibilities for automation, and a comparative discussion on the advantages and limitation of each technique. Conventional liquid-liquid extraction (LLE), protein precipitation (PP) and solid-phase extraction (SPE) techniques are now been considered as methods of the past. The last decade has witnessed a rapid development of novel sample preparation techniques in bioanalysis. Developments in SPE techniques such as selective sorbents and in the overall approach to SPE, such as hybrid SPE and molecularly imprinted polymer SPE, have been addressed. Considerable literature has been published in the area of solid-phase micro-extraction and its different versions, e.g. stir bar sorptive extraction, and their application in the development of selective and sensitive bioanalytical methods. Techniques such as dispersive solid-phase extraction, disposable pipette extraction and micro-extraction by packed sorbent offer a variety of extraction phases and provide unique advantages to bioanalytical methods. On-line SPE utilizing column-switching techniques is rapidly gaining acceptance in bioanalytical applications. PP sample preparation techniques such as PP filter plates/tubes offer many advantages like removal of phospholipids and proteins in plasma/serum. Newer approaches to conventional LLE techniques (salting-out LLE) are also covered in this review article. PMID:21154887

  7. Advanced numerical methods and software approaches for semiconductor device simulation

    SciTech Connect

    CAREY,GRAHAM F.; PARDHANANI,A.L.; BOVA,STEVEN W.

    2000-03-23

    In this article the authors concisely present several modern strategies that are applicable to drift-dominated carrier transport in higher-order deterministic models such as the drift-diffusion, hydrodynamic, and quantum hydrodynamic systems. The approaches include extensions of upwind and artificial dissipation schemes, generalization of the traditional Scharfetter-Gummel approach, Petrov-Galerkin and streamline-upwind Petrov Galerkin (SUPG), entropy variables, transformations, least-squares mixed methods and other stabilized Galerkin schemes such as Galerkin least squares and discontinuous Galerkin schemes. The treatment is representative rather than an exhaustive review and several schemes are mentioned only briefly with appropriate reference to the literature. Some of the methods have been applied to the semiconductor device problem while others are still in the early stages of development for this class of applications. They have included numerical examples from the recent research tests with some of the methods. A second aspect of the work deals with algorithms that employ unstructured grids in conjunction with adaptive refinement strategies. The full benefits of such approaches have not yet been developed in this application area and they emphasize the need for further work on analysis, data structures and software to support adaptivity. Finally, they briefly consider some aspects of software frameworks. These include dial-an-operator approaches such as that used in the industrial simulator PROPHET, and object-oriented software support such as those in the SANDIA National Laboratory framework SIERRA.

  8. Evaluation of pediatric manual wheelchair mobility using advanced biomechanical methods.

    PubMed

    Slavens, Brooke A; Schnorenberg, Alyssa J; Aurit, Christine M; Graf, Adam; Krzak, Joseph J; Reiners, Kathryn; Vogel, Lawrence C; Harris, Gerald F

    2015-01-01

    There is minimal research of upper extremity joint dynamics during pediatric wheelchair mobility despite the large number of children using manual wheelchairs. Special concern arises with the pediatric population, particularly in regard to the longer duration of wheelchair use, joint integrity, participation and community integration, and transitional care into adulthood. This study seeks to provide evaluation methods for characterizing the biomechanics of wheelchair use by children with spinal cord injury (SCI). Twelve subjects with SCI underwent motion analysis while they propelled their wheelchair at a self-selected speed and propulsion pattern. Upper extremity joint kinematics, forces, and moments were computed using inverse dynamics methods with our custom model. The glenohumeral joint displayed the largest average range of motion (ROM) at 47.1° in the sagittal plane and the largest average superiorly and anteriorly directed joint forces of 6.1% BW and 6.5% BW, respectively. The largest joint moments were 1.4% body weight times height (BW × H) of elbow flexion and 1.2% BW × H of glenohumeral joint extension. Pediatric manual wheelchair users demonstrating these high joint demands may be at risk for pain and upper limb injuries. These evaluation methods may be a useful tool for clinicians and therapists for pediatric wheelchair prescription and training. PMID:25802860

  9. Advanced Numerical Methods and Software Approaches for Semiconductor Device Simulation

    DOE PAGESBeta

    Carey, Graham F.; Pardhanani, A. L.; Bova, S. W.

    2000-01-01

    In this article we concisely present several modern strategies that are applicable to driftdominated carrier transport in higher-order deterministic models such as the driftdiffusion, hydrodynamic, and quantum hydrodynamic systems. The approaches include extensions of “upwind” and artificial dissipation schemes, generalization of the traditional Scharfetter – Gummel approach, Petrov – Galerkin and streamline-upwind Petrov Galerkin (SUPG), “entropy” variables, transformations, least-squares mixed methods and other stabilized Galerkin schemes such as Galerkin least squares and discontinuous Galerkin schemes. The treatment is representative rather than an exhaustive review and several schemes are mentioned only briefly with appropriate reference to the literature. Some of themore » methods have been applied to the semiconductor device problem while others are still in the early stages of development for this class of applications. We have included numerical examples from our recent research tests with some of the methods. A second aspect of the work deals with algorithms that employ unstructured grids in conjunction with adaptive refinement strategies. The full benefits of such approaches have not yet been developed in this application area and we emphasize the need for further work on analysis, data structures and software to support adaptivity. Finally, we briefly consider some aspects of software frameworks. These include dial-an-operator approaches such as that used in the industrial simulator PROPHET, and object-oriented software support such as those in the SANDIA National Laboratory framework SIERRA.« less

  10. Advanced Signal Processing Methods Applied to Digital Mammography

    NASA Technical Reports Server (NTRS)

    Stauduhar, Richard P.

    1997-01-01

    The work reported here is on the extension of the earlier proposal of the same title, August 1994-June 1996. The report for that work is also being submitted. The work reported there forms the foundation for this work from January 1997 to September 1997. After the earlier work was completed there were a few items that needed to be completed prior to submission of a new and more comprehensive proposal for further research. Those tasks have been completed and two new proposals have been submitted, one to NASA, and one to Health & Human Services WS). The main purpose of this extension was to refine some of the techniques that lead to automatic large scale evaluation of full mammograms. Progress on each of the proposed tasks follows. Task 1: A multiresolution segmentation of background from breast has been developed and tested. The method is based on the different noise characteristics of the two different fields. The breast field has more power in the lower octaves and the off-breast field behaves similar to a wideband process, where more power is in the high frequency octaves. After the two fields are separated by lowpass filtering, a region labeling routine is used to find the largest contiguous region, the breast. Task 2: A wavelet expansion that can decompose the image without zero padding has been developed. The method preserves all properties of the power-of-two wavelet transform and does not add appreciably to computation time or storage. This work is essential for analysis of the full mammogram, as opposed to selecting sections from the full mammogram. Task 3: A clustering method has been developed based on a simple counting mechanism. No ROC analysis has been performed (and was not proposed), so we cannot finally evaluate this work without further support. Task 4: Further testing of the filter reveals that different wavelet bases do yield slightly different qualitative results. We cannot provide quantitative conclusions about this for all possible bases

  11. Advanced hybrid particulate collector and method of operation

    DOEpatents

    Miller, Stanley J.

    1999-01-01

    A device and method for controlling particulate air pollutants of the present invention combines filtration and electrostatic collection devices. The invention includes a chamber housing a plurality of rows of filter elements. Between each row of filter elements is a grounded plate. Between the grounded plates and the filter elements are electrode grids for creating electrostatic precipitation zones between each row of filter elements. In this way, when the filter elements are cleaned by pulsing air in a reverse direction, the dust removed from the bags will collect in the electrostatic precipitation zones rather than on adjacent filter elements.

  12. Advanced hybrid particulate collector and method of operation

    DOEpatents

    Miller, S.J.

    1999-08-17

    A device and method for controlling particulate air pollutants of the present invention combines filtration and electrostatic collection devices. The invention includes a chamber housing a plurality of rows of filter elements. Between each row of filter elements is a grounded plate. Between the grounded plates and the filter elements are electrode grids for creating electrostatic precipitation zones between each row of filter elements. In this way, when the filter elements are cleaned by pulsing air in a reverse direction, the dust removed from the bags will collect in the electrostatic precipitation zones rather than on adjacent filter elements. 12 figs.

  13. Advanced Computational Aeroacoustics Methods for Fan Noise Prediction

    NASA Technical Reports Server (NTRS)

    Envia, Edmane (Technical Monitor); Tam, Christopher

    2003-01-01

    Direct computation of fan noise is presently not possible. One of the major difficulties is the geometrical complexity of the problem. In the case of fan noise, the blade geometry is critical to the loading on the blade and hence the intensity of the radiated noise. The precise geometry must be incorporated into the computation. In computational fluid dynamics (CFD), there are two general ways to handle problems with complex geometry. One way is to use unstructured grids. The other is to use body fitted overset grids. In the overset grid method, accurate data transfer is of utmost importance. For acoustic computation, it is not clear that the currently used data transfer methods are sufficiently accurate as not to contaminate the very small amplitude acoustic disturbances. In CFD, low order schemes are, invariably, used in conjunction with unstructured grids. However, low order schemes are known to be numerically dispersive and dissipative. dissipative errors are extremely undesirable for acoustic wave problems. The objective of this project is to develop a high order unstructured grid Dispersion-Relation-Preserving (DRP) scheme. would minimize numerical dispersion and dissipation errors. contains the results of the funded portion of the project. scheme on an unstructured grid has been developed. constructed in the wave number space. The characteristics of the scheme can be improved by the inclusion of additional constraints. Stability of the scheme has been investigated. Stability can be improved by adopting the upwinding strategy.

  14. Advanced criticality assessment method for sewer pipeline assets.

    PubMed

    Syachrani, S; Jeong, H D; Chung, C S

    2013-01-01

    For effective management of water and wastewater infrastructure, the United States Environmental Protection Agency (US-EPA) has long emphasized the significant role of risk in prioritizing and optimizing asset management decisions. High risk assets are defined as assets with a high probability of failure (e.g. soon to fail, old, poor condition) and high consequences of failure (e.g. environmental impact, high expense, safety concerns, social disruption). In practice, the consequences of failure are often estimated by experts through a Delphi method. However, the estimation of the probability of failure has been challenging as it requires the thorough analysis of the historical condition assessment data, repair and replacement records, and other factors influencing the deterioration of the asset. The most common predictor in estimating the probability of failure is calendar age. However, a simple reliance on calendar age as a basis for estimating the asset's deterioration pattern completely ignores the different aging characteristics influenced by various operational and environmental conditions. This paper introduces a new approach of using 'real age' in estimating the probability of failure. Unlike the traditional calendar age method, the real age represents the adjusted age based on the unique operational and environmental conditions of the asset. Depending on the individual deterioration pattern, the real age could be higher or lower than its calendar age. Using the concept of real age, the probability of failure of an asset can be more accurately estimated. PMID:23508155

  15. Recent advances in computer camera methods for machine vision

    NASA Astrophysics Data System (ADS)

    Olson, Gaylord G.; Walker, Jo N.

    1998-10-01

    During the past year, several new computer camera methods (hardware and software) have been developed which have applications in machine vision. These are described below, along with some test results. The improvements are generally in the direction of higher speed and greater parallelism. A PCI interface card has been designed which is adaptable to multiple CCD types, both color and monochrome. A newly designed A/D converter allows for a choice of 8 or 10-bit conversion resolution and a choice of two different analog inputs. Thus, by using four of these converters feeding the 32-bit PCI data bus, up to 8 camera heads can be used with a single PCI card, and four camera heads can be operated in parallel. The card has been designed so that any of 8 different CCD types can be used with it (6 monochrome and 2 color CCDs) ranging in resolution from 192 by 165 pixels up to 1134 by 972 pixels. In the area of software, a method has been developed to better utilize the decision-making capability of the computer along with the sub-array scan capabilities of many CCDs. Specifically, it is shown below how to achieve a dual scan mode camera system wherein one scan mode is a low density, high speed scan of a complete image area, and a higher density sub-array scan is used in those areas where changes have been observed. The name given to this technique is adaptive sub-array scanning.

  16. Efficacy and safety of chemotherapy for newly diagnosed advanced non-small cell lung cancer with venous thromboembolism

    PubMed Central

    Zhang, Xueli; Li, Huiqiao; Chen, Wenhui; Yang, Yuanhua; Wang, Chen; Zhang, Yuhui

    2015-01-01

    Background Venous thromboembolism (VTE) is a serious complication in patients with lung cancer. The benefit of chemotherapy for lung cancer patients with VTE remains unknown. This study was conducted to elucidate the efficacy and safety of chemotherapy for advanced non-small cell lung cancer (NSCLC) in patients with VTE. Methods Newly diagnosed patients with advanced (i.e. stage IIIB and IV) NSCLC with VTE who received systemic chemotherapy were studied. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were retrospectively analyzed. Results In this study, 21 patients who received chemotherapy plus anticoagulation therapy between December 2009 and February 2011 were included. The objective response and disease control rates within the first regimen were 14.29% (3/21) and 76.19 %(16/21), respectively. The median PFS, one-year survival rate, and median OS were 5.50 months, 33.30%, and 8.70 months, respectively. The main grade 3/4 toxicities observed included neutropenia (28.57%), nausea 4 (19.05%), and anemia 2 (9.52%). Major bleeding was not observed. Conclusion Chemotherapy for newly diagnosed patients with advanced NSCLC and VTE was feasible and had acceptable toxicity; however, the survival of these patients remained inferior to that of patients without VTE. PMID:26557917

  17. Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

    PubMed Central

    Xing, Pu-Yuan; Wang, Yan; Hao, Xue-Zhi; Wang, Bin; Yang, Lin; Shi, Yuan-Kai; Zhang, Xiang-Ru

    2013-01-01

    Objective To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC). Methods We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in 10 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-free survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%). Conclusions The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated. PMID:23592901

  18. Clinical efficacy of percutaneous vertebroplasty combined with intensity-modulated radiotherapy for spinal metastases in patients with NSCLC

    PubMed Central

    Li, Yi; Qing, Yi; Zhang, Zhimin; Li, Mengxia; Xie, Jiaying; Wang, Ge; Wang, Dong

    2015-01-01

    Objective This study aimed to evaluate the safety and efficacy of percutaneous vertebroplasty (PVP) combined with intensity-modulated radiotherapy (IMRT) for metastatic lesions of patients with non-small-cell lung cancer (NSCLC) at centrum vertebrae. Methods A total of 39 patients with spinal metastatic NSCLC (stage IV) were treated with PVP followed by IMRT (30 Gy/10F/2 W) for metastatic lesion at centrum vertebrae under local anesthesia. Retrospective analysis was done with medical records and radiological data. The change of visual analog scale (VAS), activities of daily living, and kyphotic angle was measured preoperatively. The presence of complications was assessed preoperatively (baseline) at 24 hours, 1 week, and 1, 3, 6, 12, and 24 months postoperatively, or until the patient died or was lost to follow-up. Survival was assessed in the group. Results A total of 39 consecutive patients were successfully treated with PVP via a translateral approach and IMRT. Their mean VAS score decreased from 7.93±1.09 preoperatively to 4.14±1.15 by the 24-hour postoperative time point and was 3.92±1.23 at 1 week, 4.27±1.93 at 1 month, 3.24±1.35 at 3 months, 2.27±0.96 at 6 months, and 2.59±1.55 at 12 months after the procedure. The mean VAS score at all of the postoperative time points was decreased significantly from the preoperative baseline score (P<0.05). Activities of daily living evaluation showed that the patients had a significantly high life quality after the combined approach (50.9±11.7 vs 82.3±9.9, P<0.05). No severe complications were observed. Mild complications included two cases (5.13%) of asymptomatic cement leakage into the epidural space and one case (2.56%) of paravertebral leakage. Median survival time was extended to 13 months. Conclusion The safety and efficacy of PVP combined with IMRT in patients with NSCLC with metastatic lesions at centrum vertebrae and the ability to prevent the diseased vertebrae from further deformation and tumor

  19. Comparative Assessment of Advanced Gay Hydrate Production Methods

    SciTech Connect

    M. D. White; B. P. McGrail; S. K. Wurstner

    2009-06-30

    Displacing natural gas and petroleum with carbon dioxide is a proven technology for producing conventional geologic hydrocarbon reservoirs, and producing additional yields from abandoned or partially produced petroleum reservoirs. Extending this concept to natural gas hydrate production offers the potential to enhance gas hydrate recovery with concomitant permanent geologic sequestration. Numerical simulation was used to assess a suite of carbon dioxide injection techniques for producing gas hydrates from a variety of geologic deposit types. Secondary hydrate formation was found to inhibit contact of the injected CO{sub 2} regardless of injectate phase state, thus diminishing the exchange rate due to pore clogging and hydrate zone bypass of the injected fluids. Additional work is needed to develop methods of artificially introducing high-permeability pathways in gas hydrate zones if injection of CO{sub 2} in either gas, liquid, or micro-emulsion form is to be more effective in enhancing gas hydrate production rates.

  20. Method of Suppressing Sublimation in Advanced Thermoelectric Devices

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeffrey S. (Inventor); Caillat, Thierry (Inventor); Fleurial, Jean-Pierre (Inventor); Snyder, G. Jeffrey (Inventor)

    2009-01-01

    A method of applying a physical barrier to suppress thermal decomposition near a surface of a thermoelectric material including applying a continuous metal foil to a predetermined portion of the surface of the thermoelectric material, physically binding the continuous metal foil to the surface of the thermoelectric material using a binding member, and heating in a predetermined atmosphere the applied and physically bound continuous metal foil and the thermoelectric material to a sufficient temperature in order to promote bonding between the continuous metal foil and the surface of the thermoelectric material. The continuous metal foil forms a physical barrier to enclose a predetermined portion of the surface. Thermal decomposition is suppressed at the surface of the thermoelectric material enclosed by the physical barrier when the thermoelectric element is in operation.

  1. Advancing Methods in Research on Asian American Children and Youth.

    PubMed

    Yoshikawa, Hirokazu; Mistry, Rashmita; Wang, Yijie

    2016-07-01

    Asian American children and youth constitute at the same time an immigrant group, a set of ethnic groups, and a set of cultural groups. Research on these populations can therefore take on one or more of these perspectives. This article provides guidance for research methods in three areas: (a) conceptualizing and assessing migration-related factors, (b) assessing ethnicity and national origin, and (c) using culturally and contextually relevant measures. Methodological recommendations are made for each area, with attention to small-scale studies with community samples as well as large-scale data sets. In addition, this article recommends researchers attend to within-group variations (i.e., intersections of ethnicity, generational status, gender, class, sexuality), the embeddedness of individual development in context, and specificity of developmental periods. PMID:27392797

  2. Advanced view factor analysis method for radiation exchange

    NASA Astrophysics Data System (ADS)

    Park, Sookuk; Tuller, Stanton E.

    2014-03-01

    A raster-based method for determining complex view factor patterns is presented (HURES model). The model uses Johnson and Watson's view factor analysis method for fisheye lens photographs. The entire sphere is divided into 13 different view factors: open sky; sunny and shaded building walls, vegetation (trees) and ground surfaces above and below 1.2 m from the ground surface. The HURES model gave reasonable view factor results in tests at two urban study sites on summer days: downtown Nanaimo, B.C., Canada and Changwon, Republic of Korea. HURES gave better estimates of open sky view factors determined from fisheye lens photographs than did ENVI-met 3.1 and RayMan Pro. However, all three models underestimated sky view factor. For view factor analysis in outdoor urban areas, the 10° interval of rotation angle at 100 m distance of annuli will be suitable settings for three-dimensional computer simulations. The HURES model can be used for the rapid determination of complex view factor patterns which facilitates the analysis of their effects. Examples of how differing view factor patterns can affect human thermal sensation indices are given. The greater proportion of sunny view factors increased the computed predicted mean vote (PMV) by 1.3 on the sunny side of the street compared with the shady side during mid-morning in downtown Nanaimo. In another example, effects of differing amounts of open sky, sunny ground, sunny buildings and vegetation combined to produce only slight differences in PMV and two other human thermal sensation indices, PET and UTCI.

  3. Advanced hydraulic fracturing methods to create in situ reactive barriers

    SciTech Connect

    Murdoch, L. |; Siegrist, B.; Vesper, S.

    1997-12-31

    Many contaminated areas consist of a source area and a plume. In the source area, the contaminant moves vertically downward from a release point through the vadose zone to an underlying saturated region. Where contaminants are organic liquids, NAPL may accumulate on the water table, or it may continue to migrate downward through the saturated region. Early developments of permeable barrier technology have focused on intercepting horizontally moving plumes with vertical structures, such as trenches, filled with reactive material capable of immobilizing or degrading dissolved contaminants. This focus resulted in part from a need to economically treat the potentially large volumes of contaminated water in a plume, and in part from the availability of construction technology to create the vertical structures that could house reactive compounds. Contaminant source areas, however, have thus far remained largely excluded from the application of permeable barrier technology. One reason for this is the lack of conventional construction methods for creating suitable horizontal structures that would place reactive materials in the path of downward-moving contaminants. Methods of hydraulic fracturing have been widely used to create flat-lying to gently dipping layers of granular material in unconsolidated sediments. Most applications thus far have involved filling fractures with coarse-grained sand to create permeable layers that will increase the discharge of wells recovering contaminated water or vapor. However, it is possible to fill fractures with other compounds that alter the chemical composition of the subsurface. One early application involved development and field testing micro-encapsulated sodium percarbonate, a solid compound that releases oxygen and can create aerobic conditions suitable for biodegradation in the subsurface for several months.

  4. miR-143 suppresses the proliferation of NSCLC cells by inhibiting the epidermal growth factor receptor

    PubMed Central

    Zhang, Hong-Bo; Sun, Li-Chao; Ling, Lan; Cong, Lu-Hong; Lian, Rui

    2016-01-01

    MicroRNAs (miRs) regulate the proliferation and metastasis of numerous cancer cell types. It was previously reported that miR-143 levels were downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, and that the migration and invasion of NSCLC cells was inhibited upon suppression of cell proliferation and colony formation by the upregulation of miR-143. Epidermal growth factor receptor (EGFR), which is a vital factor in the promotion of cancer cell proliferation and has been investigated as a potential focus in cancer therapy, has been reported to be a possible target of miR-143. The present study aimed to investigate the role of miR-143 in NSCLC using NSCLC cell lines and primary cells from NSCLC patients. NSCLC cells were co-transfected with EGFR and miR-143, and the mRNA and protein expression of EGFR were analyzed. Furthermore, the activity of the transfected cancer cells with regard to colony formation, migration, invasion and apoptosis were evaluated. The levels of miR-143 were decreased in the NSCLC cell lines and primary cells from patients with NSCLC compared with the controls. Following transfection with miR-143, the ability of NSCLC cells to proliferate, form colonies, migrate and invade was inhibited. Similarly, knockdown of EGFR led to the suppression of NSCLC cell proliferation. The mRNA and protein expression levels of EGFR were significantly reduced following miR-143 overexpression, and the level of miR-143 was inversely correlated with that of EGFR in NSCLC cells. The results of the present study demonstrated that miR-143 was able to suppress NSCLC cell proliferation and invasion by inhibiting the effects of EGFR, suggesting that EGFR may be considered a potential target for NSCLC therapy. PMID:27602093

  5. An evolutionary method for synthesizing technological planning and architectural advance

    NASA Astrophysics Data System (ADS)

    Cole, Bjorn Forstrom

    In the development of systems with ever-increasing performance and/or decreasing drawbacks, there inevitably comes a point where more progress is available by shifting to a new set of principles of use. This shift marks a change in architecture, such as between the piston-driven propeller and the jet engine. The shift also often involves an abandonment of previous competencies that have been developed with great effort, and so a foreknowledge of these shifts can be advantageous. A further motivation for this work is the consideration of the Micro Autonomous Systems and Technology (MAST) project, which aims to develop very small (<5 cm) robots for a variety of uses. This is primarily a technology research project, and there is no baseline morphology for a robot to be considered. This then motivates an interest in the ability to automatically compose physical architectures from a series of components and quantitatively analyze them for a basic, conceptual analysis. The ability to do this would enable researchers to turn attention to the most promising forms. This work presents a method for using technology forecasts of components that enable future architectural shifts in order to forecast those shifts. The method consists of the use of multidimensional S-curves, genetic algorithms, and a graph-based formulation of architecture that is more flexible than other morphological techniques. Potential genetic operators are explored in depth to draft a final graph-based genetic algorithm. This algorithm is then implemented in a design code called Sindri, which leverages a commercial design tool named Pacelab. The first chapters of this thesis provide context and a philosophical background to the studies and research that was conducted. In particular, the idea that technology progresses in a fundamentally gradual way is developed and supported with previous historical research. The import of this is that the future can to some degree be predicted by the past, provided that

  6. WE-E-17A-02: Predictive Modeling of Outcome Following SABR for NSCLC Based On Radiomics of FDG-PET Images

    SciTech Connect

    Li, R; Aguilera, T; Shultz, D; Rubin, D; Diehn, M; Loo, B

    2014-06-15

    Purpose: This study aims to develop predictive models of patient outcome by extracting advanced imaging features (i.e., Radiomics) from FDG-PET images. Methods: We acquired pre-treatment PET scans for 51 stage I NSCLC patients treated with SABR. We calculated 139 quantitative features from each patient PET image, including 5 morphological features, 8 statistical features, 27 texture features, and 100 features from the intensity-volume histogram. Based on the imaging features, we aim to distinguish between 2 risk groups of patients: those with regional failure or distant metastasis versus those without. We investigated 3 pattern classification algorithms: linear discriminant analysis (LDA), naive Bayes (NB), and logistic regression (LR). To avoid the curse of dimensionality, we performed feature selection by first removing redundant features and then applying sequential forward selection using the wrapper approach. To evaluate the predictive performance, we performed 10-fold cross validation with 1000 random splits of the data and calculated the area under the ROC curve (AUC). Results: Feature selection identified 2 texture features (homogeneity and/or wavelet decompositions) for NB and LR, while for LDA SUVmax and one texture feature (correlation) were identified. All 3 classifiers achieved statistically significant improvements over conventional PET imaging metrics such as tumor volume (AUC = 0.668) and SUVmax (AUC = 0.737). Overall, NB achieved the best predictive performance (AUC = 0.806). This also compares favorably with MTV using the best threshold at an SUV of 11.6 (AUC = 0.746). At a sensitivity of 80%, NB achieved 69% specificity, while SUVmax and tumor volume only had 36% and 47% specificity. Conclusion: Through a systematic analysis of advanced PET imaging features, we are able to build models with improved predictive value over conventional imaging metrics. If validated in a large independent cohort, the proposed techniques could potentially aid in

  7. Advances in calibration methods for micro- and nanoscale surfaces

    NASA Astrophysics Data System (ADS)

    Leach, R. K.; Giusca, C. L.; Coupland, J. M.

    2012-04-01

    Optical surface topography measuring instrument manufacturers often quote accuracies of the order of nanometres and claim that the instruments can reliably measure a range of surfaces with structures on the micro- to nanoscale. However, for many years there has been debate about the interpretation of the data from optical surface topography measuring instruments. Optical artefacts in the output data and a lack of a calibration infrastructure mean that it can be difficult to get optical instruments to agree with contact stylus instruments. In this paper, the current situation with areal surface topography measurements is discussed along with the ISO specification standards that are in draft form. An infrastructure is discussed whereby the ISO-defined metrological characteristics of optical instruments can be determined, but these characteristics do not allow the instrument to measure complex surfaces. Current research into methods for determining the transfer function of optical instruments is reviewed, which will allow the calibration of optical instruments to measure complex surfaces, at least in the case of weak scattering. The ability of some optical instruments to measure outside the spatial bandwidth limitation of the numerical aperture is presented and some general outlook for future work given.

  8. Advanced methods for electromagnetic investigation of PCB/PWB layouts

    NASA Astrophysics Data System (ADS)

    Codreanu, N. D.; Ionescu, C.; Svasta, P.; Golumbeanu, V.

    2007-05-01

    High Density Interconnect (HDI) technology is a way to condense electronic circuits for ruggedness, radiation hardening, and high performance. HDI minimizes the size and weight of electronic products while maximizing their performances. HDI circuits offer new solutions to signal integrity (SI) and electromagnetic compatibility (EMC) concerns, concerns which are expected to grow more and more as rise/fall times continue to drop. Because PCB manufacturers have developed new materials and technological solutions, indispensable at this moment is to perform a deep virtual characterization of structures directly related to HDI. This paper presents investigations and results focused on the main areas of SI and EMC, as noise at PCB level (reflections, and crosstalk), electromagnetic interference (EMI) and on-board interconnection delay. The authors have evaluated various HDI-PCB items and structures using the MoM full-wave electromagnetic simulation method. After modeling and simulation a link to classical circuit simulators was created by extracting RLCG elements and various parameters, which are directly related to the total current along the HDI structures. The paper offers a new way to find the solutions for keeping the integrity of signals and electromagnetic compliance.

  9. Investigation of advanced fault insertion and simulator methods

    NASA Technical Reports Server (NTRS)

    Dunn, W. R.; Cottrell, D.

    1986-01-01

    The cooperative agreement partly supported research leading to the open-literature publication cited. Additional efforts under the agreement included research into fault modeling of semiconductor devices. Results of this research are presented in this report which is summarized in the following paragraphs. As a result of the cited research, it appears that semiconductor failure mechanism data is abundant but of little use in developing pin-level device models. Failure mode data on the other hand does exist but is too sparse to be of any statistical use in developing fault models. What is significant in the failure mode data is that, unlike classical logic, MSI and LSI devices do exhibit more than 'stuck-at' and open/short failure modes. Specifically they are dominated by parametric failures and functional anomalies that can include intermittent faults and multiple-pin failures. The report discusses methods of developing composite pin-level models based on extrapolation of semiconductor device failure mechanisms, failure modes, results of temperature stress testing and functional modeling. Limitations of this model particularly with regard to determination of fault detection coverage and latency time measurement are discussed. Indicated research directions are presented.

  10. Advanced methods for preparation and characterization of infrared detector materials

    NASA Technical Reports Server (NTRS)

    Broerman, J. G.; Morris, B. J.; Meschter, P. J.

    1983-01-01

    Crystals were prepared by the Bridgman-Stockbarger method with a wide range of crystal growth rates and temperature gradients adequate to prevent constitutional supercooling under diffusion-limited, steady-state, growth conditions. The longitudinal compositional gradients for different growth conditions and alloy compositions were calculated and compared with experimental data to develop a quantitative model of solute redistribution during the crystal growth of the alloys. Measurements were performed to ascertain the effect of growth conditions on radial compositional gradients. The pseudobinary HgTe-CdTe constitutional phase diagram was determined by precision differential-thermal-analysis measurements and used to calculate the segregation coefficient of Cd as a function of x and interface temperature. Experiments were conducted to determine the ternary phase equilibria in selected regions of the Hg-Cd-Te constitutional phase diagram. Electron and hole mobilities as functions of temperature were analyzed to establish charge-carrier scattering probabilities. Computer algorithms specific to Hg(1-x)CdxTe were developed for calculations of the charge-carrier concentration, charge-carrier mobilities, Hall coefficient, and Dermi Fermi energy as functions of x, temperature, ionized donor and acceptor concentrations, and neutral defect concentrations.

  11. Advanced Extraction Methods for Actinide/Lanthanide Separations

    SciTech Connect

    Scott, M.J.

    2005-12-01

    The separation of An(III) ions from chemically similar Ln(III) ions is perhaps one of the most difficult problems encountered during the processing of nuclear waste. In the 3+ oxidation states, the metal ions have an identical charge and roughly the same ionic radius. They differ strictly in the relative energies of their f- and d-orbitals, and to separate these metal ions, ligands will need to be developed that take advantage of this small but important distinction. The extraction of uranium and plutonium from nitric acid solution can be performed quantitatively by the extraction with the TBP (tributyl phosphate). Commercially, this process has found wide use in the PUREX (plutonium uranium extraction) reprocessing method. The TRUEX (transuranium extraction) process is further used to coextract the trivalent lanthanides and actinides ions from HLLW generated during PUREX extraction. This method uses CMPO [(N, N-diisobutylcarbamoylmethyl) octylphenylphosphineoxide] intermixed with TBP as a synergistic agent. However, the final separation of trivalent actinides from trivalent lanthanides still remains a challenging task. In TRUEX nitric acid solution, the Am(III) ion is coordinated by three CMPO molecules and three nitrate anions. Taking inspiration from this data and previous work with calix[4]arene systems, researchers on this project have developed a C3-symmetric tris-CMPO ligand system using a triphenoxymethane platform as a base. The triphenoxymethane ligand systems have many advantages for the preparation of complex ligand systems. The compounds are very easy to prepare. The steric and solubility properties can be tuned through an extreme range by the inclusion of different alkoxy and alkyl groups such as methyoxy, ethoxy, t-butoxy, methyl, octyl, t-pentyl, or even t-pentyl at the ortho- and para-positions of the aryl rings. The triphenoxymethane ligand system shows promise as an improved extractant for both tetravalent and trivalent actinide recoveries form

  12. Conceptual Design Method Developed for Advanced Propulsion Nozzles

    NASA Technical Reports Server (NTRS)

    Nadell, Shari-Beth; Barnhart, Paul J.

    1998-01-01

    As part of a contract with the NASA Lewis Research Center, a simple, accurate method of predicting the performance characteristics of a nozzle design has been developed for use in conceptual design studies. The Nozzle Performance Analysis Code (NPAC) can predict the on- and off-design performance of axisymmetric or two-dimensional convergent and convergent-divergent nozzle geometries. NPAC accounts for the effects of overexpansion or underexpansion, flow divergence, wall friction, heat transfer, and small mass addition or loss across surfaces when the nozzle gross thrust and gross thrust coefficient are being computed. NPAC can be used to predict the performance of a given nozzle design or to develop a preliminary nozzle system design for subsequent analysis. The input required by NPAC consists of a simple geometry definition of the nozzle surfaces, the location of key nozzle stations (entrance, throat, exit), and the nozzle entrance flow properties. NPAC performs three analysis "passes" on the nozzle geometry. First, an isentropic control volume analysis is performed to determine the gross thrust and gross thrust coefficient of the nozzle. During the second analysis pass, the skin friction and heat transfer losses are computed. The third analysis pass couples the effects of wall shear and heat transfer with the initial internal nozzle flow solutions to produce a system of equations that is solved at steps along the nozzle geometry. Small mass additions or losses, such as those resulting from leakage or bleed flow, can be included in the model at specified geometric sections. A final correction is made to account for divergence losses that are incurred if the nozzle exit flow is not purely axial.

  13. CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance.

    PubMed

    Park, Kang-Seo; Raffeld, Mark; Moon, Yong Wha; Xi, Liqiang; Bianco, Caterina; Pham, Trung; Lee, Liam C; Mitsudomi, Tetsuya; Yatabe, Yasushi; Okamoto, Isamu; Subramaniam, Deepa; Mok, Tony; Rosell, Rafael; Luo, Ji; Salomon, David S; Wang, Yisong; Giaccone, Giuseppe

    2014-07-01

    The majority of non-small cell lung cancer (NSCLC) patients harbor EGFR-activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with EGFR mutations are refractory to EGFR-TKIs. Resistance to EGFR inhibitors reportedly involves SRC activation and induction of epithelial-to-mesenchymal transition (EMT). Here, we have demonstrated that overexpression of CRIPTO1, an EGF-CFC protein family member, renders EGFR-TKI-sensitive and EGFR-mutated NSCLC cells resistant to erlotinib in culture and in murine xenograft models. Furthermore, tumors from NSCLC patients with EGFR-activating mutations that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1 compared with tumors from patients that were sensitive to EGFR-TKIs. Primary NSCLC cells derived from a patient with EGFR-mutated NSCLC that was intrinsically erlotinib resistant were CRIPTO1 positive, but gained erlotinib sensitivity upon loss of CRIPTO1 expression during culture. CRIPTO1 activated SRC and ZEB1 to promote EMT via microRNA-205 (miR-205) downregulation. While miR-205 depletion induced erlotinib resistance, miR-205 overexpression inhibited CRIPTO1-dependent ZEB1 and SRC activation, restoring erlotinib sensitivity. CRIPTO1-induced erlotinib resistance was directly mediated through SRC but not ZEB1; therefore, cotargeting EGFR and SRC synergistically attenuated growth of erlotinib-resistant, CRIPTO1-positive, EGFR-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome intrinsic EGFR-inhibitor resistance in patients with CRIPTO1-positive, EGFR-mutated NSCLC. PMID:24911146

  14. CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance

    PubMed Central

    Park, Kang-Seo; Raffeld, Mark; Moon, Yong Wha; Xi, Liqiang; Bianco, Caterina; Pham, Trung; Lee, Liam C.; Mitsudomi, Tetsuya; Yatabe, Yasushi; Okamoto, Isamu; Subramaniam, Deepa; Mok, Tony; Rosell, Rafael; Luo, Ji; Salomon, David S.; Wang, Yisong; Giaccone, Giuseppe

    2014-01-01

    The majority of non–small cell lung cancer (NSCLC) patients harbor EGFR-activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with EGFR mutations are refractory to EGFR-TKIs. Resistance to EGFR inhibitors reportedly involves SRC activation and induction of epithelial-to-mesenchymal transition (EMT). Here, we have demonstrated that overexpression of CRIPTO1, an EGF-CFC protein family member, renders EGFR-TKI–sensitive and EGFR-mutated NSCLC cells resistant to erlotinib in culture and in murine xenograft models. Furthermore, tumors from NSCLC patients with EGFR-activating mutations that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1 compared with tumors from patients that were sensitive to EGFR-TKIs. Primary NSCLC cells derived from a patient with EGFR-mutated NSCLC that was intrinsically erlotinib resistant were CRIPTO1 positive, but gained erlotinib sensitivity upon loss of CRIPTO1 expression during culture. CRIPTO1 activated SRC and ZEB1 to promote EMT via microRNA-205 (miR-205) downregulation. While miR-205 depletion induced erlotinib resistance, miR-205 overexpression inhibited CRIPTO1-dependent ZEB1 and SRC activation, restoring erlotinib sensitivity. CRIPTO1-induced erlotinib resistance was directly mediated through SRC but not ZEB1; therefore, cotargeting EGFR and SRC synergistically attenuated growth of erlotinib-resistant, CRIPTO1-positive, EGFR-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome intrinsic EGFR-inhibitor resistance in patients with CRIPTO1-positive, EGFR-mutated NSCLC. PMID:24911146

  15. Method and system for advancement of a borehole using a high power laser

    SciTech Connect

    Moxley, Joel F.; Land, Mark S.; Rinzler, Charles C.; Faircloth, Brian O.; Zediker, Mark S.

    2014-09-09

    There is provided a system, apparatus and methods for the laser drilling of a borehole in the earth. There is further provided with in the systems a means for delivering high power laser energy down a deep borehole, while maintaining the high power to advance such boreholes deep into the earth and at highly efficient advancement rates, a laser bottom hole assembly, and fluid directing techniques and assemblies for removing the displaced material from the borehole.

  16. Knockdown of ANXA1 suppresses the biological behavior of human NSCLC cells in vitro

    PubMed Central

    FANG, YING; GUAN, XIAOYING; CAI, TONGHUI; LONG, JIE; WANG, HONGYAN; XIE, XIAOBIN; ZHANG, YAJIE

    2016-01-01

    Annexin A1 (ANXA1) is a member of the annexin superfamily. Previous studies have reported that ANXA1 is highly expressed in various types of malignant tumor; however, its role in the progression of non-small cell lung cancer (NSCLC) remains to be fully clarified. The present study aimed to investigate the oncogenic role of ANXA1 in NSCLC cells in vitro. RNA interference was used to down-regulate ANXA1 expression in A549 and H1299 cells using a small interfering RNA lentiviral vector. Subsequently, cell proliferation and migration were detected using Cell Counting kit-8, clone formation, wound healing and Transwell chamber assays. Successful transfection was confirmed using fluorescence microscopy, which demonstrated that ANXA1 had been efficiently inhibited. ANXA1 knockdown suppressed the proliferation, migration and invasion of NSCLC cells. In conclusion, the present study provided evidence suggesting that ANXA1 may contribute to the growth and invasion of NSCLC cell lines, and ANXA1 may be exploited as an in vitro therapeutic target for the treatment of NSCLC. PMID:27035116

  17. Knockdown of ANXA1 suppresses the biological behavior of human NSCLC cells in vitro.

    PubMed

    Fang, Ying; Guan, Xiaoying; Cai, Tonghui; Long, Jie; Wang, Hongyan; Xie, Xiaobin; Zhang, Yajie

    2016-05-01

    Annexin A1 (ANXA1) is a member of the annexin superfamily. Previous studies have reported that ANXA1 is highly expressed in various types of malignant tumor; however, its role in the progression of non‑small cell lung cancer (NSCLC) remains to be fully clarified. The present study aimed to investigate the oncogenic role of ANXA1 in NSCLC cells in vitro. RNA interference was used to downregulate ANXA1 expression in A549 and H1299 cells using a small interfering RNA lentiviral vector. Subsequently, cell proliferation and migration were detected using Cell Counting kit‑8, clone formation, wound healing and Transwell chamber assays. Successful transfection was confirmed using fluorescence microscopy, which demonstrated that ANXA1 had been efficiently inhibited. ANXA1 knockdown suppressed the proliferation, migration and invasion of NSCLC cells. In conclusion, the present study provided evidence suggesting that ANXA1 may contribute to the growth and invasion of NSCLC cell lines, and ANXA1 may be exploited as an in vitro therapeutic target for the treatment of NSCLC. PMID:27035116

  18. A Straightforward Method for Advance Estimation of User Charges for Information in Numeric Databases.

    ERIC Educational Resources Information Center

    Jarvelin, Kalervo

    1986-01-01

    Describes a method for advance estimation of user charges for queries in relational data model-based numeric databases when charges are based on data retrieved. Use of this approach is demonstrated by sample queries to an imaginary marketing database. The principles and methods of this approach and its relevance are discussed. (MBR)

  19. KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC: A meta-analysis of 41 studies

    PubMed Central

    Pan, Wei; Yang, Yan; Zhu, Hongcheng; Zhang, Youcheng; Zhou, Rongping; Sun, Xinchen

    2016-01-01

    Mutation of oncogene KRAS is common in non-small cell lung cancer (NSCLC), however, its clinical significance is still controversial. Independent studies evaluating its prognostic and predictive value usually drew inconsistent conclusions. Hence, We performed a meta-analysis with 41 relative publications, retrieved from multi-databases, to reconcile these controversial results and to give an overall impression of KRAS mutation in NSCLC. According to our findings, KRAS mutation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in early stage resected NSCLC (hazard ratio or HR=1.56 and 1.57, 95% CI 1.39-1.76 and 1.17-2.09 respectively), and with inferior outcomes of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment and chemotherapy (relative risk or RR=0.21 and 0.66 for objective response rate or ORR, 95% CI 0.12-0.39 and 0.54-0.81 respectively; HR=1.46 and 1.30 for progression-free survival or PFS, 95%CI 1.23-1.74 and 1.14-1.50 respectively) in advanced NSCLC. When EGFR mutant patients were excluded, KRAS mutation was still significantly associated with worse OS and PFS of EGFR-TKIs (HR=1.40 and 1.35, 95 % CI 1.21-1.61 and 1.11-1.64). Although KRAS mutant patients presented worse DFS and PFS of chemotherapy (HR=1.33 and 1.11, 95% CI 0.97-1.84 and 0.95-1.30), and lower response rate to EGFR-TKIs or chemotherapy (RR=0.55 and 0.88, 95 % CI 0.27-1.11 and 0.76-1.02), statistical differences were not met. In conclusion, KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC. There's a need for developing target therapies for KRAS mutant lung cancer and other tumors. PMID:26840022

  20. Acute myocardial infarction following erlotinib treatment for NSCLC: A case report

    PubMed Central

    DING, SHANSHAN; LONG, FEI; JIANG, SHUJUAN

    2016-01-01

    Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, is an oral targeted anticancer drug that is used to treat non-small cell lung cancer (NSCLC). Previous studies have confirmed that erlotinib is safe and is well-tolerated by patients. The most common adverse reactions observed following erlotinib treatment include a rash and mild diarrhea. In the current study, the first case of acute myocardial infarction following one month of treatment with erlotinib in a 63-year-old male NSCLC patient is presented. The present study highlights the importance of clinicians remaining cautious following erlotinib administration. In elderly NSCLC patients and those with a history of coronary heart disease, cardiac function must be carefully monitored following erlotinib treatment so that serious adverse reactions, such as myocardial infarction, may be identified early and treated quickly. PMID:27313772

  1. MiR-449c targets c-Myc and inhibits NSCLC cell progression.

    PubMed

    Miao, Li-Jun; Huang, Shi-Fu; Sun, Zhen-Tao; Gao, Zeng-Yan; Zhang, Rui-Xia; Liu, Ying; Wang, Jing

    2013-05-01

    MicroRNAs (miRNA) play an important role in tumorigenesis, proliferation, and differentiation. Altered miRNA expression in cancer indicates that miRNAs can function as tumor suppressors or oncogenes. MiR-449c downregulation in non-small cell lung cancer (NSCLC) compared with normal lung tissues was investigated in this study. NSCLC cell proliferation and invasion assays indicate that transfection of miR-449c expression plasmid inhibits the proliferation and invasion ability of NCI-H23 and NCI-H838 cells. In addition, miR-449c overexpression could suppress tumor growth in vivo. Morever, c-Myc was identified as a direct target gene of miR-449c. These findings clearly suggest that miR-449c downregulation and c-Myc amplification may be involved in the development of NSCLC. PMID:23507140

  2. The development and features of the Spanish prehospital advanced triage method (META) for mass casualty incidents.

    PubMed

    Arcos González, Pedro; Castro Delgado, Rafael; Cuartas Alvarez, Tatiana; Garijo Gonzalo, Gracia; Martinez Monzon, Carlos; Pelaez Corres, Nieves; Rodriguez Soler, Alberto; Turegano Fuentes, Fernando

    2016-01-01

    This text describes the process of development of the new Spanish Prehospital Advanced Triage Method (META) and explain its main features and contribution to prehospital triage systems in mass casualty incidents. The triage META is based in the Advanced Trauma Life Support (ATLS) protocols, patient's anatomical injuries and mechanism of injury. It is a triage method with four stages including early identification of patients with severe trauma that would benefit from a rapid evacuation to a surgical facility and introduces a new patient flow by-passing the advanced medical post to improve evacuation. The stages of triage META are: I) Stabilization triage that classifies patients according to severity to set priorities for initial emergency treatment; II) Identifying patients requiring urgent surgical treatment, this is done at the same time than stage I and creates a new flow of patients with high priority for evacuation; III) Implementation of Advanced Trauma Life Support protocols to patients previously classified according to stablished priority; and IV) Evacuation triage, stablishing evacuation priorities in case of lacks of appropriate transport resources. The triage META is to be applied only by prehospital providers with advanced knowledge and training in advanced trauma life support care and has been designed to be implemented as prehospital procedure in mass casualty incidents (MCI). PMID:27130042

  3. Metformin and salinomycin as the best combination for the eradication of NSCLC monolayer cells and their alveospheres (cancer stem cells) irrespective of EGFR, KRAS, EML4/ALK and LKB1 status

    PubMed Central

    Xiao, Zhiguang; Sperl, Bianca; Ullrich, Axel; Knyazev, Pjotr

    2014-01-01

    The presence of cancer stem cells (CSCs) is linked to preexisting or acquired drug resistance and tumor relapse. Therefore, targeting both differentiated tumor cells and CSCs was suggested as an effective approach for non-small cell lung cancer (NSCLC) treatment. After screening of chemotherapeutic agents, tyrosine kinase inhibitors (TKIs) or monoclonal antibody in combination with the putative stem cell killer Salinomycin (SAL), we found Metformin (METF), which modestly exerted a growth inhibitory effect on monolayer cells and alveospheres/CSCs of 5 NSCLC cell lines regardless of their EGFR, KRAS, EML4/ALK and LKB1 status, interacted synergistically with SAL to effectively promote cell death. Inhibition of EGFR (AKT, ERK1/2) and mTOR (p70 s6k) signaling with the combination of METF and SAL can be augmented beyond that achieved using each agent individually. Phospho-kinase assay further suggested the multiple roles of this combination in reducing oncogenic effects of modules, such as ß-catenin, Src family kinases (Src, Lyn, Yes), Chk-2 and FAK. Remarkably, significant reduction of sphere formation was seen under combinatorial treatment in all investigated NSCLC cell lines. In conclusion, METF in combination with SAL could be a promising treatment option for patients with advanced NSCLC irrespective of their EGFR, KRAS, EML4/ALK and LKB1 status. PMID:25375092

  4. Metformin and salinomycin as the best combination for the eradication of NSCLC monolayer cells and their alveospheres (cancer stem cells) irrespective of EGFR, KRAS, EML4/ALK and LKB1 status.

    PubMed

    Xiao, Zhiguang; Sperl, Bianca; Ullrich, Axel; Knyazev, Pjotr

    2014-12-30

    The presence of cancer stem cells (CSCs) is linked to preexisting or acquired drug resistance and tumor relapse. Therefore, targeting both differentiated tumor cells and CSCs was suggested as an effective approach for non-small cell lung cancer (NSCLC) treatment. After screening of chemotherapeutic agents, tyrosine kinase inhibitors (TKIs) or monoclonal antibody in combination with the putative stem cell killer Salinomycin (SAL), we found Metformin (METF), which modestly exerted a growth inhibitory effect on monolayer cells and alveospheres/CSCs of 5 NSCLC cell lines regardless of their EGFR, KRAS, EML4/ALK and LKB1 status, interacted synergistically with SAL to effectively promote cell death. Inhibition of EGFR (AKT, ERK1/2) and mTOR (p70 s6k) signaling with the combination of METF and SAL can be augmented beyond that achieved using each agent individually. Phospho-kinase assay further suggested the multiple roles of this combination in reducing oncogenic effects of modules, such as ß-catenin, Src family kinases (Src, Lyn, Yes), Chk-2 and FAK. Remarkably, significant reduction of sphere formation was seen under combinatorial treatment in all investigated NSCLC cell lines. In conclusion, METF in combination with SAL could be a promising treatment option for patients with advanced NSCLC irrespective of their EGFR, KRAS, EML4/ALK and LKB1 status. PMID:25375092

  5. FAA/NASA International Symposium on Advanced Structural Integrity Methods for Airframe Durability and Damage Tolerance

    NASA Technical Reports Server (NTRS)

    Harris, Charles E. (Editor)

    1994-01-01

    International technical experts in durability and damage tolerance of metallic airframe structures were assembled to present and discuss recent research findings and the development of advanced design and analysis methods, structural concepts, and advanced materials. The symposium focused on the dissemination of new knowledge and the peer-review of progress on the development of advanced methodologies. Papers were presented on: structural concepts for enhanced durability, damage tolerance, and maintainability; new metallic alloys and processing technology; fatigue crack initiation and small crack effects; fatigue crack growth models; fracture mechanics failure, criteria for ductile materials; structural mechanics methodology for residual strength and life prediction; development of flight load spectra for design and testing; and advanced approaches to resist corrosion and environmentally assisted fatigue.

  6. HBP1 promoter methylation augments the oncogenic β-catenin to correlate with prognosis in NSCLC

    PubMed Central

    Tseng, Ruo-Chia; Huang, Way-Ren; Lin, Su-Feng; Wu, Pei-Chen; Hsu, Han-Shui; Wang, Yi-Ching

    2014-01-01

    β-catenin nuclear accumulation is frequently identified in human non-small cell lung cancer (NSCLC). The HMG-box transcription factor 1 (HBP1) is a known repressor of β-catenin transactivation. However, the role of HBP1 in relation to β-catenin nuclear accumulation has not been addressed in human cancer patients. In addition, the mechanism of HBP1 gene alteration in NSCLC remains unclear, although HBP1 mutation and gene deletion of HBP1 are reported in breast and colon cancers. Here, we demonstrate that HBP1 acts as a tumour suppressor and serves as a prognostic biomarker in NSCLC clinical and cell models. The immunohistochemistry data indicated that 30.5% (25/82) of tumours from NSCLC patients showed absence or low expression of HBP1 protein. A significant inverse correlation between mRNA/protein expression and promoter hypermethylation suggested that promoter hypermethylation is responsible for low expression of HBP1 in NSCLC patients. Reactivation of HBP1 expression by demethylation reagent or ectopic expression of HBP1 suppressed β-catenin transactivation. Conversely, HBP1 knockdown increased β-catenin transactivation. Importantly, preserved expression of HBP1 had a significantly protective effect on prognosis in patients with β-catenin nuclear accumulation, suggesting that low expression of HBP1 in NSCLC patients with β-catenin nuclear accumulation was one of the major determinants of prognosis. Our data from cellular and clinical models suggest that HBP1 is a suppressor of cancer progression, making it a potential prognostic predictor and therapeutic target to attenuate lung cancer progression. PMID:24895061

  7. Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

    SciTech Connect

    Jin, Hyeon-Ok; Hong, Sung-Eun; Kim, Chang Soon; Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora; Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun; Park, In-Chul; Lee, Jin Kyung

    2015-08-15

    Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H + ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. - Highlights: • Co-treatment with EGFR TKIs and vATPase inhibitors induces synergistic cell death • EGFR TKIs enhance cell sensitivity to vATPase inhibitors via Hif-1α downregulation • Co-treatment of these inhibitors is potentially effective for the treatment of NSCLC.

  8. The mechanism involved in the loss of PTEN expression in NSCLC tumor cells

    SciTech Connect

    Li, Gang; Zhao, Jingfeng; Peng, Xianjing; Liang, Jian; Deng, Xin; Chen, Yuxiang

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Radiation stimulates PTEN reexpression in NSCLC independent of p53 activation. Black-Right-Pointing-Pointer PTEN reexpression is mediated by miR-29b overexpression. Black-Right-Pointing-Pointer miR-29b regulates Dnmts expression in NSCLC tumor cells. Black-Right-Pointing-Pointer Target therapy could be established by overexpressing miR-29b expression. -- Abstract: Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.

  9. DIAGNOSTIC EVALUATION OF AIR QUALITY MODELS USING ADVANCED METHODS WITH SPECIALIZED OBSERVATIONS OF SELECTED AMBIENT SPECIES -PART II

    EPA Science Inventory

    This is Part 2 of "Diagnostic Evaluation of Air Quality Models Using Advanced Methods with Specialized Observations of Selected Ambient Species". A limited field campaign to make specialized observations of selected ambient species using advanced and innovative instrumentation f...

  10. Oral vinorelbine: a feasible and safe partner for radiotherapy in the treatment of locally advanced non-small cell lung cancer

    PubMed Central

    Perri, Francesco; Lazzari, Grazia; Della Vittoria Scarpati, Giuseppina; Silvano, Giovanni

    2016-01-01

    Background Concurrent chemoradiotherapy (CCRT) using cisplatin-based doublets represents the standard of care for locally advanced non-small cell lung cancer (NSCLC), having shown good efficacy and activity in clinical trials. Locally advanced NSCLC occurs frequently in the elderly population, which is often excluded by platinum-based CCRT administration, due to severe associated toxicities. This limitation has been overcome using new-generation drugs such as gemcitabine, docetaxel, paclitaxel, and vinorelbine, which have shown not only to be efficacious but also to have a favorable toxicity spectrum, both in association with cisplatin and as single agents. Vinorelbine is a vinca alkaloid that binds to tubulin, thus inhibiting mitotic microtubule polymerization. Previous studies have clearly demonstrated that vinorelbine acts as a radiosensitizing agent when administered intravenously or orally. Moreover, oral administration of vinorelbine has shown a good clinical safety profile in both elderly and younger patients. Methods A comprehensive review of the literature data regarding use of oral vinorelbine concurrently with radiotherapy in NSCLC was done. Conclusion Single-agent oral vinorelbine may represent an effective therapy option for elderly patients with locally advanced lung cancer. This review has described the use of oral vinorelbine both as a monochemotherapy and in combination with cisplatin in the context of CCRT. PMID:27143931

  11. Matrine promotes the efficacy and safety of platinum-based doublet chemotherapy for advanced non-small cell lung cancer

    PubMed Central

    Rong, Biaoxue; Zhao, Chongchong; Gao, Wenlong; Yang, Shuanying

    2015-01-01

    Purpose: Many studies have investigated the efficacy of matrine combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is an analytic value of available evidence. Methods: twenty-two studies reporting matrine combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. Results: The overall response rate (ORR) and disease control rate (DCR) of matrine combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 15.1% and 19.7% improvement, respectively (P < 0.00001). In addition, the mean survival time (MST) and quality of life (QOL) were improved after the treatment of matrine combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, nausea and vomiting. Matrine combined with PBDC had a lower incidence of adverse reactions compared with PBDC alone (P < 0.05). Conclusions: Matrine combined with PBDC was associated with higher RR, DCR, and MST as well as superior QOL profiles compared with PBDC alone. Matrine combined with PBDC decrease the incidence of adverse reactions compared with PBDC alone. PMID:26628952

  12. Assessment of cytology based molecular analysis to guide targeted therapy in advanced non-small-cell lung cancer

    PubMed Central

    Guo, Lei; Qiu, Tian; Ling, Yun; Cao, Jian; Guo, Huiqin; Zhao, Huan; Li, Lin; Ying, Jianming

    2016-01-01

    To investigate the use of molecular testing on cytological specimens in selecting advanced non-small cell lung cancer (NSCLC) patients who are adequate for targeted treatment, a total of 137 NSCLC cases were analyzed by fluorescence in situ hybridization (FISH) for anaplastic lymphoma kinase (ALK) rearrangements, and Epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were evaluated by quantitative real-time PCR (qRT-PCR) platform combining amplification refractory mutation system (ARMS) primers and TaqMan probes. Cytological specimens included 91 fine-needle aspirates, 5 fibreoptic bronchoscopic derived samples and 41 pleural effusions. Among 137 NSCLCs analyzed for ALK FISH, 16 (11.7%, of 137) were detected to harbor ALK rearrangement. FISH positive cases were all defined as adenocarcinoma (ADC) histologic subtype and the FNA samples showed the highest ALK positive rate (13.2%, 12/91). Of the 9 ALK FISH positive patients who received crizotinib treatment, 8 (88.9%) patients exhibited tumor regression. In addition, 60 (44.8%, of 134) cases were found to harbor EGFR mutations and 22 patients with EGFR sensitive mutations who received gefitinib or erlotinib treatment showed a median PFS of 16.0 months. Mutations of KRAS occurred in 8 (6.0%, of 134) cases and this was mutually exclusive from EGFR mutation. Our results demonstrated that ALK FISH and EGFR, KRAS mutational analysis on cytological specimens are sensitive methods for screening advanced stage NSCLC patients who are adequate for targeted treatment. PMID:26789109

  13. Human-System Safety Methods for Development of Advanced Air Traffic Management Systems

    SciTech Connect

    Nelson, W.R.

    1999-05-24

    The Idaho National Engineering and Environmental Laboratory (INEEL) is supporting the National Aeronautics and Space Administration in the development of advanced air traffic management (ATM) systems as part of the Advanced Air Transportation Technologies program. As part of this program INEEL conducted a survey of human-system safety methods that have been applied to complex technical systems, to identify lessons learned from these applications and provide recommendations for the development of advanced ATM systems. The domains that were surveyed included offshore oil and gas, commercial nuclear power, commercial aviation, and military. The survey showed that widely different approaches are used in these industries, and that the methods used range from very high-level, qualitative approaches to very detailed quantitative methods such as human reliability analysis (HRA) and probabilistic safety assessment (PSA). In addition, the industries varied widely in how effectively they incorporate human-system safety assessment in the design, development, and testing of complex technical systems. In spite of the lack of uniformity in the approaches and methods used, it was found that methods are available that can be combined and adapted to support the development of advanced air traffic management systems.

  14. Some advanced parametric methods for assessing waveform distortion in a smart grid with renewable generation

    NASA Astrophysics Data System (ADS)

    Alfieri, Luisa

    2015-12-01

    Power quality (PQ) disturbances are becoming an important issue in smart grids (SGs) due to the significant economic consequences that they can generate on sensible loads. However, SGs include several distributed energy resources (DERs) that can be interconnected to the grid with static converters, which lead to a reduction of the PQ levels. Among DERs, wind turbines and photovoltaic systems are expected to be used extensively due to the forecasted reduction in investment costs and other economic incentives. These systems can introduce significant time-varying voltage and current waveform distortions that require advanced spectral analysis methods to be used. This paper provides an application of advanced parametric methods for assessing waveform distortions in SGs with dispersed generation. In particular, the Standard International Electrotechnical Committee (IEC) method, some parametric methods (such as Prony and Estimation of Signal Parameters by Rotational Invariance Technique (ESPRIT)), and some hybrid methods are critically compared on the basis of their accuracy and the computational effort required.

  15. Development of Advanced Methods of Structural and Trajectory Analysis for Transport Aircraft

    NASA Technical Reports Server (NTRS)

    Ardema, Mark D.

    1996-01-01

    In this report the author describes: (1) development of advanced methods of structural weight estimation, and (2) development of advanced methods of flight path optimization. A method of estimating the load-bearing fuselage weight and wing weight of transport aircraft based on fundamental structural principles has been developed. This method of weight estimation represents a compromise between the rapid assessment of component weight using empirical methods based on actual weights of existing aircraft and detailed, but time-consuming, analysis using the finite element method. The method was applied to eight existing subsonic transports for validation and correlation. Integration of the resulting computer program, PDCYL, has been made into the weights-calculating module of the AirCraft SYNThesis (ACSYNT) computer program. ACSYNT bas traditionally used only empirical weight estimation methods; PDCYL adds to ACSYNT a rapid, accurate means of assessing the fuselage and wing weights of unconventional aircraft. PDCYL also allows flexibility in the choice of structural concept, as well as a direct means of determining the impact of advanced materials on structural weight.

  16. Treatment and prognosis after progression in long-term responders to EGFR-tyrosine kinase inhibitor in advanced non-small cell lung cancer

    PubMed Central

    Song, Zhengbo

    2016-01-01

    Introduction The aim of this study was to investigate the treatment and prognosis of advanced non-small cell lung cancer (NSCLC) patients after failure of long-term treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Material and methods We retrospectively analyzed all NSCLC patients with EGFR-TKI (gefitinib or erlotinib) treatment at our institution between 2011 and 2013 who progressed after at least stable disease on erlotinib or gefitinib for more than 6 months. Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. Results In total, 521 patients were administered EGFR-TKI. Of these, 298 patients received EGFR-TKI with progression-free survival less than 6 months (group A), and the other 223 patients more than 6 months (group B). There was a significant difference in overall survival (OS) between group A and group B (7.2 months vs. 5.0 months, p < 0.0001). The median OS for group B patients was 5.0 months. Among the 223 patients in group B, 38 patients received chemotherapy with continued EGFR-TKI after failure of prior gefitinib or erlotinib treatment, 92 with chemotherapy alone and 93 with best supportive care. Patients who continued gefitinib or erlotinib had a significantly longer OS (median: 7.5 months), followed by chemotherapy (5.5 months) and best supportive care (4.0 months) (p < 0.001). Conclusions The prognosis of advanced NSCLC patients after failure of long-term treatment with EGFR-TKI was poor. Chemotherapy with continued EGFR-TKI beyond progression of long-term responders was feasible and led to prolonged OS in advanced NSCLC patients. PMID:26925125

  17. Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Dosimetric Study

    PubMed Central

    Kesarwala, Aparna H.; Ko, Christine J.; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E.; O’Meara, William P.; Simone, Charles B.; Rengan, Ramesh

    2015-01-01

    Background Photon involved-field radiation therapy (IFRT), the standard for locally advanced non-small cell lung cancer (LA-NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Given the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Materials and Methods IMPT IFRT plans were generated to the same total dose of 66.6–72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 CGE to elective nodal (EN) planning treatment volumes (PTV) plus 24 CGE to involved field (IF)-PTVs. Results Proton IFRT and ENI both improved D95 involved field (IF)-PTV coverage by 4% (p<0.01) compared to photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. Lung V20 and mean lung dose decreased 18% (p<0.01) and 36% (p<0.01), respectively, with proton IFRT and 11% (p=0.03) and 26% (p<0.01) with ENI. Mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all p<0.01). Conclusions This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates IMPT could allow ENI while maintaining a favorable therapeutic ratio compared to photon IFRT. PMID:25604729

  18. NOVEL CONCEPTS, METHODS AND ADVANCED TECHNOLOGY IN PARTICULATE/GAS SEPARATION

    EPA Science Inventory

    This paper discusses presentations made during a symposium on novel concepts, methods, and advanced technology in particulate/gas separation. The symposium, held at the University of Notre Dame and sponsored by the National Science Foundation and the Environmental Protection Agen...

  19. A Mixed Methods Approach to Examining an Advanced Placement Program in One Connecticut Public School District

    ERIC Educational Resources Information Center

    Docimo, Chelsey L.

    2013-01-01

    The purpose of this eleventh grade Advanced Placement (AP) program study was to determine factors associated with AP placement and subsequent student performance. This research was considered to be a mixed methods case study with elements of arrested action research. One hundred and twenty-four students, four guidance counselors, three AP…

  20. Advances in methods and algorithms in a modern quantum chemistry program package.

    PubMed

    Shao, Yihan; Molnar, Laszlo Fusti; Jung, Yousung; Kussmann, Jörg; Ochsenfeld, Christian; Brown, Shawn T; Gilbert, Andrew T B; Slipchenko, Lyudmila V; Levchenko, Sergey V; O'Neill, Darragh P; DiStasio, Robert A; Lochan, Rohini C; Wang, Tao; Beran, Gregory J O; Besley, Nicholas A; Herbert, John M; Lin, Ching Yeh; Van Voorhis, Troy; Chien, Siu Hung; Sodt, Alex; Steele, Ryan P; Rassolov, Vitaly A; Maslen, Paul E; Korambath, Prakashan P; Adamson, Ross D; Austin, Brian; Baker, Jon; Byrd, Edward F C; Dachsel, Holger; Doerksen, Robert J; Dreuw, Andreas; Dunietz, Barry D; Dutoi, Anthony D; Furlani, Thomas R; Gwaltney, Steven R; Heyden, Andreas; Hirata, So; Hsu, Chao-Ping; Kedziora, Gary; Khalliulin, Rustam Z; Klunzinger, Phil; Lee, Aaron M; Lee, Michael S; Liang, Wanzhen; Lotan, Itay; Nair, Nikhil; Peters, Baron; Proynov, Emil I; Pieniazek, Piotr A; Rhee, Young Min; Ritchie, Jim; Rosta, Edina; Sherrill, C David; Simmonett, Andrew C; Subotnik, Joseph E; Woodcock, H Lee; Zhang, Weimin; Bell, Alexis T; Chakraborty, Arup K; Chipman, Daniel M; Keil, Frerich J; Warshel, Arieh; Hehre, Warren J; Schaefer, Henry F; Kong, Jing; Krylov, Anna I; Gill, Peter M W; Head-Gordon, Martin

    2006-07-21

    Advances in theory and algorithms for electronic structure calculations must be incorporated into program packages to enable them to become routinely used by the broader chemical community. This work reviews advances made over the past five years or so that constitute the major improvements contained in a new release of the Q-Chem quantum chemistry package, together with illustrative timings and applications. Specific developments discussed include fast methods for density functional theory calculations, linear scaling evaluation of energies, NMR chemical shifts and electric properties, fast auxiliary basis function methods for correlated energies and gradients, equation-of-motion coupled cluster methods for ground and excited states, geminal wavefunctions, embedding methods and techniques for exploring potential energy surfaces. PMID:16902710

  1. Advances in explosives analysis—part I. animal, chemical, ion, and mechanical methods

    DOE PAGESBeta

    Brown, Kathryn E.; Greenfield, Margo T.; McGrane, Shawn D.; Moore, David S.

    2015-10-13

    The number and capability of explosives detection and analysis methods have increased substantially since the publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis (Moore and Goodpaster, Anal Bioanal Chem 395(2):245–246, 2009). We review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. The review consists of two parts. Moreover, Part I, reviews methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers,more » electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. Part II will review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons.« less

  2. Advances in explosives analysis—part I. animal, chemical, ion, and mechanical methods

    SciTech Connect

    Brown, Kathryn E.; Greenfield, Margo T.; McGrane, Shawn D.; Moore, David S.

    2015-10-13

    The number and capability of explosives detection and analysis methods have increased substantially since the publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis (Moore and Goodpaster, Anal Bioanal Chem 395(2):245–246, 2009). We review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. The review consists of two parts. Moreover, Part I, reviews methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers, electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. Part II will review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons.

  3. Advances in explosives analysis—part II: photon and neutron methods

    DOE PAGESBeta

    Brown, Kathryn E.; Greenfield, Margo T.; McGrane, Shawn D.; Moore, David S.

    2015-10-07

    The number and capability of explosives detection and analysis methods have increased dramatically since publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis [Moore DS, Goodpaster JV, Anal Bioanal Chem 395:245–246, 2009]. Here we review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. Our review consists of two parts. Part I discussed methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers,more » electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. In Part II, we review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons.« less

  4. Advances in explosives analysis--part I: animal, chemical, ion, and mechanical methods.

    PubMed

    Brown, Kathryn E; Greenfield, Margo T; McGrane, Shawn D; Moore, David S

    2016-01-01

    The number and capability of explosives detection and analysis methods have increased substantially since the publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis (Moore and Goodpaster, Anal Bioanal Chem 395(2):245-246, 2009). Here we review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. The review consists of two parts. This part, Part I, reviews methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers, electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. Part II will review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons. PMID:26462922

  5. Advances in explosives analysis--part II: photon and neutron methods.

    PubMed

    Brown, Kathryn E; Greenfield, Margo T; McGrane, Shawn D; Moore, David S

    2016-01-01

    The number and capability of explosives detection and analysis methods have increased dramatically since publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis [Moore DS, Goodpaster JV, Anal Bioanal Chem 395:245-246, 2009]. Here we review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. The review consists of two parts. Part I discussed methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers, electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. This part, Part II, will review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons. PMID:26446898

  6. Domain Decomposition By the Advancing-Partition Method for Parallel Unstructured Grid Generation

    NASA Technical Reports Server (NTRS)

    Pirzadeh, Shahyar Z.; Zagaris, George

    2009-01-01

    A new method of domain decomposition has been developed for generating unstructured grids in subdomains either sequentially or using multiple computers in parallel. Domain decomposition is a crucial and challenging step for parallel grid generation. Prior methods are generally based on auxiliary, complex, and computationally intensive operations for defining partition interfaces and usually produce grids of lower quality than those generated in single domains. The new technique, referred to as "Advancing Partition," is based on the Advancing-Front method, which partitions a domain as part of the volume mesh generation in a consistent and "natural" way. The benefits of this approach are: 1) the process of domain decomposition is highly automated, 2) partitioning of domain does not compromise the quality of the generated grids, and 3) the computational overhead for domain decomposition is minimal. The new method has been implemented in NASA's unstructured grid generation code VGRID.

  7. Advances in explosives analysis—part II: photon and neutron methods

    SciTech Connect

    Brown, Kathryn E.; Greenfield, Margo T.; McGrane, Shawn D.; Moore, David S.

    2015-10-07

    The number and capability of explosives detection and analysis methods have increased dramatically since publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis [Moore DS, Goodpaster JV, Anal Bioanal Chem 395:245–246, 2009]. Here we review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. Our review consists of two parts. Part I discussed methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers, electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. In Part II, we review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons.

  8. Launch Vehicle Design and Optimization Methods and Priority for the Advanced Engineering Environment

    NASA Technical Reports Server (NTRS)

    Rowell, Lawrence F.; Korte, John J.

    2003-01-01

    NASA's Advanced Engineering Environment (AEE) is a research and development program that will improve collaboration among design engineers for launch vehicle conceptual design and provide the infrastructure (methods and framework) necessary to enable that environment. In this paper, three major technical challenges facing the AEE program are identified, and three specific design problems are selected to demonstrate how advanced methods can improve current design activities. References are made to studies that demonstrate these design problems and methods, and these studies will provide the detailed information and check cases to support incorporation of these methods into the AEE. This paper provides background and terminology for discussing the launch vehicle conceptual design problem so that the diverse AEE user community can participate in prioritizing the AEE development effort.

  9. XPC inhibits NSCLC cell proliferation and migration by enhancing E-Cadherin expression

    PubMed Central

    Cui, Tiantian; Srivastava, Amit Kumar; Han, Chunhua; Yang, Linlin; Zhao, Ran; Zou, Ning; Qu, Meihua; Duan, Wenrui; Zhang, Xiaoli; Wang, Qi-En

    2015-01-01

    Xeroderma pigmentosum complementation group C (XPC) protein is an important DNA damage recognition factor in nucleotide excision repair. Deletion of XPC is associated with early stages of human lung carcinogenesis, and reduced XPC mRNA levels predict poor patient outcome for non-small cell lung cancer (NSCLC). However, the mechanisms linking loss of XPC expression and poor prognosis in lung cancer are still unclear. Here, we report evidence that XPC silencing drives proliferation and migration of NSCLC cells by down-regulating E-Cadherin. XPC knockdown enhanced proliferation and migration while decreasing E-Cadherin expression in NSCLC cells with an epithelial phenotype. Restoration of E-Cadherin in these cells suppressed XPC knockdown-induced cell growth both in vitro and in vivo. Mechanistic studies showed that the loss of XPC repressed E-Cadherin expression by activating the ERK pathway and upregulating Snail expression. Our findings indicate that XPC silencing-induced reduction of E-Cadherin expression contributes, at least in part, to the poor outcome of NSCLC patients with low XPC expression. PMID:25871391

  10. Tracheo-parenchymal fistula following concurrent chemo-radiation for stage III NSCLC.

    PubMed

    Alzghoul, Bashar; Meena, Nikhil

    2016-01-01

    Non-Small Cell Cancer (NSCLC) are frequently diagnosed at a later stage [1]. Treatment involves chemotherapy and radiation, either sequentially or concurrently [2]. Concurrent therapy is more efficacious but also associated with more complications [4-6]. We present a rare care of trachea-pulmonary fistula formation after concurrent chemo and radiation in a patient with Squamous Cell Cancer (SCC). PMID:27144112

  11. Advances in the theory and practice of DNA-hybridization as a systematic method.

    PubMed

    Sheldon, F H

    1994-01-01

    DNA hybridization continues in the 1990s to provide insight into phylogeny and evolution. The resilience of this 30-year-old distance technique may be attributed to its fundamental power as a comparative method, as well as to advances in our understanding of its operation and improvements in experimental design and data analysis. These attributes and advances, along with the assumptions and limitations of DNA hybridization, are discussed in this paper. Examples are provided of recent DNA hybridization studies of molecular, morphological, and behavioral systematics and evolution. PMID:7994110

  12. Recent Advances in the Method of Forces: Integrated Force Method of Structural Analysis

    NASA Technical Reports Server (NTRS)

    Patnaik, Surya N.; Coroneos, Rula M.; Hopkins, Dale A.

    1998-01-01

    Stress that can be induced in an elastic continuum can be determined directly through the simultaneous application of the equilibrium equations and the compatibility conditions. In the literature, this direct stress formulation is referred to as the integrated force method. This method, which uses forces as the primary unknowns, complements the popular equilibrium-based stiffness method, which considers displacements as the unknowns. The integrated force method produces accurate stress, displacement, and frequency results even for modest finite element models. This version of the force method should be developed as an alternative to the stiffness method because the latter method, which has been researched for the past several decades, may have entered its developmental plateau. Stress plays a primary role in the development of aerospace and other products, and its analysis is difficult. Therefore, it is advisable to use both methods to calculate stress and eliminate errors through comparison. This paper examines the role of the integrated force method in analysis, animation and design.

  13. Pemetrexed for advanced stage nonsquamous non-small cell lung cancer: latest evidence about its extended use and outcomes

    PubMed Central

    Tomasini, Pascale; Barlesi, Fabrice; Mascaux, Celine; Greillier, Laurent

    2016-01-01

    Non-small cell lung cancer (NSCLC) is still the leading cause of cancer-related death, and the treatment of advanced NSCLC relies on systemic treatments. During the last decade, pemetrexed, an antifolate agent, gradually became a key component of the treatment for patients with advanced nonsquamous NSCLC. It has indeed been shown to be efficient for first-line, maintenance and second- or third-line treatment in this subgroup of NSCLC. Moreover, it is usually well tolerated, with few grade 3 and 4 toxicities. Several studies have tried to identify predictive biomarkers of pemetrexed efficacy. Due to pemetrexed’s mechanism of action, thymidilate synthase expression predictive value was investigated but could not be demonstrated. Currently, more than 400 trials of pemetrexed for the treatment of nonsquamous NSCLC are ongoing. PMID:27239238

  14. Technology Alignment and Portfolio Prioritization (TAPP): Advanced Methods in Strategic Analysis, Technology Forecasting and Long Term Planning for Human Exploration and Operations, Advanced Exploration Systems and Advanced Concepts

    NASA Technical Reports Server (NTRS)

    Funaro, Gregory V.; Alexander, Reginald A.

    2015-01-01

    The Advanced Concepts Office (ACO) at NASA, Marshall Space Flight Center is expanding its current technology assessment methodologies. ACO is developing a framework called TAPP that uses a variety of methods, such as association mining and rule learning from data mining, structure development using a Technological Innovation System (TIS), and social network modeling to measure structural relationships. The role of ACO is to 1) produce a broad spectrum of ideas and alternatives for a variety of NASA's missions, 2) determine mission architecture feasibility and appropriateness to NASA's strategic plans, and 3) define a project in enough detail to establish an initial baseline capable of meeting mission objectives ACO's role supports the decision­-making process associated with the maturation of concepts for traveling through, living in, and understanding space. ACO performs concept studies and technology assessments to determine the degree of alignment between mission objectives and new technologies. The first step in technology assessment is to identify the current technology maturity in terms of a technology readiness level (TRL). The second step is to determine the difficulty associated with advancing a technology from one state to the next state. NASA has used TRLs since 1970 and ACO formalized them in 1995. The DoD, ESA, Oil & Gas, and DoE have adopted TRLs as a means to assess technology maturity. However, "with the emergence of more complex systems and system of systems, it has been increasingly recognized that TRL assessments have limitations, especially when considering [the] integration of complex systems." When performing the second step in a technology assessment, NASA requires that an Advancement Degree of Difficulty (AD2) method be utilized. NASA has used and developed or used a variety of methods to perform this step: Expert Opinion or Delphi Approach, Value Engineering or Value Stream, Analytical Hierarchy Process (AHP), Technique for the Order of

  15. Advanced fire-resistant forms of activated carbon and methods of adsorbing and separating gases using same

    DOEpatents

    Xiong, Yongliang; Wang, Yifeng

    2016-04-19

    A method of removing a target gas from a gas stream is disclosed. The method uses advanced, fire-resistant activated carbon compositions having vastly improved fire resistance. Methods for synthesizing the compositions are also provided. The advanced compositions have high gas adsorption capacities and rapid adsorption kinetics (comparable to commercially-available activated carbon), without having any intrinsic fire hazard.

  16. Study on the Integrated Geophysic Methods and Application of Advanced Geological Detection for Complicated Tunnel

    NASA Astrophysics Data System (ADS)

    Zhou, L.; Xiao, G.

    2014-12-01

    The engineering geological and hydrological conditions of current tunnels are more and more complicated, as the tunnels are elongated with deeper depth. In constructing these complicated tunnels, geological hazards prone to occur as induced by unfavorable geological bodies, such as fault zones, karst or hydrous structures, etc. The working emphasis and difficulty of the advanced geological exploration for complicated tunnels are mainly focused on the structure and water content of these unfavorable geological bodies. The technical aspects of my paper systematically studied the advanced geological exploration theory and application aspects for complicated tunnels, with discussion on the key technical points and useful conclusions. For the all-aroundness and accuracy of advanced geological exploration results, the objective of my paper is targeted on the comprehensive examination on the structure and hydrous characteristic of the unfavorable geological bodies in complicated tunnels. By the multi-component seismic modeling on a more real model containing the air medium, the wave field response characteristics of unfavorable geological bodies can be analyzed, thus providing theoretical foundation for the observation system layout, signal processing and interpretation of seismic methods. Based on the tomographic imaging theory of seismic and electromagnetic method, 2D integrated seismic and electromagnetic tomographic imaging and visualization software was designed and applied in the advanced drilling hole in the tunnel face, after validation of the forward and inverse modeling results on theoretical models. The transmission wave imaging technology introduced in my paper can be served as a new criterion for detection of unfavorable geological bodies. After careful study on the basic theory, data processing and interpretation, practical applications of TSP and ground penetrating radar (GPR) method, as well as serious examination on their application examples, my paper

  17. Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells.

    PubMed

    Jin, Hyeon-Ok; Hong, Sung-Eun; Kim, Chang Soon; Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora; Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun; Park, In-Chul; Lee, Jin Kyung

    2015-08-15

    Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H+ ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. PMID:25981168

  18. Dendritic cell vaccine and cytokine-induced killer cell therapy for the treatment of advanced non-small cell lung cancer

    PubMed Central

    ZHANG, LIHONG; YANG, XUEJING; SUN, ZHEN; LI, JIALI; ZHU, HUI; LI, JING; PANG, YAN

    2016-01-01

    The present study aimed to evaluate the survival time, immune response and safety of a dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy (DC-CIK) in advanced non-small cell lung cancer (NSCLC). The present retrospective study enrolled 507 patients with advanced NSCLC; 99 patients received DC-CIK [immunotherapy group (group I)] and 408 matched patients did not receive DC-CIK, and acted as the control [non-immunotherapy group (group NI)]. Delayed-type hypersensitivity (DTH), quality of life (QOL) and safety were analyzed in group I. The follow-up period for the two groups was 489.2±160.4 days. The overall survival (OS) time was calculated using the Kaplan-Meier method. DTH was observed in 59 out of 97 evaluated patients (60.8%) and 67 out of 98 evaluated patients (68.4%) possessed an improved QOL. Fever and a skin rash occurred in 36 out of 98 patients (36.7%) and 7 out of 98 patients (7.1%) in group I. DTH occurred more frequently in patients with squamous cell carcinoma compared with patients with adenocarcinoma (77.1 vs. 40.4%; P=0.0013). Radiotherapy was not associated with DC-CIK-induced DTH (72.7 vs. 79.6%; P=0.18), but chemotherapy significantly reduced the rate of DTH (18.2 vs. 79.6%; P=0.00). The OS time was significantly increased in group I compared with group NI (P=0.03). In conclusion, DC-CIK may induce an immune response against NSCLC, improve the QOL, and prolong the OS time of patients, without adverse effects. Therefore, the present study recommends DC-CIK for the treatment of patients with advanced NSCLC. PMID:27073525

  19. Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

    PubMed Central

    Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

    2016-01-01

    Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve

  20. Analysis of the characteristics and prognosis of advanced non-small-cell lung cancer in older patients

    PubMed Central

    Gao, Ying; Gao, Fei; Ma, Jin-lu; Zhang, Xiao-zhi; Li, Yi; Song, Li-ping; Zhao, Dong-li

    2015-01-01

    Objective Lung cancer is still the leading cause of cancer-related deaths worldwide. However, most elderly patients with advanced non-small-cell lung cancer (NSCLC) have been undertreated and the outcome related to age is controversial. A retrospective analysis was conducted for advanced NSCLC in order to investigate the characteristics and prognosis of older patients. Methods Medical records were collected from 165 patients with NSCLC (stages IIIA–IIIB) who had been treated with concurrent chemoradiotherapy (CRT) or radiotherapy from January 2009 to January 2011. The cases were divided into two age groups 1) patients ≥70 years old; 2) patients <70 years old. There were 73 patients in group I, 92 in group II. Patient characteristics, treatment toxicities, and prognosis were evaluated. Results Of the 165 patients analyzed, 34 patients (34/73) in group I received concurrent CRT while 47 (47/92) in group II completed that treatment. No significant difference was observed in the reason for patients who discontinued CRT in two groups (P>0.05). In the patients with adenocarcinoma, more cases were found in group II than that in group I; the more squamous cell carcinoma and the more smokers with squamous cell carcinoma were seen in older group (P<0.05). With a median follow-up of 20.5 months, the 1-year survival for group I and II were 49.3% and 40.2% respectively (P=0.243). Two-year survival for the two groups was 20.5% and 16.3% (P=0.483); 3-year survival was 9.6% and 9.8% (P=0.967). There was no significant difference between two groups statistically in survival by univariate analysis (P>0.05). The therapy-related toxicities in group I seem to be similar to the group II (P>0.05). Conclusion More adenocarcinoma patients were found in youthful lung cancer and the more smokers with squamous cell carcinoma were seen in older group. Age is not the important factor for the selection and allocation of treatment in advanced NSCLC. The same prognosis and toxicities had been

  1. MET Gene Copy Number Predicts Worse Overall Survival in Patients with Non-Small Cell Lung Cancer (NSCLC); A Systematic Review and Meta-Analysis

    PubMed Central

    Dimou, Anastasios; Non, Lemuel; Chae, Young Kwang; Tester, William J.; Syrigos, Konstantinos N.

    2014-01-01

    Objectives MET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC. Methods Two independent investigators applied parallel search strategies with the terms “MET AND lung cancer”, “MET AND NSCLC”, “MET gene copy number AND prognosis” in PubMed through January 2014. We selected the studies that investigated the association of MET gene copy number with survival, in patients who received surgery. Results Among 1096 titles that were identified in the initial search, we retrieved 9 studies on retrospective cohorts with adequate retrievable data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Out of those, 6 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. We calculated the I2 statistic to assess heterogeneity (I2 = 72%). MET gene copy number predicted worse overall survival when all studies were combined in a random effects model (HR = 1.78, 95% CI 1.22–2.60). When only the studies that had at least 50% of adenocarcinoma patients in their populations were included, the effect was significant (five studies, HR 1.55, 95% CI 1.23–1.94). This was not true when we included only the studies with no more than 50% of the patients having adenocarcinoma histology (four studies HR 2.18, 95% CI 0.97–4.90). Conclusions Higher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC. This prognostic impact may be adenocarcinoma histology specific. PMID:25232729

  2. Advanced Guidance and Control Methods for Reusable Launch Vehicles: Test Results

    NASA Technical Reports Server (NTRS)

    Hanson, John M.; Jones, Robert E.; Krupp, Don R.; Fogle, Frank R. (Technical Monitor)

    2002-01-01

    There are a number of approaches to advanced guidance and control (AG&C) that have the potential for achieving the goals of significantly increasing reusable launch vehicle (RLV) safety/reliability and reducing the cost. In this paper, we examine some of these methods and compare the results. We briefly introduce the various methods under test, list the test cases used to demonstrate that the desired results are achieved, show an automated test scoring method that greatly reduces the evaluation effort required, and display results of the tests. Results are shown for the algorithms that have entered testing so far.

  3. Left Ventricular Flow Analysis: Recent Advances in Numerical Methods and Applications in Cardiac Ultrasound

    PubMed Central

    Borazjani, Iman; Westerdale, John; McMahon, Eileen M.; Rajaraman, Prathish K.; Heys, Jeffrey J.

    2013-01-01

    The left ventricle (LV) pumps oxygenated blood from the lungs to the rest of the body through systemic circulation. The efficiency of such a pumping function is dependent on blood flow within the LV chamber. It is therefore crucial to accurately characterize LV hemodynamics. Improved understanding of LV hemodynamics is expected to provide important clinical diagnostic and prognostic information. We review the recent advances in numerical and experimental methods for characterizing LV flows and focus on analysis of intraventricular flow fields by echocardiographic particle image velocimetry (echo-PIV), due to its potential for broad and practical utility. Future research directions to advance patient-specific LV simulations include development of methods capable of resolving heart valves, higher temporal resolution, automated generation of three-dimensional (3D) geometry, and incorporating actual flow measurements into the numerical solution of the 3D cardiovascular fluid dynamics. PMID:23690874

  4. Outcome of active anti-cancer treatment in elderly patients with advanced non-small cell lung cancer: A single center experience

    PubMed Central

    Kim, Ji Hye; Ryu, Min Sun; Ryu, Yon Ju; Lee, Jin Hwa; Shim, Sung Shine; Kim, Yookyung; Chang, Jung Hyun

    2014-01-01

    Background This study aimed to evaluate the characteristics of active anti-cancer treatment (AAT) compared with best supportive care (BSC) in elderly patients with advanced non-small cell lung cancer (NSCLC). Methods A retrospective analysis of 144 patients, aged 70 or older, with stage IIIb/IV NSCLC from 672 patients with confirmed lung cancer, was conducted. Results Median age at diagnosis was 77 years and median survival time was five months. On multivariate analysis, AAT independently contributed to a decreased hazard ratio of death (P = 0.04), whereas male gender (P = 0.004), a body mass index of less than 18.5 (P = 0.004), and a poor performance score were associated with an increased risk of death (P < 0.001). The 52 subjects receiving AAT experienced longer survival than the 92 subjects receiving BSC (median seven months [AAT] versus three months [BSC]; P < 0.001). When sub-classified into five-year age intervals, AAT was a significant advantage in overall survival (OS) to patients aged 70–74, but not to those ≥75 years old. Conclusions AAT for patients ≥70 years old with advanced NSCLC extended OS. However, care should be taken in decisions on active anti-cancer treatments for patients over 75 years old. A prospective multicenter trial is required in the near future. PMID:26766990

  5. Impact of TG4010 Vaccine on Health-Related Quality of Life in Advanced Non-Small-Cell Lung Cancer: Results of a Phase IIB Clinical Trial

    PubMed Central

    Rotonda, Christine; Anota, Amélie; Mercier, Mariette; Bastien, Bérangère; Lacoste, Gisèle; Limacher, Jean-Marc; Quoix, Elisabeth; Bonnetain, Franck

    2015-01-01

    Background This study describes the effect of TG4010 vaccine on Health related Quality of Life (HRQOL) in patients with stage IIIb and IV non–small-cell lung cancer (NSCLC). Methods 148 patients with advanced NSCLC expressing MUC1 were randomly assigned to receive TG4010 plus chemotherapy or chemotherapy alone. HRQOL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) at baseline and every 6 weeks until disease progression. Time until definitive deterioration (TUDD) of the four well-being dimensions of the FACT-L physical (PWB), functional (FWB), emotional (EWB) and social well-being (SWB) and the Lung Cancer Subscale (LCS) domains were analyzed for a 5-point minimal clinically important difference. Results No difference of TUDD of HRQOL has been found between treatment arms. No prognostic factors have been found to have a significant impact on the TUDD of PWB, SWB and LCS domains. The gender, the performance status and the smoking habits seemed to be associated with a shorter TUDD of EWB domain. The smokers and the former smokers seemed to present a shorter TUDD of FWB domain. Conclusion This study suggests that adding therapeutic vaccination with TG4010 to standard chemotherapy in patients with advanced NSCLC is associated with a similar evolution in HRQOL compared to chemotherapy alone. PMID:26207902

  6. MSFC Advanced Concepts Office and the Iterative Launch Vehicle Concept Method

    NASA Technical Reports Server (NTRS)

    Creech, Dennis

    2011-01-01

    This slide presentation reviews the work of the Advanced Concepts Office (ACO) at Marshall Space Flight Center (MSFC) with particular emphasis on the method used to model launch vehicles using INTegrated ROcket Sizing (INTROS), a modeling system that assists in establishing the launch concept design, and stage sizing, and facilitates the integration of exterior analytic efforts, vehicle architecture studies, and technology and system trades and parameter sensitivities.

  7. Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1

    PubMed Central

    Ye, Zhiqiang; Shen, Ning; Weng, Yimin; Li, Kai; Hu, Liu; Liao, Hongyin; An, Jun; Liu, Libao; Lao, Sen; Cai, Songwang

    2015-01-01

    MiR-145 has been implicated in the progression of non-small cell lung cancer (NSCLC); however, its exact mechanism is not well established. Here, we report that miR-145 expression is decreased in NSCLC cell lines and tumor tissues and that this low level of expression is associated with DNA methylation. MiR-145 methylation in NSCLC was correlated with a more aggressive tumor phenotype and was associated with poor survival time, as shown by Kaplan-Meier analysis. Additional multivariate Cox regression analysis indicated that miR-145 methylation was an independent prognostic factor for poor survival in patients with NSCLC. Furthermore, we found that restoration of miR-145 expression inhibited proliferation, migration and invasion of NSCLC by the direct targeting of mucin 1 by miR-145. Our results indicate that low miR-145 expression, due to methylation, promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1. Therefore, miR-145 may be a valuable therapeutic target for NSCLC. PMID:25961369

  8. Development and application of a probabilistic evaluation method for advanced process technologies. Final report

    SciTech Connect

    Frey, H.C.; Rubin, E.S.

    1991-04-01

    The objective of this work is to develop and apply a method for research planning for advanced process technologies. To satisfy requirements for research planning, it is necessary to: (1) identify robust solutions to process design questions in the face of uncertainty to eliminate inferior design options; (2) identify key problem areas in a technology that should be the focus of further research to reduce the risk of technology failure; (3) compare competing technologies on a consistent basis to determine the risks associated with adopting a new technology; and (4) evaluate the effects that additional research might have on comparisons with conventional technology. An important class of process technologies are electric power plants. In particular, advanced clean coal technologies are expected to play a key role in the energy and environmental future of the US, as well as in other countries. Research planning for advanced clean coal technology development is an important part of energy and environmental policy. Thus, the research planning method developed here is applied to case studies focusing on a specific clean coal technology. The purpose of the case studies is both to demonstrate the research planning method and to obtain technology-specific conclusions regarding research strategies.

  9. Development and application of a probabilistic evaluation method for advanced process technologies

    SciTech Connect

    Frey, H.C.; Rubin, E.S.

    1991-04-01

    The objective of this work is to develop and apply a method for research planning for advanced process technologies. To satisfy requirements for research planning, it is necessary to: (1) identify robust solutions to process design questions in the face of uncertainty to eliminate inferior design options; (2) identify key problem areas in a technology that should be the focus of further research to reduce the risk of technology failure; (3) compare competing technologies on a consistent basis to determine the risks associated with adopting a new technology; and (4) evaluate the effects that additional research might have on comparisons with conventional technology. An important class of process technologies are electric power plants. In particular, advanced clean coal technologies are expected to play a key role in the energy and environmental future of the US, as well as in other countries. Research planning for advanced clean coal technology development is an important part of energy and environmental policy. Thus, the research planning method developed here is applied to case studies focusing on a specific clean coal technology. The purpose of the case studies is both to demonstrate the research planning method and to obtain technology-specific conclusions regarding research strategies.

  10. Comparison of advanced reduced-basis methods for transient structural analysis

    NASA Technical Reports Server (NTRS)

    Mcgowan, David M.; Bostic, Susan W.

    1991-01-01

    Two advanced reduced-basis methods for linear, transient structural analysis, the force-derivative method and the Lanczos method, are compared to two widely-used modal methods, the mode-displacement method and the mode-acceleration method. Comparisons are made for two linear example problems: a proportionally-damped cantilevered beam subject to a discrete tip load which varies linearly with time, and a discretely-damped multispan beam subject to a uniformly distributed load which varies as a quintic function of time. Results from the methods are compared in terms of the number of basis vectors required to obtain a desired level of accuracy and the associated computational times. The results are problem dependent, and it is shown that for the cantilevered beam problem, the mode-acceleration and force-derivative methods are the most efficient in terms of the number of basis vectors and computational time. The force-derivative method is shown to be the most effective method for solving the multispan beam problem with closely-spaced frequencies. In general, the force-derivative method is shown to produce an accurate solution using very few basis vectors and to require less computational time as compared to the other methods studied.

  11. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

    PubMed Central

    2012-01-01

    Background Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. Methods In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. Results The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. Conclusions This study showed that the

  12. Some Recent Advances of Ultrasonic Diagnostic Methods Applied to Materials and Structures (Including Biological Ones)

    NASA Astrophysics Data System (ADS)

    Nobile, Lucio; Nobile, Stefano

    This paper gives an overview of some recent advances of ultrasonic methods applied to materials and structures (including biological ones), exploring typical applications of these emerging inspection technologies to civil engineering and medicine. In confirmation of this trend, some results of an experimental research carried out involving both destructive and non-destructive testing methods for the evaluation of structural performance of existing reinforced concrete (RC) structures are discussed in terms of reliability. As a result, Ultrasonic testing can usefully supplement coring thus permitting less expensive and more representative evaluation of the concrete strength throughout the whole structure under examination.

  13. Recent advances in Euler and Navier-Stokes methods for calculating helicopter rotor aerodynamics and acoustics

    NASA Technical Reports Server (NTRS)

    Srinivasan, G. R.; Baeder, J. D.

    1991-01-01

    This paper outlines some recent advances in the application of the Euler and Navier-Stokes computational fluid dynamics methods to analyze nonlinear problems of helicopter aerodynamics and acoustics. A complete flowfield simulation of helicopters is currently not feasible with these methods. However, the use of the state-of-the-art numerical algorithms in conjunction with powerful supercomputers, like the Cray-2, have enabled notable progress to be made in modeling several individual components of this complex flow in hover and forward flight.

  14. Circulating tumor DNA identified by targeted sequencing in advanced-stage non-small cell lung cancer patients.

    PubMed

    Xu, Song; Lou, Feng; Wu, Yi; Sun, Da-Qiang; Zhang, Jing-Bo; Chen, Wei; Ye, Hua; Liu, Jing-Hao; Wei, Sen; Zhao, Ming-Yu; Wu, Wen-Jun; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F; Chen, Si-Yi; Chen, Jun

    2016-01-28

    Non-small cell lung cancers (NSCLC) have unique mutation patterns, and some of these mutations may be used to predict prognosis or guide patient treatment. Mutation profiling before and during treatment often requires repeated tumor biopsies, which is not always possible. Recently, cell-free, circulating tumor DNA (ctDNA) isolated from blood plasma has been shown to contain genetic mutations representative of those found in the primary tumor tissue DNA (tDNA), and these samples can readily be obtained using non-invasive techniques. However, there are still no standardized methods to identify mutations in ctDNA. In the current study, we used a targeted sequencing approach with a semi-conductor based next-generation sequencing (NGS) platform to identify gene mutations in matched tDNA and ctDNA samples from 42 advanced-stage NSCLC patients from China. We identified driver mutations in matched tDNA and ctDNA in EGFR, KRAS, PIK3CA, and TP53, with an overall concordance of 76%. In conclusion, targeted sequencing of plasma ctDNA may be a feasible option for clinical monitoring of NSCLC in the near future. PMID:26582655

  15. Phase II trial of S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer

    PubMed Central

    Ohyanagi, F; Yamamoto, N; Horiike, A; Harada, H; Kozuka, T; Murakami, H; Gomi, K; Takahashi, T; Morota, M; Nishimura, T; Endo, M; Nakamura, Y; Tsuya, A; Horai, T; Nishio, M

    2009-01-01

    Background: To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC). Methods: Eligible patients were 20–74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0–1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m−2 on day 1) and S-1 (orally at 40 mg m−2 per dose, b.i.d., on days 1–14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions. Results: Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1–96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progression-free survival was 12.0 months and median overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and 56%, respectively. Conclusion: This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities. PMID:19603031

  16. NSCLC subtype prediction using cytologic fluid specimens from needle aspiration biopsies.

    PubMed

    Cho, Arthur; Hur, Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Kim, Hee Yeong; Lee, Ji Won; Shim, Hyo Sup; Choi, Byoung Wook

    2013-03-01

    This study evaluated the diagnostic usefulness of tumor marker concentrations in cytologic fluids (CF) for subtyping non-small cell lung cancer (NSCLC) and assessed the relationship between fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake with serum and CF tumor marker levels. This prospective study included 88 patients diagnosed with adenocarcinoma or squamous cell carcinoma (SCC). Cytokeratin-19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) concentrations in the CF samples were correlated with serum tumor marker concentrations, (18)F-FDG uptake, and NSCLC subtype. Fifty-eight patients were diagnosed with adenocarcinoma. Multivariate analysis revealed higher CF and serum SCCA levels; smoking status predicted SCC from adenocarcinoma. CF SCCA showed the highest accuracy (83%) in distinguishing between SCC and adenocarcinoma. CF samples obtained during routine needle aspiration biopsy procedure contain tumor marker levels sufficient to distinguish between SCC and adenocarcinoma; CF SCCA had the highest diagnostic accuracy. PMID:23429366

  17. MiR-15a-16 represses Cripto and inhibits NSCLC cell progression.

    PubMed

    Chen, Feng; Hou, Shi-ke; Fan, Hao-jun; Liu, Ying-fu

    2014-06-01

    MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in cancer. The altered expressions of miRNAs and their target genes are frequently detected in various tumors. In this study, downregulation of miR-15a-16 in nonsmall cell lung cancer (NSCLC) was found to be inversely correlated with Cripto. Results from the Luciferase reporter assay and Western blot analysis also confirmed that Cripto is a direct target of miR-15a-16. In addition, transfection of miR-15a-16 expression plasmid inhibited the invasion ability and promoted the apoptosis of NCI-H23 and NCI-H358 cells. Moreover, miR-15a-16 overexpression suppressed tumor growth in vivo. These findings clearly suggest that the downregulation of miR-15a-16 with Cripto amplification may be involved in the development of NSCLC. PMID:24500260

  18. KRAS mutant NSCLC, a new opportunity for the synthetic lethality therapeutic approach

    PubMed Central

    Belda-Iniesta, Cristóbal

    2013-01-01

    K-RAS accounts for 90% of RAS mutations in lung adenocarcinomas, the most commonly mutated oncogene in NSCLC, with mutations detected in about 25% of all tumors. Direct inhibition of KRAS has proven clinically challenging. So far, no successful targeted therapy has been developed and remains an elusive target for cancer therapy. Despite significant efforts, currently there are no drugs directly targeting mutated KRAS. Thus, new strategies have emerged for targeting RAS including the use of synthetic lethality. A specific knowledge of individual tumor molecular abnormalities that result in oncogene-specific “synthetic lethal” interactions will allow the rationale to combine promising targeted therapies for KRAS-mutated NSCLC. In this article, we review the new approach based on testing drugs or combinations of agents that work downstream of activated K-RAS. PMID:25806225

  19. KRAS mutant NSCLC, a new opportunity for the synthetic lethality therapeutic approach.

    PubMed

    de Castro Carpeño, Javier; Belda-Iniesta, Cristóbal

    2013-04-01

    K-RAS accounts for 90% of RAS mutations in lung adenocarcinomas, the most commonly mutated oncogene in NSCLC, with mutations detected in about 25% of all tumors. Direct inhibition of KRAS has proven clinically challenging. So far, no successful targeted therapy has been developed and remains an elusive target for cancer therapy. Despite significant efforts, currently there are no drugs directly targeting mutated KRAS. Thus, new strategies have emerged for targeting RAS including the use of synthetic lethality. A specific knowledge of individual tumor molecular abnormalities that result in oncogene-specific "synthetic lethal" interactions will allow the rationale to combine promising targeted therapies for KRAS-mutated NSCLC. In this article, we review the new approach based on testing drugs or combinations of agents that work downstream of activated K-RAS. PMID:25806225

  20. A framework for advanced methods of control of human-induced vibrations

    NASA Astrophysics Data System (ADS)

    Reynolds, Paul

    2012-04-01

    The vibration serviceability of civil engineering structures under human dynamic excitation is becoming ever more critical with the design and redevelopment of structures with reduced mass, stiffness and damping. A large number of problems have been reported in floors, footbridges, sports stadia, staircases and other structures. Unfortunately, the range of options available to fix such problems are very limited and are primarily limited to structural modification or the implementation of passive vibration control measures, such as tuned mass dampers. This paper presents the initial development of a new framework for advanced methods of control of humaninduced vibrations in civil engineering structures. This framework includes both existing passive methods of vibration control and more advanced active, semi-active and hybrid control techniques, which may be further developed as practical solutions for these problems. Through the use of this framework, rational decisions as to the most appropriate technologies for particular human vibration problems may be made and pursued further. This framework is also intended to be used in the design of new civil engineering structures, where advanced control technologies may be used both to increase the achievable slenderness and to reduce the amount of construction materials used and hence their embodied energy. This will be an ever more important consideration with the current drive for structures with reduced environmental impact.

  1. Selenium contaminated waters: An overview of analytical methods, treatment options and recent advances in sorption methods.

    PubMed

    Santos, Sílvia; Ungureanu, Gabriela; Boaventura, Rui; Botelho, Cidália

    2015-07-15

    Selenium is an essential trace element for many organisms, including humans, but it is bioaccumulative and toxic at higher than homeostatic levels. Both selenium deficiency and toxicity are problems around the world. Mines, coal-fired power plants, oil refineries and agriculture are important examples of anthropogenic sources, generating contaminated waters and wastewaters. For reasons of human health and ecotoxicity, selenium concentration has to be controlled in drinking-water and in wastewater, as it is a potential pollutant of water bodies. This review article provides firstly a general overview about selenium distribution, sources, chemistry, toxicity and environmental impact. Analytical techniques used for Se determination and speciation and water and wastewater treatment options are reviewed. In particular, published works on adsorption as a treatment method for Se removal from aqueous solutions are critically analyzed. Recent published literature has given particular attention to the development and search for effective adsorbents, including low-cost alternative materials. Published works mostly consist in exploratory findings and laboratory-scale experiments. Binary metal oxides and LDHs (layered double hydroxides) have presented excellent adsorption capacities for selenium species. Unconventional sorbents (algae, agricultural wastes and other biomaterials), in raw or modified forms, have also led to very interesting results with the advantage of their availability and low-cost. Some directions to be considered in future works are also suggested. PMID:25847169

  2. Structured background grids for generation of unstructured grids by advancing front method

    NASA Technical Reports Server (NTRS)

    Pirzadeh, Shahyar

    1991-01-01

    A new method of background grid construction is introduced for generation of unstructured tetrahedral grids using the advancing-front technique. Unlike the conventional triangular/tetrahedral background grids which are difficult to construct and usually inadequate in performance, the new method exploits the simplicity of uniform Cartesian meshes and provides grids of better quality. The approach is analogous to solving a steady-state heat conduction problem with discrete heat sources. The spacing parameters of grid points are distributed over the nodes of a Cartesian background grid by interpolating from a few prescribed sources and solving a Poisson equation. To increase the control over the grid point distribution, a directional clustering approach is used. The new method is convenient to use and provides better grid quality and flexibility. Sample results are presented to demonstrate the power of the method.

  3. Experimental method for determination of bending and torsional rigidities of advanced composite laminates

    SciTech Connect

    Maeda, Takenori

    1995-11-01

    This paper presents an experimental method for the determination of the bending and torsional rigidities of advanced fiber composite laminates with the aid of laser holographic interferometry. The proposed method consists of a four-point bending test and a resonance test. The bending rigidity ratio (D{sub 12}/D{sub 22}) can be determined from the fringe patterns of the four-point bending test. The bending rigidities (D{sub 11} and D{sub 22}) and the torsional rigidity (D{sub 66}) are calculated from the natural frequencies of cantilever plates of the resonance test. The test specimens are carbon/epoxy cross-ply laminates. The adequacy of the experimental method is confirmed by comparing the measured rigidities with the theoretical values obtained from classical lamination theory (CLT) by using the measured tensile properties. The results show that the present method can be used to evaluate the rigidities of orthotropic laminates with reasonably good accuracy.

  4. Mitochondrial Variations in Non-Small Cell Lung Cancer (NSCLC) Survival

    PubMed Central

    Wang, Zhaoxi; Choi, Sojung; Lee, Jinseon; Huang, Yen-Tsung; Chen, Feng; Zhao, Yang; Lin, Xihong; Neuberg, Donna; Kim, Jhingook; Christiani, David C

    2015-01-01

    Mutations in the mtDNA genome have long been suspected to play an important role in cancer. Although most cancer cells harbor mtDNA mutations, the question of whether such mutations are associated with clinical prognosis of lung cancer remains unclear. We resequenced the entire mitochondrial genomes of tumor tissue from a population of 250 Korean patients with non-small cell lung cancer (NSCLC). Our analysis revealed that the haplogroup (D/D4) was associated with worse overall survival (OS) of early-stage NSCLC [adjusted hazard ratio (AHR), 1.95; 95% CI, 1.14–3.33; Ptrend = 0.03]. By comparing the mtDNA variations between NSCLC tissues and matched blood samples, we found that haplogroups M/N and/or D/D4 were hotspots for somatic mutations, suggesting a more complicated mechanism of mtDNA somatic mutations other than the commonly accepted mechanism of sequential accumulation of mtDNA mutations. PMID:25657573

  5. Systematic siRNA Screen Unmasks NSCLC Growth Dependence by Palmitoyltransferase DHHC5

    PubMed Central

    Tian, Hui; Lu, Jui-Yun; Shao, Chunli; Huffman, Kenneth E.; Carstens, Ryan M.; Larsen, Jill E.; Girard, Luc; Liu, Hui; Rodriguez-Canales, Jaime; Frenkel, Eugene P.; Wistuba, Ignacio I.; Minna, John D.; Hofmann, Sandra L.

    2015-01-01

    Protein S-palmitoylation is a widespread and dynamic post-translational modification that regulates protein-membrane interactions, protein-protein interactions, and protein stability. A large family of palmitoyl acyl transferases, termed the DHHC family due to the presence of a common catalytic motif, catalyzes S-palmitoylation; the role of these enzymes in cancer is largely unexplored. In this study, an RNAi-based screen targeting all 23 members of the DHHC family was conducted to examine the effects on the growth in non-small cell cancer (NSCLC). Interestingly, siRNAs directed against DHHC5 broadly inhibited the growth of multiple NSCLC lines but not normal human bronchial epithelial cell (HBEC) lines. Silencing of DHHC5 by lentivirus-mediated expression of DHHC5 shRNAs dramatically reduced in vitro cell proliferation, colony formation and cell invasion in a subset of cell lines that were examined in further detail. The phenotypes were restored by transfection of a wild-type DHHC5 plasmid but not by a plasmid expressing a catalytically inactive DHHC5. Tumor xenograft formation was severely inhibited by DHHC5 knockdown and rescued by DHHC5 expression, using both a conventional and tetracycline-inducible shRNA. These data indicate that DHHC5 has oncogenic capacity and contributes to tumor formation in NSCLC; thus representing a potential novel therapeutic target. PMID:25573953

  6. The Promise of Mixed-Methods for Advancing Latino Health Research

    PubMed Central

    Apesoa-Varano, Ester Carolina; Hinton, Ladson

    2015-01-01

    Mixed-methods research in the social sciences has been conducted for quite some time. More recently, mixed-methods have become popular in health research, with the National Institutes of Health leading the impetus to fund studies that implement such an approach. The public health issues facing us today are great and they range from policy and other macro-level issues, to systems level problems to individuals' health behaviors. For Latinos, who are projected to become the largest minority group bearing a great deal of the burden of social inequality in the U.S., it is important to understand the deeply-rooted nature of these health disparities in order to close the gap in health outcomes. Mixed-methodology thus holds promise for advancing research on Latino heath by tackling health disparities from a variety of standpoints and approaches. The aim of this manuscript is to provide two examples of mixed methods research, each of which addresses a health topic of considerable importance to older Latinos and their families. These two examples will illustrate a) the complementary use of qualitative and quantitative methods to advance health of older Latinos in an area that is important from a public health perspective, and b) the “translation” of findings from observational studies (informed by social science and medicine) to the development and testing of interventions. PMID:23996325

  7. A phase I study of nimotuzumab plus docetaxel in chemotherapy-refractory/resistant patients with advanced non-small-cell lung cancer

    PubMed Central

    Zhao, Jun; Zhuo, Minglei; Wang, Zhijie; Duan, Jianchun; Wang, Yuyan; Wang, Shuhang; An, Tongtong; Wu, Meina

    2016-01-01

    Background To determine the safety and therapeutic efficacy of nimotuzumab (h-R3) combined with docetaxel in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond to prior first-line chemotherapy. Methods In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor (EGFR)-expressing stage IV NSCLC were treated with nimotuzumab plus docetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed. Results There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade III–IV toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients (66.7%). The median progression-free survival (PFS) was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR (EGFR WT). The median survival time (MST) was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients. PMID:27041923

  8. Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer

    PubMed Central

    Garon, Edward B.; Christofk, Heather R.; Hosmer, Wylie; Britten, Carolyn D; Bahng, Agnes; Crabtree, Matthew J; Hong, Candice Sun; Kamranpour, Naeimeh; Pitts, Sharon; Kabbinavar, Fairooz; Patel, Cecil; von Euw, Erika; Black, Alexander; Michelakis, Evangelos D.; Dubinett, Steven M.; Slamon, Dennis J.

    2014-01-01

    Objectives Dichloroacetate (DCA) is a highly bioavailable small molecule that inhibits pyruvate dehydrogenase kinase, promoting glucose oxidation and reversing the glycolytic phenotype in preclinical cancer studies. We designed this open label phase II trial to determine the response rate, safety, and tolerability of oral DCA in patients with metastatic breast cancer and advanced stage NSCLC. Materials and Methods This trial was conducted with DCA 6.25 mg/kg orally twice daily in previously treated stage IIIB/IV non-small cell lung cancer (NSCLC) or stage IV breast cancer. Growth inhibition by DCA was also evaluated in a panel of 54 NSCLC cell lines with and without cytotoxic chemotherapeutics (cisplatin and docetaxel) in normoxic and hypoxic conditions. Results and Conclusions Under normoxic conditions in vitro, single agent IC50 was > 2 mM for all evaluated cell lines. Synergy with cisplatin was seen in some cell lines under hypoxic conditions. In the clinical trial, after seven patients were enrolled, the study was closed based on safety concerns. The only breast cancer patient had stable disease after 8 weeks, quickly followed by progression in the brain. Two patients withdrew consent within a week of enrollment. Two patients had disease progression prior to the first scheduled scans. Within one week of initiating DCA, one patient died suddenly of unknown cause, and one experienced a fatal pulmonary embolism. We conclude that patients with previously treated advanced NSCLC did not benefit from oral DCA. In the absence of a larger controlled trial, firm conclusions regarding the association between these adverse events and DCA are unclear. Further development of DCA should be in patients with longer life expectancy, in whom sustained therapeutic levels can be achieved, and potentially in combination with cisplatin. PMID:24442098

  9. Sensitivity analysis of infectious disease models: methods, advances and their application.

    PubMed

    Wu, Jianyong; Dhingra, Radhika; Gambhir, Manoj; Remais, Justin V

    2013-09-01

    Sensitivity analysis (SA) can aid in identifying influential model parameters and optimizing model structure, yet infectious disease modelling has yet to adopt advanced SA techniques that are capable of providing considerable insights over traditional methods. We investigate five global SA methods-scatter plots, the Morris and Sobol' methods, Latin hypercube sampling-partial rank correlation coefficient and the sensitivity heat map method-and detail their relative merits and pitfalls when applied to a microparasite (cholera) and macroparasite (schistosomaisis) transmission model. The methods investigated yielded similar results with respect to identifying influential parameters, but offered specific insights that vary by method. The classical methods differed in their ability to provide information on the quantitative relationship between parameters and model output, particularly over time. The heat map approach provides information about the group sensitivity of all model state variables, and the parameter sensitivity spectrum obtained using this method reveals the sensitivity of all state variables to each parameter over the course of the simulation period, especially valuable for expressing the dynamic sensitivity of a microparasite epidemic model to its parameters. A summary comparison is presented to aid infectious disease modellers in selecting appropriate methods, with the goal of improving model performance and design. PMID:23864497

  10. EGFR-TKI down-regulates PD-L1 in EGFR mutant NSCLC through inhibiting NF-κB.

    PubMed

    Lin, Kailong; Cheng, Jianan; Yang, Tao; Li, Yongsheng; Zhu, Bo

    Non-small-cell lung cancer (NSCLC) is a severe disease threatening human health. Targeted therapy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has obtained potent efficacy in the treatment of NSCLC patients. However, the effects of EGFR-TKIs on tumor immune microenvironment are unclear. In this study, we show that NSCLCs with EGFR mutation express higher programmed cell death ligand 1 (PD-L1) than NSCLCs with wild type EGFR. The EGFR activation is also associated with high expression of PD-L1. The EGFR-TKI gefitinib can reduce PD-L1 expression, via inhibiting NF-κB, in EGFR mutant NSCLC in vitro and in vivo. These findings elucidate a novel anti-tumor mechanism of EGFR-TKI and provide the possibility of combined strategy of targeted therapy and immunotherapy for EGFR mutant NSCLC patients. PMID:25998384

  11. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    PubMed Central

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance. PMID:26310719

  12. Advances in Gas Chromatographic Methods for the Identification of Biomarkers in Cancer

    PubMed Central

    Kouremenos, Konstantinos A.; Johansson, Mikael; Marriott, Philip J.

    2012-01-01

    Screening complex biological specimens such as exhaled air, tissue, blood and urine to identify biomarkers in different forms of cancer has become increasingly popular over the last decade, mainly due to new instruments and improved bioinformatics. However, despite some progress, the identification of biomarkers has shown to be a difficult task with few new biomarkers (excluding recent genetic markers) being considered for introduction to clinical analysis. This review describes recent advances in gas chromatographic methods for the identification of biomarkers in the detection, diagnosis and treatment of cancer. It presents a general overview of cancer metabolism, the current biomarkers used for cancer diagnosis and treatment, a background to metabolic changes in tumors, an overview of current GC methods, and collectively presents the scope and outlook of GC methods in oncology. PMID:23074381

  13. Immunoassay Methods and their Applications in Pharmaceutical Analysis: Basic Methodology and Recent Advances

    PubMed Central

    Darwish, Ibrahim A.

    2006-01-01

    Immunoassays are bioanalytical methods in which the quantitation of the analyte depends on the reaction of an antigen (analyte) and an antibody. Immunoassays have been widely used in many important areas of pharmaceutical analysis such as diagnosis of diseases, therapeutic drug monitoring, clinical pharmacokinetic and bioequivalence studies in drug discovery and pharmaceutical industries. The importance and widespread of immunoassay methods in pharmaceutical analysis are attributed to their inherent specificity, high-throughput, and high sensitivity for the analysis of wide range of analytes in biological samples. Recently, marked improvements were achieved in the field of immunoassay development for the purposes of pharmaceutical analysis. These improvements involved the preparation of the unique immunoanalytical reagents, analysis of new categories of compounds, methodology, and instrumentation. The basic methodologies and recent advances in immunoassay methods applied in different fields of pharmaceutical analysis have been reviewed. PMID:23674985

  14. Structural Analysis and Quantitative Determination of Clevidipine Butyrate Impurities Using an Advanced RP-HPLC Method.

    PubMed

    Zhou, Yuxia; Zhou, Fan; Yan, Fei; Yang, Feng; Yao, Yuxian; Zou, Qiaogen

    2016-03-01

    Eleven potential impurities, including process-related compounds and degradation products, have been analyzed by comprehensive studies on the manufacturing process of clevidipine butyrate. Possible formation mechanisms could also be devised. MS and NMR techniques have been used for the structural characterization of three previously unreported impurities (Imp-3, Imp-5 and Imp-11). To separate and quantify the potential impurities in a simultaneous fashion, an efficient and advanced RP-HPLC method has been developed. In doing so, four major degradation products (Imp-2, Imp-4, Imp-8 and Imp-10) can be observed under varying stress conditions. This analytical method has been validated according to ICH guidelines with respect to specificity, accuracy, linearity, robustness and stability. The method described has been demonstrated to be applicable in routine quality control processes and stability evaluation studies of clevidipine butyrate. PMID:26489435

  15. Development of Advanced Nuclide Separation and Recovery Methods using Ion-Exchanhge Techniques in Nuclear Backend

    NASA Astrophysics Data System (ADS)

    Miura, Hitoshi

    The development of compact separation and recovery methods using selective ion-exchange techniques is very important for the reprocessing and high-level liquid wastes (HLLWs) treatment in the nuclear backend field. The selective nuclide separation techniques are effective for the volume reduction of wastes and the utilization of valuable nuclides, and expected for the construction of advanced nuclear fuel cycle system and the rationalization of waste treatment. In order to accomplish the selective nuclide separation, the design and synthesis of novel adsorbents are essential for the development of compact and precise separation processes. The present paper deals with the preparation of highly functional and selective hybrid microcapsules enclosing nano-adsorbents in the alginate gel polymer matrices by sol-gel methods, their characterization and the clarification of selective adsorption properties by batch and column methods. The selective separation of Cs, Pd and Re in real HLLW was further accomplished by using novel microcapsules, and an advanced nuclide separation system was proposed by the combination of selective processes using microcapsules.

  16. Sequential Chemotherapy and Radiotherapy in the Sandwich Method for Advanced Endometrial Cancer

    PubMed Central

    Gao, Huiqiao; Zhang, Zhenyu

    2015-01-01

    Abstract Endometrial cancer is one of the most common gynecological malignancies and the standard treatment modality has not been established. To assess the efficacy and tolerability of a sandwich method consisted of chemotherapy followed by involved field irradiation and additional chemotherapy for the treatment of advanced endometrial cancer. The Medline, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) Library were searched to identify the relevant literature published between 1970 and September 2014. A meta-analysis was performed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity. A total of 5 articles were subjected to this meta-analysis. The pooled 3-year PFS and OS of patients with advanced endometrial cancer treated with the “sandwich” method was 68% (95% CI: 0.60–0.77) with no heterogeneity (I2 = 0.00%, P = 0.77) among the studies and 75% (95% CI: 0.61–0.89) with significant heterogeneity (I2 = 71.8%, P = 0.01), respectively. Pooled analysis of toxicity was not performed because of the substantial heterogeneity. Sequential chemotherapy and radiotherapy in the sandwich method is both efficacious and well tolerated. Large-scale randomized controlled trials (RCTs) are necessary in the future. PMID:25906095

  17. [Methods of advanced purification-the challenge for biosynthetic antibiotics industry].

    PubMed

    Oniscu, C; Caşcaval, D; Galaction, Anca-Irina

    2002-01-01

    Reactive extraction, permeation through liquid membranes and direct extraction are some of the new techniques applied for separation and advanced purification of biosynthetic antibiotics. Compared with the conventional separation techniques, the main advantages of these extraction methods are: high separation efficiency, the avoidance of antibiotics chemical and thermal inactivation, high purity of obtained antibiotics. Furthermore, using reactive extraction or permeation through liquid membrane, the antibiotics can be selective separated from their biosynthesis precursors or from the secondary biosynthetic compounds. This paper is a review on separation of Penicillins and Erythromycin by means of these extraction techniques, being underlined their advantages, applications and problems concerning the separation process scale-up. PMID:12638304

  18. Application of advanced multidisciplinary analysis and optimization methods to vehicle design synthesis

    NASA Technical Reports Server (NTRS)

    Consoli, Robert David; Sobieszczanski-Sobieski, Jaroslaw

    1990-01-01

    Advanced multidisciplinary analysis and optimization methods, namely system sensitivity analysis and non-hierarchical system decomposition, are applied to reduce the cost and improve the visibility of an automated vehicle design synthesis process. This process is inherently complex due to the large number of functional disciplines and associated interdisciplinary couplings. Recent developments in system sensitivity analysis as applied to complex non-hierarchic multidisciplinary design optimization problems enable the decomposition of these complex interactions into sub-processes that can be evaluated in parallel. The application of these techniques results in significant cost, accuracy, and visibility benefits for the entire design synthesis process.

  19. Cachexia Index in Advanced Non-Small-Cell Lung Cancer Patients

    PubMed Central

    Jafri, Syed Hasan Raza; Previgliano, Carlos; Khandelwal, Keerti; Shi, Runhua

    2015-01-01

    INTRODUCTION Cancer cachexia affects many advanced non-small-cell lung cancer (NSCLC) patients. Cachexia index (CXI) was developed to assess the degree of cachexia in these patients. METHODS Patients with metastatic NSCLC diagnosed between January 1, 2000, and June 30, 2011, at our institution were retrospectively studied. Abdominal computed tomography scans done within 1 month of diagnosis were reviewed to estimate skeletal muscle area (SMA) and skeletal muscle index (SMI) at the L3 level. CXI was developed as follows: CXI=SMI×AlbNLR where SMI is the skeletal muscle index, Alb is the serum albumin, and NLR is the neutrophil-to-lymphocyte ratio. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Survival among various factors was calculated using the log-rank test. Multivariate Cox regression was used to perform survival analysis in order to estimate the effects of various factors. RESULTS Patients were divided into two groups around the median into stage I cachexia (CXI ≥35, n = 56) and stage II cachexia (CXI <35, n = 56). Groups did not differ in age, gender, ethnicity, or histology of cancer. Patients with stage II cachexia had significantly worse PFS (2.45 vs 5.43 months, P < 0.0001) and OS (3.45 vs 8.8 months, P = 0.0001) than those with stage I cachexia. On multivariate analysis adjusting for gender, race, and histology, patients with stage II cachexia were found to have worse PFS (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.27–2.95) and OS (HR 1.53, 95% CI 1.0009–2.34). CONCLUSION The CXI is a novel index for estimating cachexia that also correlates with prognosis in both men and women with advanced NSCLC. PMID:26604850

  20. miR-204 suppresses non-small-cell lung carcinoma (NSCLC) invasion and migration by targeting JAK2.

    PubMed

    Wang, P; Lv, H Y; Zhou, D M; Zhang, E N

    2016-01-01

    Aberrant expression of microRNA is associated with the development and progression of cancers. MicroRNA-204 (miR-204) down-regulation has been previously demonstrated in non-small-cell lung carcinoma (NSCLC); however, the underlying mechanism by which miR-204 suppresses tumorigenesis in NSCLC remains elusive. In this study, miR-204 expression was found to be down-regulated, and that of Janus kinase 2 (JAK2) was found to be up-regulated in four NSCLC cell lines (A549, H1299, H1650, and H358) compared to the normal lung cell line. The overexpression of miR-204 suppressed the invasive and migratory capacities of H1299 cells. A luciferase assay confirmed that the binding of miR-124 to the -untranslated region of JAK2 inhibited the expression of JAK2 proteins in H1299 cells. JAK-2 overexpression effectively reversed miR-204-repressed NSCLC metastasis. Taken together, our findings revealed that miR-204 functions as a tumor suppressor in NSCLC by targeting JAK2, and that miR-204 may therefore serve as a biomarker for the diagnosis and treatment of NSCLC. PMID:27323056

  1. Recent advances in auxiliary-field methods --- simulations in lattice models and real materials

    NASA Astrophysics Data System (ADS)

    Zhang, Shiwei

    2007-03-01

    We have developed an auxiliary-field (AF) quantum Monte Carlo (QMC) method for many-body simulations. The method takes the form of a linear superposition of independent-particle calculations in fluctuating external fields. ``Entanglement'' of the different field configurations leads to random walks in Slater determinant space. We formulate an approximate constraint on the random walk paths to control the sign/phase problem, which has shown to be very accurate even with simple mean-field solutions as the constraining trial wave function. The same method can be applied to both simplified lattice models and real materials. For realistic electronic Hamiltonians, each random walk stream resembles a density-functional theory (DFT) calculation in random local fields. Thus, the AF QMC method can directly import existing technology from standard electronic structure methods into a many-body QMC framework. We have demonstrated this method with calculations in close to 100 systems, including Si solid, first- and second-row molecular systems, molecules of heavier post-d elements, transition-metal systems, and ultra-cold atomic gases. In these we have operated largely in an automated mode, inputting the DFT or Hartree-Fock solutions as trial wave functions. The AF QMC results showed consistently good agreement with near-exact quantum chemistry results and/or experiment. I will also discuss additional algorithmic advances which can further improve the method in strongly correlated systems. Supported by ARO, NSF, ONR, and DOE-cmsn.

  2. Sensitivity analysis of infectious disease models: methods, advances and their application

    PubMed Central

    Wu, Jianyong; Dhingra, Radhika; Gambhir, Manoj; Remais, Justin V.

    2013-01-01

    Sensitivity analysis (SA) can aid in identifying influential model parameters and optimizing model structure, yet infectious disease modelling has yet to adopt advanced SA techniques that are capable of providing considerable insights over traditional methods. We investigate five global SA methods—scatter plots, the Morris and Sobol’ methods, Latin hypercube sampling-partial rank correlation coefficient and the sensitivity heat map method—and detail their relative merits and pitfalls when applied to a microparasite (cholera) and macroparasite (schistosomaisis) transmission model. The methods investigated yielded similar results with respect to identifying influential parameters, but offered specific insights that vary by method. The classical methods differed in their ability to provide information on the quantitative relationship between parameters and model output, particularly over time. The heat map approach provides information about the group sensitivity of all model state variables, and the parameter sensitivity spectrum obtained using this method reveals the sensitivity of all state variables to each parameter over the course of the simulation period, especially valuable for expressing the dynamic sensitivity of a microparasite epidemic model to its parameters. A summary comparison is presented to aid infectious disease modellers in selecting appropriate methods, with the goal of improving model performance and design. PMID:23864497

  3. Advanced Fabrication Method for the Preparation of MOF Thin Films: Liquid-Phase Epitaxy Approach Meets Spin Coating Method.

    PubMed

    Chernikova, Valeriya; Shekhah, Osama; Eddaoudi, Mohamed

    2016-08-10

    Here, we report a new and advanced method for the fabrication of highly oriented/polycrystalline metal-organic framework (MOF) thin films. Building on the attractive features of the liquid-phase epitaxy (LPE) approach, a facile spin coating method was implemented to generate MOF thin films in a high-throughput fashion. Advantageously, this approach offers a great prospective to cost-effectively construct thin-films with a significantly shortened preparation time and a lessened chemicals and solvents consumption, as compared to the conventional LPE-process. Certainly, this new spin-coating approach has been implemented successfully to construct various MOF thin films, ranging in thickness from a few micrometers down to the nanometer scale, spanning 2-D and 3-D benchmark MOF materials including Cu2(bdc)2·xH2O, Zn2(bdc)2·xH2O, HKUST-1, and ZIF-8. This method was appraised and proved effective on a variety of substrates comprising functionalized gold, silicon, glass, porous stainless steel, and aluminum oxide. The facile, high-throughput and cost-effective nature of this approach, coupled with the successful thin film growth and substrate versatility, represents the next generation of methods for MOF thin film fabrication. Therefore, paving the way for these unique MOF materials to address a wide range of challenges in the areas of sensing devices and membrane technology. PMID:27415640

  4. A Mixed Methods Study: African American Students' Performance Trends and Perceptions Towards Advanced Placement Literature Courses and Examinations

    ERIC Educational Resources Information Center

    Buford, Brandie J.

    2012-01-01

    The purpose of this mixed methods study was to describe the perceptions of African American students pertaining to their engagement in Advanced Placement English Literature and Composition course and Advanced Placement English Literature and Composition examination. A purposive sampling design was employed to select 12 participants from one urban…

  5. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study

    PubMed Central

    Douillard, J-Y; Ostoros, G; Cobo, M; Ciuleanu, T; McCormack, R; Webster, A; Milenkova, T

    2014-01-01

    Background: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Methods: Treatment: gefitinib 250 mg day−1 until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. Results: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8% adenocarcinoma 97.2% never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5–77.7), DCR 90.6% (95% CI 83.5–94.8), median PFS 9.7 months (95% CI 8.5–11.0), median OS 19.2 months (95% CI 17.0–NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15% SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8–74.7). Conclusion: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable. PMID:24263064

  6. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    SciTech Connect

    Lao, Louis; Hope, Andrew J.; Maganti, Manjula; Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander; Cho, B. C. John

    2014-09-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

  7. The combination of antitumor drugs, exemestane and erlotinib, induced resistance mechanism in H358 and A549 non-small cell lung cancer (NSCLC) cell lines.

    PubMed

    Kritikou, Ismini; Giannopoulou, Efstathia; Koutras, Angelos K; Labropoulou, Vassiliki T; Kalofonos, Haralabos P

    2013-11-01

    Abstract Context: Estrogens in non-small-cell lung cancer (NSCLC) are important, and their interaction with epidermal growth factor receptor (EGFR) might be crucial. Objective: This study investigates the effect of exemestane, an aromatase inhibitor, and erlotinib, an EGFR inhibitor, on human NSCLC cell lines; H23, H358 and A549. Materials and methods: A cell proliferation assay was used for measuring cell number, apoptosis assay for detecting apoptosis and necrosis and immunoblotting for beclin-1 and Bcl-2 proteins detection. An immunofluorescence assay was used for EGFR localization. A migration assay and zymography were used for cell motility and metalloproteinases (MMPs) expression, respectively. Results: Exemestane, erlotinib or their combination decreased cell proliferation and increased apoptosis. Exemestane's half maximal inhibitory concentration (IC50) was 50 μM for H23 and H358 cells and 20 μM for A549. The IC50 of erlotinib was 25 μM for all cell lines. Apoptosis increase induced by exemestane was 58.0 (H23), 186.3 (H358) and 34.7% (A549) and by erlotinib was 16.7 (H23), 65.3 (H358) and 66.3% (A549). A synergy effect was observed only in H23 cells. Noteworthy, the combination of exemestane and erlotinib decreased beclin-1 protein levels (32.3 ± 19.2%), an indicator of autophagy, in H23 cells. The combination of exemestane and erlotinib partially reversed the EGFR translocation to mitochondria and decreased MMP levels and migration. Discussion and conclusions: The benefit from a dual targeting of aromatase and EGFR seems to be regulated by NSCLC cell content. The diverse responses of cells to agents might be influenced by the dominance of certain molecular pathways. PMID:24192333

  8. Randomized Phase II Study of Docetaxel plus Personalized Peptide Vaccination versus Docetaxel plus Placebo for Patients with Previously Treated Advanced Wild Type EGFR Non-Small-Cell Lung Cancer

    PubMed Central

    Takayama, Koichi; Sugawara, Shunichi; Saijo, Yasuo; Maemondo, Makoto; Sato, Atsushi; Takamori, Shinzo; Harada, Taishi; Sasada, Tetsuro; Kakuma, Tatsuyuki; Kishimoto, Junji; Yamada, Akira; Noguchi, Masanori; Itoh, Kyogo; Nakanishi, Yoichi

    2016-01-01

    Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC). Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m2 on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS). Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p = 0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed. PMID:27274999

  9. Advanced TEM specimen preparation methods for replication of P91 steel

    SciTech Connect

    Mitchell, D.R.G. . E-mail: drm@ansto.gov.au; Sulaiman, S.

    2006-01-15

    A range of advanced transmission electron microscopy specimen preparation methods, based on replication, have been developed for P91 steel. The results obtained have been compared with conventional replication and thin foil methods. The aim has been to obtain complimentary information from thin foil and replica specimens from the same region of interest either sequentially or simultaneously. The effects of various reagents for dissolution of the steel matrix and replica release have been investigated, and chemical methods for removing amorphous iron oxide contaminants from replicas have been identified. A method of region-specific replication is demonstrated whereby regions of thin foils previously characterised by TEM, can be subsequently replicated. This enables the former location of extracted particles, such as on grain/lath/subgrain boundaries etc., to be determined prior to microanalysis. It also permits the identification of artefacts such as stray particles and failed extractions. A second method of thin foil partial replication was developed in which both replica and thin foil are present on the same specimen. At the interface between the two regions, thin foil information such as dislocation interactions with fine scale particles and replica information such as microanalysis of particles within the same grain or lath can be obtained. Double replication of thin foils has also been successfully demonstrated. These methods are applied to a creep resistant martensitic steel (P91), but should be broadly applicable to a wide range of alloy steels.

  10. Advanced display object selection methods for enhancing user-computer productivity

    NASA Technical Reports Server (NTRS)

    Osga, Glenn A.

    1993-01-01

    The User-Interface Technology Branch at NCCOSC RDT&E Division has been conducting a series of studies to address the suitability of commercial off-the-shelf (COTS) graphic user-interface (GUI) methods for efficiency and performance in critical naval combat systems. This paper presents an advanced selection algorithm and method developed to increase user performance when making selections on tactical displays. The method has also been applied with considerable success to a variety of cursor and pointing tasks. Typical GUI's allow user selection by: (1) moving a cursor with a pointing device such as a mouse, trackball, joystick, touchscreen; and (2) placing the cursor on the object. Examples of GUI objects are the buttons, icons, folders, scroll bars, etc. used in many personal computer and workstation applications. This paper presents an improved method of selection and the theoretical basis for the significant performance gains achieved with various input devices tested. The method is applicable to all GUI styles and display sizes, and is particularly useful for selections on small screens such as notebook computers. Considering the amount of work-hours spent pointing and clicking across all styles of available graphic user-interfaces, the cost/benefit in applying this method to graphic user-interfaces is substantial, with the potential for increasing productivity across thousands of users and applications.

  11. The latest therapeutic strategies after resistance to first generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with non-small cell lung cancer (NSCLC)

    PubMed Central

    Xu, Meng; Xie, Yiqun; Ni, Songshi

    2015-01-01

    First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), gefitinib and erlotinib, produce reliable responses and survival benefits in selected patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, most patients who initially respond to first-line therapy with EGFR TKIs will experience disease progression in 1-2 years. To overcome the resistance of EGFR TKIs, the potent resistance mechanisms and novel therapeutic strategies have been developed. T790M mutation and activation of bypass signaling pathway are identified the predominant mechanisms of acquired resistance to TKIs. Several approaches have shown promise, such as next-generation EGFR TKIs, immunotherapy, and combinational therapies. And the limited clinical data suggest that all drugs are acceptable safe. Additionally, this review will also focus on the increasingly importance of re-biopsy at the time of disease progression, and the matching effective therapies is related to the identification of specific molecular types of tumors. PMID:26015938

  12. Advanced magnetic resonance imaging techniques in the preterm brain: methods and applications.

    PubMed

    Tao, Joshua D; Neil, Jeffrey J

    2014-01-01

    Brain development and brain injury in preterm infants are areas of active research. Magnetic resonance imaging (MRI), a non-invasive tool applicable to both animal models and human infants, provides a wealth of information on this process by bridging the gap between histology (available from animal studies) and developmental outcome (available from clinical studies). Moreover, MRI also offers information regarding diagnosis and prognosis in the clinical setting. Recent advances in MR methods - diffusion tensor imaging, volumetric segmentation, surface based analysis, functional MRI, and quantitative metrics - further increase the sophistication of information available regarding both brain structure and function. In this review, we discuss the basics of these newer methods as well as their application to the study of premature infants. PMID:25055864

  13. Advanced experimental applications for x-ray transmission gratings spectroscopy using a novel grating fabrication method.

    PubMed

    Hurvitz, G; Ehrlich, Y; Strum, G; Shpilman, Z; Levy, I; Fraenkel, M

    2012-08-01

    A novel fabrication method for soft x-ray transmission grating and other optical elements is presented. The method uses focused-ion-beam technology to fabricate high-quality free standing grating bars on transmission electron microscopy grids. High quality transmission gratings are obtained with superb accuracy and versatility. Using these gratings and back-illuminated CCD camera, absolutely calibrated x-ray spectra can be acquired for soft x-ray source diagnostics in the 100-3000 eV spectral range. Double grating combinations of identical or different parameters are easily fabricated, allowing advanced one-shot application of transmission grating spectroscopy. These applications include spectroscopy with different spectral resolutions, bandwidths, dynamic ranges, and may serve for identification of high-order contribution, and spectral calibrations of various x-ray optical elements. PMID:22938276

  14. Advanced experimental applications for x-ray transmission gratings spectroscopy using a novel grating fabrication method

    NASA Astrophysics Data System (ADS)

    Hurvitz, G.; Ehrlich, Y.; Strum, G.; Shpilman, Z.; Levy, I.; Fraenkel, M.

    2012-08-01

    A novel fabrication method for soft x-ray transmission grating and other optical elements is presented. The method uses focused-ion-beam technology to fabricate high-quality free standing grating bars on transmission electron microscopy grids. High quality transmission gratings are obtained with superb accuracy and versatility. Using these gratings and back-illuminated CCD camera, absolutely calibrated x-ray spectra can be acquired for soft x-ray source diagnostics in the 100-3000 eV spectral range. Double grating combinations of identical or different parameters are easily fabricated, allowing advanced one-shot application of transmission grating spectroscopy. These applications include spectroscopy with different spectral resolutions, bandwidths, dynamic ranges, and may serve for identification of high-order contribution, and spectral calibrations of various x-ray optical elements.

  15. Advanced negative detection method comparable to silver stain for SDS-PAGE separated proteins detection.

    PubMed

    Wang, Xu; Hwang, Sun-Young; Cong, Wei-Tao; Jin, Li-Tai; Choi, Jung-Kap

    2016-10-01

    In order to achieve an easy, rapid and sensitive protocol to detect proteins in polyacrylamide gel, an advanced negative detection method comparable to silver stain is described. When a gel was incubated with Phloxine B and followed by the development in acidic solution, the zones where forming protein-dye complex were selectively transparent, unlike opaque gel background. Within 50 min after electrophoresis, down to 0.1-0.4 ng of gel-separated proteins (similar with silver stain) could be observed, without labor-intensive and time-consuming procedure. Comparing with the most common negative stain method, Imidazole-zinc stain, Phloxine B stain has been shown higher sensitivity and distinct contrast between the transparent protein bands/spots and opaque background than those; furthermore, it is no longer necessary to concern about retention time of observation. This technique may provide a sensitive and practical choice for proteomics researches. PMID:27430933

  16. Advanced adaptive computational methods for Navier-Stokes simulations in rotorcraft aerodynamics

    NASA Technical Reports Server (NTRS)

    Stowers, S. T.; Bass, J. M.; Oden, J. T.

    1993-01-01

    A phase 2 research and development effort was conducted in area transonic, compressible, inviscid flows with an ultimate goal of numerically modeling complex flows inherent in advanced helicopter blade designs. The algorithms and methodologies therefore are classified as adaptive methods, which are error estimation techniques for approximating the local numerical error, and automatically refine or unrefine the mesh so as to deliver a given level of accuracy. The result is a scheme which attempts to produce the best possible results with the least number of grid points, degrees of freedom, and operations. These types of schemes automatically locate and resolve shocks, shear layers, and other flow details to an accuracy level specified by the user of the code. The phase 1 work involved a feasibility study of h-adaptive methods for steady viscous flows, with emphasis on accurate simulation of vortex initiation, migration, and interaction. Phase 2 effort focused on extending these algorithms and methodologies to a three-dimensional topology.

  17. Advanced fluorescence microscopy methods for the real-time study of transcription and chromatin dynamics

    PubMed Central

    Annibale, Paolo; Gratton, Enrico

    2014-01-01

    In this contribution we provide an overview of the recent advances allowed by the use of fluorescence microscopy methods in the study of transcriptional processes and their interplay with the chromatin architecture in living cells. Although the use of fluorophores to label nucleic acids dates back at least to about half a century ago,1 two recent breakthroughs have effectively opened the way to use fluorescence routinely for specific and quantitative probing of chromatin organization and transcriptional activity in living cells: namely, the possibility of labeling first the chromatin loci and then the mRNA synthesized from a gene using fluorescent proteins. In this contribution we focus on methods that can probe rapid dynamic processes by analyzing fast fluorescence fluctuations. PMID:25764219

  18. Finite element method for optimal guidance of an advanced launch vehicle

    NASA Technical Reports Server (NTRS)

    Hodges, Dewey H.; Bless, Robert R.; Calise, Anthony J.; Leung, Martin

    1992-01-01

    A temporal finite element based on a mixed form of Hamilton's weak principle is summarized for optimal control problems. The resulting weak Hamiltonian finite element method is extended to allow for discontinuities in the states and/or discontinuities in the system equations. An extension of the formulation to allow for control inequality constraints is also presented. The formulation does not require element quadrature, and it produces a sparse system of nonlinear algebraic equations. To evaluate its feasibility for real-time guidance applications, this approach is applied to the trajectory optimization of a four-state, two-stage model with inequality constraints for an advanced launch vehicle. Numerical results for this model are presented and compared to results from a multiple-shooting code. The results show the accuracy and computational efficiency of the finite element method.

  19. A Review of Failure Analysis Methods for Advanced 3D Microelectronic Packages

    NASA Astrophysics Data System (ADS)

    Li, Yan; Srinath, Purushotham Kaushik Muthur; Goyal, Deepak

    2016-01-01

    Advanced three dimensional (3D) packaging is a key enabler in driving form factor reduction, performance benefits, and package cost reduction, especially in the fast paced mobility and ultraportable consumer electronics segments. The high level of functional integration and the complex package architecture pose a significant challenge for conventional fault isolation (FI) and failure analysis (FA) methods. Innovative FI/FA tools and techniques are required to tackle the technical and throughput challenges. In this paper, the applications of FI and FA techniques such as Electro Optic Terahertz Pulse Reflectometry, 3D x-ray computed tomography, lock-in thermography, and novel physical sample preparation methods to 3D packages with package on package and stacked die with through silicon via configurations are reviewed, along with the key FI and FA challenges.

  20. Setting health research priorities using the CHNRI method: IV. Key conceptual advances

    PubMed Central

    Rudan, Igor

    2016-01-01

    Introduction Child Health and Nutrition Research Initiative (CHNRI) started as an initiative of the Global Forum for Health Research in Geneva, Switzerland. Its aim was to develop a method that could assist priority setting in health research investments. The first version of the CHNRI method was published in 2007–2008. The aim of this paper was to summarize the history of the development of the CHNRI method and its key conceptual advances. Methods The guiding principle of the CHNRI method is to expose the potential of many competing health research ideas to reduce disease burden and inequities that exist in the population in a feasible and cost–effective way. Results The CHNRI method introduced three key conceptual advances that led to its increased popularity in comparison to other priority–setting methods and processes. First, it proposed a systematic approach to listing a large number of possible research ideas, using the “4D” framework (description, delivery, development and discovery research) and a well–defined “depth” of proposed research ideas (research instruments, avenues, options and questions). Second, it proposed a systematic approach for discriminating between many proposed research ideas based on a well–defined context and criteria. The five “standard” components of the context are the population of interest, the disease burden of interest, geographic limits, time scale and the preferred style of investing with respect to risk. The five “standard” criteria proposed for prioritization between research ideas are answerability, effectiveness, deliverability, maximum potential for disease burden reduction and the effect on equity. However, both the context and the criteria can be flexibly changed to meet the specific needs of each priority–setting exercise. Third, it facilitated consensus development through measuring collective optimism on each component of each research idea among a larger group of experts using a simple

  1. Pemetrexed/cisplatin as first-line chemotherapy for advanced lung cancer with brain metastases

    PubMed Central

    He, Guangzhao; Xiao, Xiaoguang; Zou, Man; Zhang, Chengliang; Xia, Shu

    2016-01-01

    Abstract Background: Brain metastases (BMs) are a common and serious complication of non-small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT), surgery, and molecular targeted therapy are usually used to treat NSCLC with BM. Chemotherapeutic options for BM are limited by tumor resistance, ineffective agents, and the blood–brain barrier. Pemetrexed/cisplatin is the preferred chemotherapy in nonsquamous NSCLC, but the efficacy of this treatment for nonsquamous NSCLC with BM is uncertain. Methods: We present a case of nonsquamous NSCLC with asymptomatic BM presenting with irritating cough and right shoulder back pain (unknown sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase). Results: He benefited from administration of first-line chemotherapy of pemetrexed/cisplatin. Partial remission was achieved in the primary lesion of the lungs and BM lesion. He was further given 3 cycles of pemetrexed monotherapy and WBRT. Complete remission was further achieved in BM lesion. Conclusion: The findings of clinical trials and theoretical studies about the current pemetrexed/cisplatin in the treatment of nonsquamous NSCLC with BM are also summarized to provide a reference for the application of pemetrexed/cisplatin in nonsquamous NSCLC with BM. Whether or not pemetrexed/cisplatin is definitely effective in nonsquamous NSCLC with BM must be proven by subsequent phase III clinical trials. PMID:27512852

  2. Aquatic ecosystem protection and restoration: Advances in methods for assessment and evaluation

    USGS Publications Warehouse

    Bain, M.B.; Harig, A.L.; Loucks, D.P.; Goforth, R.R.; Mills, K.E.

    2000-01-01

    Many methods and criteria are available to assess aquatic ecosystems, and this review focuses on a set that demonstrates advancements from community analyses to methods spanning large spatial and temporal scales. Basic methods have been extended by incorporating taxa sensitivity to different forms of stress, adding measures linked to system function, synthesizing multiple faunal groups, integrating biological and physical attributes, spanning large spatial scales, and enabling simulations through time. These tools can be customized to meet the needs of a particular assessment and ecosystem. Two case studies are presented to show how new methods were applied at the ecosystem scale for achieving practical management goals. One case used an assessment of biotic structure to demonstrate how enhanced river flows can improve habitat conditions and restore a diverse fish fauna reflective of a healthy riverine ecosystem. In the second case, multitaxonomic integrity indicators were successful in distinguishing lake ecosystems that were disturbed, healthy, and in the process of restoration. Most methods strive to address the concept of biological integrity and assessment effectiveness often can be impeded by the lack of more specific ecosystem management objectives. Scientific and policy explorations are needed to define new ways for designating a healthy system so as to allow specification of precise quality criteria that will promote further development of ecosystem analysis tools.

  3. Verification of a Depletion Method in SCALE for the Advanced High Temperature Reactor

    SciTech Connect

    KELLY, RYAN; Ilas, Dan

    2013-01-01

    This study describes a new approach employing the Dancoff correction method to model the TRISO-based fuel form used by the Advanced High-Temperature Reactor (AHTR) reactor design concept. The Dancoff correction method is used to perform isotope depletion analysis using the TRITON sequence of SCALE and is verified by code-to-code comparisons. The current AHTR fuel design has TRISO particles concentrated along the edges of a slab fuel element. This geometry prevented the use of the DOUBLEHET treatment, previously developed in SCALE to model spherical and cylindrical fuel. The new method permits fuel depletion on complicated geometries that traditionally can be handled only by continuous energy based depletion code systems. The method was initially tested on a fuel configuration typical of the Next Generation Nuclear Plant (NGNP), where DOUBLEHET treatment is possible. A confirmatory study was performed on the AHTR reference core geometry using the VESTA code, which uses the continuous energy MCNP5 code as a transport solver and ORIGEN2.2 code for depletion calculations. Comparisons of the results indicate good agreement of whole core characteristics, such as the multiplication factor and the isotopics, including their spatial distribution. Key isotopes analyzed included 235U, 239Pu, 240Pu, and 241Pu. The results from this study indicate that the Dancoff factor method can generate estimates of core characteristics with reasonable precision for scoping studies of configurations where DOUBLEHET treatment cannot be performed.

  4. A Combined Method for Segmentation and Registration for an Advanced and Progressive Evaluation of Thermal Images

    PubMed Central

    Barcelos, Emilio Z.; Caminhas, Walmir M.; Ribeiro, Eraldo; Pimenta, Eduardo M.; Palhares, Reinaldo M.

    2014-01-01

    In this paper, a method that combines image analysis techniques, such as segmentation and registration, is proposed for an advanced and progressive evaluation of thermograms. The method is applied for the prevention of muscle injury in high-performance athletes, in collaboration with a Brazilian professional soccer club. The goal is to produce information on spatio-temporal variations of thermograms favoring the investigation of the athletes' conditions along the competition. The proposed method improves on current practice by providing a means for automatically detecting adaptive body-shaped regions of interest, instead of the manual selection of simple shapes. Specifically, our approach combines the optimization features in Otsu's method with a correction factor and post-processing techniques, enhancing thermal-image segmentation when compared to other methods. Additional contributions resulting from the combination of the segmentation and registration steps of our approach are the progressive analyses of thermograms in a unique spatial coordinate system and the accurate extraction of measurements and isotherms. PMID:25414972

  5. Advanced Methods for Aircraft Engine Thrust and Noise Benefits: Nozzle-Inlet Flow Analysis

    NASA Technical Reports Server (NTRS)

    Morgan, Morris H., III; Gilinsky, Mikhail M.

    2004-01-01

    In this project on the first stage (2000-Ol), we continued to develop the previous joint research between the Fluid Mechanics and Acoustics Laboratory (FM&AL) at Hampton University (HU) and the Jet Noise Team (JNT) at the NASA Langley Research Center (NASA LaRC). At the second stage (2001-03), FM&AL team concentrated its efforts on solving of problems of interest to Glenn Research Center (NASA GRC), especially in the field of propulsion system enhancement. The NASA GRC R&D Directorate and LaRC Hyper-X Program specialists in a hypersonic technology jointly with the FM&AL staff conducted research on a wide region of problems in the propulsion field as well as in experimental testing and theoretical and numerical simulation analyses for advanced aircraft and rocket engines. The last year the Hampton University School of Engineering & Technology was awarded the NASA grant, for creation of the Aeropropulsion Center, and the FM&AL is a key team of the project fulfillment responsible for research in Aeropropulsion and Acoustics (Pillar I). This work is supported by joint research between the NASA GRC/ FM&AL and the Institute of Mechanics at Moscow State University (IMMSU) in Russia under a CRDF grant. The main areas of current scientific interest of the FM&AL include an investigation of the proposed and patented advanced methods for aircraft engine thrust and noise benefits. This is the main subject of our other projects, of which one is presented. The last year we concentrated our efforts to analyze three main problems: (a) new effective methods fuel injection into the flow stream in air-breathing engines; (b) new re-circulation method for mixing, heat transfer and combustion enhancement in propulsion systems and domestic industry application; (c) covexity flow The research is focused on a wide regime of problems in the propulsion field as well as in experimental testing and theoretical and numerical simulation analyses for advanced aircraft and rocket engines (see, for

  6. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer

    PubMed Central

    2013-01-01

    Introduction Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. Methods Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45–60) followed by an SBRT boost with an average dose of 25 Gy (range 20–30) given over 5 fractions. Results With a median follow-up of 14 months (range, 1–14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. Conclusion Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC. PMID:23842112

  7. A simple HPLC-UV method for the simultaneous quantification of gefitinib and erlotinib in human plasma.

    PubMed

    Faivre, Lionel; Gomo, Charline; Mir, Olivier; Taieb, Fabrice; Schoemann-Thomas, Audrey; Ropert, Stanislas; Vidal, Michel; Dusser, Daniel; Dauphin, Alain; Goldwasser, Francois; Blanchet, Benoit

    2011-08-01

    Gefitinib and erlotinib are two oral tyrosine kinase inhibitors (TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Published methods for simultaneous analysis of erlotinib and gefitinib in plasma are exclusively based on mass spectrometry. The purpose of this study was to develop a simple and sensitive HPLC-UV method to simultaneously quantify these two TKI in plasma. Following liquid-liquid extraction, gefitinib, erlotinib and sorafenib (internal standard), were separated with gradient elution (on a C8+ Satisfaction(®) using a mobile phase of acetonitrile/20mM ammonium acetate pH 4.5). Samples were eluted at a flow rate of 0.4 ml/min throughout the 15-min run. Dual UV wavelength mode was used, with gefitinib and erlotinib monitored at 331 nm, and sorafenib at 249 nm. The calibration was linear in the range 20-1000 ng/ml and 80-4000 ng/ml for gefitinib and erlotinib, respectively. Inter- and intra-day imprecision were less than 7.2% and 7.6% for gefitinib and erlotinib, respectively. This analytical method was successfully applied to assess the steady state plasma exposure to these TKI in NSCLC patients. This simple, sensitive, accurate and cost-effective method can be used in routine clinical practice to monitor gefitinib or erlotinib concentrations in plasma from NSCLC patients. PMID:21737360

  8. Transformer 2β (Tra2β/SFRS10) positively regulates the progression of NSCLC via promoting cell proliferation.

    PubMed

    Ji, Lili; Ni, Tingting; Shen, Yanbo; Xue, Qun; Liu, Yifei; Chen, Buyou; Cui, Xuefan; Lv, Liting; Yu, Xiafei; Cui, Yuan; Lu, Xiaoning; Chen, Jie; Mao, Guoxin; Wang, Yuchan

    2014-10-01

    Transformer 2β (Tra2β), a member of the serine/arginine-rich-like protein family, is an important RNA-binding protein involved in alternative splice. Deregulation of Tra2β has been observed in several cancers. However, the detailed role of Tra2β in non-small cell lung cancer (NSCLC) has not been elucidated. In this study, the contribution of Tra2β to NSCLC development was investigated. On histological level, the expression of Tra2β was determined by Western and immunohistochemistry assays. It demonstrated that Tra2β was expressed higher in NSCLC tumor tissues compared with adjacent non-tumor tissues. In addition to confirm the association of Tra2β expression with histological differentiation and clinical stage (p < 0.05), we also confirmed significant positive correlation between the expression level of Tra2β and that of Ki67 (p < 0.05, r = 0.446) by Spearman rank correlation test. Moreover, high expression of Tra2β predicted poor prognosis by Kaplan-Meier survival analysis. And Tra2β among with other clinicopathologic variables was an independent prognostic indicator for patients' overall survival by multivariate analysis. On cellular level, Tra2β expression was demonstrated to promote proliferation of NSCLC cells through a series of assays, including serum starvation and release assay, Western blot assay and flow cytometry analysis. Moreover, knockdown of Tra2β was confirmed to inhibit proliferation and to induce apoptosis of NSCLC cells through flow cytometry analysis, western analysis, cell counting kit-8 assay and Tunnel assay. Our results indicated that Tra2β was involved in the tumorigenesis of NSCLC and might be a potential therapeutic target of NSCLC. PMID:24952301

  9. Numerical Evaluation of Fluid Mixing Phenomena in Boiling Water Reactor Using Advanced Interface Tracking Method

    NASA Astrophysics Data System (ADS)

    Yoshida, Hiroyuki; Takase, Kazuyuki

    Thermal-hydraulic design of the current boiling water reactor (BWR) is performed with the subchannel analysis codes which incorporated the correlations based on empirical results including actual-size tests. Then, for the Innovative Water Reactor for Flexible Fuel Cycle (FLWR) core, an actual size test of an embodiment of its design is required to confirm or modify such correlations. In this situation, development of a method that enables the thermal-hydraulic design of nuclear reactors without these actual size tests is desired, because these tests take a long time and entail great cost. For this reason, we developed an advanced thermal-hydraulic design method for FLWRs using innovative two-phase flow simulation technology. In this study, a detailed Two-Phase Flow simulation code using advanced Interface Tracking method: TPFIT is developed to calculate the detailed information of the two-phase flow. In this paper, firstly, we tried to verify the TPFIT code by comparing it with the existing 2-channel air-water mixing experimental results. Secondary, the TPFIT code was applied to simulation of steam-water two-phase flow in a model of two subchannels of a current BWRs and FLWRs rod bundle. The fluid mixing was observed at a gap between the subchannels. The existing two-phase flow correlation for fluid mixing is evaluated using detailed numerical simulation data. This data indicates that pressure difference between fluid channels is responsible for the fluid mixing, and thus the effects of the time average pressure difference and fluctuations must be incorporated in the two-phase flow correlation for fluid mixing. When inlet quality ratio of subchannels is relatively large, it is understood that evaluation precision of the existing two-phase flow correlations for fluid mixing are relatively low.

  10. Characterization of FGFR1 Locus in sqNSCLC Reveals a Broad and Heterogeneous Amplicon

    PubMed Central

    Rooney, Claire; Geh, Catherine; Williams, Victoria; Heuckmann, Johannes M.; Menon, Roopika; Schneider, Petra; Al-Kadhimi, Katherine; Dymond, Michael; Smith, Neil R.; Baker, Dawn; French, Tim; Smith, Paul D.; Harrington, Elizabeth A.; Barrett, J. Carl; Kilgour, Elaine

    2016-01-01

    FGFR1 amplification occurs in ~20% of sqNSCLC and trials with FGFR inhibitors have selected FGFR1 amplified patients by FISH. Lung cancer cell lines were profiled for sensitivity to AZD4547, a potent, selective inhibitor of FGFRs 1–3. Sensitivity to FGFR inhibition was associated with but not wholly predicted by increased FGFR1 gene copy number. Additional biomarker assays evaluating expression of FGFRs and correlation between amplification and expression in clinical tissues are therefore warranted. We validated nanoString for mRNA expression analysis of 194 genes, including FGFRs, from clinical tumour tissue. In a panel of sqNSCLC tumours 14.4% (13/90) were FGFR1 amplified by FISH. Although mean FGFR1 expression was significantly higher in amplified samples, there was significant overlap in the range of expression levels between the amplified and non-amplified cohorts with several non-amplified samples expressing FGFR1 to levels equivalent to amplified samples. Statistical analysis revealed increased expression of FGFR1 neighboring genes on the 8p12 amplicon (BAG4, LSM1 and WHSC1L1) in FGFR1 amplified tumours, suggesting a broad rather than focal amplicon and raises the potential for codependencies. High resolution aCGH analysis of pre-clinical and clinical samples supported the presence of a broad and heterogeneous amplicon around the FGFR1 locus. In conclusion, the range of FGFR1 expression levels in both FGFR1 amplified and non-amplified NSCLC tissues, together with the breadth and intra-patient heterogeneity of the 8p amplicon highlights the need for gene expression analysis of clinical samples to inform the understanding of determinants of response to FGFR inhibitors. In this respect the nanoString platform provides an attractive option for RNA analysis of FFPE clinical samples. PMID:26905262

  11. ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC.

    PubMed

    Cheng, Qijian; Zhou, Ling; Zhou, Jianping; Wan, Huanying; Li, Qingyun; Feng, Yun

    2016-09-01

    Angiotensin II (AngII) is a multifunctional bioactive peptide in the renin-angiotensin system (RAS). Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS. We previously reported that ACE2 overexpression may inhibit cell growth and vascular endothelial growth factor (VEGF) production in vitro and in vivo. In the present study, we investigated the effect of ACE2 on tumor-associated angiogen-esis after the development of acquired platinum resistance in non-small cell lung cancer (NSCLC). Four NSCLC cell lines, A549, LLC, A549-DDP and LLC-DDP, were used in vitro, while A549 and A549-DDP cells were used in vivo. A549-DDP and LLC-DDP cells were newly established at our institution as acquired platinum-resistant sublines by culturing the former parent cells in cisplatin (CDDP)-containing conditioned medium for 6 months. These platinum-resistant cells showed significantly higher angiotensin II type 1 receptor (AT1R), ACE and VEGF production and lower ACE2 expression than their corresponding parent cells. We showed that ACE2 overexpression inhibited the production of VEGF in vitro and in vivo compared to their corresponding parent cells. We also found that ACE2 overexpression reduced the expression of AT1R and ACE. Additionally, we confirmed that ACE2 overexpres-sion inhibited cell growth and VEGF production while simultaneously suppressing ACE and AT1R expression in human lung cancer xenografts. Our findings indicate that ACE2 overexpression may potentially suppress angiogenesis in NSCLC after the development of acquired platinum resistance. PMID:27460845

  12. Next-Generation Covalent Irreversible Kinase Inhibitors in NSCLC: Focus on Afatinib.

    PubMed

    Hirsh, Vera

    2015-06-01

    First-generation, reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, represented an important addition to the treatment armamentarium for non-small-cell lung cancer (NSCLC) patients with activating EGFR mutations. However, all patients inevitably develop acquired resistance to these agents, primarily due to secondary EGFR mutations, molecular aberrations affecting other signaling pathways, or transformation to small-cell histology. It was hypothesized that development of second-generation TKIs with broader inhibitory profiles could confer longer-lasting clinical activity and overcome acquired resistance to first-generation inhibitors. Here, we review the development of afatinib, an irreversible ErbB family blocker that potently inhibits signaling of all homodimers and heterodimers formed by the EGFR, human epidermal growth factor receptor (HER)-2, HER3, and HER4 receptors. In two phase III trials in patients with EGFR mutation-positive NSCLC, first-line afatinib significantly improved progression-free survival (PFS) and health-related quality of life versus standard-of-care chemotherapy. Moreover, in preplanned sub-analyses, afatinib significantly improved overall survival in patients harboring EGFR Del19 mutations. Afatinib has also demonstrated clinical activity in NSCLC patients who had progressed on erlotinib/gefitinib, particularly when combined with cetuximab, and offers 'treatment beyond progression' benefit when combined with paclitaxel versus chemotherapy alone. Furthermore, a recent phase III study demonstrated that PFS was significantly improved with afatinib versus erlotinib for the second-line treatment of patients with squamous cell carcinoma of the lung. The activity of afatinib in both first-line and relapsed/refractory settings may reflect its ability to irreversibly inhibit all ErbB family members. Afatinib has a well-defined safety profile with characteristic gastrointestinal (diarrhea

  13. Role of pemetrexed in advanced non-small-cell lung cancer: meta-analysis of randomized controlled trials, with histology subgroup analysis

    PubMed Central

    Al-Saleh, K.; Quinton, C.; Ellis, P.M.

    2012-01-01

    Purpose Platinum-based regimens represent the standard first-line treatment for non-small-cell lung cancer (nsclc). However, newer data have established a role for pemetrexed in the treatment of this disease. Such data suggest that histology represents a determining factor in the selection of treatment. Methods We undertook a systematic review of the literature for randomized controlled trials that compared the efficacy of pemetrexed with that of other treatments in advanced nsclc. Data and study quality were assessed according to published guidelines. Results We identified five trials that compared pemetrexed with other treatments or with placebo. Overall survival for patients treated with pemetrexed was superior to that with other treatments: hazard ratio (hr): 0.89; 95% confidence interval (ci): 0.80 to 0.99. The survival benefit was limited to patients with non-squamous histology: hr: 0.82; 95% ci: 0.73 to 0.91. Pemetrexed was inferior to other chemotherapy options in patients with squamous histology: hr: 1.19; 95% ci: 0.99 to 1.43. Conclusions Compared with other chemotherapy agents, pemetrexed is more effective for the treatment of nsclc in patients with non-squamous histology. PMID:22328848

  14. Microwave Ablation in Combination with Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Wei, Zhigang Ye, Xin Yang, Xia Zheng, Aimin Huang, Guanghui Li, Wenhong Ni, Xiang Wang, Jiao; Han, Xiaoying

    2015-02-15

    PurposeTo verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy.MethodsThirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0).ResultsMWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00–9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5–11.9). The median overall survival time was 21.3 months (95 % CI 17.0–25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients.ConclusionsPatients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable.

  15. Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression

    PubMed Central

    Walworth, Kyla; Bodas, Manish; Campbell, Ryan John; Swanson, Doug; Sharma, Ajit; Vij, Neeraj

    2016-01-01

    Elevated valosin containing protein (VCP/p97) levels promote the progression of non-small cell lung carcinoma (NSCLC). Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC) progression. The VCP inhibitor(s) (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface) were tested for their in vitro efficacy in modulating H1299 (NSCLC cells) proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (p<0.0001, MTT-assay) and migration (p<0.05; scratch-assay), and increased apoptosis (p<0.05; caspase-3/7-assay) as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ) treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting) of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion) as compared to the control-DDN treatment (p<0.05). Moreover, DDNDBeQ treatment showed a significant decrease in cell proliferation (p<0.01, MTT-assay) and increased caspase-3/7 mediated apoptotic cell death (p<0.05) as compared to DDN-control. This was further verified by cell cycle analysis (propidium-iodide-staining) that demonstrated significant cell cycle arrest in the G2/M-phase (p<0.001) by DDNDBeQ treatment as compared to control-DDN. Moreover

  16. Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression.

    PubMed

    Walworth, Kyla; Bodas, Manish; Campbell, Ryan John; Swanson, Doug; Sharma, Ajit; Vij, Neeraj

    2016-01-01

    Elevated valosin containing protein (VCP/p97) levels promote the progression of non-small cell lung carcinoma (NSCLC). Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC) progression. The VCP inhibitor(s) (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface) were tested for their in vitro efficacy in modulating H1299 (NSCLC cells) proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (p<0.0001, MTT-assay) and migration (p<0.05; scratch-assay), and increased apoptosis (p<0.05; caspase-3/7-assay) as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ) treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting) of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion) as compared to the control-DDN treatment (p<0.05). Moreover, DDNDBeQ treatment showed a significant decrease in cell proliferation (p<0.01, MTT-assay) and increased caspase-3/7 mediated apoptotic cell death (p<0.05) as compared to DDN-control. This was further verified by cell cycle analysis (propidium-iodide-staining) that demonstrated significant cell cycle arrest in the G2/M-phase (p<0.001) by DDNDBeQ treatment as compared to control-DDN. Moreover

  17. Projected role of advanced computational aerodynamic methods at the Lockheed-Georgia company

    NASA Technical Reports Server (NTRS)

    Lores, M. E.

    1978-01-01

    Experience with advanced computational methods being used at the Lockheed-Georgia Company to aid in the evaluation and design of new and modified aircraft indicates that large and specialized computers will be needed to make advanced three-dimensional viscous aerodynamic computations practical. The Numerical Aerodynamic Simulation Facility should be used to provide a tool for designing better aerospace vehicles while at the same time reducing development costs by performing computations using Navier-Stokes equations solution algorithms and permitting less sophisticated but nevertheless complex calculations to be made efficiently. Configuration definition procedures and data output formats can probably best be defined in cooperation with industry, therefore, the computer should handle many remote terminals efficiently. The capability of transferring data to and from other computers needs to be provided. Because of the significant amount of input and output associated with 3-D viscous flow calculations and because of the exceedingly fast computation speed envisioned for the computer, special attention should be paid to providing rapid, diversified, and efficient input and output.

  18. Accuracy Evaluation of a Mobile Mapping System with Advanced Statistical Methods

    NASA Astrophysics Data System (ADS)

    Toschi, I.; Rodríguez-Gonzálvez, P.; Remondino, F.; Minto, S.; Orlandini, S.; Fuller, A.

    2015-02-01

    This paper discusses a methodology to evaluate the precision and the accuracy of a commercial Mobile Mapping System (MMS) with advanced statistical methods. So far, the metric potentialities of this emerging mapping technology have been studied in few papers, where generally the assumption that errors follow a normal distribution is made. In fact, this hypothesis should be carefully verified in advance, in order to test how well the Gaussian classic statistics can adapt to datasets that are usually affected by asymmetrical gross errors. The workflow adopted in this study relies on a Gaussian assessment, followed by an outlier filtering process. Finally, non-parametric statistical models are applied, in order to achieve a robust estimation of the error dispersion. Among the different MMSs available on the market, the latest solution provided by RIEGL is here tested, i.e. the VMX-450 Mobile Laser Scanning System. The test-area is the historic city centre of Trento (Italy), selected in order to assess the system performance in dealing with a challenging and historic urban scenario. Reference measures are derived from photogrammetric and Terrestrial Laser Scanning (TLS) surveys. All datasets show a large lack of symmetry that leads to the conclusion that the standard normal parameters are not adequate to assess this type of data. The use of non-normal statistics gives thus a more appropriate description of the data and yields results that meet the quoted a-priori errors.

  19. Applications of flight control system methods to an advanced combat rotorcraft

    NASA Technical Reports Server (NTRS)

    Tischler, Mark B.; Fletcher, Jay W.; Morris, Patrick M.; Tucker, George T.

    1989-01-01

    Advanced flight control system design, analysis, and testing methodologies developed at the Ames Research Center are applied in an analytical and flight test evaluation of the Advanced Digital Optical Control System (ADOCS) demonstrator. The primary objectives are to describe the knowledge gained about the implications of digital flight control system design for rotorcraft, and to illustrate the analysis of the resulting handling-qualities in the context of the proposed new handling-qualities specification for rotorcraft. Topics covered in-depth are digital flight control design and analysis methods, flight testing techniques, ADOCS handling-qualities evaluation results, and correlation of flight test results with analytical models and the proposed handling-qualities specification. The evaluation of the ADOCS demonstrator indicates desirable response characteristics based on equivalent damping and frequency, but undersirably large effective time-delays (exceeding 240 m sec in all axes). Piloted handling-qualities are found to be desirable or adequate for all low, medium, and high pilot gain tasks; but handling-qualities are inadequate for ultra-high gain tasks such as slope and running landings.

  20. Evaluation of Advanced Stirling Convertor Net Heat Input Correlation Methods Using a Thermal Standard

    NASA Technical Reports Server (NTRS)

    Briggs, Maxwell H.; Schifer, Nicholas A.

    2012-01-01

    The U.S. Department of Energy (DOE) and Lockheed Martin Space Systems Company (LMSSC) have been developing the Advanced Stirling Radioisotope Generator (ASRG) for use as a power system for space science missions. This generator would use two high-efficiency Advanced Stirling Convertors (ASCs), developed by Sunpower Inc. and NASA Glenn Research Center (GRC). The ASCs convert thermal energy from a radioisotope heat source into electricity. As part of ground testing of these ASCs, different operating conditions are used to simulate expected mission conditions. These conditions require achieving a particular operating frequency, hot end and cold end temperatures, and specified electrical power output for a given net heat input. In an effort to improve net heat input predictions, numerous tasks have been performed which provided a more accurate value for net heat input into the ASCs, including testing validation hardware, known as the Thermal Standard, to provide a direct comparison to numerical and empirical models used to predict convertor net heat input. This validation hardware provided a comparison for scrutinizing and improving empirical correlations and numerical models of ASC-E2 net heat input. This hardware simulated the characteristics of an ASC-E2 convertor in both an operating and non-operating mode. This paper describes the Thermal Standard testing and the conclusions of the validation effort applied to the empirical correlation methods used by the Radioisotope Power System (RPS) team at NASA Glenn.

  1. On the Use of Accelerated Test Methods for Characterization of Advanced Composite Materials

    NASA Technical Reports Server (NTRS)

    Gates, Thomas S.

    2003-01-01

    A rational approach to the problem of accelerated testing for material characterization of advanced polymer matrix composites is discussed. The experimental and analytical methods provided should be viewed as a set of tools useful in the screening of material systems for long-term engineering properties in aerospace applications. Consideration is given to long-term exposure in extreme environments that include elevated temperature, reduced temperature, moisture, oxygen, and mechanical load. Analytical formulations useful for predictive models that are based on the principles of time-based superposition are presented. The need for reproducible mechanisms, indicator properties, and real-time data are outlined as well as the methodologies for determining specific aging mechanisms.

  2. Nanoscale Characterization of Mock Explosive Materials Using Advanced Atomic Force Microscopy Methods

    NASA Astrophysics Data System (ADS)

    Xu, Xin; Mares, Jesus; Groven, Lori J.; Son, Steven F.; Reifenberger, Ronald G.; Raman, Arvind

    2015-01-01

    Most explosives are micro- and nanoscale composite material systems consisting of energetic crystals, amorphous particles, binders, and additives whose response to mechanical, thermal, or electromagnetic insults is often controlled by submicrometer-scale heterogeneities and interfaces. Several advanced dynamic atomic force microscopy (AFM) techniques, including phase imaging, force volume mode, and Kelvin probe force microscopy with resonance enhancement for dielectric property mapping, have been used to map the local physical properties of mock explosive materials systems, allowing the identification of submicrometer heterogeneities in electrical and mechanical properties that could lead to the formation of hotspots under electromagnetic or mechanical stimuli. The physical interpretation of the property maps and the methods of image formation are presented. Possible interpretations of the results and future applications to energetic material systems are also discussed.

  3. Exploring Atmospheric Aerosol Chemistry with Advanced High-Resolution Mass Spectrometry and Particle Imaging Methods

    NASA Astrophysics Data System (ADS)

    Nizkorodov, S.

    2014-12-01

    Physical and chemical complexity of atmospheric aerosols presents significant challenges both to experimentalists working on aerosol characterization and to modelers trying to parameterize critical aerosol properties. Multi-modal approaches that combine state-of-the-art experimental, theoretical, and modeling methods are becoming increasingly important in aerosol research. This presentation will discuss recent applications of unique high-resolution mass spectrometry and particle imaging tools developed at two Department of Energy's user facilities, the Environmental Molecular Science Laboratory (EMSL) and Advanced Light Source (ALS), to studies of molecular composition, photochemical aging, and properties of laboratory-generated and field aerosols. Specifically, this presentation will attempt to address the following questions: (a) how do NO2, SO2, and NH3 affect molecular level composition of anthropogenic aerosols?; (b) what factors determine viscosity/surface tension of organic aerosol particles?; (c) how does photolysis affect molecular composition and optical properties of organic aerosols?

  4. Advances in the Development and Validation of Test Methods in the United States

    PubMed Central

    Casey, Warren M.

    2016-01-01

    The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) provides validation support for US Federal agencies and the US Tox21 interagency consortium, an interagency collaboration that is using high throughput screening (HTS) and other advanced approaches to better understand and predict chemical hazards to humans and the environment. The use of HTS data from assays relevant to the estrogen receptor signaling data pathway is used as an example of how HTS data can be combined with computational modeling to meet the needs of US agencies. As brief summary of US efforts in the areas of biologics testing, acute toxicity, and skin sensitization will also be provided. PMID:26977254

  5. Soil remediation by an advanced oxidative method assisted with ultrasonic energy.

    PubMed

    Flores, Roberto; Blass, Georgina; Domínguez, Vanessa

    2007-02-01

    A new process for the remediation of soil contaminated with hydrocarbons is proposed. The innovation consists on coupling an advanced oxidative method, using a Fenton-type catalyst, with the application of ultrasonic energy. The use of ultrasonic energy not only assists the desorption of the contaminants from the soil, but also promotes the formation of OH radicals, which are the oxidant agents involved in the oxidation process. Different Fenton-like catalysts were employed in the present study; however, the highest removal of toluene and xylenes were obtained with iron sulfate and copper sulfate, respectively. Also, hydrogen peroxide was tested at different concentrations, and it was found that increasing its concentration enhanced the removal of all the contaminants. Finally, it was demonstrated that applying ultrasonic energy to the reacting system process noticeably enhanced the global efficiency of the process due to a synergistic effect in conjunction with the hydrogen peroxide concentration and type of catalyst. PMID:17079076

  6. ADVANCED MR IMAGING METHODS FOR PLANNING AND MONITORING RADIATION THERAPY IN PATIENTS WITH HIGH GRADE GLIOMA

    PubMed Central

    Lupo, Janine M.; Nelson, Sarah J.

    2016-01-01

    This review explores how the integration of advanced imaging methods with high quality anatomic images significantly improves the characterization, target definition, assessment of response to therapy, and overall management of patients with high-grade glioma. Metrics derived from diffusion, perfusion, and susceptibility weighted MR imaging in conjunction with MR spectroscopic imaging, allows us to characterize regions of edema, hypoxia, increased cellularity, and necrosis within heterogeneous tumor and surrounding brain tissue. Quantification of such measures may provide a more reliable initial representation of tumor delineation and response to therapy than changes in the contrast enhancing or T2 lesion alone and have a significant impact on targeting resection, planning radiation, and assessing treatment effectiveness. In the long-term, implementation of these imaging methodologies can also aid in the identification of recurrent tumor and its differentiation from treatment-related confounds and facilitate the detection of radiation-induced vascular injury in otherwise normal appearing brain tissue. PMID:25219809

  7. A weak Hamiltonian finite element method for optimal guidance of an advanced launch vehicle

    NASA Technical Reports Server (NTRS)

    Hodges, Dewey H.; Calise, Anthony J.; Bless, Robert R.; Leung, Martin

    1989-01-01

    A temporal finite-element method based on a mixed form of the Hamiltonian weak principle is presented for optimal control problems. The mixed form of this principle contains both states and costates as primary variables, which are expanded in terms of nodal values and simple shape functions. Time derivatives of the states and costates do not appear in the governing variational equation; the only quantities whose time derivatives appear therein are virtual states and virtual costates. Numerical results are presented for an elementary trajectory optimization problem; they show very good agreement with the exact solution along with excellent computational efficiency and self-starting capability. The feasibility of this approach for real-time guidance applications is evaluated. A simplified model for an advanced launch vehicle application that is suitable for finite-element solution is presented.

  8. Can EGFR-TKIs be used in first line treatment for advanced non-small cell lung cancer based on selection according to clinical factors ? -- A literature-based meta-analysis

    PubMed Central

    2012-01-01

    Background In the first line treatment of non-small cell lung cancer (NSCLC), several clinical trials have shown that not all NSCLC patients can benefit from treatment with tyrosine kinase inhibitors (TKIs) than receiving chemotherapy. Some trials treated patients with TKI according to their clinical characteristics. A few studies only chose patients with an epidermal grouth factor receptor (EGFR) mutation for TKI therapy. We aimed to determine whether patients could be treated with TKIs based on clinical factors in the first-line setting. Methods We performed a meta-analysis of randomized trials involving patients with advanced NSCLC treated with chemotherapy or TKIs by different selections. Efficacy outcomes of interest were the objective response rate (ORR), progression-free survival (PFS) and the overall survival (OS) of each treatment arm. Results Four trials enrolled unselected patients, and two trials selected East Asian patients using the clinical factors of gender and smoking history. Five trials chose patients with an EGFR mutation who were randomized for treatment with TKI or chemotherapy. For unselected patients, the risk ratio (RR) of the ORR was 3.52, the hazard ratio (HR) of the PFS was 1.29 and the HR of the OS was 1.35. For the clinically selected patients, the RR of the ORR was 0.64. The HRs of the PFS and OS were 0.83 and 0.92, respectively. The ORR and PFS were better for TKIs than for chemotherapy in patients with an EGFR mutation. The ORR was 0.47, and the HRs of the PFS and OS were 0.36 and 1.00, respectively. Conclusions Advanced NSCLC patients with an EGFR mutation benefit most from TKIs. EGFR-TKI treatment is justified for patients with unknown EGFR status,and those who cannot tolerate chemotherapy owing to age, poor performance status (PS) or other medical conditions, when selected according to clinical factors in the first-line setting. PMID:23050865

  9. Assessment of Crack Detection in Cast Austenitic Piping Components Using Advanced Ultrasonic Methods.

    SciTech Connect

    Anderson, Michael T.; Crawford, Susan L.; Cumblidge, Stephen E.; Diaz, Aaron A.; Doctor, Steven R.

    2007-01-01

    Studies conducted at the Pacific N¬orthwest National Laboratory (PNNL) in Richland, Washington, have focused on developing and evaluating the reliability of nondestructive examination (NDE) approaches for inspecting coarse-grained, cast stainless steel reactor components. The objective of this work is to provide information to the United States Nuclear Regulatory Commission (NRC) on the utility, effec¬tiveness and limitations of ultrasonic testing (UT) inspection techniques as related to the in-service inspec¬tion of primary system piping components in pressurized water reactors (PWRs). Cast stainless steel pipe specimens were examined that contain thermal and mechanical fatigue cracks located close to the weld roots and have inside/outside surface geometrical conditions that simulate several PWR primary piping configurations. In addition, segments of vintage centrifugally cast piping were also examined to understand inherent acoustic noise and scattering due to grain structures and determine consistency of UT responses from different locations. The advanced UT methods were applied from the outside surface of these specimens using automated scanning devices and water coupling. The low-frequency ultrasonic method employed a zone-focused, multi-incident angle inspection protocol (operating at 250-450 kHz) coupled with a synthetic aperture focusing technique (SAFT) for improved signal-to-noise and advanced imaging capabilities. The phased array approach was implemented with a modified instrument operating at 500 kHz and composite volumetric images of the specimens were generated. Re¬sults from laboratory studies for assessing detection, localization and sizing effectiveness are discussed in this paper.

  10. Advanced Remedial Methods for Metals and Radionuclides in Vadose Zone Environments

    SciTech Connect

    Wellman, Dawn M.; Mattigod, Shas V.; Hubbard, Susan; Miracle, Ann L.; Zhong, Lirong; Foote, Martin; Wu, Yuxin; Jansik, Danielle P.

    2010-10-03

    Functionally, the methods for addressing contamination must remove and/or reduce transport or toxicity of contaminants. This problem is particularly challenging in arid environments where the vadose zone can be up to hundreds of feet thick, rendering transitional excavation methods exceedingly costly and ineffective. Delivery of remedial amendments is one of the most challenging and critical aspects for all remedy-based approaches. The conventional approach for delivery is through injection of aqueous remedial solutions. However, heterogeneous vadose zone environments present hydrologic and geochemical challenges that limit the effectiveness. Because the flow of solution infiltration is dominantly controlled by gravity and suction, injected liquid preferentially percolates through highly permeable pathways, by-passing low-permeability zones which frequently contain the majority of the contamination. Moreover, the wetting front can readily mobilize and enhance contaminant transport to underlying aquifers prior to stabilization. Development of innovative, in-situ technologies may be the only way to meet remedial action objectives and long-term stewardship goals. Shear-thinning fluids (i.e., surfactants) can be used to lower the liquid surface tension and create stabile foams, which readily penetrate low permeability zones. Although surfactant foams have been utilized for subsurface mobilization efforts in the oil and gas industry, so far, the concept of using foams as a delivery mechanism for transporting reactive remedial amendments into deep vadose zone environments to stabilize metal and long-lived radionuclide contaminants has not been explored. Foam flow can be directed by pressure gradients, rather than being dominated by gravity; and, foam delivery mechanisms limit the volume of water (< 20% vol.) required for remedy delivery and emplacement, thus mitigating contaminant mobilization. We will present the results of a numerical modeling and integrated laboratory

  11. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

    PubMed Central

    Ahmed, Rafay; Oborski, Matthew J; Hwang, Misun; Lieberman, Frank S; Mountz, James M

    2014-01-01

    Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas. PMID:24711712

  12. Advanced Method for In-Field Measurement, Monitoring and Verification of Total Soil Carbon

    NASA Astrophysics Data System (ADS)

    Ebinger, M. H.; Harris, R. D.; Ploss, J. C.; Clegg, S. M.

    2005-12-01

    The Earth`s oceans, forests, agricultural lands and other natural areas absorb about half of the carbon dioxide emitted from anthropogenic sources. Terrestrial carbon sequestration strategies are immediately available to bridge the gap between current terrestrial sequestration capacity and high-capacity geologic sequestration projects available in 10 to 20 years. Terrestrial carbon sequestration strategies consist of implementing land management practices aimed at decreasing CO2 emitted into the atmosphere and developing advanced measurement tools to inventory and monitor carbon processes in soils and biota. In addition to atmospheric CO2 mitigation and carbon trading advantages, terrestrial carbon sequestration produces a variety of benefits which include reclamation of degraded lands, increased soil productivity, increased land value and a more secure food source. Carbon storage in soil depends on climate and management practices, with potential yearly increases estimated from 0 to 150 kg-C ha-1 yr-1 in semiarid environments and up to 1000 kg-C ha-1 yr-1 in more humid environments. Measuring these increases, or in some cases losses of C, is currently a challenge with conventional instrumentation. Development of rapid, accurate, and cost effective and methods of measuring soil carbon are needed to address terrestrial sequestration issues and other aspects of global change. Laser-induced breakdown spectroscopy (LIBS) is one promising advanced measurement method for soil carbon. LIBS has several advantages to conventional analytical tools including speed, analysis takes minutes, and portability as well as increased accuracy and precision. We will show the development of LIBS instrumentation for soil carbon measurement and test results to demonstrate the potential of LIBS to help address the measurement challenge.

  13. miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion.

    PubMed

    Zhang, Hong; Zhu, Xiaoxia; Li, Na; Li, Dianhe; Sha, Zhou; Zheng, Xiaokang; Wang, Haofei

    2015-07-01

    Metastasis-associated gene 1 (MTA1) is associated with cell growth, metastasis, and survival in non-small-cell lung cancer (NSCLC). Several previous reports have demonstrated that microRNAs affect gene expression through interaction between their seed region and the 3'-untranslated region of the target mRNA, resulting in post-transcriptional regulation. The aim of this study was to identify miRNAs that suppress malignancy in NSCLC cells by targeting MTA1. Two human NSCLC cell lines were analyzed for the expression of MTA1 by quantitative RT-PCR and western blotting after transfection with MTA1 mimics. A luciferase reporter assay was established to test the direct connection between MTA1 and its upstream miRNAs. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2'-deoxyuridine analysis, and colony formation assay. Cell migration and invasive capacity were evaluated by wound-healing assay and transwell assay. The miRNA/MTA1 axis was also probed by quantitative RT-PCR and western blotting in samples from eight NSCLC patients. Among the candidate miRNAs, miR-125a-3p was shown to post-transcriptionally regulate MTA1 in NSCLC cells. These data were reinforced by the luciferase reporter assay, in addition to the demonstration that MTA1 is inversely correlated with miR-125a-3p in NSCLC tissues. Furthermore, miR-125a-3p was found to inhibit NSCLC cell proliferation, migration, and invasion, through the same mechanisms of down-regulated MTA1. Our report demonstrates that miR-125a-3p inhibits the proliferation, migration, and invasion of NSCLC cells through down-regulation of MTA1, indicating the role of the miR-125a-3p/MTA1 axis in NSCLC, and may provide novel insight into the molecular mechanisms underpinning the disease and potential therapeutic targets. PMID:25998575

  14. Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors

    PubMed Central

    Jin, Hyeon-Ok; Hong, Sung-Eun; Park, Jin-Ah; Chang, Yoon Hwan; Hong, Young Jun; Park, In-Chul; Lee, Jin Kyung

    2016-01-01

    As the activation of autophagy contributes to the efficacy of many anticancer therapies, deciphering the precise role of autophagy in cancer therapy is critical. Here, we report that the dual mTORC1/2 inhibitors PP242 and OSI-027 decreased cell viability but did not induce apoptosis in the non-small cell lung cancer (NSCLC) cell lines H460 and A549. PP242 induced autophagy in NSCLC cells as demonstrated by the formation of massive vacuoles and acidic vesicular organelles and the accumulation of LC3-II. JNK was activated by PP242, and PP242-induced autophagy was blocked by inhibiting JNK pathway with SP600125 or JNK siRNA, suggesting that JNK activation is required for the mTORC1/2 inhibitor-mediated induction of autophagy in NSCLC cells. Inhibiting JNK or autophagy increased the sensitivity of H460 cells to mTORC1/2 inhibitors, indicating that JNK or autophagy promoted survival in NSCLC cells treated with mTORC1/2 inhibitors. Together, these data suggest that combining mTORC1/2 inhibitors with inhibitors of JNK or autophagy might be an effective approach for improving therapeutic outcomes in NSCLC. PMID:27358039

  15. Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors.

    PubMed

    Jin, Hyeon-Ok; Hong, Sung-Eun; Park, Jin-Ah; Chang, Yoon Hwan; Hong, Young Jun; Park, In-Chul; Lee, Jin Kyung

    2016-01-01

    As the activation of autophagy contributes to the efficacy of many anticancer therapies, deciphering the precise role of autophagy in cancer therapy is critical. Here, we report that the dual mTORC1/2 inhibitors PP242 and OSI-027 decreased cell viability but did not induce apoptosis in the non-small cell lung cancer (NSCLC) cell lines H460 and A549. PP242 induced autophagy in NSCLC cells as demonstrated by the formation of massive vacuoles and acidic vesicular organelles and the accumulation of LC3-II. JNK was activated by PP242, and PP242-induced autophagy was blocked by inhibiting JNK pathway with SP600125 or JNK siRNA, suggesting that JNK activation is required for the mTORC1/2 inhibitor-mediated induction of autophagy in NSCLC cells. Inhibiting JNK or autophagy increased the sensitivity of H460 cells to mTORC1/2 inhibitors, indicating that JNK or autophagy promoted survival in NSCLC cells treated with mTORC1/2 inhibitors. Together, these data suggest that combining mTORC1/2 inhibitors with inhibitors of JNK or autophagy might be an effective approach for improving therapeutic outcomes in NSCLC. PMID:27358039

  16. Plasma cell-free DNA levels and integrity in patients with chest radiological findings: NSCLC versus benign lung nodules.

    PubMed

    Szpechcinski, Adam; Rudzinski, Piotr; Kupis, Wlodzimierz; Langfort, Renata; Orlowski, Tadeusz; Chorostowska-Wynimko, Joanna

    2016-05-01

    Effective discrimination between lung cancer and benign tumours is a common clinical problem in the differential diagnosis of solitary pulmonary nodules. The analysis of cell-free DNA (cfDNA) in blood may greatly aid the early detection of lung cancer by evaluating cancer-related alterations. The plasma cfDNA levels and integrity were analysed in 65 non-small cell lung cancer (NSCLC) patients, 28 subjects with benign lung tumours, and 16 healthy controls using real-time PCR. The NSCLC patients demonstrated significantly higher mean plasma cfDNA levels compared with those with benign tumours (P = 0.0009) and healthy controls (P < 0.0001). The plasma cfDNA integrity in healthy individuals was significantly different than that found in patients with NSCLC or benign lung tumours (P < 0.0003). In ROC curve analysis, plasma cfDNA levels >2.8 ng/ml provided 86.4% sensitivity and 61.4% specificity in discriminating NSCLC from benign lung pathologies and healthy controls. cfDNA integrity showed better discriminatory power (91% sensitivity, 68.2% specificity). These data demonstrate that plasma cfDNA concentration and integrity analyses can significantly differentiate between NSCLC and benign lung tumours. The diagnostic capacity of the quantitative cfDNA assay is comparable to the values presented by conventional imaging modalities used in clinical practice. PMID:26854716

  17. An advanced synthetic eddy method for the computation of aerofoil-turbulence interaction noise

    NASA Astrophysics Data System (ADS)

    Kim, Jae Wook; Haeri, Sina

    2015-04-01

    This paper presents an advanced method to synthetically generate flow turbulence via an inflow boundary condition particularly designed for three-dimensional aeroacoustic simulations. The proposed method is virtually free of spurious noise that might arise from the synthetic turbulence, which enables a direct calculation of propagated sound waves from the source mechanism. The present work stemmed from one of the latest outcomes of synthetic eddy method (SEM) derived from a well-defined vector potential function creating a divergence-free velocity field with correct convection speeds of eddies, which in theory suppresses pressure fluctuations. In this paper, a substantial extension of the SEM is introduced and systematically optimised to create a realistic turbulence field based on von Kármán velocity spectra. The optimised SEM is then combined with a well-established sponge-layer technique to quietly inject the turbulent eddies into the domain from the upstream boundary, which results in a sufficiently clean acoustic field. Major advantages in the present approach are: a) that genuinely three-dimensional turbulence is generated; b) that various ways of parametrisation can be created to control/characterise the randomly distributed eddies; and, c) that its numerical implementation is efficient as the size of domain section through which the turbulent eddies should be passing can be adjusted and minimised. The performance and reliability of the proposed SEM are demonstrated by a three-dimensional simulation of aerofoil-turbulence interaction noise.

  18. Weathering Patterns of Ignitable Liquids with the Advanced Distillation Curve Method

    PubMed Central

    Bruno, Thomas J; Allen, Samuel

    2013-01-01

    One can take advantage of the striking similarity of ignitable liquid vaporization (or weathering) patterns and the separation observed during distillation to predict the composition of residual compounds in fire debris. This is done with the advanced distillation curve (ADC) metrology, which separates a complex fluid by distillation into fractions that are sampled, and for which thermodynamically consistent temperatures are measured at atmospheric pressure. The collected sample fractions can be analyzed by any method that is appropriate. Analytical methods we have applied include gas chromatography (with flame ionization, mass spectrometric and sulfur chemiluminescence detection), thin layer chromatography, FTIR, Karl Fischer coulombic titrimetry, refractometry, corrosivity analysis, neutron activation analysis and cold neutron prompt gamma activation analysis. We have applied this method on product streams such as finished fuels (gasoline, diesel fuels, aviation fuels, rocket propellants), crude oils (including a crude oil made from swine manure) and waste oils streams (used automotive and transformer oils). In this paper, we present results on a variety of ignitable liquids that are not commodity fuels, chosen from the Ignitable Liquids Reference Collection (ILRC). These measurements are assembled into a preliminary database. From this selection, we discuss the significance and forensic application of the temperature data grid and the composition explicit data channel of the ADC. PMID:26401423

  19. Weathering Patterns of Ignitable Liquids with the Advanced Distillation Curve Method.

    PubMed

    Bruno, Thomas J; Allen, Samuel

    2013-01-01

    One can take advantage of the striking similarity of ignitable liquid vaporization (or weathering) patterns and the separation observed during distillation to predict the composition of residual compounds in fire debris. This is done with the advanced distillation curve (ADC) metrology, which separates a complex fluid by distillation into fractions that are sampled, and for which thermodynamically consistent temperatures are measured at atmospheric pressure. The collected sample fractions can be analyzed by any method that is appropriate. Analytical methods we have applied include gas chromatography (with flame ionization, mass spectrometric and sulfur chemiluminescence detection), thin layer chromatography, FTIR, Karl Fischer coulombic titrimetry, refractometry, corrosivity analysis, neutron activation analysis and cold neutron prompt gamma activation analysis. We have applied this method on product streams such as finished fuels (gasoline, diesel fuels, aviation fuels, rocket propellants), crude oils (including a crude oil made from swine manure) and waste oils streams (used automotive and transformer oils). In this paper, we present results on a variety of ignitable liquids that are not commodity fuels, chosen from the Ignitable Liquids Reference Collection (ILRC). These measurements are assembled into a preliminary database. From this selection, we discuss the significance and forensic application of the temperature data grid and the composition explicit data channel of the ADC. PMID:26401423

  20. Advanced nodal neutron diffusion method with space-dependent cross sections: ILLICO-VX

    SciTech Connect

    Rajic, H.L.; Ougouag, A.M.

    1987-01-01

    Advanced transverse integrated nodal methods for neutron diffusion developed since the 1970s require that node- or assembly-homogenized cross sections be known. The underlying structural heterogeneity can be accurately accounted for in homogenization procedures by the use of heterogeneity or discontinuity factors. Other (milder) types of heterogeneity, burnup-induced or due to thermal-hydraulic feedback, can be resolved by explicitly accounting for the spatial variations of material properties. This can be done during the nodal computations via nonlinear iterations. The new method has been implemented in the code ILLICO-VX (ILLICO variable cross-section method). Numerous numerical tests were performed. As expected, the convergence rate of ILLICO-VX is lower than that of ILLICO, requiring approx. 30% more outer iterations per k/sub eff/ computation. The methodology has also been implemented as the NOMAD-VX option of the NOMAD, multicycle, multigroup, two- and three-dimensional nodal diffusion depletion code. The burnup-induced heterogeneities (space dependence of cross sections) are calculated during the burnup steps.

  1. Fast discrimination of danshen from different geographical areas by NIR spectroscopy and advanced cluster analysis method

    NASA Astrophysics Data System (ADS)

    Li, Ning; Wang, Yan; Xu, Kexin

    2006-09-01

    Near infrared (NIR) diffuse reflection spectroscopy has been an effective way to perform quantitative analysis without the requirement of sample pretreatnient. In this paper, NIR Fourier transform infrared (FTIR) spectroscopy has been introduced to probe spectral features of traditional Chinese medicine Danshen. Infrared fingerprint spectra of Danshen can be established. Influence of differentiation of spectrum is also discussed. After pretreatment and derivation on the spectral data, methods of principal analysis (PCA), soft independent modeling of class analogy (SIMCA) and Artificial Neural Network (ANN) are combined to sort the geographical origins of 53 samples by local modeling. The result show that, as a basis of the other two methods, PCA is a more efficient one for identifying the geographical origins of Danshen. Combining SIMCA with PCA, an effective model is built to analyze the data after normalization and differentiation, the correct identification rate reaches above 90%. Then 36 samples are chosen as training set while other 17 samples being verifying set. Using ANN-based Back Propagation method, after proper training of BP network, the origins of Danshen are completely classified. Therefore, combined with advanced mathematical analysis, NIR diffuse spectroscopy can be a novel and rapid way to accurately evaluate the origin of Chinese medicine, and also to accelerate the modernization process of Chinese drugs.

  2. PILOT STUDY OF GEFITINIB AND FULVESTRANT IN THE TREATMENT OF POST-MENOPAUSAL WOMEN WITH ADVANCED NON-SMALL CELL LUNG CANCER

    PubMed Central

    Traynor, Anne M.; Schiller, Joan H.; Stabile, Laura P.; Kolesar, Jill M.; Eickhoff, Jens C.; Dacic, Sanja; Hoang, Tien; Dubey, Sarita; Marcotte, Sarah M.; Siegfried, Jill M.

    2011-01-01

    SUMMARY Introduction Estrogen receptor beta (ERβ) has been detected in NSCLC cell lines and tumor specimens. The ER down-regulator, fulvestrant, blocked estradiol-stimulation of tumor growth and gene transcription in NSCLC preclinical models and showed additive effects with the EGFR inhibitor gefitinib. The safety and tolerability of combination therapy with the EGFR inhibitor, gefitinib, and fulvestrant was explored. Methods Post-menopausal women with advanced NSCLC received gefitinib 250 mg po daily and fulvestrant 250 mg IM monthly. Results Twenty-two patients were enrolled. Eight patients had adenocarcinoma, 6 NSCLC-NOS, 4 squamous cell, and 4 BAC. Seven patients were never smokers. Eight patients received ≥ 2 lines of prior chemotherapy, 6 received one prior chemotherapy, and 8 were treatment naive. One patient experienced grade 4 dyspnea possibly related to treatment; all other grade 3/4 toxicities were unrelated to treatment. Twenty patients were evaluable for response: 3 PRs were confirmed (response rate of 15%, 95% CI: 5% – 36%). The median PFS, OS, and estimated 1 yr OS were 12 wks (3–112 wks), 38.5 weeks (7–135 wks), and 41% (95% CI 20–62%), respectively. Survival outcomes did not differ by prior lines of therapy. A subset analysis revealed that OS in the 8 patients whose tumors exhibited at least 60% ERβ nuclear IHC staining measured 65.5 weeks, while that of the 5 patients with ERβ staining of less than 60% was 21 weeks. One patient with BAC and a PR had an EGFR L858R mutation in exon 21. There was no correlation between ERβ IHC expression and histology or smoking history. Conclusions Combination therapy with gefitinib and fulvestrant in this population was well-tolerated and demonstrated disease activity. PMID:18701186

  3. Clinical effect of pemetrexed as the first‐line treatment in Chinese patients with advanced anaplastic lymphoma kinase‐positive non‐small cell lung cancer

    PubMed Central

    Ma, Di; Hao, Xuezhi; Wang, Yan; Xing, Puyuan

    2016-01-01

    Background The efficacy of pemetrexed‐based first‐line chemotherapy in anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations. Methods The clinicopathological characteristics and treatment outcomes of 52 patients with ALK‐positive advanced NSCLC who received pemetrexed as first‐line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression‐free survival (PFS). Results The gender proportion was balanced and the median age was 51 years (range 26–76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454–11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2. Conclusions Pemetrexed is efficient and tolerated as first‐line treatment for ALK‐positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK‐positive NSCLC. PMID:27385988

  4. Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC

    PubMed Central

    Che, Ting-Fang; Lin, Ching-Wen; Wu, Yi-Ying; Chen, Yu-Ju; Han, Chia-Li; Chang, Yih-leong; Wu, Chen-Tu; Hsiao, Tzu-Hung

    2015-01-01

    Dysfunction of the mitochondria is well-known for being associated with cancer progression. In the present study, we analyzed the mitochondria proteomics of lung cancer cell lines with different invasion abilities and found that EGFR is highly expressed in the mitochondria of highly invasive non-small-cell lung cancer (NSCLC) cells. EGF induces the mitochondrial translocation of EGFR; further, it leads to mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo. Moreover, EGFR can regulate mitochondrial dynamics by interacting with Mfn1 and disturbing Mfn1 polymerization. Overexpression of Mfn1 reverses the phenotypes resulting from EGFR mitochondrial translocation. We show that the mitochondrial EGFR expressions are higher in paired samples of the metastatic lymph node as compared with primary lung tumor and are inversely correlated with the overall survival in NSCLC patients. Therefore, our results demonstrate that besides the canonical role of EGFR as a receptor tyrosine, the mitochondrial translocation of EGFR may enhance cancer invasion and metastasis through regulating mitochondria dynamics. PMID:26497368

  5. Rebiopsy during disease progression in patients treated by TKI for oncogene-addicted NSCLC.

    PubMed

    Bosc, Cecile; Ferretti, Gilbert R; Cadranel, Jacques; Audigier-Valette, Clarisse; Besse, Benjamin; Barlesi, Fabrice; Decroisette, Chantal; Lantuejoul, Sylvie; Arbib, François; Moro-Sibilot, Denis

    2015-06-01

    All lung cancer patients with mutant epidermal growth factor receptor (EGFR) or rearranged EML4-ALK eventually develop acquired resistance to treatment. Rebiopsy may give insight into the resistance mechanisms and direct further lines of treatment. Here, we evaluate the potential interest and limitations of rebiopsy. Patients with mutant EGFR or rearranged EML4-ALK non-small cell lung cancer (NSCLC) and acquired resistance to tyrosine kinase inhibitors were included in a retrospective study to determine the percentage of patients who underwent rebiopsy and whether rebiopsy would have been possible, or not, in the remaining patients. In a cohort of 84 patients from 6 institutions, a biopsy had been performed in 39 cases. Biopsy samples were sufficient for histopathological or cytological examination in 35 cases (89.7 %). Complete or partial response had been observed in 84.5 % of patients whose cancer further progressed and who underwent rebiopsy. A biopsy could have been considered in 30 of the 45 remaining patients. Those with brain (N = 9) and bone (N = 2) metastases and/or with contraindications (N = 6) were excluded (two patients had both brain metastases and a contraindication). The rebiopsy target was thoracic in 62 % of cases and on distant metastases in 38 % of cases. Patients with NSCLC and an activating mutation could undergo a rebiopsy in 72 % of cases. A response to treatment does not preclude the possibility of rebiopsy at the time of progression. PMID:25119973

  6. [Jinlong capsule combined with chemoradiotherapy for NSCLC: a Meta-analysis].

    PubMed

    Lu, Qiang; Luo, Jing-bin; Feng, Yi-fan; She, Qin; Shi, Zhong-feng

    2015-11-01

    The purpose of this study was to evaluate the effect and safety of Jinlong capsule combined with chemotherapy or radio-therapy for non-small cell lung cancer (NSCLS) using Meta-analysis. PubMed, Embase, CNKI and Wanfang databases were all searched without language restriction, and searching time was from January 1990 to July 2015. All eligible published studies were included in this study for quality assessment and data extraction. All the data were analyzed using Revman 5.3. A total of ten studies including 736 subjects (370 in Jinlong capsule plus chemoradiotherapy and 366 in chemoradiotherapy only) were finally included in this Meta-analysis. The result of Meta analysis showed that compared with pure chemoradiotherapy group, Jinlong capsule combined with chemoradiotherapy for NSCLC could improve the patients' curative effect (OR = 1.77, 95% CI: 1.29-2.43, P < 0.05), clinical benefit rate (OR = 1.89, 95% CI: 1.22-2.91, P < 0.05), life quality improvement rate (OR = 2. 56, 95% CI: 1.61-4.05, P < 0.05), and decrease leucopenia incidence rate (OR = 0.35, 95% CI: 0. 22-0.56, P < 0.05) and gastrointestinal reaction rate (OR = 0.67, 95% CI: 0.40-1.11, P < 0.05). The pooled results showed that Jinlong capsule combined with chemoradiotherapy for NSCLC could improve the curative effect and life quality, and decrease the adverse reaction of patients. PMID:27097429

  7. Recent advancements in the electromechanical (E/M) impedance method for structural health monitoring and NDE

    NASA Astrophysics Data System (ADS)

    Giurgiutiu, Victor; Rogers, Craig A.

    1998-07-01

    The emerging electro-mechanical impedance technology has high potential for in-situ health monitoring and NDE of structural systems and complex machinery. At first, the fundamental principles of the electro-mechanical impedance method are briefly reviewed and ways for practical implementation are highlighted. The equations of piezo- electric material response are given, and the coupled electro-mechanical impedance of a piezo-electric wafer transducer as affixed to the monitored structure is discussed. Due to the high frequency operation of this NDE method, wave propagation phenomena are identified as the primary coupling method between the structural substrate and the piezo-electric wafer transducer. Attention is then focused on several recent advancements that have extended the electro-mechanical impedance method into new areas of applications and/or have developed its underlying principles. US Army Construction Engineering Research Laboratory used the electro-mechanical impedance method to monitor damage development in composite overlaid civil infrastructure specimens under full-scale static testing. A simplified E/M impedance measuring technique was employed at the Polytechnic University of Madrid, Spain, to detect damage in GFRP composite specimens. The development of miniaturized `bare-bones' impedance analyzer equipment that could be easily packaged into transponder-size dimensions is being studied at the University of South Carolina. US Army Research Laboratory developed novel piezo-composite film transducers for embedment into composite structures. Disbond gauges for monitoring the structural joints of adhesively bonded rotor blades have been studies in the Mechanical Engineering Department at the University of South Carolina. These recent developments accentuate the importance and benefits of using the electro-mechanical impedance method for on-line health monitoring and damage detection in a variety of applications. Further investigation of the electro

  8. Training toward Advanced 3D Seismic Methods for CO2 Monitoring, Verification, and Accounting

    SciTech Connect

    Christopher Liner

    2012-05-31

    The objective of our work is graduate and undergraduate student training related to improved 3D seismic technology that addresses key challenges related to monitoring movement and containment of CO{sub 2}, specifically better quantification and sensitivity for mapping of caprock integrity, fractures, and other potential leakage pathways. We utilize data and results developed through previous DOE-funded CO{sub 2} characterization project (DE-FG26-06NT42734) at the Dickman Field of Ness County, KS. Dickman is a type locality for the geology that will be encountered for CO{sub 2} sequestration projects from northern Oklahoma across the U.S. midcontinent to Indiana and Illinois. Since its discovery in 1962, the Dickman Field has produced about 1.7 million barrels of oil from porous Mississippian carbonates with a small structural closure at about 4400 ft drilling depth. Project data includes 3.3 square miles of 3D seismic data, 142 wells, with log, some core, and oil/water production data available. Only two wells penetrate the deep saline aquifer. In a previous DOE-funded project, geological and seismic data were integrated to create a geological property model and a flow simulation grid. We believe that sequestration of CO{sub 2} will largely occur in areas of relatively flat geology and simple near surface, similar to Dickman. The challenge is not complex geology, but development of improved, lower-cost methods for detecting natural fractures and subtle faults. Our project used numerical simulation to test methods of gathering multicomponent, full azimuth data ideal for this purpose. Our specific objectives were to apply advanced seismic methods to aide in quantifying reservoir properties and lateral continuity of CO{sub 2} sequestration targets. The purpose of the current project is graduate and undergraduate student training related to improved 3D seismic technology that addresses key challenges related to monitoring movement and containment of CO{sub 2

  9. Development of Advanced Life Cycle Costing Methods for Technology Benefit/Cost/Risk Assessment

    NASA Technical Reports Server (NTRS)

    Yackovetsky, Robert (Technical Monitor)

    2002-01-01

    The overall objective of this three-year grant is to provide NASA Langley's System Analysis Branch with improved affordability tools and methods based on probabilistic cost assessment techniques. In order to accomplish this objective, the Aerospace Systems Design Laboratory (ASDL) needs to pursue more detailed affordability, technology impact, and risk prediction methods and to demonstrate them on variety of advanced commercial transports. The affordability assessment, which is a cornerstone of ASDL methods, relies on the Aircraft Life Cycle Cost Analysis (ALCCA) program originally developed by NASA Ames Research Center and enhanced by ASDL. This grant proposed to improve ALCCA in support of the project objective by updating the research, design, test, and evaluation cost module, as well as the engine development cost module. Investigations into enhancements to ALCCA include improved engine development cost, process based costing, supportability cost, and system reliability with airline loss of revenue for system downtime. A probabilistic, stand-alone version of ALCCA/FLOPS will also be developed under this grant in order to capture the uncertainty involved in technology assessments. FLOPS (FLight Optimization System program) is an aircraft synthesis and sizing code developed by NASA Langley Research Center. This probabilistic version of the coupled program will be used within a Technology Impact Forecasting (TIF) method to determine what types of technologies would have to be infused in a system in order to meet customer requirements. A probabilistic analysis of the CER's (cost estimating relationships) within ALCCA will also be carried out under this contract in order to gain some insight as to the most influential costs and the impact that code fidelity could have on future RDS (Robust Design Simulation) studies.

  10. Measurement of fracture toughness by nanoindentation methods: Recent advances and future challenges

    DOE PAGESBeta

    Sebastiani, Marco; Johanns, K. E.; Herbert, Erik G.; Pharr, George M.

    2015-04-30

    In this study, we describe recent advances and developments for the measurement of fracture toughness at small scales by the use of nanoindentation-based methods including techniques based on micro-cantilever beam bending and micro-pillar splitting. A critical comparison of the techniques is made by testing a selected group of bulk and thin film materials. For pillar splitting, cohesive zone finite element simulations are used to validate a simple relationship between the critical load at failure, the pillar radius, and the fracture toughness for a range of material properties and coating/substrate combinations. The minimum pillar diameter required for nucleation and growth ofmore » a crack during indentation is also estimated. An analysis of pillar splitting for a film on a dissimilar substrate material shows that the critical load for splitting is relatively insensitive to the substrate compliance for a large range of material properties. Experimental results from a selected group of materials show good agreement between single cantilever and pillar splitting methods, while a discrepancy of ~25% is found between the pillar splitting technique and double-cantilever testing. It is concluded that both the micro-cantilever and pillar splitting techniques are valuable methods for micro-scale assessment of fracture toughness of brittle ceramics, provided the underlying assumptions can be validated. Although the pillar splitting method has some advantages because of the simplicity of sample preparation and testing, it is not applicable to most metals because their higher toughness prevents splitting, and in this case, micro-cantilever bend testing is preferred.« less

  11. Measurement of fracture toughness by nanoindentation methods: Recent advances and future challenges

    SciTech Connect

    Sebastiani, Marco; Johanns, K. E.; Herbert, Erik G.; Pharr, George M.

    2015-04-30

    In this study, we describe recent advances and developments for the measurement of fracture toughness at small scales by the use of nanoindentation-based methods including techniques based on micro-cantilever beam bending and micro-pillar splitting. A critical comparison of the techniques is made by testing a selected group of bulk and thin film materials. For pillar splitting, cohesive zone finite element simulations are used to validate a simple relationship between the critical load at failure, the pillar radius, and the fracture toughness for a range of material properties and coating/substrate combinations. The minimum pillar diameter required for nucleation and growth of a crack during indentation is also estimated. An analysis of pillar splitting for a film on a dissimilar substrate material shows that the critical load for splitting is relatively insensitive to the substrate compliance for a large range of material properties. Experimental results from a selected group of materials show good agreement between single cantilever and pillar splitting methods, while a discrepancy of ~25% is found between the pillar splitting technique and double-cantilever testing. It is concluded that both the micro-cantilever and pillar splitting techniques are valuable methods for micro-scale assessment of fracture toughness of brittle ceramics, provided the underlying assumptions can be validated. Although the pillar splitting method has some advantages because of the simplicity of sample preparation and testing, it is not applicable to most metals because their higher toughness prevents splitting, and in this case, micro-cantilever bend testing is preferred.

  12. Efficient method development strategy for challenging separation of pharmaceutical molecules using advanced chromatographic technologies.

    PubMed

    Xiao, Kang Ping; Xiong, Yuan; Liu, Fang Zhu; Rustum, Abu M

    2007-09-01

    In this paper, we describe a strategy that can be used to efficiently develop a high-performance liquid chromatography (HPLC) separation of challenging pharmaceutical molecules. This strategy involves use of advanced chromatographic technologies, such as a computer-assisted chromatographic method development tool (ChromSword) and an automated column switching system (LC Spiderling). This process significantly enhances the probability of achieving adequate separations and can be a large time saver for bench analytical scientists. In our study, the ChromSword was used for mobile phase screening and separation optimization, and the LC Spiderling was used to identify the most appropriate HPLC columns. For proof of concept, the analytes employed in this study are the structural epimers betamethylepoxide and alphamethylepoxide (also known as 16-beta methyl epoxide and 16-alpha methyl epoxide). Both of these compounds are used in the synthesis of various active pharmaceutical ingredients that are part of the steroid pharmaceutical products. While these molecules are relatively large in size and contain various polar functional groups and non-polar cyclic carbon chains, their structures differ only in the orientation of one methyl group. To our knowledge, there is no reported HPLC separation of these two molecules. A simple gradient method was quickly developed on a 5 cm YMC Hydrosphere C(18) column that separated betamethylepoxide and alphamethylepoxide in 10 min with a resolution factor of 3.0. This high resolution provided a true baseline separation even when the concentration ratio between these two epimers was 10,000:1. Although outside of the scope of this paper, stability-indicating assay and impurity profile methods for betamethylepoxide and for alphamethylepoxide have also been developed by our group based on a similar method development strategy. PMID:17628579

  13. Temporality Matters: Advancing a Method for Analyzing Problem-Solving Processes in a Computer-Supported Collaborative Environment

    ERIC Educational Resources Information Center

    Kapur, Manu

    2011-01-01

    This paper argues for a need to develop methods for examining temporal patterns in computer-supported collaborative learning (CSCL) groups. It advances one such quantitative method--Lag-sequential Analysis (LsA)--and instantiates it in a study of problem-solving interactions of collaborative groups in an online, synchronous environment. LsA…

  14. Anti-angiogenic drugs for second-line treatment of NSCLC patients: just new pawns on the chessboard?

    PubMed

    Bronte, Giuseppe; Passiglia, Francesco; Galvano, Antonio; Russo, Antonio

    2016-01-01

    Tumor angiogenesis is one of the main pathways targeted to treat cancer. Bevacizumab added survival benefit when combined with platinum-based chemotherapy in NSCLC. Recently, Phase III trials showed survival benefit when anti-angiogenic drugs are added to docetaxel as second-line treatment for NSCLC. These anti-angiogenic agents include nintedanib and ramucirumab, a tyrosine-kinase inhibitor and a monoclonal antibody, respectively, which target receptors involved in angiogenesis. These studies have some similarities and differences. We propose a new algorithm for treatment sequences in performance status 0-1 patients with non-oncogene-addicted NSCLC type adenocarcinoma. Indeed clearer scientific evidences are available for this subgroup of patients. PMID:26235195

  15. Inhibition of non-small cell lung cancer (NSCLC) growth by a novel small molecular inhibitor of EGFR

    PubMed Central

    Fang, Yuanzhang; Vaughn, Amanda; Cai, Xiaopan; Xu, Leqin; Wan, Wei; Li, Zhenxi; Chen, Shijie; Yang, Xinghai; Wu, Song; Xiao, Jianru

    2015-01-01

    The epidermal growth factor receptor (EGFR) is a therapeutic target (oncotarget) in NSCLC. Using in vitro EGFR kinase activity system, we identified a novel small molecule, WB-308, as an inhibitor of EGFR. WB-308 decreased NSCLC cell proliferation and colony formation, by causing G2/M arrest and apoptosis. Furthermore, WB-308 inhibited the engraft tumor growths in two animal models in vivo (lung orthotopic transplantation model and patient-derived engraft mouse model). WB-308 impaired the phosphorylation of EGFR, AKT, and ERK1/2 protein. WB-308 was less cytotoxic than Gefitinib. Our study suggests that WB-308 is a novel EGFR-TKI and may be considered to substitute for Gefitinib in clinical therapy for NSCLC. PMID:25730907

  16. Recent advances in the modeling of plasmas with the Particle-In-Cell methods

    NASA Astrophysics Data System (ADS)

    Vay, Jean-Luc; Lehe, Remi; Vincenti, Henri; Godfrey, Brendan; Lee, Patrick; Haber, Irv

    2015-11-01

    The Particle-In-Cell (PIC) approach is the method of choice for self-consistent simulations of plasmas from first principles. The fundamentals of the PIC method were established decades ago but improvements or variations are continuously being proposed. We report on several recent advances in PIC related algorithms, including: (a) detailed analysis of the numerical Cherenkov instability and its remediation, (b) analytic pseudo-spectral electromagnetic solvers in Cartesian and cylindrical (with azimuthal modes decomposition) geometries, (c) arbitrary-order finite-difference and generalized pseudo-spectral Maxwell solvers, (d) novel analysis of Maxwell's solvers' stencil variation and truncation, in application to domain decomposition strategies and implementation of Perfectly Matched Layers in high-order and pseudo-spectral solvers. Work supported by US-DOE Contracts DE-AC02-05CH11231 and the US-DOE SciDAC program ComPASS. Used resources of NERSC, supported by US-DOE Contract DE-AC02-05CH11231.

  17. Advanced development of the boundary element method for steady-state heat conduction

    NASA Technical Reports Server (NTRS)

    Dargush, G. F.; Banerjee, Prasanta K.

    1989-01-01

    Considerable progress has been made in recent years toward advancing the state-of-the-art in solid mechanics boundary element technology. In the present work, much of this new technology is applied in the development of a general-purpose boundary element method (BEM) for steady-state heat conduction. In particular, the BEM implementation involves the use of higher-order conforming elements, self-adaptive integration and multi-region capability. Two- and three-dimensional, as well as axisymmetric analysis, are incorporated within a unified framework. In addition, techniques are introduced for the calculation of boundary flux, and for the inclusion of thermal resistance across interfaces. As a final extension, an efficient formulation is developed for the analysis of solid three-dimensional bodies with embedded holes. For this last class of problems, the new BEM formulation is particularly attractive, since use of the alternatives (i.e. finite element or finite difference methods) is not practical. A number of detailed examples illustrate the suitability and robustness of the present approach for steady-state heat conduction.

  18. Application of advanced methods for the prognosis of production energy consumption

    NASA Astrophysics Data System (ADS)

    Stetter, R.; Witczak, P.; Staiger, B.; Spindler, C.; Hertel, J.

    2014-12-01

    This paper, based on a current research project, describes the application of advanced methods that are frequently used in fault-tolerance control and addresses the issue of the prognosis of energy efficiency. Today, the energy a product requires during its operation is the subject of many activities in research and development. However, the energy necessary for the production of goods is very often not analysed in comparable depth. In the field of electronics, studies come to the conclusion that about 80% of the total energy used by a product is from its production [1]. The energy consumption in production is determined very early in the product development process by designers and engineers, for example through selection of raw materials, explicit and implicit requirements concerning the manufacturing and assembly processes, or through decisions concerning the product architecture. Today, developers and engineers have at their disposal manifold design and simulation tools which can help to predict the energy consumption during operation relatively accurately. In contrast, tools with the objective to predict the energy consumption in production and disposal are not available. This paper aims to present an explorative study of the use of methods such as Fuzzy Logic to predict the production energy consumption early in the product development process.

  19. Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

    PubMed Central

    Bayraktar, Soley; Rocha-Lima, Caio M

    2013-01-01

    Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death in both men and women in the United States. Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease. Improvements in overall survival and quality of life have been modest. Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics, thus changing the treatment paradigm for many NSCLC patients. In this review, we present a summary of many of the currently investigated biologic targets in NSCLC, discuss their current clinical trial status, and also discuss the potential for development of other targeted agents. PMID:23696960

  20. Developing Advanced Seismic Imaging Methods For Characterizing the Fault Zone Structure

    NASA Astrophysics Data System (ADS)

    Zhang, Haijiang

    2015-04-01

    Here I present a series of recent developments on seismic imaging of fault zone structure. The goals of these advanced methods are to better determine the physical properties (including seismic velocity, attenuation, and anisotropy) around the fault zone and its boundaries. In order to accurately determine the seismic velocity structure of the fault zone, we have recently developed a wavelet-based double-difference seismic tomography method, in which the wavelet coefficients of the velocity model, rather than the model itself, are solved using both the absolute and differential arrival times. This method takes advantage of the multiscale nature of the velocity model and the multiscale wavelet representation property. Because of the velocity model is sparse in the wavelet domain, a sparsity constraint is applied to tomographic inversion. Compared to conventional tomography methods, the new method is both data- and model-adaptive, and thus can better resolve the fault zone structure. In addition to seismic velocity property of the fault zone, seismic anisotropy and attenuation properties are also important to characterize the fault zone structure. For this reason, we developed the seismic anisotropy tomography method to image the three-dimensional anisotropy strength model of the fault zone using shear wave splitting delay times between fast and slow shear waves. The applications to the San Andreas fault around Parkfield, California and north Anatolian fault in Turkey will be shown. To better constrain the seismic attenuation structure, we developed a new seismic attenuation tomography method using measured t* values for first arrival body waves, in which the structures of attenuation and velocity models are similar through the cross-gradient constraint. Seismic tomography can, however, only resolve the smooth variations in elastic properties in Earth's interior. To image structure at length scales smaller than what can be resolved tomographically, including

  1. Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells

    PubMed Central

    Della Corte, Carminia Maria; Ciaramella, Vincenza; Mauro, Concetta Di; Castellone, Maria Domenica; Papaccio, Federica; Fasano, Morena; Sasso, Ferdinando Carlo; Martinelli, Erika; Troiani, Teresa; De Vita, Ferdinando; Orditura, Michele; Bianco, Roberto; Ciardiello, Fortunato; Morgillo, Floriana

    2016-01-01

    Purpose Metformin, widely used as antidiabetic drug, showed antitumoral effects expecially in combination with chemotherapy. Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells. In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization. Experimental design Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene. Results The combination of metformin with MEK-I showed a strong anti-proliferative and proapoptotic effect in Calu-3, H1299, H358 and H1975 human NSCLC cell lines, independently from the KRAS mutational status. The combination reduced the metastatic behaviour of NSCLC cells, via a downregulation of GLI1 trascritional activity, thus affecting the transition from an epithelial to a mesenchymal phenotype. Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters. Conclusions Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9. PMID:26673006

  2. Intratumoral Heterogeneity in EGFR-Mutant NSCLC Results in Divergent Resistance Mechanisms in Response to EGFR Tyrosine Kinase Inhibition.

    PubMed

    Soucheray, Margaret; Capelletti, Marzia; Pulido, Inés; Kuang, Yanan; Paweletz, Cloud P; Becker, Jeffrey H; Kikuchi, Eiki; Xu, Chunxiao; Patel, Tarun B; Al-Shahrour, Fatima; Carretero, Julián; Wong, Kwok-Kin; Jänne, Pasi A; Shapiro, Geoffrey I; Shimamura, Takeshi

    2015-10-15

    Non-small cell lung cancers (NSCLC) that have developed resistance to EGF receptor (EGFR) tyrosine kinase inhibitor (TKI), including gefitinib and erlotinib, are clinically linked to an epithelial-to-mesenchymal transition (EMT) phenotype. Here, we examined whether modulating EMT maintains the responsiveness of EGFR-mutated NSCLCs to EGFR TKI therapy. Using human NSCLC cell lines harboring mutated EGFR and a transgenic mouse model of lung cancer driven by mutant EGFR (EGFR-Del19-T790M), we demonstrate that EGFR inhibition induces TGFβ secretion followed by SMAD pathway activation, an event that promotes EMT. Chronic exposure of EGFR-mutated NSCLC cells to TGFβ was sufficient to induce EMT and resistance to EGFR TKI treatment. Furthermore, NSCLC HCC4006 cells with acquired resistance to gefitinib were characterized by a mesenchymal phenotype and displayed a higher prevalence of the EGFR T790M mutated allele. Notably, combined inhibition of EGFR and the TGFβ receptor in HCC4006 cells prevented EMT but was not sufficient to prevent acquired gefitinib resistance because of an increased emergence of the EGFR T790M allele compared with cells treated with gefitinib alone. Conversely, another independent NSCLC cell line, PC9, reproducibly developed EGFR T790M mutations as the primary mechanism underlying EGFR TKI resistance, even though the prevalence of the mutant allele was lower than that in HCC4006 cells. Thus, our findings underscore heterogeneity within NSCLC cells lines harboring EGFR kinase domain mutations that give rise to divergent resistance mechanisms in response to treatment and anticipate the complexity of EMT suppression as a therapeutic strategy. PMID:26282169

  3. Advanced Methods for Acoustic and Thrust Benefits for Aircraft Engine Nozzles

    NASA Technical Reports Server (NTRS)

    Morgan, Morris H., III; Gilinsky, Mikhail M.

    2000-01-01

    The Fluid Mechanics and Acoustics Laboratory (FM&AL) was established At Hampton University in June of 1996. In addition, the FM&AL jointly conducted research with the Central AeroHydrodynamics Institute (TsAGI, Moscow) in Russia under a 2.5 year Civilian Research and Development Foundation (CRDF). The goals of the FM&AL programs are two fold: 1) to improve the working efficiency of the FM&AL team in generating new innovative ideas and in conducting research in the field of fluid dynamics and acoustics, basically for improvement of supersonic and subsonic aircraft engines, and 2) to attract promising minority students to this research and training and, in cooperation with other HU departments, to teach them basic knowledge in Aerodynamics, Gas Dynamics, and Theoretical and Experimental Methods in Aeroacoustics and Computational Fluid Dynamics (CFD). The research at the FM&AL supports reduction schemes associated with the emission of engine pollutants for commercial aircraft and concepts for reduction of observables for military aircraft. These research endeavors relate to the goals of the NASA Strategic Enterprise in Aeronautics concerning the development of environmentally acceptable aircraft. It is in this precise area, where the US aircraft industry, academia, and Government are in great need of trained professionals and which is a high priority goal of the Minority University Research and Education (MUREP) Program, that the HU FM&AL can make its most important contribution. This project already benefits NASA and HU because: First, the innovation, testing, and further development of new techniques for advanced propulsion systems are necessary for the successful attainment of the NASA Long Term Goals in Aeronautics and Space Transportation Technology (ASTT) including Global Civil Aviation, Revolutionary Technology Leaps, Access to Space, R&D Services, and the economic competitiveness of the US Aircraft Industry in the 2 1 st century. Secondly, the joint

  4. BOOK REVIEW: Advanced Topics in Computational Partial Differential Equations: Numerical Methods and Diffpack Programming

    NASA Astrophysics Data System (ADS)

    Katsaounis, T. D.

    2005-02-01

    The scope of this book is to present well known simple and advanced numerical methods for solving partial differential equations (PDEs) and how to implement these methods using the programming environment of the software package Diffpack. A basic background in PDEs and numerical methods is required by the potential reader. Further, a basic knowledge of the finite element method and its implementation in one and two space dimensions is required. The authors claim that no prior knowledge of the package Diffpack is required, which is true, but the reader should be at least familiar with an object oriented programming language like C++ in order to better comprehend the programming environment of Diffpack. Certainly, a prior knowledge or usage of Diffpack would be a great advantage to the reader. The book consists of 15 chapters, each one written by one or more authors. Each chapter is basically divided into two parts: the first part is about mathematical models described by PDEs and numerical methods to solve these models and the second part describes how to implement the numerical methods using the programming environment of Diffpack. Each chapter closes with a list of references on its subject. The first nine chapters cover well known numerical methods for solving the basic types of PDEs. Further, programming techniques on the serial as well as on the parallel implementation of numerical methods are also included in these chapters. The last five chapters are dedicated to applications, modelled by PDEs, in a variety of fields. The first chapter is an introduction to parallel processing. It covers fundamentals of parallel processing in a simple and concrete way and no prior knowledge of the subject is required. Examples of parallel implementation of basic linear algebra operations are presented using the Message Passing Interface (MPI) programming environment. Here, some knowledge of MPI routines is required by the reader. Examples solving in parallel simple PDEs using

  5. Computed 88% TCP dose for SBRT of NSCLC from tumour hypoxia modelling

    NASA Astrophysics Data System (ADS)

    Ruggieri, Ruggero; Stavreva, Nadejda; Naccarato, Stefania; Stavrev, Pavel

    2013-07-01

    In small NSCLC, 88% local control at three years from SBRT was reported both for schedule (20-22 Gy ×3) (Fakiris et al 2009 Int. J. Radiat. Oncol. Biol. Phys. 75 677-82), actually close to (18-20 Gy ×3) if density correction is properly applied, and for schedules (18 Gy ×3) and (11 Gy ×5) (Palma et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 82 1149-56). Here, we compare our computed iso-TCP = 88% dose per fraction (d88) for three and five fractions (n) with such clinically adopted ones. Our TCP model accounts for tumour repopulation, at rate λ (d-1), reoxygenation of chronic hypoxia (ch-), at rate a (d-1) and fluctuating oxygenation of acute hypoxia (ah-), with hypoxic fraction (C) of the acutely hypoxic fractional volume (AHF). Out of the eight free parameters whose values we had fitted to in vivo animal data (Ruggieri et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 83 1603-8), we here maintained (a(d-1), C, OERch, OERah/OERch, AHF, CHF) = (0.026, 0.17, 1.9, 2.2, 0.033, 0.145) while rescaling the initial total number of clonogens (No) according to the ratio of NSCLC on animal median tumour volumes. From the clinical literature, the usually assumed (αo/βo(Gy), λ(d-1)) = (10, 0.217) for the well-oxygenated (o-)cells were taken. By normal (lognormal) random sampling of all parameter values over their 95% C.I., the uncertainty on present d88(n) computations was estimated. Finally, SBRT intra-tumour dose heterogeneity was simulated by a 1.3 dose boost ratio on 50% of tumour volume. Computed d88(±1σ) were 19.0 (16.3; 21.7) Gy, for n = 3; 10.4 (8.7; 12.1) Gy, for n = 5; 5.8 (5.2; 6.4) Gy, for n = 8; 4.0 (3.6; 4.3) Gy, for n = 12. Furthermore, the iso-TCP = 88% total dose, D88(n) = d88(n)*n, exhibited a relative minimum around n = 8. Computed d88(n = 3, 5) are strictly consistent with the clinically adopted ones, which confirms the validity of LQ-model-based TCP predictions at the doses used in SBRT if a highly radioresistant cell subpopulation is properly

  6. An Advanced Electrospinning Method of Fabricating Nanofibrous Patterned Architectures with Controlled Deposition and Desired Alignment

    NASA Astrophysics Data System (ADS)

    Rasel, Sheikh Md

    We introduce a versatile advanced method of electrospinning for fabricating various kinds of nanofibrous patterns along with desired alignment, controlled amount of deposition and locally variable density into the architectures. In this method, we employed multiple electrodes whose potentials have been altered in milliseconds with the help of microprocessor based control system. Therefore, key success of this method was that the electrical field as well as charge carrying fibers could be switched shortly from one electrode's location to another, as a result, electrospun fibers could be deposited on the designated areas with desired alignment. A wide range of nanofibrous patterned architectures were constructed using proper arrangement of multiple electrodes. By controlling the concurrent activation time of two adjacent electrodes, we demonstrated that amount of fibers going into the pattern can be adjusted and desired alignment in electrospun fibers can be obtained. We also revealed that the deposition density of electrospun fibers in different areas of patterned architectures can be varied. We showed that by controlling the deposition time between two adjacent electrodes, a number of functionally graded patterns can be generated with uniaxial alignment. We also demonstrated that this handy method was capable of producing random, aligned, and multidirectional nanofibrous mats by engaging a number of electrodes and switching them in desired patterns. A comprehensive study using finite element method was carried out to understand the effects of electrical field. Simulation results revealed that electrical field strength alters shortly based on electrode control switch patterns. Nanofibrous polyvinyl alcohol (PVA) scaffolds and its composite reinforced with wollastonite and wood flour were fabricated using rotating drum electrospinning technique. Morphological, mechanical, and thermal, properties were characterized on PVA/wollastonite and PVA/wood flour nanocomposites

  7. Advancing Higher Education with Mobile Learning Technologies: Cases, Trends, and Inquiry-Based Methods

    ERIC Educational Resources Information Center

    Keengwe, Jared, Ed.; Maxfield, Marian B., Ed.

    2015-01-01

    Rapid advancements in technology are creating new opportunities for educators to enhance their classroom techniques with digital learning resources. Once used solely outside of the classroom, smartphones, tablets, and e-readers are becoming common in many school settings. "Advancing Higher Education with Mobile Learning Technologies: Cases,…

  8. Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

    SciTech Connect

    Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Goodman, Karyn A.; Keating, Nancy L.

    2009-08-01

    Purpose: To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally advanced, unresectable non-small-cell lung cancer (NSCLC). Methods and Materials: We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists' treatment recommendations for three scenarios with the least agreement. Results: Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55 year old. However, there was substantial variability in recommendations for a 55 year old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p < 0.05), but the impact was modest. Conclusions: Nearly all radiation oncologists report following the evidence-based recommendation of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC, but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly affected treatment recommendations. Additional clinical trial data are necessary to guide recommendations for treatment of elderly patients and patients with poor pulmonary function to optimize their management.

  9. Treatment Recommendations for Locally Advanced, Non-small Cell Lung Cancer: The Influence of Physician and Patient Factors

    PubMed Central

    Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Tao, May Lin; Goodman, Karyn A.; Keating, Nancy L.

    2011-01-01

    Purpose To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally-advanced, unresectable non-small cell lung cancer (NSCLC). Methods and Materials We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists’ treatment recommendations for 3 scenarios with the least agreement. Results Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55-year-old. However, there was substantial variability in recommendations for a 55-year-old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p <0.05) but the impact was modest. Conclusions Nearly all radiation oncologists report following evidence-based recommendations of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC; but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly impacted treatment recommendations. Additional clinical trial data are needed to guide recommendations for treatment of elderly patients and patients with poor pulmonary function in order to optimize their management. PMID:19409730

  10. Development and validation of an advanced low-order panel method

    NASA Technical Reports Server (NTRS)

    Ashby, Dale L.; Iguchi, Steven K.; Dudley, Michael

    1988-01-01

    A low-order potential-flow panel code, PMARC, for modeling complex three-dimensional geometries, is currently being developed at NASA Ames Research Center. The PMARC code was derived from a code named VSAERO that was developed for Ames Research Center by Analytical Methods, Inc. In addition to modeling potential flow over three-dimensional geometries, the present version of PMARC includes several advanced features such as an internal flow model, a simple jet wake model, and a time-stepping wake model. Data management within the code was optimized by the use of adjustable size arrays for rapidly changing the size capability of the code, reorganization of the output file and adopting a new plot file format. Preliminary versions of a geometry preprocessor and a geometry/aerodynamic data postprocessor are also available for use with PMARC. Several test cases are discussed to highlight the capabilities of the internal flow model, the jet wake model, and the time-stepping wake model.

  11. Limitations of the Conventional Phase Advance Method for Constant Power Operation of the Brushless DC Motor

    SciTech Connect

    Lawler, J.S.

    2001-10-29

    The brushless dc motor (BDCM) has high-power density and efficiency relative to other motor types. These properties make the BDCM well suited for applications in electric vehicles provided a method can be developed for driving the motor over the 4 to 6:1 constant power speed range (CPSR) required by such applications. The present state of the art for constant power operation of the BDCM is conventional phase advance (CPA) [1]. In this paper, we identify key limitations of CPA. It is shown that the CPA has effective control over the developed power but that the current magnitude is relatively insensitive to power output and is inversely proportional to motor inductance. If the motor inductance is low, then the rms current at rated power and high speed may be several times larger than the current rating. The inductance required to maintain rms current within rating is derived analytically and is found to be large relative to that of BDCM designs using high-strength rare earth magnets. Th us, the CPA requires a BDCM with a large equivalent inductance.

  12. Advanced Methods for Aircraft Engine Thrust and Noise Benefits: Nozzle-Inlet Flow Analysis

    NASA Technical Reports Server (NTRS)

    Morgan, Morris H.; Gilinsky, Mikhail; Patel, Kaushal; Coston, Calvin; Blankson, Isaiah M.

    2003-01-01

    The research is focused on a wide regime of problems in the propulsion field as well as in experimental testing and theoretical and numerical simulation analyses for advanced aircraft and rocket engines. Results obtained are based on analytical methods, numerical simulations and experimental tests at the NASA LaRC and Hampton University computer complexes and experimental facilities. The main objective of this research is injection, mixing and combustion enhancement in propulsion systems. The sub-projects in the reporting period are: (A) Aero-performance and acoustics of Telescope-shaped designs. The work included a pylon set application for SCRAMJET. (B) An analysis of sharp-edged nozzle exit designs for effective fuel injection into the flow stream in air-breathing engines: triangular-round and diamond-round nozzles. (C) Measurement technique improvements for the HU Low Speed Wind Tunnel (HU LSWT) including an automatic data acquisition system and a two component (drag-lift) balance system. In addition, a course in the field of aerodynamics was developed for the teaching and training of HU students.

  13. A hybrid method for damage detection and quantification in advanced X-COR composite structures

    NASA Astrophysics Data System (ADS)

    Neerukatti, Rajesh Kumar; Rajadas, Abhishek; Borkowski, Luke; Chattopadhyay, Aditi; Huff, Daniel W.

    2016-04-01

    Advanced composite structures, such as foam core carbon fiber reinforced polymer composites, are increasingly being used in applications which require high strength, high in-plane and flexural stiffness, and low weight. However, the presence of in situ damage due to manufacturing defects and/or service conditions can complicate the failure mechanisms and compromise their strength and reliability. In this paper, the capability of detecting damages such as delaminations and foam-core separations in X-COR composite structures using non-destructive evaluation (NDE) and structural health monitoring (SHM) techniques is investigated. Two NDE techniques, flash thermography and low frequency ultrasonics, were used to detect and quantify the damage size and locations. Macro fiber composites (MFCs) were used as actuators and sensors to study the interaction of Lamb waves with delaminations and foam-core separations. The results indicate that both flash thermography and low frequency ultrasonics were capable of detecting damage in X-COR sandwich structures, although low frequency ultrasonic methods were capable of detecting through thickness damages more accurately than flash thermography. It was also observed that the presence of foam-core separations significantly changes the wave behavior when compared to delamination, which complicates the use of wave based SHM techniques. Further, a wave propagation model was developed to model the wave interaction with damages at different locations on the X-COR sandwich plate.

  14. Advanced and High-Throughput Method for Mitochondrial Bioenergetics Evaluation in Neurotrauma.

    PubMed

    Pandya, Jignesh D; Sullivan, Patrick G; Leung, Lai Yee; Tortella, Frank C; Shear, Deborah A; Deng-Bryant, Ying

    2016-01-01

    Mitochondrial dysfunction is one of the key posttraumatic neuropathological events observed in various experimental models of traumatic brain injury (TBI). The extent of mitochondrial dysfunction has been associated with the severity and time course of secondary injury following brain trauma. Critically, several mitochondrial targeting preclinical drugs used in experimental TBI models have shown improved mitochondrial bioenergetics, together with cortical tissue sparing and cognitive behavioral outcome. Mitochondria, being a central regulator of cellular metabolic pathways and energy producer of cells, are of a great interest for researchers aiming to adopt cutting-edge methodology for mitochondrial bioenergetics assessment. The traditional way of mitochondrial bioenergetics analysis utilizing a Clark-type oxygen electrode (aka. oxytherm) is time-consuming and labor-intensive. In the present chapter, we describe an advanced and high-throughput method for mitochondrial bioenergetics assessments utilizing the Seahorse Biosciences XF(e)24 Flux Analyzer. This allows for simultaneous measurement of multiple samples with higher efficiency than the oxytherm procedure. This chapter provides helpful guidelines for conducting mitochondrial isolation and studying mitochondrial bioenergetics in brain tissue homogenates following experimental TBI. PMID:27604740

  15. Response monitoring using quantitative ultrasound methods and supervised dictionary learning in locally advanced breast cancer

    NASA Astrophysics Data System (ADS)

    Gangeh, Mehrdad J.; Fung, Brandon; Tadayyon, Hadi; Tran, William T.; Czarnota, Gregory J.

    2016-03-01

    A non-invasive computer-aided-theragnosis (CAT) system was developed for the early assessment of responses to neoadjuvant chemotherapy in patients with locally advanced breast cancer. The CAT system was based on quantitative ultrasound spectroscopy methods comprising several modules including feature extraction, a metric to measure the dissimilarity between "pre-" and "mid-treatment" scans, and a supervised learning algorithm for the classification of patients to responders/non-responders. One major requirement for the successful design of a high-performance CAT system is to accurately measure the changes in parametric maps before treatment onset and during the course of treatment. To this end, a unified framework based on Hilbert-Schmidt independence criterion (HSIC) was used for the design of feature extraction from parametric maps and the dissimilarity measure between the "pre-" and "mid-treatment" scans. For the feature extraction, HSIC was used to design a supervised dictionary learning (SDL) method by maximizing the dependency between the scans taken from "pre-" and "mid-treatment" with "dummy labels" given to the scans. For the dissimilarity measure, an HSIC-based metric was employed to effectively measure the changes in parametric maps as an indication of treatment effectiveness. The HSIC-based feature extraction and dissimilarity measure used a kernel function to nonlinearly transform input vectors into a higher dimensional feature space and computed the population means in the new space, where enhanced group separability was ideally obtained. The results of the classification using the developed CAT system indicated an improvement of performance compared to a CAT system with basic features using histogram of intensity.

  16. Advanced Remedial Methods for Metals and Radionuclides in Vadose Zone Environments

    SciTech Connect

    Wellman, Dawn M.; Mattigod, Shas V.; Hubbard, Susan S.; Miracle, Ann L.; Zhong, Lirong; Foote, Martin W.; Wu, Yuxin; Jansik, Danielle P.

    2012-02-03

    Functionally, the methods for addressing contamination must remove and/or reduce transport or toxicity of contaminants. This problem is particularly challenging in arid environments where the vadose zone can be up to hundreds of feet thick, rendering transitional excavation methods exceedingly costly and ineffective. Delivery of remedial amendments is one of the most challenging and critical aspects for all remedy-based approaches. The conventional approach for delivery is through injection of aqueous remedial solutions. However, heterogeneous vadose zone environments present hydrologic and geochemical challenges that limit the effectiveness. Because the flow of solution infiltration is dominantly controlled by gravity and suction, injected liquid preferentially percolates through highly permeable pathways, bypassing low-permeability zones which frequently contain the majority of the contamination. Moreover, the wetting front can readily mobilize and enhance contaminant transport to underlying aquifers prior to stabilization. Development of innovative, in-situ technologies may be the only way to meet remedial action objectives and long-term stewardship goals. Shear-thinning fluids (i.e., surfactants) can be used to lower the liquid surface tension and create stabile foams, which readily penetrate low permeability zones. Although surfactant foams have been utilized for subsurface mobilization efforts in the oil and gas industry, so far, the concept of using foams as a delivery mechanism for transporting reactive remedial amendments into deep vadose zone environments to stabilize metal and long-lived radionuclide contaminants has not been explored. Foam flow can be directed by pressure gradients rather than being dominated by gravity, and, foam delivery mechanisms limit the volume of water (< 20% vol.) required for remedy delivery and emplacement, thus mitigating contaminant mobilization. We will present the results of an integrated laboratory- / intermediate

  17. A Significant Statistical Advancement on the Predictive Values of ERCC1 Polymorphisms for Clinical Outcomes of Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: An Updated Meta-Analysis

    PubMed Central

    Han, Yali; Liu, Jie; Sun, Meili; Zhang, Zongpu; Liu, Chuanyong; Sun, Yuping

    2016-01-01

    Background. There is no definitive conclusion so far on the predictive values of ERCC1 polymorphisms for clinical outcomes of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We updated this meta-analysis with an expectation to obtain some statistical advancement on this issue. Methods. Relevant studies were identified by searching MEDLINE, EMBASE databases from inception to April 2015. Primary outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). All analyses were performed using the Review Manager version 5.3 and the Stata version 12.0. Results. A total of 33 studies including 5373 patients were identified. ERCC1 C118T and C8092A could predict both ORR and OS for platinum-based chemotherapy in Asian NSCLC patients (CT + TT versus CC, ORR: OR = 0.80, 95% CI = 0.67–0.94; OS: HR = 1.24, 95% CI = 1.01–1.53) (CA + AA versus CC, ORR: OR = 0.76, 95% CI = 0.60–0.96; OS: HR = 1.37, 95% CI = 1.06–1.75). Conclusions. Current evidence strongly indicated the prospect of ERCC1 C118T and C8092A as predictive biomarkers for platinum-based chemotherapy in Asian NSCLC patients. However, the results should be interpreted with caution and large prospective studies are still required to further investigate these findings. PMID:27057082

  18. Feasibility, tolerability, and efficacy of the concurrent addition of erlotinib to thoracic radiotherapy in locally advanced unresectable non-small-cell lung cancer: a Phase II trial

    PubMed Central

    Martínez, Enrique; Martínez, Maite; Rico, Mikel; Hernández, Berta; Casas, Francesc; Viñolas, Nuria; Pérez-Casas, Ana; Dómine, Manuel; Mínguez, Julián

    2016-01-01

    Purpose Although many studies have confirmed the synergic effects of combining chemotherapy (CT) and radiotherapy (RT), clinical data evaluating safety and efficacy of erlotinib in combination with RT in locally advanced non-small-cell lung cancer (NSCLC) are limited. The aim of this study was to determine the feasibility, tolerability, and efficacy of the concurrent addition of erlotinib to the standard three-dimensional conformal thoracic RT in patients with unresectable or locally advanced NSCLC who are not candidates for receiving standard CT. Patients and methods Feasibility and tolerability, assessed by evaluating adverse events (AEs), and effectiveness, by calculating progression-free survival (PFS), overall survival (OS), cancer-specific survival (CSS), and objective response rate (ORR), were analyzed in 30 patients receiving RT alone and 60 receiving RT and erlotinib. Results Erlotinib with RT showed an extended CSS and a higher rate of complete responses compared with RT alone. No differences between groups were found regarding OS, PFS, and ORR. AEs were significantly higher in the combined treatment, which mainly included cutaneous toxicity, dyspnea, fatigue, hyporexia, diarrhea, and infection. Erlotinib did not increase the toxicity produced by RT. Conclusion The combination of erlotinib with RT produced, in our study, a scarce clinical benefit in the treatment of unresectable or locally advanced NSCLC, limited to complete responses and longer CSS rate compared with RT alone. Increased toxicity events were associated with combined therapy, which mainly included cutaneous toxicity. In our opinion, further studies in molecularly unselected lung cancer patients treated with EGFR TKIs and RT are not indicated. The use of biomarkers for the identification of patients that are most likely to benefit from this treatment is an essential next step in the research of this condition. PMID:27042098

  19. Optimized selection of three major EGFR-TKIs in advanced EGFR-positive non-small cell lung cancer: a network metaanalysis

    PubMed Central

    Fang, Wenfeng; Kang, Shiyang; He, Yang; Hong, Shaodong; Zhan, Jianhua; Zhao, Yuanyuan; Xue, Cong; Ma, Yuxiang; Zhou, Ting; Ma, Shuxiang; Gao, Fangfang; Qin, Tao; Hu, Zhihuang; Tian, Ying; Hou, Xue; Huang, Yan; Zhou, Ningning; Zhao, Hongyun; Zhang, Li

    2016-01-01

    Background: To answer which epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the best choice for advanced non-small cell lung cancer (NSCLC) EGFR mutants. Results: 16 phase III randomized trials involving 2962 advanced NSCLC EGFR mutants were enrolled. Multiple treatment comparisons showed different EGFR-TKIs shared equivalent curative effect in terms of all outcome measures among the overall, chemo-naïve and previously treated patients. Rank probabilities showed that erlotinib and afatinib had potentially better efficacy compared with gefitinib in both of the overall and chemo-naïve patients. Potentially survival benefit of erlotinib was also observed in previously treated patients compared with gefitinib. Additionally, EGFR-TKI showed numerically greater survival benefit in 19 Del compared with chemotherapy, while it was opposite in 21 L858R. Furthermore, afatinib, erlotinib and gefitinib had high, moderate and low risk of rash & diarrhea, respectively, while the occurrence of elevated liver transaminase was more common in gefitinib. Methods: Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were extracted from included studies. Efficacy and toxicity of all included treatments were integrated by network meta-analyses. Conclusion: Our study indicated a high efficacy-high toxicity pattern of afatinib, a high efficacy-moderate toxicity pattern of erlotinib and a medium efficacy-moderate toxicity pattern of gefitinib. Recommended EGFR-TKI should be suggested according to patients' tolerability and therapeutic efficacy in clinical practice. Moreover, the treatment for advanced EGFR-positive NSCLC might be different between 19 Del and 21 L858R. PMID:26933807

  20. Assessment on the Efficacy and Safety of Aidi Injection Combined with Vinorelbine and Cisplatin for Treatment of Advanced Nonsmall Cell Lung Cancer

    PubMed Central

    Zhao, Hua-Ye; Zhou, Hai-Yan; Wang, Yan-Ting; Chen, Wei; Qi, Shu-Ya; Cao, Jun-Ling; Li, Guo-Hui

    2016-01-01

    Background: The aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC). Methods: Pertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIP, and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses. Results: Twelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m2, combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] = 1.24, 95% confidence interval [CI] [1.05–1.47], P = 0.010) and reducing the incidence of Grade II or above nausea and vomiting (RR = 0.49, 95% CI [0.30–0.80], P = 0.005). Meanwhile, with cisplatin ranging from 80 to 120 mg/m2, no significant differences in efficiency (RR = 1.11, 95% CI [0.87–1.42], P = 0.390) and Grade II or above nausea and vomiting (RR = 0.88, 95% CI [0.71–1.10], P = 0.260) were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia. Conclusions: Aidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC. PMID:26960377

  1. Minimally invasive (robotic assisted thoracic surgery and video-assisted thoracic surgery) lobectomy for the treatment of locally advanced non-small cell lung cancer

    PubMed Central

    Yang, Hao-Xian; Woo, Kaitlin M.; Sima, Camelia S.

    2016-01-01

    Background Insufficient data exist on the results of minimally invasive surgery (MIS) for locally advanced non-small cell lung cancer (NSCLC) traditionally approached by thoracotomy. The use of telerobotic surgical systems may allow for greater utilization of MIS approaches to locally advanced disease. We will review the existing literature on MIS for locally advanced disease and briefly report on the results of a recent study conducted at our institution. Methods We performed a retrospective review of a prospective single institution database to identify patients with clinical stage II and IIIA NSCLC who underwent lobectomy following induction chemotherapy. The patients were classified into two groups (MIS and thoracotomy) and were compared for differences in outcomes and survival. Results From January 2002 to December 2013, 428 patients {397 thoracotomy, 31 MIS [17 robotic and 14 video-assisted thoracic surgery (VATS)]} underwent induction chemotherapy followed by lobectomy. The conversion rate in the MIS group was 26% (8/31) The R0 resection rate was similar between the groups (97% for MIS vs. 94% for thoracotomy; P=0.71), as was postoperative morbidity (32% for MIS vs. 33% for thoracotomy; P=0.99). The median length of hospital stay was shorter in the MIS group (4 vs. 5 days; P<0.001). The 3-year overall survival (OS) was 48.3% in the MIS group and 56.6% in the thoracotomy group (P=0.84); the corresponding 3-year DFS were 49.0% and 42.1% (P=0.19). Conclusions In appropriately selected patients with NSCLC, MIS approaches to lobectomy following induction therapy are feasible and associated with similar disease-free and OS to those following thoracotomy. PMID:27195138

  2. MicroRNA-187-5p suppresses cancer cell progression in non-small cell lung cancer (NSCLC) through down-regulation of CYP1B1.

    PubMed

    Mao, Ming; Wu, Zhouqing; Chen, Jiakuan

    2016-09-16

    Lung cancer remains a leading cause of cancer-associated mortality worldwide and non-small lung cancer (NSCLC) is responsible for over 80% of lung cancer-related deaths. Identifying novel molecular biomarker that can inhibit the progression of lung cancer will facilitate the development of new treatment strategies. Herein, we demonstrated that miR-187-5p is a tumor-suppressor miRNA in NSCLC progression. We found that expression of miR-187-5p was decreased obviously in NSCLC tissues. Down-regulation of miR-187-5p was associated with TNM stage and postoperative survival. Overexpression of miR-187-5p inhibited the growth and metastasis of NSCLC cells. The CYP1B1 was a direct target of miR-187-5p and promoted the growth and metastasis of NSCLC cells. Further study showed that CYP1B1 could reverse the inhibitory effect of miR-187-5p on growth and metastasis of NSCLC cells. Taken together, our data highlight the pivotal role of miR-187-5p in the progression of NSCLC. Thus, miR-187-5p may be a potential prognostic marker and of treatment relevance for NSCLC progression intervention. PMID:27495872

  3. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer

    PubMed Central

    Cheema, P.K.; Burkes, R.L.

    2013-01-01

    An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4–ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc. PMID:23559882

  4. Development of new methods and polyphosphazene chemistries for advanced materials applications

    NASA Astrophysics Data System (ADS)

    Hindenlang, Mark D.

    The work described within this thesis focuses on the design, synthesis, and characterization of new phosphazenes with potential in advanced materials applications. Additionally, these unique polymers required the development of novel reaction methods or the investigation of new phosphazene chemistry to achieve their synthesis. Chapter 1 lays out some of the basic principles and fundamentals of polymer chemistry. Chapter 2 investigates the use of iodinated polyphosphazenes as x-ray opaque materials. Single-substituent polymers with 4-iodophenoxy or 4-iodophenylanaline ethyl ester units as the only side groups were prepared. Although a single-substitutent polymer with 3,5-diiodotyrosine ethyl ester groups was difficult to synthesize, probably because of steric hindrance, mixed-substituent polymers that contained the non-iodinated ethyl esters of glycyine, alanine, or phenylalanine plus a corresponding iodinated substituent, could be synthesized. Multinuclear NMR spectroscopy was used to follow the substitution of side groups onto the phosphazene back bone and judge the ratio of substituents. Chapter 3 details the initial investigation into 3,4-dihydroxy-L-phenylalanine ethyl ester and dopamine substituted polyphosphazenes that could be applied to a number of applications. L-DOPAEE was acetonide protected to prevent crosslinking reactions by the catechole functionality. Cyclic small molecule studies and macromolecular substitution reactions on the linear high polymer were conducted with the protected L-DOPA. Continuing studies into protection of the dopamine catechol have elucidated a viable method for the synthesis of amino-linked dopamine polymers. Chapter 4 describes a method for the synthesis of phosphazenes with quaternary amine complexes as potential antibacterial agents. Replacement reactions of pyridine alkoxides and chlorophosphazenes were first attempted at the small molecule level to study the reactivities of pyridine alkoxides. The formation of an

  5. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    PubMed

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  6. MCL-1 is the key target of adjuvant chemotherapy to reverse the cisplatin-resistance in NSCLC.

    PubMed

    Ma, Jun; Zhao, Zhenxian; Wu, Kaiming; Xu, Zhe; Liu, Kuanzhi

    2016-08-10

    Cisplatin is one of the most effective chemotherapeutic agents for the treatment of lung cancer. However, the acquired resistance occurred in cancer cells limits the clinical application of cisplatin. MCL-1, which is an important member in the pro-survival Bcl-2 family, plays a critical role in multidrug resistance (MDR). The aim of the present study is to investigate the value of Pan-Bcl-2 inhibitor as sensitizer for the chemotherapy of cisplatin-resistant non-small cell lung cancer (NSCLC) cells. We found the obatoclax but not the ABT-737 significantly decreased the IC50 (half maximal inhibitory concentration) of cisplatin in cisplatin-resistant NSCLC cells. Furthermore, we demonstrated that the mechanism of obatoclax-promoted cell death induced by cisplatin was dependent on the inhibition of MCL-1, which couldn't be inhibited by ABT-737 but is the target of obatoclax. Moreover, inhibition of MCL-1 recovered the function of NOXA and BAK in cisplatin-resistant NSCLC cells, leading to the promotion of mitochondrial apoptosis induced by cisplatin. Interestingly, our date indicated the obatoclax also reversed the cross-resistance in cisplatin-resistant NSCLC cells. Therefore, we demonstrated that the targeted therapy with MCL-1 inhibitors, such as obatoclax, may represent a novel strategy for cancer therapy. PMID:27138804

  7. Metformin Enhances the Therapy Effects of Anti-IGF-1R mAb Figitumumab to NSCLC.

    PubMed

    Cao, Hongxin; Dong, Wei; Qu, Xiao; Shen, Hongchang; Xu, Jun; Zhu, Linhai; Liu, Qi; Du, Jiajun

    2016-01-01

    The insulin-like growth factor (IGF) signaling system plays a critical role in tumorigenesis, highlighting the potential of targeting IGF-1R as an anti-cancer therapy. Although multiple anti-IGF-1R monoclonal antibody (mAb) drugs have been developed, challenges remain in the validation of the therapeutic effects and understanding the molecular mechanism of these mAbs. Herein, we conducted a study to validate the effect of Figitumumab (CP), an anti-IGF-1R mAb, in a panel of non-small cell lung cancer (NSCLC) cell lines. We found all tested cell lines were sensitive to CP, and CP could block IGF-1R and the downstream PI3K/AKT pathway activation. Unexpectedly, we found CP could activate ERK signaling pathway in IGF-1R kinase independent manner, which we further verified was mainly mediated by β-arrestin2. We also investigated the anti-tumor effect of metformin alone as well as its combination with CP to target NSCLC. Metformin could target IGF-1R signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down-regulating IGF-1R. Finally, we found that combining metformin with CP could further induce IGF-1R down-regulation and was more effective to target NSCLC cells. Our data suggests the combining of metformin with CP has additive therapeutic value against NSCLC. PMID:27488947

  8. Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation

    PubMed Central

    Barnett, Reagan; Bachaboina, Lavanya; Scalici, Jennifer; Rocconi, Rodney P.; Owen, Laurie B.; Piazza, Gary A.

    2015-01-01

    Allyl isothiocyanate (AITC), a constituent of many cruciferous vegetables exhibits significant anticancer activities in many cancer models. Our studies provide novel insights into AITC-induced anticancer mechanisms in human A549 and H1299 non-small cell lung cancer (NSCLC) cells. AITC exposure induced replication stress in NSCLC cells as evidenced by γH2AX and FANCD2 foci, ATM/ATR-mediated checkpoint responses and S and G2/M cell cycle arrest. Furthermore, AITC-induced FANCD2 foci displayed co-localization with BrdU foci, indicating stalled or collapsed replication forks in these cells. Although PITC (phenyl isothiocyanate) exhibited concentration-dependent cytotoxic effects, treatment was less effective compared to AITC. Previously, agents that induce cell cycle arrest in S and G2/M phases were shown to sensitize tumor cells to radiation. Similar to these observations, combination therapy involving AITC followed by radiation treatment exhibited increased DDR and cell killing in NSCLC cells compared to single agent treatment. Combination index (CI) analysis revealed synergistic effects at multiple doses of AITC and radiation, resulting in CI values of less than 0.7 at Fa of 0.5 (50% reduction in survival). Collectively, these studies identify an important anticancer mechanism displayed by AITC, and suggest that the combination of AITC and radiation could be an effective therapy for NSCLC. PMID:25742788

  9. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.

    PubMed

    Ou, Sai-Hong Ignatius; Weitz, Michael; Jalas, John R; Kelly, Daniel F; Wong, Vanessa; Azada, Michele C; Quines, Oliver; Klempner, Samuel J

    2016-06-01

    Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment. PMID:27133743

  10. Metformin Enhances the Therapy Effects of Anti-IGF-1R mAb Figitumumab to NSCLC

    PubMed Central

    Cao, Hongxin; Dong, Wei; Qu, Xiao; Shen, Hongchang; Xu, Jun; Zhu, Linhai; Liu, Qi; Du, Jiajun

    2016-01-01

    The insulin-like growth factor (IGF) signaling system plays a critical role in tumorigenesis, highlighting the potential of targeting IGF-1R as an anti-cancer therapy. Although multiple anti-IGF-1R monoclonal antibody (mAb) drugs have been developed, challenges remain in the validation of the therapeutic effects and understanding the molecular mechanism of these mAbs. Herein, we conducted a study to validate the effect of Figitumumab (CP), an anti-IGF-1R mAb, in a panel of non-small cell lung cancer (NSCLC) cell lines. We found all tested cell lines were sensitive to CP, and CP could block IGF-1R and the downstream PI3K/AKT pathway activation. Unexpectedly, we found CP could activate ERK signaling pathway in IGF-1R kinase independent manner, which we further verified was mainly mediated by β-arrestin2. We also investigated the anti-tumor effect of metformin alone as well as its combination with CP to target NSCLC. Metformin could target IGF-1R signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down-regulating IGF-1R. Finally, we found that combining metformin with CP could further induce IGF-1R down-regulation and was more effective to target NSCLC cells. Our data suggests the combining of metformin with CP has additive therapeutic value against NSCLC. PMID:27488947

  11. Advanced Methods for Aircraft Engine Thrust and Noise Benefits: Nozzle-Inlet Flow Analysis

    NASA Technical Reports Server (NTRS)

    Morgan, Morris H.; Gilinsky, Mikhail M.

    2001-01-01

    Three connected sub-projects were conducted under reported project. Partially, these sub-projects are directed to solving the problems conducted by the HU/FM&AL under two other NASA grants. The fundamental idea uniting these projects is to use untraditional 3D corrugated nozzle designs and additional methods for exhaust jet noise reduction without essential thrust lost and even with thrust augmentation. Such additional approaches are: (1) to add some solid, fluid, or gas mass at discrete locations to the main supersonic gas stream to minimize the negative influence of strong shock waves forming in propulsion systems; this mass addition may be accompanied by heat addition to the main stream as a result of the fuel combustion or by cooling of this stream as a result of the liquid mass evaporation and boiling; (2) to use porous or permeable nozzles and additional shells at the nozzle exit for preliminary cooling of exhaust hot jet and pressure compensation for non-design conditions (so-called continuous ejector with small mass flow rate; and (3) to propose and analyze new effective methods fuel injection into flow stream in air-breathing engines. Note that all these problems were formulated based on detailed descriptions of the main experimental facts observed at NASA Glenn Research Center. Basically, the HU/FM&AL Team has been involved in joint research with the purpose of finding theoretical explanations for experimental facts and the creation of the accurate numerical simulation technique and prediction theory for solutions for current problems in propulsion systems solved by NASA and Navy agencies. The research is focused on a wide regime of problems in the propulsion field as well as in experimental testing and theoretical and numerical simulation analysis for advanced aircraft and rocket engines. The F&AL Team uses analytical methods, numerical simulations, and possible experimental tests at the Hampton University campus. We will present some management activity

  12. Probing the Detailed Seismic Velocity Structure of Subduction Zones Using Advanced Seismic Tomography Methods

    NASA Astrophysics Data System (ADS)

    Zhang, H.; Thurber, C. H.

    2005-12-01

    -P times in a manner similar to double-difference tomography. Obtaining a reliable Vp/Vs model of the subduction zone is more helpful for understanding its mechanical and petrologic properties. Our applications of the original version of double-difference tomography to several subduction zones beneath northern Honshu, Japan, the Wellington region, New Zealand, and Alaska, United States, have shown evident velocity variations within and around the subducting slab, which likely is evidence of dehydration reactions of various hydrous minerals that are hypothesized to be responsible for intermediate depth earthquakes. We will show the new velocity models for these subduction zones by applying our advanced tomographic methods.

  13. Advanced Optical Diagnostic Methods for Describing Fuel Injection and Combustion Flowfield Phenomena

    NASA Technical Reports Server (NTRS)

    Locke, Randy J.; Hicks, Yolanda R.; Anderson, Robert C.

    2004-01-01

    Over the past decade advanced optical diagnostic techniques have evolved and matured to a point where they are now widely applied in the interrogation of high pressure combusting flows. At NASA Glenn Research Center (GRC), imaging techniques have been used successfully in on-going work to develop the next generation of commercial aircraft gas turbine combustors. This work has centered on providing a means by which researchers and designers can obtain direct visual observation and measurements of the fuel injection/mixing/combustion processes and combustor flowfield in two- and three-dimensional views at actual operational conditions. Obtaining a thorough understanding of the chemical and physical processes at the extreme operating conditions of the next generation of combustors is critical to reducing emissions and increasing fuel efficiency. To accomplish this and other tasks, the diagnostic team at GRC has designed and constructed optically accessible, high pressurer high temperature flame tubes and sectar rigs capable of optically probing the 20-60 atm flowfields of these aero-combustors. Among the techniques employed at GRC are planar laser-induced fluorescence (PLIF) for imaging molecular species as well as liquid and gaseous fuel; planar light scattering (PLS) for imaging fuel sprays and droplets; and spontaneous Raman scattering for species and temperature measurement. Using these techniques, optical measurements never before possible have been made in the actual environments of liquid fueled gas turbines. 2-D mapping of such parameters as species (e.g. OH-, NO and kerosene-based jet fuel) distribution, injector spray angle, and fuel/air distribution are just some of the measurements that are now routinely made. Optical imaging has also provided prompt feedback to researchers regarding the effects of changes in the fuel injector configuration on both combustor performance and flowfield character. Several injector design modifications and improvements have

  14. Advanced methods for controlling untethered magnetic devices using rotating magnetic fields

    NASA Astrophysics Data System (ADS)

    Mahoney, Arthur W., Jr.

    This dissertation presents results documenting advancements on the control of untethered magnetic devices, such as magnetic "microrobots" and magnetically actuated capsule endoscopes, motivated by problems in minimally invasive medicine. This dissertation focuses on applying rotating magnetic fields for magnetic manipulation. The contributions include advancements in the way that helical microswimmers (devices that mimic the propulsion of bacterial flagella) are controlled in the presence of gravitational forces, advancements in ways that groups of untethered magnetic devices can be differentiated and semi-independently controlled, advancements in the way that untethered magnetic device can be controlled with a single rotating permanent magnet, and an improved understanding in the nature of the magnetic force applied to an untethered device by a rotating magnet.

  15. Advanced treatment planning methods for efficient radiation therapy with laser accelerated proton and ion beams

    SciTech Connect

    Schell, Stefan; Wilkens, Jan J.

    2010-10-15

    lateral clustering and reduce the number of particles that have to be blocked in the beam delivery system. Furthermore, the optimization routine can be adjusted to reduce the number of dose spots and laser shots. The authors implemented these methods into a research treatment planning system for laser accelerated particles. Results: The authors' proposed methods can decrease the amount of secondary radiation produced when blocking particles with wrong energies or when reducing the total number of particles from one laser shot. Additionally, caused by the efficient use of the beam, the treatment time is reduced considerably. Both improvements can be achieved without extensively changing the quality of the treatment plan since conventional intensity modulated particle therapy usually includes a certain amount of unused degrees of freedom which can be used to adapt to laser specific properties. Conclusions: The advanced beam delivery and treatment planning methods reduce the need to have a perfect laser-based accelerator reproducing the properties of conventional accelerators that might not be possible without increasing treatment time and secondary radiation to the patient. The authors show how some of the differences to conventional beams can be overcome and efficiently used for radiation treatment.

  16. 41 CFR 302-7.106 - What documentation is required to receive an advance under the commuted rate method?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false What documentation is required to receive an advance under the commuted rate method? 302-7.106 Section 302-7.106 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES TRANSPORTATION AND STORAGE OF PROPERTY 7-TRANSPORTATION...

  17. Advanced Methods for Aircraft Engine Thrust and Noise Benefits: Nozzle-Inlet Flow Analysis

    NASA Technical Reports Server (NTRS)

    Gilinsky, Mikhail; Morgan, Morris H.; Povitsky, Alex; Schkolnikov, Natalia; Njoroge, Norman; Coston, Calvin; Blankson, Isaiah M.

    2001-01-01

    The Fluid Mechanics and Acoustics Laboratory at Hampton University (HU/FM&AL) jointly with the NASA Glenn Research Center has conducted four connected subprojects under the reporting project. Basically, the HU/FM&AL Team has been involved in joint research with the purpose of theoretical explanation of experimental facts and creation of accurate numerical simulation techniques and prediction theory for solution of current problems in propulsion systems of interest to the NAVY and NASA agencies. This work is also supported by joint research between the NASA GRC and the Institute of Mechanics at Moscow State University (IM/MSU) in Russia under a CRDF grant. The research is focused on a wide regime of problems in the propulsion field as well as in experimental testing and theoretical and numerical simulation analyses for advanced aircraft and rocket engines. The FM&AL Team uses analytical methods, numerical simulations and possible experimental tests at the Hampton University campus. The fundamental idea uniting these subprojects is to use nontraditional 3D corrugated and composite nozzle and inlet designs and additional methods for exhaust jet noise reduction without essential thrust loss and even with thrust augmentation. These subprojects are: (1) Aeroperformance and acoustics of Bluebell-shaped and Telescope-shaped designs; (2) An analysis of sharp-edged nozzle exit designs for effective fuel injection into the flow stream in air-breathing engines: triangular-round, diamond-round and other nozzles; (3) Measurement technique improvement for the HU Low Speed Wind Tunnel; a new course in the field of aerodynamics, teaching and training of HU students; experimental tests of Mobius-shaped screws: research and training; (4) Supersonic inlet shape optimization. The main outcomes during this reporting period are: (l) Publications: The AIAA Paper #00-3170 was presented at the 36th AIAA/ASME/SAE/ASEE Joint Propulsion Conference, 17-19 June, 2000, Huntsville, AL. The AIAA

  18. Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications

    NASA Astrophysics Data System (ADS)

    Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan

    2008-02-01

    Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.

  19. Characterization and risk assessment of PAH-contaminated river sediment by using advanced multivariate methods.

    PubMed

    Wang, Yeuh-Bin; Liu, Chen-Wuing; Kao, Yu-Hsuan; Jang, Cheng-Shin

    2015-08-15

    This study applied advanced multivariate methods and risk assessment to evaluate the characteristics of polycyclic aromatic hydrocarbons (PAHs) in the sediment of the severely polluted Erjen River in Taiwan. High-molecular-weight PAHs (HPAHs) dominated in the rainy season. The ecological risk of PAHs in the sediment was low, whereas the total health risk through ingestion and dermal contact was considerably high. The SOM (self-organizing map) analysis clustered the datasets of PAH-contaminated sediment into five groups with similar concentration levels. Factor analysis identified major factors, namely coal combustion, traffic, petrogenic, and petrochemical industry factors, accounting for 88.67% of the variance in the original datasets. The major tributary and the downstream of the river were identified as PAH-contamination hotspots. The PMF (positive matrix factorization) was combined with toxicity assessment to estimate the possible apportionment of sources and the associated toxicity. Spills of petroleum-related products, vehicle exhaust, coal combustion, and exhaust from a petrochemical industry complex constituted respectively 12%, 6%, 74%, and 86% of PAHs in the sediment, but contributed respectively 7%, 15%, 22%, and 56% of toxicity posed by PAHs in the sediment. To improve the sediment quality, best management practices should be adopted to eliminate nonpoint sources of PAHs flushed by storm water into the major tributary and the downstream of the Erjen River. The proposed methodologies and results provide useful information on remediating river PAH-contaminated sediment and may be applicable to other basins with similar properties that are experiencing resembled river environmental issues. PMID:25889545

  20. SU-F-BRD-16: Under Dose Regions Recalculated by Monte Carlo Cannot Predict the Local Failure for NSCLC Patients Treated with SBRT

    SciTech Connect

    Liu, H; Cherian, S; Stephans, K; Videtic, G; Qi, P; Xia, P; Zhuang, T

    2014-06-15

    Purpose: To investigate whether Monte Carlo (MC) recalculated dose distributions can predict the geometric location of the recurrence for nonsmall cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Methods: Thirty NSCLC patients with local recurrence were retrospectively selected for this study. The recurred gross target volumes (rGTV) were delineated on the follow-up CT/PET images and then rigidly transferred via imaging fusion to the original planning CTs. Failure pattern was defined according to the overlap between the rGTV and planning GTV (pGTV) as: (a) in-field failure (≥80%), (b) marginal failure (20%–80%), and (c) out-of-field failure (≤20%). All clinical plans were calculated initially with pencil beam (PB) with or without heterogeneity correction dependent of protocols. These plans were recalculated with MC with heterogeneity correction. Because of non-uniform dose distributions in the rGTVs, the rGTVs were further divided into four regions: inside the pGTV (GTVin), inside the PTV (PTVin), outside the pGTV (GTVout), and outside the PTV (PTVout). The mean doses to these regions were reported and analyzed separately. Results: Among 30 patients, 10 patients had infield recurrences, 15 marginal and 5 out-of-field failures. With MC calculations, D95 and D99 of the PTV were reduced by (10.6 ± 7.4)% and (11.7 ± 7.9)%. The average MC calculated mean doses of GTVin, GTVout, PTVin and PTVout were 48.2 ± 5.3 Gy, 48.2 ± 5.5 Gy, 46.3 ± 6.2 Gy and 46.6 ± 5.6 Gy, respectively. No significant dose differences between GTVin and GTVout (p=0.65), PTVin and PTVout (p=0.19) were observed, using the paired students t-test. Conclusion: Although the PB calculations underestimated the tumor target doses, the geometric location of the recurrence did not correlate with the mean doses of subsections of the recurrent GTV. Under dose regions recalculated by MC cannot predict the local failure for NSCLC patients treated with SBRT.

  1. Assessment of an ancient bridge combining geophysical and advanced photogrammetric methods: Application to the Pont De Coq, France

    NASA Astrophysics Data System (ADS)

    Fauchard, Cyrille; Antoine, Raphaël; Bretar, Frédéric; Lacogne, Julien; Fargier, Yannick; Maisonnave, Cindy; Guilbert, Vincent; Marjerie, Pierre; Thérain, Paul-Franck; Dupont, Jean-Paul; Pierrot-Deseilligny, Marc

    2013-11-01

    A high resolution geophysical survey was carried out on the Pont De Coq, a medieval stone arch bridge located in Normandy (France) in 2011 and 2012. Two complementary methods are used: Electrical Resistivity Tomography (ERT) and Ground PenetratingRadar (GPR). They allow to evaluate the structural state of the bridge and to characterize the subsurface around and beneath the bridge. An excellent correlation is obtained between the geophysical methods and the geological data obtained around the bridge. In order to improve the restitution of the geophysical data, an advanced photogrammetric method is performed, providing a high resolution 3D Digital Terrain Model (DTM) of the Pont de Coq. The advanced photogrammetry enhances the presentation of the GPR and ERT data. This approach is an easy-to-use, rapid and cost-effective tool for stakeholders. Finally, it is a promising and original method for improved interpretations of future geophysical surveys.

  2. Advanced Instrumentation and Control Methods for Small and Medium Reactors with IRIS Demonstration

    SciTech Connect

    J. Wesley Hines; Belle R. Upadhyaya; J. Michael Doster; Robert M. Edwards; Kenneth D. Lewis; Paul Turinsky; Jamie Coble

    2011-05-31

    Development and deployment of small-scale nuclear power reactors and their maintenance, monitoring, and control are part of the mission under the Small Modular Reactor (SMR) program. The objectives of this NERI-consortium research project are to investigate, develop, and validate advanced methods for sensing, controlling, monitoring, diagnosis, and prognosis of these reactors, and to demonstrate the methods with application to one of the proposed integral pressurized water reactors (IPWR). For this project, the IPWR design by Westinghouse, the International Reactor Secure and Innovative (IRIS), has been used to demonstrate the techniques developed under this project. The research focuses on three topical areas with the following objectives. Objective 1 - Develop and apply simulation capabilities and sensitivity/uncertainty analysis methods to address sensor deployment analysis and small grid stability issues. Objective 2 - Develop and test an autonomous and fault-tolerant control architecture and apply to the IRIS system and an experimental flow control loop, with extensions to multiple reactor modules, nuclear desalination, and optimal sensor placement strategy. Objective 3 - Develop and test an integrated monitoring, diagnosis, and prognosis system for SMRs using the IRIS as a test platform, and integrate process and equipment monitoring (PEM) and process and equipment prognostics (PEP) toolboxes. The research tasks are focused on meeting the unique needs of reactors that may be deployed to remote locations or to developing countries with limited support infrastructure. These applications will require smaller, robust reactor designs with advanced technologies for sensors, instrumentation, and control. An excellent overview of SMRs is described in an article by Ingersoll (2009). The article refers to these as deliberately small reactors. Most of these have modular characteristics, with multiple units deployed at the same plant site. Additionally, the topics focus

  3. Recombinant nematode anticoagulant protein c2 inhibits cell invasion by decreasing uPA expression in NSCLC cells.

    PubMed

    Tong, Yu; Yue, Jun; Mao, Meng; Liu, Qingqing; Zhou, Jing; Yang, Jiyun

    2015-04-01

    Nematode anticoagulant protein c2 (NAPc2) is an 85-residue polypeptide originally isolated from the hematophagous hookworm, Ancylostoma caninum. Several studies have shown that rNAPc2 inhibits the growth of primary and metastatic tumors in mice independently of its ability to initiate coagulation. We obtained bioactive recombinant rNAPc2 by splicing of the rNAPc2-intein-CBD fusion proteins expressed in E. coli ER2566. In the in vitro assay, rNAPc2 obviously inhibited the invasive ability of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Furthermore, rNAPc2 suppressed tumor growth in vivo by daily intraperitoneal injection of rNAPc2 in an NSCLC cell xenograft model of nude mice. Respectively, rNAPc2 downregulated the production of urokinase plasminogen activator (uPA) (P<0.05) and suppressed nuclear factor-κB (NF-κB) activity. We also identified that inhibition of NF-κB activity impaired cell invasion and reduced the uPA production in NSCLC cells. Meanwhile, NF-κB was found to directly bind to the uPA promoter in vitro. These results demonstrated that rNAPc2 inhibits cell invasion at least in part through the downregulation of the NF-κB-dependent metastasis-related gene expression in NSCLC. Our results also suggest that uPA, a known metastasis-promoting gene, is indirectly regulated by rNAPc2 through NF-κB activation. These results indicate that rNAPc2 may be a potent agent for the prevention of NSCLC progression. PMID:25672417

  4. Promoter methylation of APC and RAR-β genes as prognostic markers in non-small cell lung cancer (NSCLC).

    PubMed

    Feng, Hongxiang; Zhang, Zhenrong; Qing, Xin; Wang, Xiaowei; Liang, Chaoyang; Liu, Deruo

    2016-02-01

    Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non-tumor samples, and with smoking (P=0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients. PMID:26681652

  5. Advanced Spectral Analysis Methods for Quantification of Coherent Ultrasound Scattering: Applications in the Breast

    NASA Astrophysics Data System (ADS)

    Rosado-Mendez, Ivan M.

    The goal of this dissertation was to improve the diagnostic value of parametric images generated from Quantitative Ultrasound (QUS) methods based on the power spectral density (PSD) of radiofrequency echo signals. This was achieved by testing for local adherence to conventional QUS assumptions that echo signals originate from incoherent scattering, and that signals are stationary over PSD estimation windows. For this purpose, we designed a novel algorithm that empirically evaluates the statistical significance of coherent-scattering signatures in the echo signals. Signatures are quantified through a set of optimized metrics describing the stationary or non-stationary features of the echo signals. We compared Nakagami-model based metrics and model-free metrics of the statistics of the echo signal amplitude for analyzing stationary features. For non-stationary features, we advanced the use of the echo-signal generalized spectrum by comparing single- and multi-taper estimators of this spectrum to the time-domain singular spectrum analysis method. Tests of statistical significance were done through empirical comparisons with values of the same metrics estimated from a uniform reference material exhibiting incoherent scattering. The metrics that quantify these features were selected after simulation- and phantom-based optimizations centered on the task of creating parametric images, where tradeoffs must be made between spatial resolution and detection performance. The connection of the analyses of the stationary and the non-stationary features provided a way to estimate descriptors of the tissue organization scales below and above the resolution limit imposed by the size of the acoustic pulse. A preliminary application of the developed algorithm was done on echo data from human breast lesions scanned in vivo. Results supported the idea of a more homogeneously random distribution of subresolution scatterers within invasive ductal carcinomas than within fibroadenomas

  6. Evaluation of 29 indicators for the prognosis of advanced non-small cell lung cancer with cytokine-induced killer cell therapy combined with chemotherapy

    PubMed Central

    JIA, HEJIN; TIAN, YAPING; JIANG, CHAO GUANG; HAN, WEIDONG

    2016-01-01

    The aim of the present study was to evaluate 29 whole blood or serum indicators to identify factors able to predict clinical outcome following cytokine-induced killer (CIK) cell therapy combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the 5-year prognosis of the patients. From March 2008 to October 2013, 42 patients with advanced NSCLC (stages III and IV) were enrolled in the study. These patients were from a single hospital, and had been treated with CIK therapy combined with chemotherapy. Evaluation of the correlation between prognosis and age, gender, tumor stage, surgery resection status, number of CIK therapy cycles, tumor subtype, and the differential whole blood or serum indicators were analyzed by Kaplan-Meier methods and the log-rank test. The prognostic factors were analyzed by Cox proportional models. The median progression-free survival (mPFS) time of patients with high expression levels of albumin [20.0 months; 95% confidence interval (CI): 17.4–22.6 months] was significantly longer than the mPFS for patients with low expression levels of albumin (36.0 months; 95% CI: 24.7–47.3 months) (P=0.034). Other factors demonstrated no significant difference. Following analysis using the Cox proportional hazards regression model, the number of CIK therapy cycles (P=0.041) and the expression level of albumin (P=0.038) were revealed to be independent prognostic factors following the use of CIK cell therapy combined with chemotherapy for patients with advanced NSCLC. The risk of adverse outcomes in patients receiving ≥4 CIK therapy cycles and in patients with increased expression levels of albumin were 0.38 (95% CI: 0.14–1.13) and 0.32 (95% CI: 0.10–1.24)-fold those of patients receiving <4 CIK therapy cycles and with decreased expression levels of albumin, respectively. The serum albumin concentration may therefore be a predictor of the 5-year survival rate of patients with advanced NSCLC treated

  7. Immunotherapy in locally-advanced non-small cell lung cancer: releasing the brakes on consolidation?

    PubMed Central

    2016-01-01

    Locally-advanced non-small cell lung cancer (LA-NSCLC) is optimally treated with definitive chemoradiation or surgery in combination with chemotherapy or chemoradiation. Prognosis, however, remains poor, and attempts to improve outcomes using consolidation or maintenance chemotherapy have not improved overall survival. Given the limited success of traditional cytotoxic chemotherapies as maintenance therapy for LA-NSCLC, recent studies have investigated the role of novel agents such as maintenance or consolidation, including antiangiogenic agents and molecular targeted therapy. With multiple newly reported trials demonstrating improved outcomes with immunotherapy over cytotoxic chemotherapy for stage IV NSCLC, integrating immunotherapy with definitive chemoradiation regimens or as consolidative therapy for LA-NSCLC is an attractive option. The recently published START trial is the first to test immunotherapy in LA-NSCLC in a randomized, phase III setting. In that trial, the administration of maintenance tecemotide (L-BLP25), which induces a T-cell response to the mucin 1 (MUC1) glycoprotein, was found to be well tolerated and improve overall survival compared with placebo among patients receiving concurrent, but not sequential, chemoradiation. Despite the promising findings of this trial, numerous questions regarding immunotherapy for LA-NSCLC remain, and several additional immunotherapy trials are underway or planned in this patient population. PMID:26958509

  8. Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Fang, Wenfeng; Yan, Yue; Hu, Zhihuang; Hong, Shaodong; Wu, Xuan; Qin, Tao; Liang, Wenhua; Zhang, Li

    2014-01-01

    Backgrounds It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered. Methods Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively. Results A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies. Conclusions For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs. PMID:25222496

  9. Prognostic value of the standardized uptake value maximum change calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography imaging in patients with advanced non-small-cell lung cancer

    PubMed Central

    Jin, Feng; Zhu, Hui; Fu, Zheng; Kong, Li; Yu, Jinming

    2016-01-01

    Purpose The purpose of this study was to investigate the prognostic value of the standardized uptake value maximum (SUVmax) change calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography (PET) imaging in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods We conducted a retrospective review of 115 patients with advanced NSCLC who underwent pretreatment dual-time-point 18F-fluorodeoxyglucose PET acquired at 1 and 2 hours after injection. The SUVmax from early images (SUVmax1) and SUVmax from delayed images (SUVmax2) were recorded and used to calculate the SUVmax changes, including the SUVmax increment (ΔSUVmax) and percent change of the SUVmax (%ΔSUVmax). Progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan–Meier method and were compared with the studied PET parameters, and the clinicopathological prognostic factors in univariate analyses and multivariate analyses were constructed using Cox proportional hazards regression. Results One hundred and fifteen consecutive patients were reviewed, and the median follow-up time was 12.5 months. The estimated median PFS and OS were 3.8 and 9.6 months, respectively. In univariate analysis, SUVmax1, SUVmax2, ΔSUVmax, %ΔSUVmax, clinical stage, and Eastern Cooperative Oncology Group (ECOG) scores were significant prognostic factors for PFS. Similar results were significantly correlated with OS, except %ΔSUVmax. In multivariate analysis, ΔSUVmax and %ΔSUVmax were significant factors for PFS. On the other hand, ECOG scores were only identified as independent predictors of OS. Conclusion Our results demonstrated the prognostic value of the SUVmax change in predicting the PFS of patients with advanced NSCLC. However, SUVmax change could not predict OS. PMID:27284249

  10. FAA/NASA International Symposium on Advanced Structural Integrity Methods for Airframe Durability and Damage Tolerance, part 2

    NASA Technical Reports Server (NTRS)

    Harris, Charles E. (Editor)

    1994-01-01

    The international technical experts in the areas of durability and damage tolerance of metallic airframe structures were assembled to present and discuss recent research findings and the development of advanced design and analysis methods, structural concepts, and advanced materials. The principal focus of the symposium was on the dissemination of new knowledge and the peer-review of progress on the development of advanced methodologies. Papers were presented on the following topics: structural concepts for enhanced durability, damage tolerance, and maintainability; new metallic alloys and processing technology; fatigue crack initiation and small crack effects; fatigue crack growth models; fracture mechanics failure criteria for ductile materials; structural mechanics methodology for residual strength and life prediction; development of flight load spectra for design and testing; and corrosion resistance.

  11. Exploration of polymethacrylate structure-property correlations: Advances towards combinatorial and high-throughput methods for biomaterials discovery

    PubMed Central

    Holmes, Paul F.; Bohrer, Mike; Kohn, Joachim

    2008-01-01

    In this review, we discuss the synthesis, characterization, physical properties, and applications of polymethacrylates and describe physical and biological structure-property correlations relevant to many high performance applications. We also track the advancement of material-property space from the ‘traditional’ mode of materials design to the emerging, state-of-the-art combinatorial and in silico methods. Particularly, this article places emphasis on recent advances in the automated combinatorial synthesis and development of high-throughput characterization methods. As a future perspective, we believe that the realization of combinatorial, high-throughput, and computational methods will allow for the rapid exploration of a vast polymethacrylate library property space. PMID:19649142

  12. Methods of validating the Advanced Diagnosis and Warning system for aircraft ICing Environments (ADWICE)

    NASA Astrophysics Data System (ADS)

    Rosczyk, S.; Hauf, T.; Leifeld, C.

    2003-04-01

    In-flight icing is one of the most hazardous problems in aviation. It was determined as contributing factor in more than 800 incidents worldwide. And though the meteorological factors of airframe icing become more and more transparent, they have to be integrated into the Federal Aviation Administration's (FAA) certification rules first. Therefore best way to enhance aviational safety is to know the areas of dangerous icing conditions in order to prevent flying in them. For this reason the German Weather Service (DWD), the Institute for Atmospheric Physics at the German Aerospace Centre (DLR) and the Institute of Meteorology and Climatology (ImuK) of the University of Hanover started developingADWICE - theAdvanced Diagnosis and Warning system for aircraft ICing Environments - in 1998. This algorithm is based on the DWDLocal Model (LM) forecast of temperature and humidity, in fusion with radar and synop and, coming soon, satellite data. It gives an every-hour nowcast of icing severity and type - divided into four categories: freezing rain, convective, stratiform and general - for the middle European area. A first validation of ADWICE took place in 1999 with observational data from an in-flight icing campaign during EURICE in 1997. The momentary validation deals with a broader database. As first step the output from ADWICE is compared to observations from pilots (PIREPs) to get a statistic of the probability of detecting icing and either no-icing conditions within the last icing-seasons. There were good results of this method with the AmericanIntegrated Icing Diagnostic Algorithm (IIDA). A problem though is the small number of PIREPs from Europe in comparison to the US. So a temporary campaign of pilots (including Lufthansa and Aerolloyd) collecting cloud and icing information every few miles is intended to solve this unpleasant situation. Another source of data are the measurements of theFalcon - a DLR research aircraft carrying an icing sensor. In addition to that

  13. Monitoring of infrastructural sites by means of advanced multi-temporal DInSAR methods

    NASA Astrophysics Data System (ADS)

    Vollrath, Andreas; Zucca, Francesco; Stramondo, Salvatore

    2013-10-01

    With the launch of Sentinel-1, advanced interferometric measurements will become more applicable then ever. The foreseen standard Wide Area Product (WAP), with its higher spatial and temporal resolution than comparable SAR missions, will provide the basement for the use of new wide scale and multitemporal analysis. By now the use of SAR interferometry methods with respect to risk assessment are mainly conducted for active tectonic zones, plate boundaries, volcanoes as well as urban areas, where local surface movement rates exceed the expected error and enough pixels per area contain a relatively stable phase. This study, in contrast, aims to focus on infrastructural sites that are located outside cities and are therefore surrounded by rural landscapes. The stumbling bock was given by the communication letter by the European Commission with regard to the stress tests of nuclear power plants in Europe in 2012. It is mentioned that continuously re-evaluated risk and safety assessments are necessary to guarantee highest possible security to the European citizens and environment. This is also true for other infrastructural sites, that are prone to diverse geophysical hazards. In combination with GPS and broadband seismology, multitemporal Differential Interferometric SAR approaches demonstrated great potential in contributing valuable information to surface movement phenomenas. At this stage of the project, first results of the Stamps-MTI approach (combined PSInSAR and SBAS) will be presented for the industrial area around Priolo Gargallo in South East Sicily by using ENVISAT ASAR IM mode data from 2003-2010. This area is located between the Malta Escarpment fault system and the Hyblean plateau and is prone to earthquake and tsunami risk. It features a high density of oil refineries that are directly located at the coast. The general potential of these techniques with respect to the SENTINEL-1 mission will be shown for this area and a road-map for further improvements