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Sample records for scanning detects kras

  1. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

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    Yanagihara Kazuyoshi

    2009-06-01

    Full Text Available Abstract Background Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS, which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. Methods DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. Results DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20 of gastric cancer cell lines (8–18-fold amplification and 4.7% (4/86 of primary gastric tumors (8–50-fold amplification. KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild

  2. A new scintillation proximity assay-based approach for the detection of KRAS mutations

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    Lee, So-Young; Lim, Jae-Cheong; Cho, Eun-Ha; Jung, Sung-Hee [Korea Atomic Energy Research Institute (KAERI), Daejeon (Korea, Republic of). Radioisotope Research Div.

    2016-04-01

    KRAS is very commonly mutated resulting in a constitutively activated protein, which is independent of epidermal growth factor receptor (EGFR) ligand binding and resistant to anti-EGFR therapy. Although KRAS is frequently studied, there is still no uniform standard for detecting of KRAS mutations. In this report, a new scintillation proximity assay-based approach is described that determines the relative affinities of wild-type and mutated KRAS to the anti-KRAS antibody. We performed in vitro experiments using normal human colonic cells (CCD18Co), KRAS wild type (Caco-2) and KRAS mutant (HCT 116) cell lines to determine the relative affinities of wild type or mutated KRAS toward an anti-KRAS monoclonal antibody. The process consists of two primary steps: immunoprecipitation from cell lysate to enrich the KRAS protein and the scintillation proximity assay of the immunoprecipitant to determine the relative affinity against the antibody. A fixed concentration of cell lysates was purified by the immunoprecipitation method. The expressions of the KRAS protein in all cell lines was quantitatively confirmed by western blot analysis. For the scintillation proximity assay, the KRAS standard protein was radiolabeled with {sup 125}I by a simple mixing process in the iodogen tube immediately at room temperature immediately before use. The obtained CPM (count per minute) values of were used to calculate the KRAS concentration using purified KRAS as the standard. The calculated relative affinities of 7 μg of Caco-2 and HCT 116 immunoprecipitants for the anti-KRAS antibody were 77 and 0%, respectively. The newly developed scintillation proximity assay-based strategy determines the relative affinities of wild-type or mutated KRAS towards the anti-KRAS monoclonal antibody. This determination can help distinguish mutated KRAS from the wild type protein. The new SPA based approach for detecting KRAS mutations is applicable to many other cancer-related mutations.

  3. Loopback rolling circle amplification for ultrasensitive detection of Kras gene.

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    Xu, Huo; Wu, Dong; Jiang, Yifan; Zhang, Rongbo; Wu, Qingzheng; Liu, Yiyun; Li, Feng; Wu, Zai-Sheng

    2017-03-01

    Mutations in Kras gene may be used as a diagnostic marker and a target for treatment of the broad spectrum of human cancers. In this study, we developed a new class of amplification assay, double-hairpin molecular beacon (DHMB)-based cascade rolling circle amplification (RCA), for ultrasensitive and selective detection of Kras gene in a homogenous solution. Specifically, target DNA can hybridize with DHMB and activate cyclical target strand-displacement polymerization (CTDP) and nicking-mediated strand-displacement polymerization (NMDP). The resulting nicked/displaced fragments substantially outnumber target DNA and cause the cascade rolling circle amplification (C-RCA) and nicked fragment-induced strand-displacement polymerization (NFDP). Even if four amplification processes are designed, only DHMB, padlock probe and polymerization primer are involved. Under optimized conditions, this screening system exhibits a linear range of 5 orders of magnitude (from 100fM to 20nM), and the detection limit is down to 16fM. Moreover, the developed biosensing system offers a high assay specificity for perfectly matched target DNA, and the measured data from practical samples demonstrated the potential application in the cancer diagnoses. As a proof-of-concept genetic assay, the novel signaling strategy, as well as desirable analytical capability, would significantly benefit the development of versatile amplification gene profiling platforms, revealing great promise in biological studies and medical diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma.

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    Takamochi, Kazuya; Mogushi, Kaoru; Kawaji, Hideya; Imashimizu, Kota; Fukui, Mariko; Oh, Shiaki; Itoh, Masayoshi; Hayashizaki, Yoshihide; Ko, Weijey; Akeboshi, Masao; Suzuki, Kenji

    2017-01-01

    18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality based on glucose metabolism. The correlation between EGFR or KRAS mutation status and the standardized uptake value (SUV) of 18F-FDG PET scanning has not been fully elucidated. Correlations between EGFR or KRAS mutation status and clinicopathological factors including SUVmax were statistically analyzed in 734 surgically resected lung adenocarcinoma patients. Molecular causal relationships between EGFR or KRAS mutation status and glucose metabolism were then elucidated in 62 lung adenocarcinomas using cap analysis of gene expression (CAGE), a method to determine and quantify the transcription initiation activities of mRNA across the genome. EGFR and KRAS mutations were detected in 334 (46%) and 83 (11%) of the 734 lung adenocarcinomas, respectively. The remaining 317 (43%) patients had wild-type tumors for both genes. EGFR mutations were more frequent in tumors with lower SUVmax. In contrast, no relationship was noted between KRAS mutation status and SUVmax. CAGE revealed that 4 genes associated with glucose metabolism (GPI, G6PD, PKM2, and GAPDH) and 5 associated with the cell cycle (ANLN, PTTG1, CIT, KPNA2, and CDC25A) were positively correlated with SUVmax, although expression levels were lower in EGFR-mutated than in wild-type tumors. No similar relationships were noted with KRAS mutations. EGFR-mutated adenocarcinomas are biologically indolent with potentially lower levels of glucose metabolism than wild-type tumors. Several genes associated with glucose metabolism and the cell cycle were specifically down-regulated in EGFR-mutated adenocarcinomas.

  5. Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma.

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    Kazuya Takamochi

    Full Text Available 18F-fluoro-2-deoxy-glucose (18F-FDG positron emission tomography (PET is a functional imaging modality based on glucose metabolism. The correlation between EGFR or KRAS mutation status and the standardized uptake value (SUV of 18F-FDG PET scanning has not been fully elucidated.Correlations between EGFR or KRAS mutation status and clinicopathological factors including SUVmax were statistically analyzed in 734 surgically resected lung adenocarcinoma patients. Molecular causal relationships between EGFR or KRAS mutation status and glucose metabolism were then elucidated in 62 lung adenocarcinomas using cap analysis of gene expression (CAGE, a method to determine and quantify the transcription initiation activities of mRNA across the genome.EGFR and KRAS mutations were detected in 334 (46% and 83 (11% of the 734 lung adenocarcinomas, respectively. The remaining 317 (43% patients had wild-type tumors for both genes. EGFR mutations were more frequent in tumors with lower SUVmax. In contrast, no relationship was noted between KRAS mutation status and SUVmax. CAGE revealed that 4 genes associated with glucose metabolism (GPI, G6PD, PKM2, and GAPDH and 5 associated with the cell cycle (ANLN, PTTG1, CIT, KPNA2, and CDC25A were positively correlated with SUVmax, although expression levels were lower in EGFR-mutated than in wild-type tumors. No similar relationships were noted with KRAS mutations.EGFR-mutated adenocarcinomas are biologically indolent with potentially lower levels of glucose metabolism than wild-type tumors. Several genes associated with glucose metabolism and the cell cycle were specifically down-regulated in EGFR-mutated adenocarcinomas.

  6. Biochip-Based Detection of KRAS Mutation in Non-Small Cell Lung Cancer

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    Barbara Ziegler

    2011-11-01

    Full Text Available This study is aimed at evaluating the potential of a biochip assay to sensitively detect KRAS mutation in DNA from non-small cell lung cancer (NSCLC tissue samples. The assay covers 10 mutations in codons 12 and 13 of the KRAS gene, and is based on mutant-enriched PCR followed by reverse-hybridization of biotinylated amplification products to an array of sequence-specific probes immobilized on the tip of a rectangular plastic stick (biochip. Biochip hybridization identified 17 (21% samples to carry a KRAS mutation of which 16 (33% were adenocarcinomas and 1 (3% was a squamous cell carcinoma. All mutations were confirmed by DNA sequencing. Using 10 ng of starting DNA, the biochip assay demonstrated a detection limit of 1% mutant sequence in a background of wild-type DNA. Our results suggest that the biochip assay is a sensitive alternative to protocols currently in use for KRAS mutation testing on limited quantity samples.

  7. Detection and Analysis of EGFR and KRAS Mutations 
in the Patients with Lung Squamous Cell Carcinomas

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    Hui ZHANG

    2015-10-01

    Full Text Available Background and objective Activating mutations in epidermal growth factor receptor (EGFR and KRAS are important markers in non-small cell lung cancer. However, EGFR and KRAS gene mutations in lung squamous cell carcinoma are rarely reported. The aim of this study was to analyze EGFR and KRAS gene mutation rate and their relationship with clinical features in patients with lung squamous cell carcinomas. Methods A total of 139 patients undergoing treatment for naïve lung squamous cell carcinomas with tumor tissue samples available for testing were recruited. EGFR and KRAS mutation statuses of the tumor samples were detected using a mutant enriched liquid chip. Results Of the 139 cases of lung squamous cell carcinoma, EGFR mutations were detected in 25 cases (18%, KRAS mutations were detected in 7 cases (5%, and the presence of both EGFR and KRAS mutations was detected in 1 case (0.7%. EGFR mutations occurred more often in females than in males (33.3% vs 16.5% and in patients that never smoked than in those who smoke (29.6% vs 16.1%. However, the difference did not reach statistical significance (P>0.05. No significant differences were observed in age, stage, and different biopsy type. KRAS mutations occurred more often in males than in females (5.5% vs 0%, but the difference did not reach statistical significance (P>0.05. No significant differences were observed in age, stage, different biopsy type, and smoking status (P>0.05. Conclusion EGFR and KRAS mutations were low in lung squamous cell carcinomas, and had no significant correlation with clinical features. Before using tyrosine kinase inhibitor targeted therapy, EGFR and KRAS mutations should be detected in patients with lung squamous cell carcinomas.

  8. Detection of K-ras gene mutations in feces by magnetic nanoprobe in patients with pancreatic cancer: A preliminary study.

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    Wang, Xiaoguang; Wang, Jingshuai; Chen, Fei; Zhong, Zhengxiang; Qi, Lifeng

    2018-01-01

    The present study aimed to investigate the feasibility and effectiveness of detecting K-ras mutation by using magnetic nanoparticles in fecal samples of patients with pancreatic cancer at different stages. The novel methodology of K-ras mutation detection was compared to the existing methodology of cancer antigen (CA)19-9 examination. Patients with pancreatic cancer (n=88), pancreatic benign diseases who displayed chronic pancreatitis (n=35), pancreatic mucinous cyst neoplasms (n=10) and pancreatic serous cyst (n=9) admitted to the Department of Surgery, Jiaxing Second Hospital were enrolled in the present study. Fecal samples were collected from all patients, DNA was extracted and magnetic nanoprobe was then used to detect K-ras mutation. The results obtained using the novel magnetic nanoprobe detection technique showed a K-ras mutation rate of 81.8% (72/88) in the patients with pancreatic cancer and 18.5% (10/54) in patients with pancreatic benign diseases. In patients with pancreatic cancer, the K-ras mutation rate was comparable in stages I + IIA and IIB + III + IV (78.9 vs. 84.0%; P>0.05). The sensitivity and specificity of K-ras mutation for detection of pancreatic cancer was 81.8 and 81.5%, respectively. Sixty-eight pancreatic cancer patients had >37 U/ml CA99 with a sensitivity and specificity for pancreatic cancer detection of 77.3 and 77.8%, which was not significantly lower than detection by the fecal K-ras mutations (P>0.05). Combinational detection of fecal K-ras mutations and serum CA19-9 significantly increased the sensitivity regarding pancreatic cancer detection to 97.7% (P0.05) compared with fecal K-ras mutations or CA19-9 alone. The findings showed that the magnetic nanoprobe is able to detect fecal K-ras mutations in different stages of pancreatic cancer, with comparable sensitivity and specificity to CA19-9 examination for differentiating pancreatic cancer. Furthermore, combined detection of CA19-9 and K-ras mutations has enhanced sensitivity

  9. Key differences between 13 KRAS mutation detection technologies and their relevance for clinical practice

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    Sherwood, James L; Brown, Helen; Rettino, Alessandro; Schreieck, Amelie; Clark, Graeme; Claes, Bart; Agrawal, Bhuwnesh; Chaston, Ria; Kong, Benjamin S G; Choppa, Paul; Nygren, Anders O H; Deras, Ina L; Kohlmann, Alexander

    2017-01-01

    Introduction This study assessed KRAS mutation detection and functional characteristics across 13 distinct technologies and assays available in clinical practice, in a blinded manner. Methods Five distinct KRAS-mutant cell lines were used to study five clinically relevant KRAS mutations: p.G12C, p.G12D, p.G12V, p.G13D and p.Q61H. 50 cell line admixtures with low (50 and 100) mutant KRAS allele copies at 20%, 10%, 5%, 1% and 0.5% frequency were processed using quantitative PCR (qPCR) (n=3), matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF) (n=2), next-generation sequencing (NGS) (n=6), digital PCR (n=1) and Sanger capillary sequencing (n=1) assays. Important performance differences were revealed, particularly assay sensitivity and turnaround time. Results Overall 406/728 data points across all 13 technologies were identified correctly. Successful genotyping of admixtures ranged from 0% (Sanger sequencing) to 100% (NGS). 5/6 NGS platforms reported similar allelic frequency for each sample. One NGS assay detected mutations down to a frequency of 0.5% and correctly identified all 56 samples (Oncomine Focus Assay, Thermo Fisher Scientific). One qPCR (Idylla, Biocartis) and MALDI-TOF (UltraSEEK, Agena Bioscience) assay identified 96% (all 100 copies and 23/25 at 50 copies input) and 92% (23/25 at 100 copies and 23/25 at 50 copies input) of samples, respectively. The digital PCR assay (KRAS PrimePCR ddPCR, Bio-Rad Laboratories) identified 60% (100 copies) and 52% (50 copies) of samples correctly. Turnaround time from sample to results ranged from ~2 hours (Idylla CE-IVD) to 2 days (TruSight Tumor 15 and Sentosa CE-IVD), to 2 weeks for certain NGS assays; the level of required expertise ranged from minimal (Idylla CE-IVD) to high for some technologies. Discussion This comprehensive parallel assessment used high molecular weight cell line DNA as a model system to address key questions for a laboratory when implementing routine

  10. Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer.

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    Kinugasa, Hideaki; Nouso, Kazuhiro; Miyahara, Koji; Morimoto, Yuki; Dohi, Chihiro; Tsutsumi, Koichiro; Kato, Hironari; Matsubara, Takehiro; Okada, Hiroyuki; Yamamoto, Kazuhide

    2015-07-01

    Cell-free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer. The authors compared K-ras mutations detected in endoscopic ultrasound-guided fine-needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K-ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates. The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3%), 22 of 75 samples (29.3%), and 6 of 75 samples (8.0%), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6%), 29 of 75 samples (38.6%), and 4 of 75 samples (5.3%), respectively. Overall, the K-ras mutation rates in tissue and ctDNA were 74.7% and 62.6%, respectively, and the concordance rate between them was 58 of 75 samples (77.3%). Survival did not appear to differ by the presence of K-ras mutations in tissue DNA, but the survival of patients with K-ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation. Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival. © 2015 American Cancer Society.

  11. Detection of KRAS, NRAS and BRAF by mass spectrometry - a sensitive, reliable, fast and cost-effective technique.

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    Kriegsmann, Mark; Arens, Norbert; Endris, Volker; Weichert, Wilko; Kriegsmann, Jörg

    2015-07-30

    According to current clinical guidelines mutational analysis for KRAS and NRAS is recommended prior to EGFR-directed therapy of colorectal cancer (CRC) in the metastatic setting. Therefore, reliable, fast, sensitive and cost-effective methods for routine tissue based molecular diagnostics are required that allow the assessment of the CRC mutational status in a high throughput fashion. We have developed a custom designed assay for routine mass-spectrometric (MS) (MassARRAY, Agena Bioscience) analysis to test the presence/absence of 18 KRAS, 14 NRAS and 4 BRAF mutations. We have applied this assay to 93 samples from patients with CRC and have compared the results with Sanger sequencing and a chip hybridization assay (KRAS LCD-array Kit, Chipron). In cases with discordant results, next-generation sequencing (NGS) was performed. MS detected a KRAS mutation in 46/93 (49%), a NRAS mutation in 2/93 (2%) and a BRAF mutation in 1/93 (1%) of the cases. MS results were in agreement with results obtained by combination of the two other methods in 92 (99%) of 93 cases. In 1/93 (1%) of the cases a G12V mutation has been detected by Sanger sequencing and MS, but not by the chip assay. In this case, NGS has confirmed the G12V mutation in KRAS. Mutational analysis by MS is a reliable method for routine diagnostic use, which can be easily extended for testing of additional mutations.

  12. Detection of TET2, KRAS and CBL variants by Next Generation Sequencing and analysis of their correlation with JAK2 and FLT3 in childhood AML

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    Dilara Fatma Akin

    2016-04-01

    Conclusion: We found novel mutations for TET2, KRAS, and CBL. The detected variants in this article seem to be the first screening results of genes studied by NGS in childhood AML patients. Our results also showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations.

  13. Frequent detection of K-ras mutation in stool samples of colorectal carcinoma patients after improved DNA extraction: comparison with tissue samples.

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    Ito, Yasushi; Kobayashi, Susumu; Taniguchi, Tetsushi; Kainuma, Osamu; Hara, Tsuyosi; Ochiai, Takenori

    2002-06-01

    Fecal occult blood testing is widely used in the clinical screening of colorectal tumors. However, this method has so frequent false-positive results that more accurate screening-strategy should be established. Although the molecular screening using K-ras gene mutation in stools has been attempted to improve the results, the low rate of DNA extraction from stools leaves this measurement under utility value. In this study, we investigated whether or not our applied DNA extraction method from stools could produce enough DNA for the molecular screening of colorectal tumors by K-ras gene mutations in stools. We applied cetyltrimethylammonium bromide (CTAB) solution to improve human DNA extraction from stools and a mutant-allele-sensitive amplification (MASA) method to detect K-ras mutation within codon 12. We were able to confirm the stool DNA by identifying K-ras fragments in all the 20 patients. Tissue K-ras mutation was identified in 4 (2 cancers and 2 adenomas) of 20 patients. Stool K-ras mutations were found in 6 patients, 3 tissue K-ras mutation positive patients (2 cancers and an adenoma) and 3 tissue K-ras mutation negative patients. These results indicate that it is possible to extract enough DNA from human stool samples of all patients with colorectal tumors for K-ras mutation studies. K-ras mutations are more frequently detected in stools than in resected colorectal tumors. This study indicates that K-ras mutation screening in stools for colorectal cancer may include not only a primary colorectal cancer but also precancerous lesions in all parts of a gastrointestinal tract.

  14. Detection of K-ras Mutations in Predicting Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase (EGFR-TK Inhibitor in Patients with Metastatic Colorectal Cancer.

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    Ze Li

    Full Text Available Epidermal growth factor receptor tyrosine kinase (EGFR-TK inhibitors are useful in treating different advanced human cancers; however, their clinical efficacy varies. This study detected K-ras mutations to predict the efficacy of EGFR-TK inhibitor cetuximab treatment on Chinese patients with metastatic colorectal cancer (mCRC. A total of 87 patients with metastatic colorectal cancer were treated with cetuximab for 2-16 months, in combination with chemotherapy between August 2008 and July 2012, and tissue samples were used to detect K-ras mutations. The data showed that K-ras mutation occurred in 27/87 (31%. The objective response rates and disease control rate in K-ras wild type and mutant patients were 42% (25/60 versus 11% (3/27 (p<0.05 and 60% (36/60 versus 26% (7/27 (p<0.05, respectively. Patients with the wild-type K-ras had significantly higher median survival times and progression-free survival, than patients with mutated K-ras (21 months versus 17 months, p=0.017; 10 months versus 6 months, p=0.6. These findings suggest that a high frequency of K-ras mutations occurs in Chinese mCRC patients and that K-ras mutation is required to select patients for eligibility for cetuximab therapy. Further prospective studies using a large sample size are needed to confirm these preliminary findings.

  15. Sensitive detection of KRAS mutations in archived formalin-fixed paraffin-embedded tissue using mutant-enriched PCR and reverse-hybridization.

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    Ausch, Christoph; Buxhofer-Ausch, Veronika; Oberkanins, Christian; Holzer, Barbara; Minai-Pour, Michael; Jahn, Stephan; Dandachi, Nadia; Zeillinger, Robert; Kriegshäuser, Gernot

    2009-11-01

    Recently, evidence has emerged indicating that assessment of KRAS mutations before anti-epidermal growth factor receptor therapy improves outcome in patients with metastatic colorectal cancer (CRC). We report here a novel reverse-hybridization (RH) assay to screen for KRAS mutations in formalin-fixed paraffin-embedded colorectal tissue samples. We combined mutant-enriched PCR based on peptide nucleic acid clamping and RH of amplification products to nitrocellulose test strips that contained a parallel array of oligonucleotide probes targeting 10 frequent mutations in codons 12 and 13 of the KRAS gene. DNA mixing experiments, which included eight different tumor cell lines with known KRAS mutations, were performed to examine the sensitivity of mutation detection. All KRAS mutations present in tumor cell lines were unambiguously identified by the RH assay with 1% of each cell line DNA diluted in normal DNA. RH was then used to screen for KRAS mutations in 74 colorectal tumor and 4 normal control samples. Twenty-six (35%) of the 74 tumor samples showed KRAS mutations. No mutation was found in the four samples of normal colorectal tissue. DNA sequencing without previous mutant enrichment, however, failed to detect four (15%) out of 26 KRAS-positive formalin-fixed paraffin-embedded samples (FFPE). This finding suggests that even after microdissection, mutant sequences in a given DNA isolate can be rare and more sensitive methods are needed for mutation analysis.

  16. Prospective Validation of Rapid Plasma Genotyping for the Detection of EGFR and KRAS Mutations in Advanced Lung Cancer.

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    Sacher, Adrian G; Paweletz, Cloud; Dahlberg, Suzanne E; Alden, Ryan S; O'Connell, Allison; Feeney, Nora; Mach, Stacy L; Jänne, Pasi A; Oxnard, Geoffrey R

    2016-08-01

    Plasma genotyping of cell-free DNA has the potential to allow for rapid noninvasive genotyping while avoiding the inherent shortcomings of tissue genotyping and repeat biopsies. To prospectively validate plasma droplet digital PCR (ddPCR) for the rapid detection of common epidermal growth factor receptor (EGFR) and KRAS mutations, as well as the EGFR T790M acquired resistance mutation. Patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) who either (1) had a new diagnosis and were planned for initial therapy or (2) had developed acquired resistance to an EGFR kinase inhibitor and were planned for rebiopsy underwent initial blood sampling and immediate plasma ddPCR for EGFR exon 19 del, L858R, T790M, and/or KRAS G12X between July 3, 2014, and June 30, 2015, at a National Cancer Institute-designated comprehensive cancer center. All patients underwent biopsy for tissue genotyping, which was used as the reference standard for comparison; rebiopsy was required for patients with acquired resistance to EGFR kinase inhibitors. Test turnaround time (TAT) was measured in business days from blood sampling until test reporting. Plasma ddPCR assay sensitivity, specificity, and TAT. Of 180 patients with advanced NSCLC (62% female; median [range] age, 62 [37-93] years), 120 cases were newly diagnosed; 60 had acquired resistance. Tumor genotype included 80 EGFR exon 19/L858R mutants, 35 EGFR T790M, and 25 KRAS G12X mutants. Median (range) TAT for plasma ddPCR was 3 (1-7) days. Tissue genotyping median (range) TAT was 12 (1-54) days for patients with newly diagnosed NSCLC and 27 (1-146) days for patients with acquired resistance. Plasma ddPCR exhibited a positive predictive value of 100% (95% CI, 91%-100%) for EGFR 19 del, 100% (95% CI, 85%-100%) for L858R, and 100% (95% CI, 79%-100%) for KRAS, but lower for T790M at 79% (95% CI, 62%-91%). The sensitivity of plasma ddPCR was 82% (95% CI, 69%-91%) for EGFR 19 del, 74% (95% CI, 55%-88%) for L858R, and 77% (95% CI, 60

  17. Electrochemical biosensor based on functional composite nanofibers for detection of K-ras gene via multiple signal amplification strategy.

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    Wang, Xiaoying; Shu, Guofang; Gao, Chanchan; Yang, Yu; Xu, Qian; Tang, Meng

    2014-12-01

    An electrochemical biosensor based on functional composite nanofibers for hybridization detection of specific K-ras gene that is highly associated with colorectal cancer via multiple signal amplification strategy has been developed. The carboxylated multiwalled carbon nanotubes (MWCNTs) doped nylon 6 (PA6) composite nanofibers (MWCNTs-PA6) was prepared using electrospinning, which served as the nanosized backbone for thionine (TH) electropolymerization. The functional composite nanofibers [MWCNTs-PA6-PTH, where PTH is poly(thionine)] used as supporting scaffolds for single-stranded DNA1 (ssDNA1) immobilization can dramatically increase the amount of DNA attachment and the hybridization sensitivity. Through the hybridization reaction, a sandwich format of ssDNA1/K-ras gene/gold nanoparticle-labeled ssDNA2 (AuNPs-ssDNA2) was fabricated, and the AuNPs offered excellent electrochemical signal transduction. The signal amplification was further implemented by forming network-like thiocyanuric acid/gold nanoparticles (TA/AuNPs). A significant sensitivity enhancement was obtained; the detection limit was down to 30fM, and the discriminations were up to 54.3 and 51.9% between the K-ras gene and the one-base mismatched sequences including G/C and A/T mismatched bases, respectively. The amenability of this method to the analyses of K-ras gene from the SW480 colorectal cancer cell lysates was demonstrated. The results are basically consistent with those of the K-ras Kit (HRM: high-resolution melt). The method holds promise for the diagnosis and management of cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Detection of TET2, KRAS and CBL variants by Next Generation ...

    African Journals Online (AJOL)

    Dilara Fatma Akin

    2015-10-01

    Oct 1, 2015 ... CBL. KRAS. FLT3. ITD. Rs number. Nucleotide change. Localization Amino acid change. Rs number. Nucleotide change. Localization Amino acid change. Rs number. Nucleotide change. Localization Amino acid change. 6. M/7. AML. M4 HR. 47, XY,+ 22[12] Inv (16;16), Fragile X syndrome. Rs. 17253972.

  19. Detection of TET2 , KRAS and CBL variants by Next Generation ...

    African Journals Online (AJOL)

    Methods: Eight patients who were diagnosed with pediatric AML at Losante Pediatric Hematology–Oncology Hospital were included to the study. Hot-spot exons of TET2, KRAS and CBL genes were screened using the NGS method. Furthermore, FLT3-Internal Tandem Duplicate (FLT3-ITD) and JAK2-V617F were analyzed ...

  20. Detection of low-abundance KRAS mutations in colorectal cancer using microfluidic capillary electrophoresis-based restriction fragment length polymorphism method with optimized assay conditions.

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    Huidan Zhang

    Full Text Available Constitutively active KRAS mutations have been found to be involved in various processes of cancer development, and render tumor cells resistant to EGFR-targeted therapies. Mutation detection methods with higher sensitivity will increase the possibility of choosing the correct individual therapy. Here, we established a highly sensitive and efficient microfluidic capillary electrophoresis-based restriction fragment length polymorphism (µCE-based RFLP platform for low-abundance KRAS genotyping with the combination of µCE and RFLP techniques. By using our self-built sensitive laser induced fluorescence (LIF detector and a new DNA intercalating dye YOYO-1, the separation conditions of µCE for ΦX174 HaeIII DNA marker were first optimized. Then, a Mav I digested 107-bp KRAS gene fragment was directly introduced into the microfluidic device and analyzed by µCE, in which field amplified sample stacking (FASS technique was employed to obtain the enrichment of the RFLP digestion products and extremely improved the sensitivity. The accurate analysis of KRAS statuses in HT29, LS174T, CCL187, SW480, Clone A, and CX-1 colorectal cancer (CRC cell lines by µCE-based RFLP were achieved in 5 min with picoliter-scale sample consumption, and as low as 0.01% of mutant KRAS could be identified from a large excess of wild-type genomic DNA (gDNA. In 98 paraffin-embedded CRC tissues, KRAS codon 12 mutations were discovered in 28 (28.6%, significantly higher than that obtained by direct sequencing (13, 13.3%. Clone sequencing confirmed these results and showed this system could detect at least 0.4% of the mutant KRAS in CRC tissue slides. Compared with direct sequencing, the new finding of the µCE-based RFLP platform was that KRAS mutations in codon 12 were correlated with the patient's age. In conclusion, we established a sensitive, fast, and cost-effective screening method for KRAS mutations, and successfully detected low-abundance KRAS mutations in clinical

  1. Lateral flow strip for visual detection of K-ras mutations based on allele-specific PCR.

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    Wang, Cong; Chen, Xiaomin; Wu, Yuying; Li, Hao; Wang, Yu; Pan, Xiaofu; Tang, Tingting; Liu, Ziying; Li, Xiaokun

    2016-10-01

    To develop a convenient and sensitive point-of-care test for detecting gene mutations based on allele-specific PCR. To develop a lateral flow strip for visual detection of K-ras mutations based on a modified PCR, a specific DNA tag was covalently linked to the 5'-end of each primer by a nine-carbon linker to produce a sticky end. One of the sticky ends of the PCR products bound to gold nano-particles, while the other sticky end was captured onto a nitrocellulose membrane of lateral flow strips. The lateral flow strip showed a great sensitivity, which detected mutations in as low as 10 tumor cells. The positive rate and accuracy of the lateral flow strip for blood samples were over 92 and 96 %, respectively. The lateral flow strip provides an easy method for sensitive detection of gene mutations based on allele specific-PCR.

  2. DETECTION OF K-RAS AND P53 MUTATIONS IN SPUTUM SAMPLES OF LUNG CANCER PATIENTS USING LASER CAPTURE MICRODISSECTION MICROSCOPE AND MUTATION ANALYSIS

    Science.gov (United States)

    Detection of K-ras and p53 Mutations in Sputum Samples of Lung Cancer Patients Using Laser Capture Microdissection Microscope and Mutation AnalysisPhouthone Keohavong a,*, Wei-Min Gao a, Kui-Cheng Zheng a, Hussam Mady b, Qing Lan c, Mona Melhem b, and Judy Mumford d.<...

  3. Effectiveness of circulating tumor DNA for detection of KRAS gene mutations in colorectal cancer patients: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Hao Y

    2017-02-01

    Full Text Available Yi-Xin Hao,1,* Qiang Fu,2,* Yan-Yan Guo,1 Ming Ye,1 Hui-Xia Zhao,1 Qi Wang,1 Xiu-Mei Peng,1 Qiu-Wen Li,1 Ru-Liang Wang,1 Wen-Hua Xiao1 1Department of Oncology, First Affiliated Hospital, 2Department of Anesthesiology, People’s Liberation Army General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Circulating tumor DNA (ctDNA can be identified in the peripheral blood of patients and harbors the genomic alterations found in tumor tissues, which provides a noninvasive approach for detection of gene mutations. We conducted this meta-analysis to investigate whether ctDNA can be used for monitoring KRAS gene mutations in colorectal cancer (CRC patients. Medline, Embase, Cochrane Library and Web of Science were searched for the included eligible studies in English, and data were extracted for statistical analysis according to the numbers of true-positive (TP, true-negative (TN, false-positive (FP and false-negative (FN cases. Sensitivity, specificity and diagnostic odds ratio (DOR were calculated, and the area under the receiver operating characteristic curve (AUROC was used to evaluate the diagnostic performance. After independent searching and reviewing, 21 studies involving 1,812 cancer patients were analyzed. The overall sensitivity, specificity and DOR were 0.67 (95% confidence interval [CI] =0.55–0.78, 0.96 (95% CI =0.93–0.98 and 53.95 (95% CI =26.24–110.92, respectively. The AUROC was 0.95 (95% CI =0.92–0.96, which indicated the high diagnostic accuracy of ctDNA. After stratified analysis, we found the higher diagnostic accuracy in subgroup of patients detected in blood sample of plasma. The ctDNA may be an ideal source for detection of KRAS gene mutations in CRC patients with high specificity and diagnostic value. Keywords: cancer, KRAS, mutation, circulating tumor DNA

  4. Lumber Scanning System for Surface Defect Detection

    Science.gov (United States)

    D. Earl Kline; Y. Jason Hou; Richard W. Conners; Daniel L. Schmoldt; Philip A. Araman

    1992-01-01

    This paper describes research aimed at developing a machine vision technology to drive automated processes in the hardwood forest products manufacturing industry. An industrial-scale machine vision system has been designed to scan variable-size hardwood lumber for detecting important features that influence the grade and value of lumber such as knots, holes, wane,...

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

    Directory of Open Access Journals (Sweden)

    James L Sherwood

    Full Text Available 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.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.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.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.

  6. Automatic change detection using mobile laser scanning

    Science.gov (United States)

    Hebel, M.; Hammer, M.; Gordon, M.; Arens, M.

    2014-10-01

    Automatic change detection in 3D environments requires the comparison of multi-temporal data. By comparing current data with past data of the same area, changes can be automatically detected and identified. Volumetric changes in the scene hint at suspicious activities like the movement of military vehicles, the application of camouflage nets, or the placement of IEDs, etc. In contrast to broad research activities in remote sensing with optical cameras, this paper addresses the topic using 3D data acquired by mobile laser scanning (MLS). We present a framework for immediate comparison of current MLS data to given 3D reference data. Our method extends the concept of occupancy grids known from robot mapping, which incorporates the sensor positions in the processing of the 3D point clouds. This allows extracting the information that is included in the data acquisition geometry. For each single range measurement, it becomes apparent that an object reflects laser pulses in the measured range distance, i.e., space is occupied at that 3D position. In addition, it is obvious that space is empty along the line of sight between sensor and the reflecting object. Everywhere else, the occupancy of space remains unknown. This approach handles occlusions and changes implicitly, such that the latter are identifiable by conflicts of empty space and occupied space. The presented concept of change detection has been successfully validated in experiments with recorded MLS data streams. Results are shown for test sites at which MLS data were acquired at different time intervals.

  7. Modified mismatch polymerase chain reaction-restriction fragment length polymorphism detected mutations in codon 12 and 13 of exon 2 of K-ras gene in colorectal cancer patients and its association with liver metastases: Data from a South Asian country

    Directory of Open Access Journals (Sweden)

    Fathima Dhilhani Mohamed Faleel

    2016-01-01

    Conclusion: Codon 12 of exon 2 of K--ras gene detected by modified mismatch PCR-RFLP assay is significantly associated with liver metastasis in CRC patients during the first 5 years after surgery. Thus, modified mismatch PCR-RFLP protocol is a suitable method in this setting to detect K-ras gene mutations predicting liver metastasis in CRC patients.

  8. KRAS and BRAF mutations in anal carcinoma

    DEFF Research Database (Denmark)

    Serup-Hansen, Eva; Linnemann, Dorte; Høgdall, Estrid

    2015-01-01

    The EGF receptor (EGFR) is expressed in most cases of anal carcinomas. Anecdotal benefit from EGFR-targeted therapy has been reported in anal cancer and a negative correlation with Kirsten Ras (KRAS) mutation status has been proposed. The purpose of this retrospective study was to investigate...... the frequency and the prognostic value of KRAS and BRAF mutations in a large cohort of patients with anal cancer. One hundred and ninety-three patients with T1-4N0-3M0-1 anal carcinoma were included in the study. Patients were treated with curative (92%) or palliative intent (8%) between January 2000...... and January 2010. KRAS mutations were detected using Therascreen(®)KRAS real-time PCR assay (Qiagen) and V600E or V600D/K BRAF mutations were uncovered using Pyrosequencing. The frequency of KRAS and BRAF mutations was low; KRAS mutations were detected in 1.6% and BRAF mutations in 4.7% of the biopsies...

  9. Detection of up to 65% of Precancerous Lesions of the Human Colon and Rectum by Mutation Analysis of APC, K-Ras, B-Raf and CTNNB1

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Mandy; Scholtka, Bettina, E-mail: scholtka@uni-potsdam.de [Chair of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur- Scheunert-Allee 114-116, 14558 Nuthetal (Germany); Gottschalk, Uwe [Maria Heimsuchung Caritas-Klinik Pankow, Breite Straße 46/47, 13187 Berlin (Germany); Faiss, Siegbert [III. Medizinische Abteilung - Gastroenterologie und Hepatologie, Asklepios Klinik Barmbek, Rubenkamp 220, 22291 Hamburg (Germany); Schatz, Daniela; Berghof-Jäger, Kornelia [BIOTECON Diagnostics GmbH, Hermannswerder Haus 17, 14473 Potsdam (Germany); Steinberg, Pablo, E-mail: scholtka@uni-potsdam.de [Chair of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur- Scheunert-Allee 114-116, 14558 Nuthetal (Germany); Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover (Germany)

    2010-12-29

    In the present study a recently conceived 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signaling pathways was used to analyze 20 colorectal serrated lesions and 41 colorectal adenoma samples and to determine the percentage of each of the above-mentioned potentially precancerous lesions carrying at least one of the four above-mentioned genes in a mutated form. CTNNB1 and B-Raf were screened by PCR-single-strand conformation polymorphism analysis, K-Ras by restriction fragment length polymorphism analysis and the APC gene mutation cluster region (codons 1243–1567) by direct DNA sequencing. APC mutations were only detected in 10% of the serrated lesions but in 34% of the adenomas. Twenty percent of the serrated lesions and 14% of the adenomas carried a mutated K-Ras. B-Raf was found to be mutated in 50% of the serrated lesions and in 22% of the adenomas. CTNNB1 was altered in 12% of the adenomas, but not in serrated lesions. By using the above gene marker panel it could be shown that 65% of the serrated lesions and 61% of the adenomas carried at least one of the four genes in a mutated form. Based on its excellent performance in detecting mutations in sporadic preneoplastic (in this study) and neoplastic lesions (in a previous study) of the human colon and rectum, this primer combination might also be suited to efficiently and non-invasively detect genetic alterations in stool DNA of patients with early colorectal cancer.

  10. MutScan: fast detection and visualization of target mutations by scanning FASTQ data.

    Science.gov (United States)

    Chen, Shifu; Huang, Tanxiao; Wen, Tiexiang; Li, Hong; Xu, Mingyan; Gu, Jia

    2018-01-22

    Some types of clinical genetic tests, such as cancer testing using circulating tumor DNA (ctDNA), require sensitive detection of known target mutations. However, conventional next-generation sequencing (NGS) data analysis pipelines typically involve different steps of filtering, which may cause miss-detection of key mutations with low frequencies. Variant validation is also indicated for key mutations detected by bioinformatics pipelines. Typically, this process can be executed using alignment visualization tools such as IGV or GenomeBrowse. However, these tools are too heavy and therefore unsuitable for validating mutations in ultra-deep sequencing data. We developed MutScan to address problems of sensitive detection and efficient validation for target mutations. MutScan involves highly optimized string-searching algorithms, which can scan input FASTQ files to grab all reads that support target mutations. The collected supporting reads for each target mutation will be piled up and visualized using web technologies such as HTML and JavaScript. Algorithms such as rolling hash and bloom filter are applied to accelerate scanning and make MutScan applicable to detect or visualize target mutations in a very fast way. MutScan is a tool for the detection and visualization of target mutations by only scanning FASTQ raw data directly. Compared to conventional pipelines, this offers a very high performance, executing about 20 times faster, and offering maximal sensitivity since it can grab mutations with even one single supporting read. MutScan visualizes detected mutations by generating interactive pile-ups using web technologies. These can serve to validate target mutations, thus avoiding false positives. Furthermore, MutScan can visualize all mutation records in a VCF file to HTML pages for cloud-friendly VCF validation. MutScan is an open source tool available at GitHub: https://github.com/OpenGene/MutScan.

  11. [Method validation according to ISO 15189 and SH GTA 04: application for the detection of KRAS mutations using PCR TaqMan assay].

    Science.gov (United States)

    Harlé, Alexandre; Dubois, Cindy; Rouyer, Marie; Merlin, Jean-Louis

    2013-01-01

    Since January 16(th) 2010, the French legislation requires that the medical laboratories must be accredited according to ISO 15189 standards. Thus, all medical laboratories in France must be accredited for at least part of their biological tests before the end of October 2013. Molecular biology tests are also concerned by the accreditation. Validation of molecular biology methods is made difficult, for reasons related to the methods, but also by the type of analytes that are basically rare. This article describes the validation of the qualitative detection of KRAS mutations in metastatic colorectal cancer using TaqMan PCR according to ISO 15189 and to the technical guide for accreditation in Human Health, SH-GTA-04, edited by the COFRAC.

  12. Detection of defects in red oak deckboards by ultrasonic scanning

    Science.gov (United States)

    Mohammed F. Kabir; Daniel L. Schmoldt; Mark E. Schafer

    2000-01-01

    Experiments were conducted to detect defects in red oak (Quercus rubra, L.) deckboards by ultrasonic scanning. Scanning of the deckboards was carried out with two rolling transducers in a pitch-catch arrangement with pallet parts moving between the transducers at 70 ft/m and 220 ft/m. Data were collected, stored and processed using LabViewTM software. The defects...

  13. A flexibly shaped spatial scan statistic for detecting clusters

    Directory of Open Access Journals (Sweden)

    Takahashi Kunihiko

    2005-05-01

    Full Text Available Abstract Background The spatial scan statistic proposed by Kulldorff has been applied to a wide variety of epidemiological studies for cluster detection. This scan statistic, however, uses a circular window to define the potential cluster areas and thus has difficulty in correctly detecting actual noncircular clusters. A recent proposal by Duczmal and Assunção for detecting noncircular clusters is shown to detect a cluster of very irregular shape that is much larger than the true cluster in our experiences. Methods We propose a flexibly shaped spatial scan statistic that can detect irregular shaped clusters within relatively small neighborhoods of each region. The performance of the proposed spatial scan statistic is compared to that of Kulldorff's circular spatial scan statistic with Monte Carlo simulation by considering several circular and noncircular hot-spot cluster models. For comparison, we also propose a new bivariate power distribution classified by the number of regions detected as the most likely cluster and the number of hot-spot regions included in the most likely cluster. Results The circular spatial scan statistics shows a high level of accuracy in detecting circular clusters exactly. The proposed spatial scan statistic is shown to have good usual powers plus the ability to detect the noncircular hot-spot clusters more accurately than the circular one. Conclusion The proposed spatial scan statistic is shown to work well for small to moderate cluster size, up to say 30. For larger cluster sizes, the method is not practically feasible and a more efficient algorithm is needed.

  14. Frequent mutations in EGFR, KRAS and TP53 genes in human lung cancer tumors detected by ion torrent DNA sequencing.

    Directory of Open Access Journals (Sweden)

    Xin Cai

    Full Text Available Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

  15. Frequent mutations in EGFR, KRAS and TP53 genes in human lung cancer tumors detected by ion torrent DNA sequencing.

    Science.gov (United States)

    Cai, Xin; Sheng, Jianhui; Tang, Chuanning; Nandakumar, Vijayalakshmi; Ye, Hua; Ji, Hong; Tang, Haiying; Qin, Yu; Guan, Hongwei; Lou, Feng; Zhang, Dandan; Sun, Hong; Dong, Haichao; Zhang, Guangchun; Liu, Zhiyuan; Dong, Zhishou; Guo, Baishuai; Yan, He; Yan, Chaowei; Wang, Lu; Su, Ziyi; Li, Yangyang; Jones, Lindsey; Huang, Xue F; Chen, Si-Yi; Wu, Taihua; Lin, Hongli

    2014-01-01

    Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

  16. Scanning the macula for detecting glaucoma

    Directory of Open Access Journals (Sweden)

    Viquar U Begum

    2014-01-01

    Full Text Available Background: With the advent of spectral domain optical coherence tomography (SDOCT, there has been a renewed interest in macular region for detection of glaucoma. However, most macular SDOCT parameters currently are thickness parameters which evaluate thinning of the macular layers but do not quantify the extent of area over which the thinning has occurred. We therefore calculated a new macular parameter, "ganglion cell complex surface abnormality ratio (GCC SAR" that represented the surface area over which the macular thickness was decreased. Purpose: To evaluate the ability of SAR in detecting perimetric and preperimetric glaucoma. Design: Retrospective image analysis. Materials and Methods: 68 eyes with perimetric glaucoma, 62 eyes with preperimetric glaucoma and 165 control eyes underwent GCC imaging with SDOCT. SAR was calculated as the ratio of the abnormal to total area on the GCC significance map. Statistical Analysis: Diagnostic ability of SAR in glaucoma was compared against that of the standard parameters generated by the SDOCT software using area under receiver operating characteristic curves (AUC and sensitivities at fixed specificities. Results: AUC of SAR (0.91 was statistically significantly better than that of GCC average thickness (0.86, P = 0.001 and GCC global loss volume (GLV; 0.88, P = 0.01 in differentiating perimetric glaucoma from control eyes. In differentiating preperimetric glaucoma from control eyes, AUC of SAR (0.72 was comparable to that of GCC average thickness (0.70, P > 0.05 and GLV (0.72, P > 0.05. Sensitivities at specificities of 80% and 95% of SAR were comparable (P > 0.05 for all comparisons to that of GCC average thickness and GLV in diagnosing perimetric and preperimetric glaucoma. Conclusion: GCC SAR had a better ability to diagnose perimetric glaucoma compared to the SDOCT software provided global GCC parameters. However, in diagnosing preperimetric glaucoma, the ability of SAR was similar to that of

  17. Modified mismatch polymerase chain reaction-restriction fragment length polymorphism detected mutations in codon 12 and 13 of exon 2 of K-ras gene in colorectal cancer patients and its association with liver metastases: Data from a South Asian country.

    Science.gov (United States)

    Faleel, Fathima Dhilhani Mohamed; Zoysa, M I M De; Lokuhetti, M D S; Gunawardena, Y I N S; Chandrasekharan, Vishvanath Naduviladath; Dassanayake, Ranil Samantha

    2016-01-01

    Mutations in K-ras codon 12 and 13 of exon 2 are known to affect prognosis and impart resistance to anti-epidermal growth factor monoclonal antibody therapy in colorectal carcinoma (CRC). Our aim was to investigate the utility value of modified mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to detect mutation in K-ras codons of CRC patients and to relate the mutational status to liver metastasis. Mismatch PCR-RFLP was developed to detect K-ras mutations in DNA isolated from paraffinized tumor tissue of thirty CRC patients. All patients had 5 year follow-up data to detect liver metastasis. Cross-tabulations were generated between K-ras mutations and the metastatic status. The Chi-square test was used to indicate statistical significance of the association. Of the 30 CRC patients investigated, K-ras mutations of codons 12 and/or 13 of exon 2 were detected in 14 (46.6%). Meanwhile, 13 patients (43.3%) were observed to have developed liver metastases. There was a significant association between the presence of the K-ras mutation in codon 12 and the occurrence of liver metastasis (χ2 = 4.693, P = 0.030) on the contrary to the mutation in codon 13 to which such occurrence of liver metastases was not seen (χ2 = 1.884, P = 0.169). Codon 12 of exon 2 of K--ras gene detected by modified mismatch PCR-RFLP assay is significantly associated with liver metastasis in CRC patients during the first 5 years after surgery. Thus, modified mismatch PCR-RFLP protocol is a suitable method in this setting to detect K-ras gene mutations predicting liver metastasis in CRC patients.

  18. Transmission environmental scanning electron microscope with scintillation gaseous detection device

    Energy Technology Data Exchange (ETDEWEB)

    Danilatos, Gerasimos, E-mail: gerry@danilatos.com [ESEM Research Laboratory, 28 Wallis Parade, North Bondi, NSW 2026 (Australia); Kollia, Mary [Laboratory of Electron Microscopy and Microanalysis, School of Natural Sciences, University of Patras, GR-26504 Patras (Greece); Dracopoulos, Vassileios [Foundation for Research & Technology-Hellas (FORTH), Institute of Chemical Engineering Sciences (ICE-HT), Stadiou Str., Platani P.O.Box 1414, GR-26504 Patras (Greece)

    2015-03-15

    A transmission environmental scanning electron microscope with use of a scintillation gaseous detection device has been implemented. This corresponds to a transmission scanning electron microscope but with addition of a gaseous environment acting both as environmental and detection medium. A commercial type of low vacuum machine has been employed together with appropriate modifications to the detection configuration. This involves controlled screening of various emitted signals in conjunction with a scintillation gaseous detection device already provided with the machine for regular surface imaging. Dark field and bright field imaging has been obtained along with other detection conditions. With a progressive series of modifications and tests, the theory and practice of a novel type of microscopy is briefly shown now ushering further significant improvements and developments in electron microscopy as a whole. - Highlights: • Novel scanning transmission electron microscopy (STEM) with an environmental scanning electron microscope (ESEM) called TESEM. • Use of the gaseous detection device (GDD) in scintillation mode that allows high resolution bright and dark field imaging in the TESEM. • Novel approach towards a unification of both vacuum and environmental conditions in both bulk/surface and transmission mode of electron microscopy.

  19. Detection of codon 12 mutation in the k-ras oncogene in pancreatic tumors Detecção de mutação no códon 12 do oncogene K-ras em tumores pancreáticos

    Directory of Open Access Journals (Sweden)

    Márcia Saldanha Kubrusly

    1999-02-01

    Full Text Available Mutations at codons 12, 13, or 61 of the H-ras, K-ras, and N-ras have been detected in human neoplasias by a variety of techniques. Some of these techniques are very sensitive and can detect K-ras mutation in 90% of the cases of pancreatic adenocarcinomas. We analyzed 11 samples of pancreatic adenocarcinoma, three samples of pancreatic mucinous cystadenoma, and two samples without tumors in formalin-fixed paraffin embedded tissue sections. K-ras mutations at codon 12 were detected by a two-step PCR-enriched technique in all the samples of pancreatic adenocarcinoma, but not in cystadenoma or control samples. This technique may be useful for early detection of pancreatic cancer.Muitos dos oncogenes detectados em neoplasias malignas humanas pertencem à família do gene ras. Mutações nos códons 12, 13 ou 61 em um dos tres genes ras; H-ras, K-ras e N-ras, convertem esses genes em oncogenes ativos. Ensaios rápidos para detecção dessas mutações pontuais, tais como a reação em cadeia de polimertização têm sido desenvolvidos nas últimas décadas e usados para investigar o papel dos genes ras mutados na patogênese de tumores humanos. As mutações no gene ras podem ser encontradas numa variedade de tipos de tumores. Incidências mais altas aparecem em adenocarcinomas do pâncreas (90% e cólon (50%. Analisamos 11 amostras de tumores primários de pâncreas com diferentes metástases, três amostras de cistadenoma mucinoso e dois casos de ausência de tumor de material incluído em parafina, de onde extraímos o DNA para realização das amplificações. Os resultados mostraram que todos os casos de tumores apresentaram a banda de 135 pares de bases correspondente ao gene mutado e para os normais, a banda característica de 106 pares de bases. Nos três casos de cistadenoma mucinosos, não detectamos a banda de 135 pares de bases , apenas a banda de 106 pares de bases.

  20. Hybrid detection of lung nodules on CT scan images

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Lin; Tan, Yongqiang; Schwartz, Lawrence H.; Zhao, Binsheng, E-mail: bz2166@columbia.edu [Department of Radiology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032 (United States)

    2015-09-15

    Purpose: The diversity of lung nodules poses difficulty for the current computer-aided diagnostic (CAD) schemes for lung nodule detection on computed tomography (CT) scan images, especially in large-scale CT screening studies. We proposed a novel CAD scheme based on a hybrid method to address the challenges of detection in diverse lung nodules. Methods: The hybrid method proposed in this paper integrates several existing and widely used algorithms in the field of nodule detection, including morphological operation, dot-enhancement based on Hessian matrix, fuzzy connectedness segmentation, local density maximum algorithm, geodesic distance map, and regression tree classification. All of the adopted algorithms were organized into tree structures with multi-nodes. Each node in the tree structure aimed to deal with one type of lung nodule. Results: The method has been evaluated on 294 CT scans from the Lung Image Database Consortium (LIDC) dataset. The CT scans were randomly divided into two independent subsets: a training set (196 scans) and a test set (98 scans). In total, the 294 CT scans contained 631 lung nodules, which were annotated by at least two radiologists participating in the LIDC project. The sensitivity and false positive per scan for the training set were 87% and 2.61%. The sensitivity and false positive per scan for the testing set were 85.2% and 3.13%. Conclusions: The proposed hybrid method yielded high performance on the evaluation dataset and exhibits advantages over existing CAD schemes. We believe that the present method would be useful for a wide variety of CT imaging protocols used in both routine diagnosis and screening studies.

  1. Processing of Graphene combining Optical Detection and Scanning Probe Lithography

    Directory of Open Access Journals (Sweden)

    Zimmermann Sören

    2015-01-01

    Full Text Available This paper presents an experimental setup tailored for robotic processing of graphene with in-situ vision based control. A robust graphene detection approach is presented applying multiple image processing operations of the visual feedback provided by a high-resolution light microscope. Detected graphene flakes can be modified using a scanning probe based lithographical process that is directly linked to the in-situ optical images. The results of this process are discussed with respect to further application scenarios.

  2. Line-scanning Raman imaging spectroscopy for detection of fingerprints.

    Science.gov (United States)

    Deng, Sunan; Liu, Le; Liu, Zhiyi; Shen, Zhiyuan; Li, Guohua; He, Yonghong

    2012-06-10

    Fingerprints are the best form of personal identification for criminal investigation purposes. We present a line-scanning Raman imaging system and use it to detect fingerprints composed of β-carotene and fish oil on different substrates. Although the line-scanning Raman system has been used to map the distribution of materials such as polystyrene spheres and minerals within geological samples, this is the first time to our knowledge that the method is used in imaging fingerprints. Two Raman peaks of β-carotene (501.2, 510.3 nm) are detected and the results demonstrate that both peaks can generate excellent images with little difference between them. The system operates at a spectra resolution of about 0.4 nm and can detect β-carotene signals in petroleum ether solution with the limit of detection of 3.4×10(-9) mol/L. The results show that the line-scanning Raman imaging spectroscopy we have built has a high accuracy and can be used in the detection of latent fingerprints in the future.

  3. KRAS mutation analysis by PCR: a comparison of two methods.

    Directory of Open Access Journals (Sweden)

    Louise Bolton

    Full Text Available KRAS mutation assays are important companion diagnostic tests to guide anti-EGFR antibody treatment of metastatic colorectal cancer. Direct comparison of newer diagnostic methods with existing methods is an important part of validation of any new technique. In this this study, we have compared the Therascreen (Qiagen ARMS assay with Competitive Allele-Specific TaqMan PCR (castPCR, Life Technologies to determine equivalence for KRAS mutation analysis.DNA was extracted by Maxwell (Promega from 99 colorectal cancers. The ARMS-based Therascreen and a customized castPCR assay were performed according to the manufacturer's instructions. All assays were performed on either an Applied Biosystems 7500 Fast Dx or a ViiA7 real-time PCR machine (both from Life Technologies. The data were collected and discrepant results re-tested with newly extracted DNA from the same blocks in both assay types.Of the 99 tumors included, Therascreen showed 62 tumors to be wild-type (WT for KRAS, while 37 had KRAS mutations on initial testing. CastPCR showed 61 tumors to be wild-type (WT for KRAS, while 38 had KRAS mutations. Thirteen tumors showed BRAF mutation in castPCR and in one of these there was also a KRAS mutation. The custom castPCR plate included several other KRAS mutations and BRAF V600E, not included in Therascreen, explaining the higher number of mutations detected by castPCR. Re-testing of discrepant results was required in three tumors, all of which then achieved concordance for KRAS. CastPCR assay Ct values were on average 2 cycles lower than Therascreen.There was excellent correlation between the two methods. Although castPCR assay shows lower Ct values than Therascreen, this is unlikely to be clinically significant.

  4. Bremstrahlung Detection and Chamber Obstruction Localisation Using Scanning Radiation Detectors

    CERN Document Server

    Naylor, G A; Robinson, D

    2005-01-01

    Radiation monitors consisting of scintillating plastic coupled to photomultipliers are used for diagnostic purposes. By scanning such a detector or a radiation scatterer, two applications are demonstrated: i) Monitoring of vacuum chamber conditioning by monitoring gas Bremstrahlung from residual gas. ii) Localisation of beam interception (beam losses) by longitudinal scanning of a radiation detector. The measurement of gas pressure inside long, small cross section, vacuum vessels is difficult due to the distance between the centre of the vacuum vessel and vacuum gauges (leading to a low vacuum conductance). The narrow beam of gamma Bremstrahlung radiation is intercepted by scanning tungsten blades in the beam line front-end allowing a radiation shower to be detected outside the vacuum vessel proportional to the gas pressure in the corresponding storage ring straight section. A second detector mounted on rails can be moved over a length of 6.5m parallel to the ESRF storage ring so as to localise regions of bea...

  5. Colitis detection on abdominal CT scans by rich feature hierarchies

    Science.gov (United States)

    Liu, Jiamin; Lay, Nathan; Wei, Zhuoshi; Lu, Le; Kim, Lauren; Turkbey, Evrim; Summers, Ronald M.

    2016-03-01

    Colitis is inflammation of the colon due to neutropenia, inflammatory bowel disease (such as Crohn disease), infection and immune compromise. Colitis is often associated with thickening of the colon wall. The wall of a colon afflicted with colitis is much thicker than normal. For example, the mean wall thickness in Crohn disease is 11-13 mm compared to the wall of the normal colon that should measure less than 3 mm. Colitis can be debilitating or life threatening, and early detection is essential to initiate proper treatment. In this work, we apply high-capacity convolutional neural networks (CNNs) to bottom-up region proposals to detect potential colitis on CT scans. Our method first generates around 3000 category-independent region proposals for each slice of the input CT scan using selective search. Then, a fixed-length feature vector is extracted from each region proposal using a CNN. Finally, each region proposal is classified and assigned a confidence score with linear SVMs. We applied the detection method to 260 images from 26 CT scans of patients with colitis for evaluation. The detection system can achieve 0.85 sensitivity at 1 false positive per image.

  6. Detection of mutant KRAS and TP53 DNA in circulating exosomes from healthy individuals and patients with pancreatic cancer.

    Science.gov (United States)

    Yang, Sujuan; Che, Sara P Y; Kurywchak, Paul; Tavormina, Jena L; Gansmo, Liv B; Correa de Sampaio, Pedro; Tachezy, Michael; Bockhorn, Maximilian; Gebauer, Florian; Haltom, Amanda R; Melo, Sonia A; LeBleu, Valerie S; Kalluri, Raghu

    2017-03-04

    Pancreatic cancer presents with a dismal mortality rate and is in urgent need of methods for early detection with potential for timely intervention. All living cells, including cancer cells, generate exosomes. We previously discovered double stranded genomic DNA in exosomes derived from the circulation of pancreatic cancer patients, which enabled the detection of prevalent mutations associated with the disease. Here, we report a proof-of-concept study that demonstrates the potential clinical utility of circulating exosomal DNA for identification of KRASG12D and TP53R273H mutations in patients with pancreas-associated pathologies, including pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP) and intraductal papillary mucinous neoplasm (IPMN), and in healthy human subjects. In 48 clinically annotated serum samples from PDAC patients, digital PCR analyses of exosomal DNA identified KRASG12D mutation in 39.6% of cases, and TP53R273H mutation in 4.2% of cases. KRASG12D and TP53R273H mutations were also detected in exosomal DNA from IPMN patients (2 out of 7 with KRASG12D, one of which also co-presented with TP53R273H mutation). Circulating exosomal DNA in 5 out of 9 CP patients enabled the detection of KRASG12D mutation. In 114 healthy subject-derived circulating exosomal DNA, 2.6% presented with KRASG12D mutation and none with TP53R273H mutation. This study highlights the value of circulating exosomal DNA for a rapid, low-cost identification of cancer driving mutations. The identification of mutations in IPMN patients and healthy subjects suggests that liquid biopsies may allow potential assessment of cancer risk but with a cautionary note that detection of clinical cancer cannot be assumed.

  7. Fault detection by surface seismic scanning tunneling macroscope: Field test

    KAUST Repository

    Hanafy, Sherif M.

    2014-08-05

    The seismic scanning tunneling macroscope (SSTM) is proposed for detecting the presence of near-surface impedance anomalies and faults. Results with synthetic data are consistent with theory in that scatterers closer to the surface provide brighter SSTM profiles than those that are deeper. The SSTM profiles show superresolution detection if the scatterers are in the near-field region of the recording line. The field data tests near Gulf of Aqaba, Haql, KSA clearly show the presence of the observable fault scarp, and identify the subsurface presence of the hidden faults indicated in the tomograms. Superresolution detection of the fault is achieved, even when the 35 Hz data are lowpass filtered to the 5-10 Hz band.

  8. Linear and Nonlinear Damage Detection Using a Scanning Laser Vibrometer

    Directory of Open Access Journals (Sweden)

    Steve Vanlanduit

    2002-01-01

    Full Text Available Because a Scanning Laser Vibrometer (SLV can perform vibration measurements with a high spatial resolution, it is an ideal instrument to accurately locate damage in a structure. Unfortunately, the use of linear damage detection features, as for instance FRFs or modal parameters, does not always lead to a successful identification of the damage location. Measurement noise and nonlinear distortions can make the damage detection procedure difficult. In this article, a combined linear-nonlinear strategy to detect and locate damage in a structure with the aid of a SLV, will be proposed. To minimize the effect of noise, the modal parameters will be estimated using a Maximum Likelihood Estimator (MLE. Both noise and nonlinear distortion levels are extracted using the residuals of a two-dimensional spline fit. The validation of the technique will be performed on SLV measurements of a delaminated composite plate.

  9. Detecting positive selection from genome scans of linkage disequilibrium

    Directory of Open Access Journals (Sweden)

    Rogers Alan R

    2010-01-01

    Full Text Available Abstract Background Though a variety of linkage disequilibrium tests have recently been introduced to measure the signal of recent positive selection, the statistical properties of the various methods have not been directly compared. While most applications of these tests have suggested that positive selection has played an important role in recent human history, the results of these tests have varied dramatically. Results Here, we evaluate the performance of three statistics designed to detect incomplete selective sweeps, LRH and iHS, and ALnLH. To analyze the properties of these tests, we introduce a new computational method that can model complex population histories with migration and changing population sizes to simulate gene trees influenced by recent positive selection. We demonstrate that iHS performs substantially better than the other two statistics, with power of up to 0.74 at the 0.01 level for the variation best suited for full genome scans and a power of over 0.8 at the 0.01 level for the variation best suited for candidate gene tests. The performance of the iHS statistic was robust to complex demographic histories and variable recombination rates. Genome scans involving the other two statistics suffer from low power and high false positive rates, with false discovery rates of up to 0.96 for ALnLH. The difference in performance between iHS and ALnLH, did not result from the properties of the statistics, but instead from the different methods for mitigating the multiple comparison problem inherent in full genome scans. Conclusions We introduce a new method for simulating genealogies influenced by positive selection with complex demographic scenarios. In a power analysis based on this method, iHS outperformed LRH and ALnLH in detecting incomplete selective sweeps. We also show that the single-site iHS statistic is more powerful in a candidate gene test than the multi-site statistic, but that the multi-site statistic maintains a low

  10. BRAZILIAN AMAZONIA DEFORESTATION DETECTION USING SPATIO-TEMPORAL SCAN STATISTICS

    Directory of Open Access Journals (Sweden)

    C. A. O. Vieira

    2012-07-01

    Full Text Available The spatio-temporal models, developed for analyses of diseases, can also be used for others fields of study, including concerns about forest and deforestation. The aim of this paper is to quantitatively check priority areas in order to combat deforestation on the Amazon forest, using the space-time scan statistic. The study area location is at the south of the Amazonas State and cover around 297.183 kilometre squares, including the municipality of Boca do Acre, Labrea, Canutama, Humaita, Manicore, Novo Aripuana e Apui County on the north region of Brazil. This area has showed a significant change for land cover, which has increased the number of deforestation's alerts. Therefore this situation becomes a concern and gets more investigation, trying to stop factors that increase the number of cases in the area. The methodology includes the location and year that deforestation’s alert occurred. These deforestation's alerts are mapped by the DETER (Detection System of Deforestation in Real Time in Amazonia, which is carry out by the Brazilian Space Agency (INPE. The software SatScanTM v7.0 was used in order to define space-time permutation scan statistic for detection of deforestation cases. The outcome of this experiment shows an efficient model to detect space-time clusters of deforestation’s alerts. The model was efficient to detect the location, the size, the order and characteristics about activities at the end of the experiments. Two clusters were considered actives and kept actives up to the end of the study. These clusters are located in Canutama and Lábrea County. This quantitative spatial modelling of deforestation warnings allowed: firstly, identifying actives clustering of deforestation, in which the environment government official are able to concentrate their actions; secondly, identifying historic clustering of deforestation, in which the environment government official are able to monitoring in order to avoid them to became

  11. AN AUTOMATED ROAD ROUGHNESS DETECTION FROM MOBILE LASER SCANNING DATA

    Directory of Open Access Journals (Sweden)

    P. Kumar

    2017-05-01

    Full Text Available Rough roads influence the safety of the road users as accident rate increases with increasing unevenness of the road surface. Road roughness regions are required to be efficiently detected and located in order to ensure their maintenance. Mobile Laser Scanning (MLS systems provide a rapid and cost-effective alternative by providing accurate and dense point cloud data along route corridor. In this paper, an automated algorithm is presented for detecting road roughness from MLS data. The presented algorithm is based on interpolating smooth intensity raster surface from LiDAR point cloud data using point thinning process. The interpolated surface is further processed using morphological and multi-level Otsu thresholding operations to identify candidate road roughness regions. The candidate regions are finally filtered based on spatial density and standard deviation of elevation criteria to detect the roughness along the road surface. The test results of road roughness detection algorithm on two road sections are presented. The developed approach can be used to provide comprehensive information to road authorities in order to schedule maintenance and ensure maximum safety conditions for road users.

  12. X-ray scan detection for cargo integrity

    Science.gov (United States)

    Valencia, Juan; Miller, Steve

    2011-04-01

    The increase of terrorism and its global impact has made the determination of the contents of cargo containers a necessity. Existing technology allows non-intrusive inspections to determine the contents of a container rapidly and accurately. However, some cargo shipments are exempt from such inspections. Hence, there is a need for a technology that enables rapid and accurate means of detecting whether such containers were non-intrusively inspected. Non-intrusive inspections are most commonly performed utilizing high powered X-ray equipment. The challenge is creating a device that can detect short duration X-ray scans while maintaining a portable, battery powered, low cost, and easy to use platform. The Pacific Northwest National Laboratory (PNNL) has developed a methodology and prototype device focused on this challenge. The prototype, developed by PNNL, is a battery powered electronic device that continuously measures its X-ray and Gamma exposure, calculates the dose equivalent rate, and makes a determination of whether the device has been exposed to the amount of radiation experienced during an X-ray inspection. Once an inspection is detected, the device will record a timestamp of the event and relay the information to authorized personnel via a visual alert, USB connection, and/or wireless communication. The results of this research demonstrate that PNNL's prototype device can be effective at determining whether a container was scanned by X-ray equipment typically used for cargo container inspections. This paper focuses on laboratory measurements and test results acquired with the PNNL prototype device using several X-ray radiation levels.

  13. PEDESTRIAN DETECTION BY LASER SCANNING AND DEPTH IMAGERY

    Directory of Open Access Journals (Sweden)

    A. Barsi

    2016-06-01

    Full Text Available Pedestrian flow is much less regulated and controlled compared to vehicle traffic. Estimating flow parameters would support many safety, security or commercial applications. Current paper discusses a method that enables acquiring information on pedestrian movements without disturbing and changing their motion. Profile laser scanner and depth camera have been applied to capture the geometry of the moving people as time series. Procedures have been developed to derive complex flow parameters, such as count, volume, walking direction and velocity from laser scanned point clouds. Since no images are captured from the faces of pedestrians, no privacy issues raised. The paper includes accuracy analysis of the estimated parameters based on video footage as reference. Due to the dense point clouds, detailed geometry analysis has been conducted to obtain the height and shoulder width of pedestrians and to detect whether luggage has been carried or not. The derived parameters support safety (e.g. detecting critical pedestrian density in mass events, security (e.g. detecting prohibited baggage in endangered areas and commercial applications (e.g. counting pedestrians at all entrances/exits of a shopping mall.

  14. Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers

    Science.gov (United States)

    Niya, Mohammad Hadi Karbalaie; Basi, Ali; Koochak, Aghigh; Tameshkel, Fahimeh Safarnezhad; Rakhshani, Nasser; Zamani, Farhad; Imanzade, Farid; Rezvani, Hamid; sereshki, Mohammad Mahdi Adib; Sohrabi, Masoud Reza

    2016-01-01

    Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes. PMID:28122448

  15. Electron beam detection of a Nanotube Scanning Force Microscope.

    Science.gov (United States)

    Siria, Alessandro; Niguès, Antoine

    2017-09-14

    Atomic Force Microscopy (AFM) allows to probe matter at atomic scale by measuring the perturbation of a nanomechanical oscillator induced by near-field interaction forces. The quest to improve sensitivity and resolution of AFM forced the introduction of a new class of resonators with dimensions at the nanometer scale. In this context, nanotubes are the ultimate mechanical oscillators because of their one dimensional nature, small mass and almost perfect crystallinity. Coupled to the possibility of functionalisation, these properties make them the perfect candidates as ultra sensitive, on-demand force sensors. However their dimensions make the measurement of the mechanical properties a challenging task in particular when working in cavity free geometry at ambient temperature. By using a focused electron beam, we show that the mechanical response of nanotubes can be quantitatively measured while approaching to a surface sample. By coupling electron beam detection of individual nanotubes with a custom AFM we image the surface topography of a sample by continuously measuring the mechanical properties of the nanoresonators. The combination of very small size and mass together with the high resolution of the electron beam detection method offers unprecedented opportunities for the development of a new class of nanotube-based scanning force microscopy.

  16. High-Speed Edge-Detecting Line Scan Smart Camera

    Science.gov (United States)

    Prokop, Norman F.

    2012-01-01

    A high-speed edge-detecting line scan smart camera was developed. The camera is designed to operate as a component in a NASA Glenn Research Center developed inlet shock detection system. The inlet shock is detected by projecting a laser sheet through the airflow. The shock within the airflow is the densest part and refracts the laser sheet the most in its vicinity, leaving a dark spot or shadowgraph. These spots show up as a dip or negative peak within the pixel intensity profile of an image of the projected laser sheet. The smart camera acquires and processes in real-time the linear image containing the shock shadowgraph and outputting the shock location. Previously a high-speed camera and personal computer would perform the image capture and processing to determine the shock location. This innovation consists of a linear image sensor, analog signal processing circuit, and a digital circuit that provides a numerical digital output of the shock or negative edge location. The smart camera is capable of capturing and processing linear images at over 1,000 frames per second. The edges are identified as numeric pixel values within the linear array of pixels, and the edge location information can be sent out from the circuit in a variety of ways, such as by using a microcontroller and onboard or external digital interface to include serial data such as RS-232/485, USB, Ethernet, or CAN BUS; parallel digital data; or an analog signal. The smart camera system can be integrated into a small package with a relatively small number of parts, reducing size and increasing reliability over the previous imaging system..

  17. Detecting Terrain Stoniness From Airborne Laser Scanning Data †

    Directory of Open Access Journals (Sweden)

    Paavo Nevalainen

    2016-08-01

    Full Text Available Three methods to estimate the presence of ground surface stones from publicly available Airborne Laser Scanning (ALS point clouds are presented. The first method approximates the local curvature by local linear multi-scale fitting, and the second method uses Discrete-Differential Gaussian curvature based on the ground surface triangulation. The third baseline method applies Laplace filtering to Digital Elevation Model (DEM in a 2 m regular grid data. All methods produce an approximate Gaussian curvature distribution which is then vectorized and classified by logistic regression. Two training data sets consisted of 88 and 674 polygons of mass-flow deposits, respectively. The locality of the polygon samples is a sparse canopy boreal forest, where the density of ALS ground returns is sufficiently high to reveal information about terrain micro-topography. The surface stoniness of each polygon sample was categorized for supervised learning by expert observation on the site. The leave-pair-out (L2O cross-validation of the local linear fit method results in the area under curve A U C = 0 . 74 and A U C = 0 . 85 on two data sets, respectively. This performance can be expected to suit real world applications such as detecting coarse-grained sediments for infrastructure construction. A wall-to-wall predictor based on the study was demonstrated.

  18. K-ras gene mutation as an early prognostic marker of colon cancer.

    Science.gov (United States)

    Szpon, Łukasz; Stal, Aleksander; Zawadzki, Marcin; Lis-Nawara, Anna; Kielan, Wojciech; Grzebieniak, Zygmunt

    2016-01-01

    Due to increased colorectal cancer incidence there is a necessity of seeking new both prognostic and prediction factors that will allow to evolve new diagnostic tests. K-ras gene seems to be such a factor and its mutations are considered to be an early marker of progression of colorectal cancer. The aim of the study was to find a correlation between K-ras gene mutation in patients with diagnosed colorectal cancer and selected clinical parameters. A total of 104 patients (41 women and 63 men) with diagnosed colorectal cancer were included in this study. The average age of male group was 68.3 and in female group - 65.9. Samples were taken from paraffine blocks with tissue from diagnosed patients and K-ras gene mutation were identified. Afterwards the statistical analysis was made seeking the correlation between K-ras gene mutation incidence and clinical TNM staging system, tumour localisation, histological type, sex, age. K-ras gene mutations were detected in 20.1% of all colorectal cancers. Significantly higher rate of K-ras gene mutations were diagnosed among patients classified at stage I (40%), stage IIC (50%) and stage IV (50%) according to the TNM classification. The results of our study are compatible with other studies and indicate the correlation between K-ras gene mutation and colorectal cancer incidence. Identification of K-ras gene mutation may complement other diagnostic methods at early stage of colorectal cancer.

  19. Mutations in epidermal growth factor receptor and K-ras in Chinese patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Xueke Zhou

    2010-02-01

    Full Text Available Abstract Background Mutations of EGFR and K-ras are biomarkers for predicting the efficacy of targeting agents in non-small-cell lung cancer (NSCLC and colorectal cancer (CRC. Data on the gene mutation status of EGFR and K-ras in Chinese patients with CRC are limited. Methods EGFR mutations in exon 18-21 and K-ras mutations in exon 1 and 2 were detected in tumor samples from 101 Chinese patients with CRC by polymerase chain reaction-single strand conformational polymorphism. The relationship between patients' characteristics and survival time and gene mutation status were analyzed using the Statistical Package for the Social Sciences. Results Only two samples (2.0% had EGFR mutations in exon 18 or 21, and 33 of 101 samples (32.7% had K-ras mutations in codon 12, 13, 45, 69, or 80. Univariate analysis suggested that differentiation might be correlated with K-ras mutations (p = 0.05, which was confirmed by a logistic regression model (p = 0.04. The median overall survival (OS and median survival after metastasis were 44.0 and 18.0 months, respectively, in the mutant K-ras group, and 53.3 and 19.0 months, respectively, in the wild K-ras group. K-ras mutation was not an independent prognostic factor for OS or survival after metastasis (p = 0.79 and 0.78, respectively. Conclusions In Chinese patients with CRC, EGFR mutations were rare, and K-ras mutations were similar to those of Europeans. New mutations in codons 45, 69, and 80 were found in the Chinese population. Poor differentiation was an independent factor related to K-ras mutations.

  20. Differences in EGFR and KRAS mutation spectra in lung adenocarcinoma of never and heavy smokers.

    Science.gov (United States)

    Takamochi, Kazuya; Oh, Shiaki; Suzuki, Kenji

    2013-11-01

    Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinomas of never smokers, while KRAS mutations are more frequent among heavy smokers. Different clinicopathological and biological characteristics may, therefore, exist in lung adenocarcinoma according to smoking status. In the present study, a retrospective review was performed using 521 patients with surgically resected lung adenocarcinomas. The clinicopathological factors of age, gender, pathological tumor size, nodal status, lymphatic permeation and blood vessel invasion and the EGFR and KRAS mutation spectra were compared between never and heavy smokers. EGFR mutations were detected in 233 (45%) patients, while KRAS mutations were detected in 56 (11%) patients. EGFR-mutated adenocarcinomas had a higher prevalence of females in the never smokers compared with the heavy smokers (Pnever smokers compared with the heavy smokers. Minor EGFR mutations, excluding exon 21 L858R and exon 19 deletions, were more common in heavy smokers than never smokers (P=0.055). KRAS G to A transition was more common in never smokers, while KRAS G to T and G to C transversions were more common in heavy smokers (P=0.036). The clinicopathological characteristics and the spectra of the EGFR and KRAS mutations in lung adenocarcinoma were different between the never and heavy smokers. Further large-scale studies are required to evaluate the efficacy of molecular targeting agents with consideration to specific EGFR and KRAS mutations.

  1. KRAS-mutated plasma DNA as predictor of outcome from irinotecan monotherapy in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, K G; Appelt, A L; Pallisgaard, N

    2013-01-01

    Background:We investigated the clinical implications of KRAS and BRAF mutations detected in both archival tumor tissue and plasma cell-free DNA in metastatic colorectal cancer patients treated with irinotecan monotherapy.Methods:Two hundred and eleven patients receiving second-line irinotecan (350...... with mutations detectable in plasma responded to therapy. Response rate and disease control rate in plasma KRAS wt patients were 19 and 66% compared with 0 and 37%, in patients with pKRAS mutations, (P=0.04 and 0.01). Tumor KRAS status was not associated with PFS but with OS in the validation cohort. Plasma BRAF...... mg m(-2) q3w) were included in two independent cohorts. Plasma was obtained from pretreatment EDTA blood-samples. Mutations were detected in archival tumour and plasma with qPCR methods.Results:Mutation status in tumor did not correlate to efficacy in either cohort, whereas none of the patients...

  2. [Determination of K-ras gene mutation in colorectal cancer tissue by capillary electrophoresis].

    Science.gov (United States)

    Shi, Dongqin; Wang, Rong; Xie, Hua; Tian, Wei; Jia, Zhengping; Guo, Jiankui

    2013-06-01

    The codons 12/13 of K-ras genomic DNA from 76 colorectal cancer tissues and normal tissues were amplified by PCR. The amplified 152 samples were purified, denatured, and then detected using capillary electrophoresis (CE)-laser induced fluorescence (LIF) with single-strand conformation polymorphism (SSCP). The abnormal samples were further confirmed by direct-sequencing. The 30 patients of the 76 colorectal cancer patients were found gene mutation, of which the results of base G --> A point mutation were confirmed by the gene sequence. To detect K-ras gene mutation that has important role in clinical forecast, diagnosis, therapy and prognosis, the CE-LIF with SSCP was applied for detecting K-ras gene. It becomes a promising tool to analyse K-ras gene mutation in the clinical diagnosis and therapy of colorectal cancer tissue.

  3. If brain scans really detected deception, who would volunteer to be scanned?

    Science.gov (United States)

    Spence, Sean A; Hope-Urwin, Alexandra; Lankappa, Sudheer T; Woodhead, Jean; Burgess, Jenny C L; Mackay, Alice V

    2010-09-01

    Recent neuroimaging studies investigating the neural correlates of deception among healthy people, have raised the possibility that such methods may eventually be applied during legal proceedings. Were this so, who would volunteer to be scanned? We report a "natural experiment" casting some light upon this question. Following broadcast of a television series describing our team's investigative neuroimaging of deception in 2007, we received unsolicited (public) correspondence for 12 months. Using a customized template to examine this material, three independent assessors unanimously rated 30 of an initial 56 communications as unequivocally constituting requests for a "scan" (to demonstrate their author's "innocence"). Compared with the rest, these index communications were more likely to originate from incarcerated males, who were also more likely to engage in further correspondence. Hence, in conclusion, if neuroimaging were to become an acceptable means of demonstrating innocence then incarcerated males may well constitute those volunteering for such investigation. © 2010 American Academy of Forensic Sciences.

  4. Coexistence of K-ras mutations and HPV infection in colon cancer

    Directory of Open Access Journals (Sweden)

    Tezol Ayda

    2006-05-01

    Full Text Available Abstract Background Activation of the ras genes or association with human papillomavirus infection have been extensively studied in colorectal cancer. However, the correlation between K-ras mutations and HPV in colorectal cancer has not been investigated yet. In this study we aimed to investigate the presence of K-ras mutations and their correlation with HPV infection in colon cancer. Methods K-ras mutations were analyzed by a mutagenic PCR assay and digestion with specific restriction enzymes to distinguish the wild-type and mutant codons. HPV infection was analyzed by PCR amplification and hybridization with specific probes by Southern blotting. Stattistical analyses were performed by the chi-square and Fisher's exact tests Results HPV gene fragments were detected in 43 tumors and 17 normal tissue samples. HPV 18 was the prevalent type in the tumor tissue. A mutation at codon 12 of the K-ras gene was present in 31 patients. 56% of the HPV-positive tumors also harbored a K-ras mutation. Codon 13 mutations were not observed. These data indicate that infection with high risk HPV types and mutational activation of the K-ras gene are frequent events in colorectal carcinogenesis. Conclusion Our findings suggest that mutational activation of the K-ras gene is a common event in colon carcinogenesis and that HPV infection may represent an important factor in the development of the premalignant lesions leading to the neoplastic phenotype.

  5. Sensitive and specific KRAS somatic mutation analysis on whole-genome amplified DNA from archival tissues.

    Science.gov (United States)

    van Eijk, Ronald; van Puijenbroek, Marjo; Chhatta, Amiet R; Gupta, Nisha; Vossen, Rolf H A M; Lips, Esther H; Cleton-Jansen, Anne-Marie; Morreau, Hans; van Wezel, Tom

    2010-01-01

    Kirsten RAS (KRAS) is a small GTPase that plays a key role in Ras/mitogen-activated protein kinase signaling; somatic mutations in KRAS are frequently found in many cancers. The most common KRAS mutations result in a constitutively active protein. Accurate detection of KRAS mutations is pivotal to the molecular diagnosis of cancer and may guide proper treatment selection. Here, we describe a two-step KRAS mutation screening protocol that combines whole-genome amplification (WGA), high-resolution melting analysis (HRM) as a prescreen method for mutation carrying samples, and direct Sanger sequencing of DNA from formalin-fixed, paraffin-embedded (FFPE) tissue, from which limited amounts of DNA are available. We developed target-specific primers, thereby avoiding amplification of homologous KRAS sequences. The addition of herring sperm DNA facilitated WGA in DNA samples isolated from as few as 100 cells. KRAS mutation screening using high-resolution melting analysis on wgaDNA from formalin-fixed, paraffin-embedded tissue is highly sensitive and specific; additionally, this method is feasible for screening of clinical specimens, as illustrated by our analysis of pancreatic cancers. Furthermore, PCR on wgaDNA does not introduce genotypic changes, as opposed to unamplified genomic DNA. This method can, after validation, be applied to virtually any potentially mutated region in the genome.

  6. A high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice.

    Science.gov (United States)

    Philip, Bincy; Roland, Christina L; Daniluk, Jaroslaw; Liu, Yan; Chatterjee, Deyali; Gomez, Sobeyda B; Ji, Baoan; Huang, Haojie; Wang, Huamin; Fleming, Jason B; Logsdon, Craig D; Cruz-Monserrate, Zobeida

    2013-12-01

    Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice. We studied mice with acinar cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice. Pancreata were collected from mice and analyzed for Kras activity, levels of phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic intraepithelial neoplasia (PanIN), and PDACs. Pancreatic tissues from LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity, fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice fed control diets; the mice fed the HFDs also had shorter survival times than mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT mice prevented these effects of HFDs. We also observed a significant reduction in survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs. In mice, an HFD can activate oncogenic Kras via COX2, leading to pancreatic inflammation and fibrosis and development of PanINs and PDAC. This

  7. A flexibly shaped space-time scan statistic for disease outbreak detection and monitoring

    Directory of Open Access Journals (Sweden)

    Tango Toshiro

    2008-04-01

    Full Text Available Abstract Background Early detection of disease outbreaks enables public health officials to implement disease control and prevention measures at the earliest possible time. A time periodic geographical disease surveillance system based on a cylindrical space-time scan statistic has been used extensively for disease surveillance along with the SaTScan software. In the purely spatial setting, many different methods have been proposed to detect spatial disease clusters. In particular, some spatial scan statistics are aimed at detecting irregularly shaped clusters which may not be detected by the circular spatial scan statistic. Results Based on the flexible purely spatial scan statistic, we propose a flexibly shaped space-time scan statistic for early detection of disease outbreaks. The performance of the proposed space-time scan statistic is compared with that of the cylindrical scan statistic using benchmark data. In order to compare their performances, we have developed a space-time power distribution by extending the purely spatial bivariate power distribution. Daily syndromic surveillance data in Massachusetts, USA, are used to illustrate the proposed test statistic. Conclusion The flexible space-time scan statistic is well suited for detecting and monitoring disease outbreaks in irregularly shaped areas.

  8. Internal fingerprint zone detection in optical coherence tomography fingertip scans

    CSIR Research Space (South Africa)

    Darlow, LN

    2015-04-01

    Full Text Available details and tests a k-means clustering approach for papillary junction detection. All tested metrics are of a standard comparable to the measured human error. The technique presented in this research is highly successful in detection of the location...

  9. Scan statistics with local vote for target detection in distributed system

    Science.gov (United States)

    Luo, Junhai; Wu, Qi

    2017-12-01

    Target detection has occupied a pivotal position in distributed system. Scan statistics, as one of the most efficient detection methods, has been applied to a variety of anomaly detection problems and significantly improves the probability of detection. However, scan statistics cannot achieve the expected performance when the noise intensity is strong, or the signal emitted by the target is weak. The local vote algorithm can also achieve higher target detection rate. After the local vote, the counting rule is always adopted for decision fusion. The counting rule does not use the information about the contiguity of sensors but takes all sensors' data into consideration, which makes the result undesirable. In this paper, we propose a scan statistics with local vote (SSLV) method. This method combines scan statistics with local vote decision. Before scan statistics, each sensor executes local vote decision according to the data of its neighbors and its own. By combining the advantages of both, our method can obtain higher detection rate in low signal-to-noise ratio environment than the scan statistics. After the local vote decision, the distribution of sensors which have detected the target becomes more intensive. To make full use of local vote decision, we introduce a variable-step-parameter for the SSLV. It significantly shortens the scan period especially when the target is absent. Analysis and simulations are presented to demonstrate the performance of our method.

  10. Detection Mechanism of Parallel Defect using Scanning Inductive Thermography

    Science.gov (United States)

    Zuo, Xianzhang; Song, Benchu; Hu, Yongjiang; He, Yunze

    2017-06-01

    Aiming at the requirement of workpiece integrity for parts processing line, on-line detection using inductive heating thermography for the moving workpieces on the assembly line is studied. In this paper, the detection mechanism of pulsed eddy current thermography for moving workpieces defects is analysed. A two-dimensional model of a magnetic material (45 steel), on which there is a crack parallel to the coil is established by the finite element software named COMSOL 5.2. By analysing the changes of the temperature curves, normalized curves and the temperature difference curves, the optimal detection area for parallel cracks is proposed. The consistency of the conclusions is verified by the experimental platform. The paper can provide a theoretical guidance for quantitative detection using eddy current thermography.

  11. Expanding the Scope of Electrophiles Capable of Targeting K-Ras Oncogenes.

    Science.gov (United States)

    McGregor, Lynn M; Jenkins, Meredith L; Kerwin, Caitlin; Burke, John E; Shokat, Kevan M

    2017-06-27

    There is growing interest in reversible and irreversible covalent inhibitors that target noncatalytic amino acids in target proteins. With a goal of targeting oncogenic K-Ras variants (e.g., G12D) by expanding the types of amino acids that can be targeted by covalent inhibitors, we survey a set of electrophiles for their ability to label carboxylates. We functionalized an optimized ligand for the K-Ras switch II pocket with a set of electrophiles previously reported to react with carboxylates and characterized the ability of these compounds to react with model nucleophiles and oncogenic K-Ras proteins. Here, we report that aziridines and stabilized diazo groups preferentially react with free carboxylates over thiols. Although we did not identify a warhead that potently labels K-Ras G12D, we were able to study the interactions of many electrophiles with K-Ras, as most of the electrophiles rapidly label K-Ras G12C. We characterized the resulting complexes by crystallography, hydrogen/deuterium exchange, and differential scanning fluorimetry. Our results both demonstrate the ability of a noncatalytic cysteine to react with a diverse set of electrophiles and emphasize the importance of proper spatial arrangements between a covalent inhibitor and its intended nucleophile. We hope that these results can expand the range of electrophiles and nucleophiles of use in covalent protein modulation.

  12. The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations

    Directory of Open Access Journals (Sweden)

    Zheng DF

    2016-02-01

    Full Text Available Difan Zheng,1,2,* Rui Wang,1,2,* Yang Zhang,1,2 Yunjian Pan,1,2 Xinghua Cheng,3 Chao Cheng,1,2 Shanbo Zheng,1,2 Hang Li,1,2 Ranxia Gong,1,2 Yuan Li,2,4 Xuxia Shen,2,4 Yihua Sun,1,2 Haiquan Chen1–3,51Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, 4Department of Pathology, Fudan University Shanghai Cancer Center, 5Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients.Patients and methods: Patients from 2007 to 2013 diagnosed with primary lung adenocarcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor–lymph node–metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.Result: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations.Conclusion: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368 of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of

  13. Detection of in vitro proximal caries in storage phosphor plate radiographs scanned with different resolutions

    NARCIS (Netherlands)

    Li, G.; Berkhout, W.E.R.; Sanderink, G.C.H.; Martins, M.; van der Stelt, P.F.

    2008-01-01

    Objectives: To investigate the effect of the scanning resolution of storage phosphor plate (SPP) radiographs on the detection of proximal caries lesions. Methods: 10 dentists evaluated 72 proximal surfaces of premolars with respect to caries from SPP radiographs scanned with theoretical spatial

  14. Range image segmentation for tree detection in forest scans

    Directory of Open Access Journals (Sweden)

    A. Bienert

    2013-10-01

    Full Text Available To make a tree-wise analysis inside a forest stand, the trees have to be identified. An interactive segmentation is often labourintensive and time-consuming. Therefore, an automatic detection process will aspired using a range image. This paper presents a method for the segmentation of range images extracted from terrestrial laser scanner point clouds of forest stands. After range image generation the segmentation is carried out with a connectivity analysis using the differences of the range values as homogeneity criterion. Subsequently, the tree detection is performed interactively by analysing one horizontal image line. When passing objects with a specific width, the object indicates a potential tree. By using the edge points of a segmented pixel group the tree position and diameter is calculated. Results from one test site are presented to show the performance of the method.

  15. Genotyping of KRAS Mutational Status by the In-Check Lab-on-Chip Platform.

    Science.gov (United States)

    Guarnaccia, Maria; Iemmolo, Rosario; San Biagio, Floriana; Alessi, Enrico; Cavallaro, Sebastiano

    2018-01-05

    The KRAS oncogene is involved in the pathogenesis of several types of cancer, particularly colorectal cancer (CRC). The most frequent mutations in this gene are associated with poor survival, increased tumor aggressiveness and resistance to therapy with anti-epidermal growth factor receptor (EGFR) antibodies. For this reason, KRAS mutation testing has become increasingly common in clinical practice for personalized cancer treatments of CRC patients. Detection methods for KRAS mutations are currently expensive, laborious, time-consuming and often lack of diagnostic sensitivity and specificity. In this study, we describe the development of a Lab-on-Chip assay for genotyping of KRAS mutational status. This assay, based on the In-Check platform, integrates microfluidic handling, a multiplex polymerase chain reaction (PCR) and a low-density microarray. This integrated sample-to-result system enables the detection of KRAS point mutations, including those occurring in codons 12 and 13 of exon 2, 59 and 61 of exon 3, 117 and 146 of exon 4. Thanks to its miniaturization, automation, rapid analysis, minimal risk of sample contamination, increased accuracy and reproducibility of results, this Lab-on-Chip platform may offer immediate opportunities to simplify KRAS genotyping into clinical routine.

  16. Genotyping of KRAS Mutational Status by the In-Check Lab-on-Chip Platform

    Directory of Open Access Journals (Sweden)

    Maria Guarnaccia

    2018-01-01

    Full Text Available The KRAS oncogene is involved in the pathogenesis of several types of cancer, particularly colorectal cancer (CRC. The most frequent mutations in this gene are associated with poor survival, increased tumor aggressiveness and resistance to therapy with anti-epidermal growth factor receptor (EGFR antibodies. For this reason, KRAS mutation testing has become increasingly common in clinical practice for personalized cancer treatments of CRC patients. Detection methods for KRAS mutations are currently expensive, laborious, time-consuming and often lack of diagnostic sensitivity and specificity. In this study, we describe the development of a Lab-on-Chip assay for genotyping of KRAS mutational status. This assay, based on the In-Check platform, integrates microfluidic handling, a multiplex polymerase chain reaction (PCR and a low-density microarray. This integrated sample-to-result system enables the detection of KRAS point mutations, including those occurring in codons 12 and 13 of exon 2, 59 and 61 of exon 3, 117 and 146 of exon 4. Thanks to its miniaturization, automation, rapid analysis, minimal risk of sample contamination, increased accuracy and reproducibility of results, this Lab-on-Chip platform may offer immediate opportunities to simplify KRAS genotyping into clinical routine.

  17. Comparison of envelope detection techniques in coherence scanning interferometry.

    Science.gov (United States)

    Gianto, G; Salzenstein, F; Montgomery, P

    2016-08-20

    The aim of this work is to make a comparison of the most current signal processing techniques used to analyze the fringe signal in coherence scanning interferometry (CSI), a major technique for optical surface roughness measurements. We focus here on classical AM-FM signal-processing algorithms such as the Hilbert transform (HT), the five-sample adaptive (FSA), and the continuous wavelet transform (CWT). We have recently also introduced a new family of compact and robust algorithms using the Teager-Kaiser energy operator (TKEO). We propose an improved version of TKEO using a combination of different techniques of pre-filtering and demodulation processing to remove the noise and offset component and to retrieve the fringe envelope to either determine the surface height information or to separate adjacent transparent layers. In particular, as a pre-filtering approach, we have focused on empirical mode decomposition in combination with the Savitzky-Golay filter. An added Gaussian post-filtering is helpful for a precise peak extraction. The experimental results show that TKEO performs better than CWT in terms of computation time and provides a better surface extraction than HT and FSA. Results have been obtained on synthetic and real data taken from a layer of resin on a silicon substrate.

  18. Catenary System Detection, Localization and Classification Using Mobile Scanning Data

    Directory of Open Access Journals (Sweden)

    Elżbieta Pastucha

    2016-09-01

    Full Text Available This paper presents a new method for detecting, locating and classifying overhead contact systems (catenary systems in point clouds collected by mobile mapping systems (MMS on rail roads. Contrary to many other application types, railway embankments are highly regulated and standardized. Railway infrastructure geometric relations remain roughly unchanged within established regions and have similarities between them. The newly-developed method exploits both these characteristics, as well as the survey process. There are several steps in this approach. Firstly, it restricts the search for catenaries relative to the distance to registered MMS trajectory, then finds possible support structures according to the density of points above the track. Subsequently, the method verifies the structures’ presence and classifies the points with the use of the RANSAC algorithm. It establishes the presence of cantilevers, as well as poles or structural beams, depending on the type of detected support structure. The method also determines the coordinates of the identified object on the ground. Finally, a classification is clarified with the use of a modified DBSCAN algorithm. The design method has been verified with data collected in four surveys where the cumulative length of the route was almost 90 km. Over 97% of support structures were correctly detected, and out of these, over 95% were completely classified.

  19. Detection of in vitro proximal caries in storage phosphor plate radiographs scanned with different resolutions.

    Science.gov (United States)

    Li, G; Berkhout, W E R; Sanderink, G C H; Martins, M; van der Stelt, P F

    2008-09-01

    To investigate the effect of the scanning resolution of storage phosphor plate (SPP) radiographs on the detection of proximal caries lesions. 10 dentists evaluated 72 proximal surfaces of premolars with respect to caries from SPP radiographs scanned with theoretical spatial resolutions of: (1) the Digora FMX at 7.8 lp mm(-1); (2) the Digora Optime at both 7.8 lp mm(-1) and 12.5 lp mm(-1); and (3) the Dürr VistaScan at 10 lp mm(-1) and 20 lp mm(-1), respectively. The lesions were validated by histological examination. Receiver operating characteristic (ROC) analysis was employed. The A(z) value for the radiographs scanned with the Dürr VistaScan at 10 lp mm(-1) is significantly lower than those for the other series of radiographs (P = 0.000). For SPP radiographs, an increased theoretical spatial resolution per se is not related to an improved detection of proximal caries.

  20. Automatic detection of Hyperreflective Foci in optical coherence tomography B-scans using Morphological Component Analysis.

    Science.gov (United States)

    Mokhtari, Marzieh; Ghasemi Kamasi, Zeinab; Rabbani, Hossein

    2017-07-01

    Hyperreflective Foci (HF) is one of the most common complications distributed in cross-sectional images of patients with Diabetic Macular Edema (DME). Scanning Laser Ophthalmoscope (SLO) images usually consists of several B-scans that represent a cross-sectional reconstruction of a plane through the anterior or posterior regions of retina. In each B-scan, HFs are geometrically distinct constituents in different retinal layers. Since the intensity levels of HFs and many other subjects in B-scans are the same, in this paper we try to separate HFs from other objects by detection of the point and curve singularities in each B-scan. The decomposition algorithm presented in this paper is based on sparse image representation of B-scans using Morphological Component Analysis (MCA) technique. By using curvelet transform and Daubechies wavelet basis, two different over-complete dictionaries are constructed which represent two various aspects of B-scans. The HFs are more distinguished in reconstructed image with wavelet dictionary and other objects are mostly detectable by curvelet dictionary. So, HFs can be detected by applying an optimum threshold criterion on reconstructed image by wavelet atoms. Finally, the false positive points are reduced by removing the candidate points in RNFL and RPE layers, which are automatically segmented based on ridgelet transform. Our simulation results on 1924 HFs show that sensitivity and specificity for HF detection is 91.0% and 100%, respectively.

  1. Technetium-99m Bone Scan and Panoramic Radiography in Detection of Bone Invasion by Oral Carcinoma

    Science.gov (United States)

    John, Ani

    2014-01-01

    Objective: The correct extension of cancer in the bone usually remains undetected on static imaging which may lead to inadequate or over excision. The conventional radiography as well as other anatomical imaging modalities like computed tomography, magnetic resonance imaging often fails to detect functional changes in the bone. However, bone scinitigraphy is highly sensitive in detecting earlier changes in the bone but lack anatomical definition. The purpose of the study was to evaluate the accuracy of combining technetium-99m bone scan and panoramic radiography (Tc scan/PR) over using single diagnostic modality in detection of jaw bone invasion by oral carcinomas. The accuracy of these imaging modalities either alone or in combination were determined by comparing with the histopathological findings. Materials and Methods: Twenty patients with biopsy-proven oral malignant tumors were randomly selected from Oral Medicine and Radiology department over a period of two years. All patients were investigated preoperatively by Tc scan and PR. Lewis – Jones’s designed diagnostic criterion was applied on Tc scan/PR to evaluate bone involvement by cancer. To test the accuracy of Tc scan, PR and Tc scan/PR, their results were compared with the histopathological findings of resected specimen. Results: Hybrid Tc scan/PR had higher specificity, accuracy and positive predictive value (83.3%, 94.7%, 92.8%) than Tc scan alone (50%, 84.2%, 81.2%) and higher sensitivity and negative predictive value (100%, 100%) than PR (69.2%, 55.5%). Conclusion: Combination of Tc scan and PR was more accurate in detecting jaw bone invasion by oral squamous cell carcinoma than Tc scan and PR alone. PMID:24995244

  2. Rapid-scan Fourier-transform coherent anti-Stokes Raman scattering spectroscopy with heterodyne detection.

    Science.gov (United States)

    Hiramatsu, Kotaro; Luo, Yizhi; Ideguchi, Takuro; Goda, Keisuke

    2017-11-01

    High-speed Raman spectroscopy has become increasingly important for analyzing chemical dynamics in real time. To address the need, rapid-scan Fourier-transform coherent anti-Stokes Raman scattering (FT-CARS) spectroscopy has been developed to realize broadband CARS measurements at a scan rate of more than 20,000 scans/s. However, the detection sensitivity of FT-CARS spectroscopy is inherently low due to the limited number of photons detected during each scan. In this Letter, we show our experimental demonstration of enhanced sensitivity in rapid-scan FT-CARS spectroscopy by heterodyne detection. Specifically, we implemented heterodyne detection by superposing the CARS electric field with an external local oscillator (LO) for their interference. The CARS signal was amplified by simply increasing the power of the LO without the need for increasing the incident power onto the sample. Consequently, we achieved enhancement in signal intensity and the signal-to-noise ratio by factors of 39 and 5, respectively, compared to FT-CARS spectroscopy with homodyne detection. The sensitivity-improved rapid-scan FT-CARS spectroscopy is expected to enable the sensitive real-time observation of chemical dynamics in a broad range of settings, such as combustion engines and live biological cells.

  3. The efficacy of i-SCAN for detecting reflux esophagitis: a prospective randomized controlled trial.

    Science.gov (United States)

    Kang, H S; Hong, S N; Kim, Y S; Park, H S; Kim, B K; Lee, J H; Kim, S I; Lee, T Y; Kim, J H; Lee, S Y; Sung, I K; Shim, C S

    2013-01-01

    New imaging technologies have been applied in endoscopy to improve the detection and differentiation of subtle mucosal changes using a digital contrast method. Among them, i-SCAN technology is the most recently developed image-enhancing technology. We investigated whether i-SCAN could improve the detection rate of reflux esophagitis. Interobserver agreement between endoscopists was compared with conventional white light (WL) endoscopic examination. We performed a prospective randomized controlled trial. A consecutive series of 514 subjects that underwent an esophagogastroduodenoscopy for health inspection were enrolled and randomized into the i-SCAN group (n = 246) and WL group (n = 268). An esophagogastroduodenoscopy with video recording was used for detecting reflux esophagitis, and reflux esophagitis were categorized by the modified Los Angeles (LA) classification. The total number of reflux esophagitis identified by WL and i-SCAN was 58 (21.7%) and 74 (30.1%), respectively. The diagnostic yield of reflux esophagitis was significantly higher (P = 0.034) in the i-SCAN group (30.1%) as compared to the WL group (21.6%). Using the modified LA classification, the detection rate of minimal changes was significantly higher (P = 0.017) in the i-SCAN group (11.8%) as compared to the WL group (5.6%), but the detection rates of LA-A and LA-B were not significantly different between the two groups (P = 0.897 and P = 0.311, respectively). After comparison of the interobserver agreement using randomly selected video clips, the i-SCAN group showed better agreement than the WL group (Kappa value, 0.793 vs. 0.473). Compared to WL endoscopy, applying i-SCAN in daily practice can improve the diagnostic yield of reflux esophagitis by detecting more minimal changes in the squamo-columnar junction of the esophagus and can improve the interobserver agreement of the modified Los Angeles classification.

  4. Reliability of KRAS mutation testing in metastatic colorectal cancer patients across five laboratories

    Directory of Open Access Journals (Sweden)

    Feigelson Heather

    2012-04-01

    Full Text Available Abstract Background Mutations in the KRAS gene are associated with poor response to epidermal growth factor receptor inhibitors used in the treatment of metastatic colorectal cancer. Factors influencing KRAS test results in tumor specimens include: tumor heterogeneity, sample handling, slide preparation, techniques for tumor enrichment, DNA preparation, assay design and sensitivity. We evaluated comparability and consistency of KRAS test results among five laboratories currently being used to determine KRAS mutation status of metastatic colorectal cancer specimens in a large, multi-center observational study. Findings Twenty formalin-fixed paraffin-embedded human colorectal cancer samples from colon resections previously tested for KRAS mutations were selected based on mutation status (6 wild type, 8 codon 12 mutations, and 6 codon 13 mutations. We found good agreement across laboratories despite differences in mutation detection methods. Eighteen of twenty samples (90% were concordant across all five labs. Discordant results are likely not due to laboratory error, but instead to tumor heterogeneity, contamination of the tumor sample with normal tissue, or analytic factors affecting assay sensitivity. Conclusions Our results indicate commercial and academic laboratories provide reliable results for the common KRAS gene mutations at codons 12 and 13 when an adequate percentage of tumor cells is present in the sample.

  5. EGFR Expression and KRAS and BRAF Mutational Status in Intestinal-Type Sinonasal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Valérie Costes

    2013-03-01

    Full Text Available Accumulation of molecular alterations, including EGFR overexpression and mutations in KRAS and BRAF, contribute to colorectal carcinogenesis. Since intestinal-type adenocarcinoma (ITAC of the nasal cavity and paranasal sinus has morphologic and phenotypic features that are usually indistinguishable from colorectal cancer (CRC, it is likely that both tumor types share equivalent genetic alterations. Data from a series of 43 patients treated surgically for ITAC in Montpellier, France between November 1998 and December 2012 were collected. Tumors were characterized for mutations in KRAS and BRAF as well as EGFR overexpression. Kaplan-Meier survival curves were constructed using overall survival as the primary end points. Patient survival was analyzed using the hazards ratio. Twenty seven tumors (63% showed EGFR positivity and 30% exhibited a high expression level (+2/+3. KRAS mutations were detected in 43% of cases. BRAF mutations were identified in 3.6% of specimens. Patients with age superior to 60 years, metastatic status, and KRAS mutations had significant overall survival values (p = 0.026, p = 0.001 and p = 0.03, respectively. Our results indicate that KRAS mutations and EGFR expression are frequent in ITAC and that KRAS mutations predict good patient prognosis in ITAC. Finally, EGFR directed molecular treatments could be investigated in a subset of patients affected by ITAC.

  6. Pelvic artery calcification detection on CT scans using convolutional neural networks

    Science.gov (United States)

    Liu, Jiamin; Lu, Le; Yao, Jianhua; Bagheri, Mohammadhadi; Summers, Ronald M.

    2017-03-01

    Artery calcification is observed commonly in elderly patients, especially in patients with chronic kidney disease, and may affect coronary, carotid and peripheral arteries. Vascular calcification has been associated with many clinical outcomes. Manual identification of calcification in CT scans requires substantial expert interaction, which makes it time-consuming and infeasible for large-scale studies. Many works have been proposed for coronary artery calcification detection in cardiac CT scans. In these works, coronary artery extraction is commonly required for calcification detection. However, there are few works about abdominal or pelvic artery calcification detection. In this work, we present a method for automatic pelvic artery calcification detection on CT scan. This method uses the recent advanced faster region-based convolutional neural network (R-CNN) to directly identify artery calcification without a need for artery extraction since pelvic artery extraction itself is challenging. Our method first generates category-independent region proposals for each slice of the input CT scan using region proposal networks (RPN). Then, each region proposal is jointly classified and refined by softmax classifier and bounding box regressor. We applied the detection method to 500 images from 20 CT scans of patients for evaluation. The detection system achieved a 77.4% average precision and a 85% sensitivity at 1 false positive per image.

  7. Study on Point Mutations of K-ras Gene in Non-small Cell Lung Cancer in Guangxi

    Directory of Open Access Journals (Sweden)

    Weixiang ZHONG

    2011-06-01

    Full Text Available Background and objective Recent studies indicated that non-small cell lung cancer (NSCLC patients with mutant K-ras were resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs. The aim of this study is to explore the relationship between the mutation of K-ras gene and NSCLC in Guangxi by detecting the point mutations in codon 12, 13 and 61 of K-ras gene in NSCLC. Methods The point mutations in codon 12, 13 and 61 of K-ras gene were detected by single-strand conformation polymorphism (SSCP analysis of polymerase chain reaction (PCR products and DNA sequencing analysis in 105 cases of NSCLC tissues and 30 cases of adjacent normal tissues. Results No point mutation in codon 12, 13 and 61 of K-ras gene was found in 105 cases of NSCLC tissues and 30 cases of adjacent normal tissues. In this study, the mutation frequency of K-ras gene in NSCLC was 0 (0/105. Conclusion The high proportion of K-ras gene in wild-type indicates that patients with NSCLC in Guangxi could take more benefits from the therapy with EGFR-TKIs.

  8. [Study on point mutations of K-ras gene in non-small cell lung cancer in Guangxi].

    Science.gov (United States)

    Zhong, Weixiang; Chen, Mingwu; Xian, Lei; Li, Manhong

    2011-06-01

    Recent studies indicated that non-small cell lung cancer (NSCLC) patients with mutant K-ras were resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). The aim of this study is to explore the relationship between the mutation of K-ras gene and NSCLC in Guangxi by detecting the point mutations in codon 12, 13 and 61 of K-ras gene in NSCLC. The point mutations in codon 12, 13 and 61 of K-ras gene were detected by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products and DNA sequencing analysis in 105 cases of NSCLC tissues and 30 cases of adjacent normal tissues. No point mutation in codon 12, 13 and 61 of K-ras gene was found in 105 cases of NSCLC tissues and 30 cases of adjacent normal tissues. In this study, the mutation frequency of K-ras gene in NSCLC was 0 (0/105). The high proportion of K-ras gene in wild-type indicates that patients with NSCLC in Guangxi could take more benefits from the therapy with EGFR-TKIs.

  9. Using Cognitive Control in Software Defined Networking for Port Scan Detection

    Science.gov (United States)

    2017-07-01

    ARL-TR-8059 ● July 2017 US Army Research Laboratory Using Cognitive Control in Software -Defined Networking for Port Scan...Cognitive Control in Software -Defined Networking for Port Scan Detection by Vinod K Mishra Computational and Information Sciences Directorate, ARL...Technical Report 3. DATES COVERED (From - To) 15 June–31 July 2016 4. TITLE AND SUBTITLE Using Cognitive Control in Software -Defined Networking for

  10. The Role of Gallium Scanning in the Detection of Bone and Joint Sepsis

    OpenAIRE

    Gavin, Anna; Laird, J. D.; Roberts, S D

    1984-01-01

    The value of gallium (67Ga) scanning in the diagnosis of septic disease of bone or joint was assessed in 34 patients. The results show a sensitivity of 60 per cent and specificity of 64 per cent. The low accuracy of this method for the detection of bone and joint sepsis (62 per cent) means that gallium scanning can be used only as an adjunct to other investigative techniques.

  11. Spatial scan statistics for detection of multiple clusters with arbitrary shapes.

    Science.gov (United States)

    Lin, Pei-Sheng; Kung, Yi-Hung; Clayton, Murray

    2016-12-01

    In applying scan statistics for public health research, it would be valuable to develop a detection method for multiple clusters that accommodates spatial correlation and covariate effects in an integrated model. In this article, we connect the concepts of the likelihood ratio (LR) scan statistic and the quasi-likelihood (QL) scan statistic to provide a series of detection procedures sufficiently flexible to apply to clusters of arbitrary shape. First, we use an independent scan model for detection of clusters and then a variogram tool to examine the existence of spatial correlation and regional variation based on residuals of the independent scan model. When the estimate of regional variation is significantly different from zero, a mixed QL estimating equation is developed to estimate coefficients of geographic clusters and covariates. We use the Benjamini-Hochberg procedure (1995) to find a threshold for p-values to address the multiple testing problem. A quasi-deviance criterion is used to regroup the estimated clusters to find geographic clusters with arbitrary shapes. We conduct simulations to compare the performance of the proposed method with other scan statistics. For illustration, the method is applied to enterovirus data from Taiwan. © 2016, The International Biometric Society.

  12. Competitive amplification of differentially melting amplicons (CADMA improves KRAS hotspot mutation testing in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Kristensen Lasse

    2012-11-01

    Full Text Available Abstract Background Cancer is an extremely heterogeneous group of diseases traditionally categorized according to tissue of origin. However, even among patients with the same cancer subtype the cellular alterations at the molecular level are often very different. Several new therapies targeting specific molecular changes found in individual patients have initiated the era of personalized therapy and significantly improved patient care. In metastatic colorectal cancer (mCRC a selected group of patients with wild-type KRAS respond to antibodies against the epidermal growth factor receptor (EGFR. Testing for KRAS mutations is now required prior to anti-EGFR treatment, however, less sensitive methods based on conventional PCR regularly fail to detect KRAS mutations in clinical samples. Methods We have developed sensitive and specific assays for detection of the seven most common KRAS mutations based on a novel methodology named Competitive Amplification of Differentially Melting Amplicons (CADMA. The clinical applicability of these assays was assessed by analyzing 100 colorectal cancer samples, for which KRAS mutation status has been evaluated by the commercially available TheraScreen® KRAS mutation kit. Results The CADMA assays were sensitive to at least 0.5% mutant alleles in a wild-type background when using 50 nanograms of DNA in the reactions. Consensus between CADMA and the TheraScreen kit was observed in 96% of the colorectal cancer samples. In cases where disagreement was observed the CADMA result could be confirmed by a previously published assay based on TaqMan probes and by fast COLD-PCR followed by Sanger sequencing. Conclusions The high analytical sensitivity and specificity of CADMA may increase diagnostic sensitivity and specificity of KRAS mutation testing in mCRC patients.

  13. Real-time underwater object detection based on an electrically scanned high-resolution sonar

    DEFF Research Database (Denmark)

    Henriksen, Lars

    1994-01-01

    The paper describes an approach to real time detection and tracking of underwater objects, using image sequences from an electrically scanned high-resolution sonar. The use of a high resolution sonar provides a good estimate of the location of the objects, but strains the computers on board......, because of the high rate of raw data. The amount of data can be cut down by decreasing the scanned area, but this reduces the possibility of planning an optimal path. In the paper methods are described, that maintains the wide area of detection, without significant loss of precision or speed. This is done...

  14. CT scan range estimation using multiple body parts detection: let PACS learn the CT image content.

    Science.gov (United States)

    Wang, Chunliang; Lundström, Claes

    2016-02-01

    The aim of this study was to develop an efficient CT scan range estimation method that is based on the analysis of image data itself instead of metadata analysis. This makes it possible to quantitatively compare the scan range of two studies. In our study, 3D stacks are first projected to 2D coronal images via a ray casting-like process. Trained 2D body part classifiers are then used to recognize different body parts in the projected image. The detected candidate regions go into a structure grouping process to eliminate false-positive detections. Finally, the scale and position of the patient relative to the projected figure are estimated based on the detected body parts via a structural voting. The start and end lines of the CT scan are projected to a standard human figure. The position readout is normalized so that the bottom of the feet represents 0.0, and the top of the head is 1.0. Classifiers for 18 body parts were trained using 184 CT scans. The final application was tested on 136 randomly selected heterogeneous CT scans. Ground truth was generated by asking two human observers to mark the start and end positions of each scan on the standard human figure. When compared with the human observers, the mean absolute error of the proposed method is 1.2% (max: 3.5%) and 1.6% (max: 5.4%) for the start and end positions, respectively. We proposed a scan range estimation method using multiple body parts detection and relative structure position analysis. In our preliminary tests, the proposed method delivered promising results.

  15. Loss of RASSF1A Expression in Colorectal Cancer and Its Association with K-ras Status

    Directory of Open Access Journals (Sweden)

    Dan Cao

    2013-01-01

    Full Text Available Background. The RAS-association domain family 1 A (RASSF1A is a classical member of RAS effectors regulating cell proliferation and apoptosis. Loss of RASSF1A expression may shift the balance towards a growth-promoting effect without the necessity of activating K-ras mutations. Its potential association with K-ras mutations in colorectal cancer (CRC is unclear. Methods. RASSF1A expression was examined in normal mucosa, adenoma, and tumor tissues of colon and rectum, respectively. We examined the association of RASSF1A expression, mutations of K-ras, and EGFR status in 76 primary CRCs. The relationship between clinicopathological characteristics and RASSF1A expression was also analyzed. Results. RASSF1A expression level decreased progressively in normal mucosa, adenoma and, tumor tissues, and the loss of RASSF1A expression occurred more frequently in tumor tissues. Of 76 primary CRCs, loss of RASSF1A expression and/or K-ras mutations were detected in 77% cases. Loss of RASSF1A expression was more frequent in K-ras wild-type than in mutation cases (63% versus 32%, . Conclusions. Our study indicates that loss of RASSF1A may be involved in pathogenesis of CRC, its expression was found predominantly in K-ras wild-type CRCs, suggesting that it may be another way of affecting RAS signaling, in addition to K-ras mutations.

  16. DMSO increases mutation-scanning detection sensitivity in clinical samples using high resolution melting

    Science.gov (United States)

    Song, Chen; Castellanos-Rizaldos, Elena; Bejar, Rafael; Ebert, Benjamin L.; Makrigiorgos, G. Mike

    2016-01-01

    BACKGROUND Mutation scanning provides the simplest, lowest cost method for identifying DNA variations on single PCR amplicons, and it may be performed prior to sequencing to avoid screening of non-informative wild type samples. High resolution melting (HRM) is the most commonly used method for mutation scanning. However, by using PCR-HRM mutations below ≈ 3–10% that can still be clinically significant may often be missed. Therefore, enhancing HRM detection sensitivity is important for mutation scanning and its clinical application. METHODS We used serial dilution of TP53 exon 8 mutation containing cell lines to demonstrate the improvement in detection sensitivity for conventional-PCR-HRM in the presence of DMSO. We also conducted full-COLD-PCR to further enrich low-level mutations prior to HRM±DMSO and employed droplet-digital PCR to derive the optimal conditions for mutation enrichment. Both conventional-PCR-HRM and full-COLD-PCR-HRM ±DMSO were used for mutation scanning in TP53 exon 8 in cancer samples containing known mutations and in myelodysplastic syndrome samples with unknown mutations. Mutations in other genes were also examined. RESULTS The detection sensitivity of PCR-HRM-scanning increases 2–5-fold in the presence of DMSO, depending also on mutation type and sequence context, and can typically detect mutation abundance of about 1%. When mutation enrichment is applied during amplification using full-COLD-PCR and followed by HRM in the presence of DMSO, mutations with 0.2–0.3% mutation abundance in TP53 exon 8 can be detected. CONCLUSIONS DMSO improves HRM mutation scanning sensitivity. When full-COLD-PCR is employed, followed by DMSO-HRM, the overall improvement is about 20-fold as compared to conventional PCR-HRM. PMID:26432802

  17. Improved detection of differentially expressed genes in microarray experiments through multiple scanning and image integration

    Science.gov (United States)

    Romualdi, Chiara; Trevisan, Silvia; Celegato, Barbara; Costa, Germano; Lanfranchi, Gerolamo

    2003-01-01

    The variability of results in microarray technology is in part due to the fact that independent scans of a single hybridised microarray give spot images that are not quite the same. To solve this problem and turn it to our advantage, we introduced the approach of multiple scanning and of image integration of microarrays. To this end, we have developed specific software that creates a virtual image that statistically summarises a series of consecutive scans of a microarray. We provide evidence that the use of multiple imaging (i) enhances the detection of differentially expressed genes; (ii) increases the image homogeneity; and (iii) reveals false-positive results such as differentially expressed genes that are detected by a single scan but not confirmed by successive scanning replicates. The increase in the final number of differentially expressed genes detected in a microarray experiment with this approach is remarkable; 50% more for microarrays hybridised with targets labelled by reverse transcriptase, and 200% more for microarrays developed with the tyramide signal amplification (TSA) technique. The results have been confirmed by semi-quantitative RT–PCR tests. PMID:14627839

  18. DETECTION OF WATER SURFACES IN FULL-WAVEFORM LASER SCANNING DATA

    Directory of Open Access Journals (Sweden)

    A. Schmidt

    2012-09-01

    Full Text Available Airborne laser scanning has become a standard method for recording topographic data. A new generation of laser scanners digitises the complete waveform of the backscattered signal and thus offers the possibility of analysing the signal shape. As a product of the laser scanning, a digital surface model (DSM or a digital terrain model (DTM can be derived. In water regions, data acquisition by laser scanning is limited to the water surface because the near-infrared laser pulses hardly penetrate water. Therefore, a height model generated from laser scanner point clouds over water regions does not represent the actual terrain. The generation of a DTM thus requires the detection of water surfaces. In this study, a method for the detection and classification of water surfaces in airborne laser scanning data is proposed. The method works with both geometrical features (e.g. height or height variation and characteristics of the pulses derived from the full waveform of the returned signal (e.g. intensity or pulse width. In our strategy, based on fuzzy logic, all classification parameters are derived automatically from training areas. According to their statistical distributions, the features are considered with individual weights. The aim of this paper is to analyse crucial features for classification and to investigate the potential of full waveform laser scanning data for this application. We present results from different areas with lakes and rivers, analysing the contribution of the individual groups of features for the detection of water surfaces.

  19. Automatic concrete cracks detection and mapping of terrestrial laser scan data

    Directory of Open Access Journals (Sweden)

    Mostafa Rabah

    2013-12-01

    The current paper submits a method for automatic concrete cracks detection and mapping from the data that was obtained during laser scanning survey. The method of cracks detection and mapping is achieved by three steps, namely the step of shading correction in the original image, step of crack detection and finally step of crack mapping and processing steps. The detected crack is defined in a pixel coordinate system. To remap the crack into the referred coordinate system, a reverse engineering is used. This is achieved by a hybrid concept of terrestrial laser-scanner point clouds and the corresponding camera image, i.e. a conversion from the pixel coordinate system to the terrestrial laser-scanner or global coordinate system. The results of the experiment show that the mean differences between terrestrial laser scan and the total station are about 30.5, 16.4 and 14.3 mms in x, y and z direction, respectively.

  20. Evaluation of Intraductal Ultrasonography, Endoscopic Brush Cytology and K-ras, P53 Gene Mutation in the Early Diagnosis of Malignant Bile Duct Stricture

    Directory of Open Access Journals (Sweden)

    Ping Huang

    2015-01-01

    Conclusions: IDUS combined with brush cytology and K-ras, P53 gene mutation detection is better than the separate detection and contribute to the early diagnosis of malignant biliary stricture. Its more widespread use is recommended.

  1. Highly sensitive surface-scanning detector for the direct bacterial detection using magnetoelastic (ME) biosensors

    Science.gov (United States)

    Liu, Yuzhe; Horikawa, Shin; Chen, I.-Hsuan; Du, Songtao; Wikle, Howard C.; Suh, Sang-Jin; Chin, Bryan A.

    2017-05-01

    This paper demonstrates a highly sensitive surface-scanning detector used for magnetoelastic (ME) biosensors for the detection of Salmonella on the surface of a polyethylene (PE) food preparation surface. The design and fabrication methods of the new planar spiral coil are introduced. Different concentrations of Salmonella were measured on the surface of a PE board. The efficacy of Salmonella capture and detection is discussed.

  2. Dynamic occlusion detection and inpainting of in situ captured terrestrial laser scanning point clouds sequence

    Science.gov (United States)

    Chen, Chi; Yang, Bisheng

    2016-09-01

    Laser point clouds captured using terrestrial laser scanning (TLS) in an uncontrollable urban outdoor or indoor scene suffer from irregular shaped data blanks caused by dynamic occlusion that temporarily exists, i.e., moving objects, such as pedestrians or cars, resulting in integrality and quality losses of the scene data. This paper proposes a novel automatic dynamic occlusion detection and inpainting method for sequential TLS point clouds captured from one scan position. In situ collected laser point clouds sequences are indexed by establishing a novel panoramic space partition that assigns a three dimensional voxel to each laser point according to the scanning setups. Then two stationary background models are constructed at the ray voxel level using the laser reflectance intensity and geometrical attributes of the point set inside each voxel across the TLS sequence. Finally, the background models are combined to detect the points on the dynamic object, and the ray voxels of the detected dynamic points are tracked for further inpainting by replacing the ray voxels with the corresponding background voxels from another scan. The resulting scene is free of dynamic occlusions. Experiments validated the effectiveness of the proposed method for indoor and outdoor TLS point clouds captured by a commercial terrestrial scanner. The proposed method achieves high precision and recall rate for dynamic occlusion detection and produces clean inpainted point clouds for further processing.

  3. Autoblocker: a system for detecting and blocking of network scanning based on analysis of netflow data

    Energy Technology Data Exchange (ETDEWEB)

    Bobyshev, A.; Lamore, D.; Demar, P.; /Fermilab

    2004-12-01

    In a large campus network, such at Fermilab, with tens of thousands of nodes, scanning initiated from either outside of or within the campus network raises security concerns. This scanning may have very serious impact on network performance, and even disrupt normal operation of many services. In this paper we introduce a system for detecting and automatic blocking excessive traffic of different kinds of scanning, DoS attacks, virus infected computers. The system, called AutoBlocker, is a distributed computing system based on quasi-real time analysis of network flow data collected from the border router and core switches. AutoBlocker also has an interface to accept alerts from IDS systems (e.g. BRO, SNORT) that are based on other technologies. The system has multiple configurable alert levels for the detection of anomalous behavior and configurable trigger criteria for automated blocking of scans at the core or border routers. It has been in use at Fermilab for about 2 years, and has become a very valuable tool to curtail scan activity within the Fermilab campus network.

  4. Damage Detection on Thin-walled Structures Utilizing Laser Scanning and Standing Waves

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Se Hyeok; Jeon, Jun Young; Kim, Du Hwan; Park, Gyuhae [Chonnam Nat’l Univ., Gwangju (Korea, Republic of); Kang, To; Han, Soon Woo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2017-05-15

    This paper describes wavenumber filtering for damage detection using single-frequency standing wave excitation and laser scanning sensing. An embedded piezoelectric sensor generates ultrasonic standing waves, and the responses are measured using a laser Doppler vibrometer and mirror tilting device. After scanning, newly developed damage detection techniques based on wavenumber filtering are applied to the full standing wave field. To demonstrate the performance of the proposed techniques, several experiments were performed on composite plates with delamination and aluminum plates with corrosion damage. The results demonstrated that the developed techniques could be applied to various structures to localize the damage, with the potential to improve the damage detection capability at a high interrogation speed.

  5. Low-Level Detection of Poly(amidoamine PAMAM Dendrimers Using Immunoimaging Scanning Probe Microscopy

    Directory of Open Access Journals (Sweden)

    Chevelle A. Cason

    2012-01-01

    Full Text Available Immunoimaging scanning probe microscopy was utilized for the low-level detection and quantification of biotinylated G4 poly(amidoamine PAMAM dendrimers. Results were compared to those of high-performance liquid chromatography (HPLC and found to provide a vastly improved analytical method for the low-level detection of dendrimers, improving the limit of detection by a factor of 1000 (LOD=2.5×10−13 moles. The biorecognition method is reproducible and shows high specificity and good accuracy. In addition, the capture assay platform shows a promising approach to patterning dendrimers for nanotechnology applications.

  6. Low-Level Detection of Poly(amidoamine) PAMAM Dendrimers Using Immunoimaging Scanning Probe Microscopy.

    Science.gov (United States)

    Cason, Chevelle A; Fabré, Thomas A; Buhrlage, Andrew; Haik, Kristi L; Bullen, Heather A

    2012-01-01

    Immunoimaging scanning probe microscopy was utilized for the low-level detection and quantification of biotinylated G4 poly(amidoamine) PAMAM dendrimers. Results were compared to those of high-performance liquid chromatography (HPLC) and found to provide a vastly improved analytical method for the low-level detection of dendrimers, improving the limit of detection by a factor of 1000 (LOD = 2.5 × 10(-13) moles). The biorecognition method is reproducible and shows high specificity and good accuracy. In addition, the capture assay platform shows a promising approach to patterning dendrimers for nanotechnology applications.

  7. Genotyping of K-ras codons 12 and 13 mutations in colorectal cancer by capillary electrophoresis.

    Science.gov (United States)

    Chen, Yen-Ling; Chang, Ya-Sian; Chang, Jan-Gowth; Wu, Shou-Mei

    2009-06-26

    Point mutations of the K-ras gene located in codons 12 and 13 cause poor responses to the anti-epidermal growth factor receptor (anti-EGFR) therapy of colorectal cancer (CRC) patients. Besides, mutations of K-ras gene have also been proven to play an important role in human tumor progression. We established a simple and effective capillary electrophoresis (CE) method for simultaneous point mutation detection in codons 12 and 13 of K-ras gene. We combined one universal fluorescence-based nonhuman-sequence primer and two fragment-oriented primers in one tube, and performed this two-in-one polymerase chain reaction (PCR). PCR fragments included wild type and seven point mutations at codons 12 and 13 of K-ras gene. The amplicons were analyzed by single-strand conformation polymorphism (SSCP)-CE method. The CE analysis was performed by using a 1x Tris-borate-EDTA (TBE) buffer containing 1.5% (w/v) hydroxyethylcellulose (HEC) (MW 250,000) under reverse polarity with 15 degrees C and 30 degrees C. Ninety colorectal cancer patients were blindly genotyped using this developed method. The results showed good agreement with those of DNA sequencing method. The SSCP-CE was feasible for mutation screening of K-ras gene in populations.

  8. Neutral evolution of drug resistant colorectal cancer cell populations is independent of their KRAS status.

    Directory of Open Access Journals (Sweden)

    Krastan B Blagoev

    Full Text Available Emergence of tumor resistance to an anti-cancer therapy directed against a putative target raises several questions including: (1 do mutations in the target/pathway confer resistance? (2 Are these mutations pre-existing? (3 What is the relative fitness of cells with/without the mutation? We addressed these questions in patients with metastatic colorectal cancer (mCRC. We conducted an exhaustive review of published data to establish a median doubling time for CRCs and stained a cohort of CRCs to document mitotic indices. We analyzed published data and our own data to calculate rates of growth (g and regression (d, decay of tumors in patients with CRC correlating these results with the detection of circulating MT-KRAS DNA. Additionally we estimated mathematically the caloric burden of such tumors using data on mitotic and apoptotic indices. We conclude outgrowth of cells harboring intrinsic or acquired MT-KRAS cannot explain resistance to anti-EGFR (epidermal growth factor receptor antibodies. Rates of tumor growth with panitumumab are unaffected by presence/absence of MT-KRAS. While MT-KRAS cells may be resistant to anti-EGFR antibodies, WT-KRAS cells also rapidly bypass this blockade suggesting inherent resistance mechanisms are responsible and a neutral evolution model is most appropriate. Using the above clinical data on tumor doubling times and mitotic and apoptotic indices we estimated the caloric intake required to support tumor growth and suggest it may explain in part cancer-associated cachexia.

  9. Detection of bladder cancer: comparison of low-dose scans with AIDR 3D and routine-dose scans with FBP on the excretory phase in CT urography.

    Science.gov (United States)

    Juri, Hiroshi; Tsuboyama, Takahiro; Kumano, Seishi; Inada, Yuki; Koyama, Mitsuhiro; Azuma, Haruhito; Narumi, Yoshifumi

    2016-01-01

    To prospectively compare the detection of bladder cancer between low-dose scans with adaptive iterative dose reduction three dimensional projection (AIDR 3D) and routine-dose scans with filtered back projection (FBP) on the excretory phase (EP) in CT urography. 42 patients were included. Routine- and low-dose EP were performed in each patient. Routine-dose images were reconstructed with FBP, and low-dose images were reconstructed with AIDR 3D. Two radiologists scored confidence levels for the presence or absence of bladder cancer using a 5-point scale. The CT dose index of each EP was measured, and the dose reduction was calculated. Sensitivity, specificity and accuracy were 86.4%, 95.0% and 90.5% on routine-dose scans and were 86.4%, 90.0% and 88.1% on low-dose scans, respectively. There was no significant difference (p; not significant, 1.00 and 1.00, respectively). The average CT dose index was 8.07 and 2.63 mGy on routine- and low-dose scans, and the ratio of dose reduction was 67.6%. The detection of bladder cancer on low-dose scans with AIDR 3D is almost equal to that on routine-dose scans with FBP on the EP, with nearly 70% dose reduction. Using AIDR 3D, the radiation dose may be reduced on the EP in CT urography for the detection of bladder cancer.

  10. Automated Detection of Healthy and Diseased Aortae from Images Obtained by Contrast-Enhanced CT Scan

    Directory of Open Access Journals (Sweden)

    Michael Gayhart

    2013-01-01

    Full Text Available Purpose. We developed the next stage of our computer assisted diagnosis (CAD system to aid radiologists in evaluating CT images for aortic disease by removing innocuous images and highlighting signs of aortic disease. Materials and Methods. Segmented data of patient’s contrast-enhanced CT scan was analyzed for aortic dissection and penetrating aortic ulcer (PAU. Aortic dissection was detected by checking for an abnormal shape of the aorta using edge oriented methods. PAU was recognized through abnormally high intensities with interest point operators. Results. The aortic dissection detection process had a sensitivity of 0.8218 and a specificity of 0.9907. The PAU detection process scored a sensitivity of 0.7587 and a specificity of 0.9700. Conclusion. The aortic dissection detection process and the PAU detection process were successful in removing innocuous images, but additional methods are necessary for improving recognition of images with aortic disease.

  11. Image processing based detection of lung cancer on CT scan images

    Science.gov (United States)

    Abdillah, Bariqi; Bustamam, Alhadi; Sarwinda, Devvi

    2017-10-01

    In this paper, we implement and analyze the image processing method for detection of lung cancer. Image processing techniques are widely used in several medical problems for picture enhancement in the detection phase to support the early medical treatment. In this research we proposed a detection method of lung cancer based on image segmentation. Image segmentation is one of intermediate level in image processing. Marker control watershed and region growing approach are used to segment of CT scan image. Detection phases are followed by image enhancement using Gabor filter, image segmentation, and features extraction. From the experimental results, we found the effectiveness of our approach. The results show that the best approach for main features detection is watershed with masking method which has high accuracy and robust.

  12. KRAS Allelic Imbalance: Strengths and Weaknesses in Numbers.

    Science.gov (United States)

    Doherty, Gary J; Kerr, Emma M; Martins, Carla P

    2017-05-01

    The identification of therapeutic vulnerabilities in mutant KRAS tumors has proven difficult to achieve. Burgess and colleagues recently reported in Cell that mutant/wild-type Kras allelic dosage determines clonal fitness and MEK inhibitor sensitivity in a leukemia model, demonstrating that KRAS allelic imbalance is likely an important and overlooked variable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Oil spill detection in northern Europe using ScanSAR data

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, J.P. [Tromso Satellite Station, Tromso (Norway); Bauna, T.; Enoksen, R.T.; Seljelv, L.G.; Landmark, F.

    1998-12-31

    In 1991 a project was initiated at the Norwegian Space Centre in which ERS-1 SAR data was used for detecting oil spills at sea. The goal of the project was to develop service infrastructure for near real-time processing, analysis and distribution. It was shown that satellite data is capable of establishing early warning of illegal oil spills. A total of 15 RADARSAT scenes from the ScanSAR modes covering Norwegian and Baltic Sea water were acquired under the RADARSAT Application Development and Research Opportunity (ADRO) program. Several of the scenes show oil spills at the sea surface. The results demonstrated overall detection capabilities of ScanSAR better than expected.

  14. Real time coarse orientation detection in MR scans using multi-planar deep convolutional neural networks

    Science.gov (United States)

    Bhatia, Parmeet S.; Reda, Fitsum; Harder, Martin; Zhan, Yiqiang; Zhou, Xiang Sean

    2017-02-01

    Automatically detecting anatomy orientation is an important task in medical image analysis. Specifically, the ability to automatically detect coarse orientation of structures is useful to minimize the effort of fine/accurate orientation detection algorithms, to initialize non-rigid deformable registration algorithms or to align models to target structures in model-based segmentation algorithms. In this work, we present a deep convolution neural network (DCNN)-based method for fast and robust detection of the coarse structure orientation, i.e., the hemi-sphere where the principal axis of a structure lies. That is, our algorithm predicts whether the principal orientation of a structure is in the northern hemisphere or southern hemisphere, which we will refer to as UP and DOWN, respectively, in the remainder of this manuscript. The only assumption of our method is that the entire structure is located within the scan's field-of-view (FOV). To efficiently solve the problem in 3D space, we formulated it as a multi-planar 2D deep learning problem. In the training stage, a large number coronal-sagittal slice pairs are constructed as 2-channel images to train a DCNN to classify whether a scan is UP or DOWN. During testing, we randomly sample a small number of coronal-sagittal 2-channel images and pass them through our trained network. Finally, coarse structure orientation is determined using majority voting. We tested our method on 114 Elbow MR Scans. Experimental results suggest that only five 2-channel images are sufficient to achieve a high success rate of 97.39%. Our method is also extremely fast and takes approximately 50 milliseconds per 3D MR scan. Our method is insensitive to the location of the structure in the FOV.

  15. Atlantoaxial Ankylosis Detected on Neck CT Scans in a Patient with Ankylosing Spondylitis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Ah; Lee, Seung Hun; Joo, Kyung Bin [Dept. of Radiology, Seoul Hospital, Hanyang University College of Medicine, Seoul (Korea, Republic of); Ryu, Jeong Ah [Dept. of Radiology, Guri Hospital, Hanyang University College of Medicine, Guri (Korea, Republic of); Kim, Tae Hwan [Dept. of Rheynmatology, Seoul Hospital, Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2011-07-15

    Ankylosing spondylitis is a chronic inflammatory disorder of unknown cause that principally affects the axial skeleton. The cervical spine is also vulnerable to this disease process and the characteristic feature of cervical involvement is atlantoaxial subluxation. However, only a few cases of atlantoaxial ankylosis have been reported to date. We report a case of atlantoaxial ankylosis in a patient with ankylosing spondylitis with radiologic findings incidentally detected on neck CT scans.

  16. A scanning method for detecting clustering pattern of both attribute and structure in social networks

    Science.gov (United States)

    Wang, Tai-Chi; Phoa, Frederick Kin Hing

    2016-03-01

    Community/cluster is one of the most important features in social networks. Many cluster detection methods were proposed to identify such an important pattern, but few were able to identify the statistical significance of the clusters by considering the likelihood of network structure and its attributes. Based on the definition of clustering, we propose a scanning method, originated from analyzing spatial data, for identifying clusters in social networks. Since the properties of network data are more complicated than those of spatial data, we verify our method's feasibility via simulation studies. The results show that the detection powers are affected by cluster sizes and connection probabilities. According to our simulation results, the detection accuracy of structure clusters and both structure and attribute clusters detected by our proposed method is better than that of other methods in most of our simulation cases. In addition, we apply our proposed method to some empirical data to identify statistically significant clusters.

  17. PIK3CB and K-ras in oral squamous Cell carcinoma. A possible cross-talk!

    Directory of Open Access Journals (Sweden)

    Natheer H Al-Rawi

    2014-01-01

    Full Text Available Background: PIK3 and K-ras are signal transducing proteins involved and mediating many responses related to cell cycle growth regulation. Until date, there has been only limited evidence about the expression of K-ras and PKI3CB in oral squamous cell carcinoma (OSCC. AIMS : This study aimed to examine both proteins in OSCC and their relation to clinic- pathological findings. Setting and Design: A total of 31 formalin-fixed paraffin-embedded specimens of OSCC were selected in this study. PIK3CB and K-ras expressions were detected using standard immunohistochemical techniques. Materials and Methods: PIK3CB and k-ras immune reactivity was semi-quantitatively evaluated in at least five representative fields at 400X magnification and recorded as percentage of PIK3CB and k-ras positive tumor cells over the total number of cells examined in the same area. Results and Conclusion: All examined specimens of OSCC were positive for monoclonal antibodies directed against PIK3CB and K-ras proteins especially at advanced stage of the disease. No significant relation was observed between the tested proteins and the clinic-pathological findings of OSCC; however a highly significant direct relationship was observed between K-ras and PIK3CB. This lead to conclusion that both K-ras and PIK3CB signaling pathway were activated in the advanced stage of OSCC, and possibly a cross-talk between them. This could make these mutant proteins a potential target for an effective molecular therapy.

  18. Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer.

    Science.gov (United States)

    Del Re, Marzia; Vivaldi, Caterina; Rofi, Eleonora; Vasile, Enrico; Miccoli, Mario; Caparello, Chiara; d'Arienzo, Paolo Davide; Fornaro, Lorenzo; Falcone, Alfredo; Danesi, Romano

    2017-08-11

    Pancreatic cancer (PDAC) is still lacking of reliable markers to monitor tumor response. CA 19-9 is the only biomarker approved, despite it has several limitations in sensitivity and specificity. Since mutations of KRAS occur in more than 90% of tumors, its detection in circulating free tumor DNA (cftDNA) could represent a biomarker to monitor chemotherapy response. Twenty-seven advanced PDAC patients given first-line 5-fluorouracil, irinotecan and oxaliplatin or gemcitabine and nab-paclitaxel were enrolled. Three ml of plasma were collected: 1) before starting chemotherapy (baseline); 2) at day 15 of treatment; and 3) at each clinical follow-up. cftDNA was extracted and analysed for KRAS mutations ((mut)KRAS) by digital droplet PCR. Nineteen patients displayed a (mut)KRAS in baseline plasma samples. There was a statistically significant difference in progression-free survival (PFS) and overall survival (OS) in patients with increase vs. stability/reduction of cftDNA in the sample collected at day 15 (median PFS 2.5 vs 7.5 months, p = 0.03; median OS 6.5 vs 11.5 months, p = 0.009). The results of this study demonstrate that cftDNA (mut)KRAS changes are associated with tumor response to chemotherapy and support the evidence that (mut)KRAS in plasma may be used as a new marker for monitoring treatment outcome and disease progression in PDAC.

  19. [Correlation analysis between abundance of K-ras mutation in plasma free DNA and its correlation with clinical outcome and prognosis in patients with metastatic colorectal cancer].

    Science.gov (United States)

    Bai, Yan-qing; Liu, Xiao-jing; Wang, Yan; Ge, Fei-jiao; Zhao, Chuan-hua; Fu, Ya-li; Lin, Li; Xu, Jian-ming

    2013-09-01

    To detect K-ras gene mutations in plasma free DNA by peptide nucleic acid clamp PCR assay (PNA-PCR) and nested primer PCR, and to analyze the correlation between K-ras mutations and prognosis in patients with metastatic colorectal cancer (mCRC). Peripheral blood was collected and free DNA was extracted from plasma in 106 patients with mCRC. Nested primer PCR and PNA-PCR were used to detect K-ras gene mutation in the plasma free DNA. The patients were divided into three groups by K-ras status: wild-type group (wild-type determined by both methods), low mutation group (mutation by PNA-PCR method, wild-type by nested primer PCR method) and high mutation group (mutation by two methods). The correlation between K-ras mutations and prognosis was analyzed. The mutation rate of K-ras in tumor tissues of the 106 patients was 40.6%. The Mutation rate of K-ras in plasma free DNA detected by PNA-PCR was 31.1%, significantly higher than that of 15.1% detected by nested primer PCR (P = 0.006). The consistent rate of the K-ras status in plasma free DNA detected by PNA-PCR and that in tumor tissue detected by traditional method was up to 83.0%. The median overall survival (OS) of patients of the wild type, low mutation and high mutation groups was 23.5 months, 17.3 months and 13.9 months, respectively (P = 0.002). The median progression-free survival (PFS) of the K-ras wild-type, low mutation and high mutation groups with first-line chemotherapy was 6.8 months, 6.1 months and 3.2 months, respectively (P = 0.002), and the median OS of them were 23.0 months, 15.5 months and 13.9 months, respectively (P = 0.036). The overall response rate (ORR) was improved in the K-ras wide-type patients who received cetuximab combined with chemotherapy as first-line therapy (75.0% vs. 23.4%, P = 0.058). Cetuximab combined with in second-line therapy chemotherapy led to a significant improvement in disease control rate (DCR) ( 100% vs. 35.7%, P mutation in plasma free DNA can be used to substitute

  20. Clinicopathologic characteristics and gene expression analyses of non-KRAS 12/13, RAS-mutated metastatic colorectal cancer.

    Science.gov (United States)

    Morris, V K; Lucas, F A San; Overman, M J; Eng, C; Morelli, M P; Jiang, Z-Q; Luthra, R; Meric-Bernstam, F; Maru, D; Scheet, P; Kopetz, S; Vilar, E

    2014-10-01

    KRAS mutations in codons 12 and 13 are present in ∼40% of all colorectal cancers (CRC). Activating mutations in codons 61 and 146 of KRAS and in codons 12, 13, and 61 of NRAS also occur but are less frequent. The clinicopathologic features and gene expression profiles of this latter subpopulation of RAS-mutant colorectal tumors have not yet been clearly defined but in general are treated similarly to those with KRAS 12 or 13 mutations. Records of patients with metastatic CRC (mCRC) treated at MD Anderson Cancer Center between December 2000 and August 2012 were reviewed for RAS (KRAS or NRAS) and BRAF mutation status, clinical characteristics, and survival outcomes. To study further with an independent cohort, data from The Cancer Genome Atlas were analyzed to define a gene expression signature for patients whose tumors feature these atypical RAS mutations and explore differences with KRAS 12/13-mutated colorectal tumors. Among the 484 patients reviewed, KRAS 12/13, KRAS 61/146, NRAS, and BRAF mutations were detected in 47.7%, 3.0%, 4.1%, and 7.4%, respectively, of patients who were tested for each of these aberrations. Lung metastases were more common in both the KRAS 12/13-mutated and atypical RAS-mutated cohorts relative to patients with RAS/BRAF wild-type tumors. Gene expression analyses revealed similar patterns regardless of the site of RAS mutation, and in silico functional algorithms predicted that KRAS and NRAS mutations in codons 12, 13, 61, and 146 alter the protein function and drive tumorgenesis. Clinicopathologic characteristics, survival outcomes, functional impact, and gene expression profiling were similar between patients with KRAS 12/13 and those with NRAS or KRAS 61/146-mutated mCRC. These clinical and bioinformatic findings support the notion that colorectal tumors driven by these RAS mutations are phenotypically similar. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights

  1. A CAD of fully automated colonic polyp detection for contrasted and non-contrasted CT scans.

    Science.gov (United States)

    Tulum, Gökalp; Bolat, Bülent; Osman, Onur

    2017-04-01

    Computer-aided detection (CAD) systems are developed to help radiologists detect colonic polyps over CT scans. It is possible to reduce the detection time and increase the detection accuracy rates by using CAD systems. In this paper, we aimed to develop a fully integrated CAD system for automated detection of polyps that yields a high polyp detection rate with a reasonable number of false positives. The proposed CAD system is a multistage implementation whose main components are: automatic colon segmentation, candidate detection, feature extraction and classification. The first element of the algorithm includes a discrete segmentation for both air and fluid regions. Colon-air regions were determined based on adaptive thresholding, and the volume/length measure was used to detect air regions. To extract the colon-fluid regions, a rule-based connectivity test was used to detect the regions belong to the colon. Potential polyp candidates were detected based on the 3D Laplacian of Gaussian filter. The geometrical features were used to reduce false-positive detections. A 2D projection image was generated to extract discriminative features as the inputs of an artificial neural network classifier. Our CAD system performs at 100% sensitivity for polyps larger than 9 mm, 95.83% sensitivity for polyps 6-10 mm and 85.71% sensitivity for polyps smaller than 6 mm with 5.3 false positives per dataset. Also, clinically relevant polyps ([Formula: see text]6 mm) were identified with 96.67% sensitivity at 1.12 FP/dataset. To the best of our knowledge, the novel polyp candidate detection system which determines polyp candidates with LoG filters is one of the main contributions. We also propose a new 2D projection image calculation scheme to determine the distinctive features. We believe that our CAD system is highly effective for assisting radiologist interpreting CT.

  2. Advanced Approach of Material Region Detections on Fibre-Reinforced Concrete CT-Scans

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    Marek Pecha

    2017-01-01

    Full Text Available Detections of material regions on CT-scans of solids are commonly treated manually by an expert. Although such manual detections have many advantages, some amount of human error is also incorporated. Moreover, expert opinions may vary significantly. We present an application of the k-means++ clustering as an alternative option to manual way of material area detections. k-means++ clustering is derived from k-means (the method of vector quantization, originally from signal processing, popular for cluster analysis in data mining and image processing communities. The algorithm s main advantages are its simple implementation and fast convergence to a local optimum of an objective function. We benchmark the suggested approach on transverse CT-scans of a fibre-reinforced concrete solid. Moreover, we introduce a technique for processing air distribution, such that the appropriate pixels detected as the pixels of air are converted into pixels representing concrete. The technique is based on the connected component algorithm. Benchmark and results of proposed method conclude the paper.

  3. Oil detection in RADARSAT-2 quad-polarization imagery: implications for ScanSAR performance

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    Cheng, Angela; Arkett, Matt; Zagon, Tom; De Abreu, Roger; Mueller, Derek; Vachon, Paris; Wolfe, John

    2011-11-01

    Environment Canada's Integrated Satellite Tracking of Pollution (ISTOP) program uses RADARSAT-2 data to vector pollution surveillance assets to areas where oil discharges/spills are suspected in support of enforcement and/or cleanup efforts. RADARSAT-2's new imaging capabilities and ground system promises significant improvement's in ISTOP's ability to detect and report on oil pollution. Of specific interest is the potential of dual polarization ScanSAR data acquired with VV polarization to improve the detection of oil pollution compared to data acquired with HH polarization, and with VH polarization to concurrently detect ship targets. A series of 101 RADARSAT-2 fine quad images were acquired over Coal Oil Point, near Santa Barbara, California where a seep field naturally releases hydrocarbons. The oil and gas releases in this region are visible on the sea surface and have been well documented allowing for the remote sensing of a constant source of oil at a fixed location. Although the make-up of the oil seep field could be different from that of oil spills, it provides a representative target that can be routinely imaged under a variety of wind conditions. Results derived from the fine quad imagery with a lower noise floor were adjusted to mimic the noise floor limitations of ScanSAR. In this study it was found that VV performed better than HH for oil detection, especially at higher incidence angles.

  4. Incidental detection of colorectal lesions by FDG PET/CT scans in melanoma patients.

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    Young, Christopher J; Zahid, Assad; Choy, Ian; Thompson, John F; Saw, Robyn P M

    2017-11-01

    Increased use of PET/CT scans in oncology patients has raised detection of Colorectal incidentalomas (CIs). The frequency and diagnostic outcomes of identifying these lesions in melanoma patients have not previously been studied. This studies primary objective was to determine the prevalence of CIs found on PET/CT scans in melanoma patients. The secondary objectives were to correlate the PET/CT findings with the pathology found at colonoscopy, and identify which patients were referred for colonoscopy. A retrospective analysis of patients identified from the prospectively collected research database of Melanoma Institute Australia. 2509 patients with melanoma underwent PET/CT scans between 2001 and 2013. The prevalence of CIs, the correlation of lesions, and the survival of patients who underwent colonoscopy versus patients who did not were analyzed. The prevalence of CIs in melanoma patients who had PET/CT scans was 3.2%. Forty-five of the 81 (56%) patients with CIs underwent colonoscopy. Of these, premalignant or malignant disease was found in 58%. Patients with previous metastatic melanoma were significantly less likely to be referred for colonoscopy. Patients undergoing colonoscopy had significantly better survival, as did those without previous distant metastases before the CIs were found, and those without any metastases at the time the CIs were found. These factors were not significant on multivariate analysis. The prevalence of incidental colorectal lesions identified on PET/CT scans in melanoma patients was found to be equivalent to that in the general cancer population. Patients undergoing colonoscopy had better survival than those who did not. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  5. COLD-PCR enhanced melting curve analysis improves diagnostic accuracy for KRAS mutations in colorectal carcinoma.

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    Pritchard, Colin C; Akagi, Laura; Reddy, Poluru L; Joseph, Loren; Tait, Jonathan F

    2010-11-26

    KRAS mutational analysis is the standard of care prior to initiation of treatments targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer. Sensitive methods are required to reliably detect KRAS mutations in tumor samples due to admixture with non-mutated cells. Many laboratories have implemented sensitive tests for KRAS mutations, but the methods often require expensive instrumentation and reagents, parallel reactions, multiple steps, or opening PCR tubes. We developed a highly sensitive, single-reaction, closed-tube strategy to detect all clinically significant mutations in KRAS codons 12 and 13 using the Roche LightCycler® instrument. The assay detects mutations via PCR-melting curve analysis with a Cy5.5-labeled sensor probe that straddles codons 12 and 13. Incorporating a fast COLD-PCR cycling program with a critical denaturation temperature (Tc) of 81°C increased the sensitivity of the assay >10-fold for the majority of KRAS mutations. We compared the COLD-PCR enhanced melting curve method to melting curve analysis without COLD-PCR and to traditional Sanger sequencing. In a cohort of 61 formalin-fixed paraffin-embedded colorectal cancer specimens, 29/61 were classified as mutant and 28/61 as wild type across all methods. Importantly, 4/61 (6%) were re-classified from wild type to mutant by the more sensitive COLD-PCR melting curve method. These 4 samples were confirmed to harbor clinically-significant KRAS mutations by COLD-PCR DNA sequencing. Five independent mixing studies using mutation-discordant pairs of cell lines and patient specimens demonstrated that the COLD-PCR enhanced melting curve assay could consistently detect down to 1% mutant DNA in a wild type background. We have developed and validated an inexpensive, rapid, and highly sensitive clinical assay for KRAS mutations that is the first report of COLD-PCR combined with probe-based melting curve analysis. This assay significantly improved diagnostic

  6. COLD-PCR enhanced melting curve analysis improves diagnostic accuracy for KRAS mutations in colorectal carcinoma

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    Joseph Loren

    2010-11-01

    Full Text Available Abstract Background KRAS mutational analysis is the standard of care prior to initiation of treatments targeting the epidermal growth factor receptor (EGFR in patients with metastatic colorectal cancer. Sensitive methods are required to reliably detect KRAS mutations in tumor samples due to admixture with non-mutated cells. Many laboratories have implemented sensitive tests for KRAS mutations, but the methods often require expensive instrumentation and reagents, parallel reactions, multiple steps, or opening PCR tubes. Methods We developed a highly sensitive, single-reaction, closed-tube strategy to detect all clinically significant mutations in KRAS codons 12 and 13 using the Roche LightCycler® instrument. The assay detects mutations via PCR-melting curve analysis with a Cy5.5-labeled sensor probe that straddles codons 12 and 13. Incorporating a fast COLD-PCR cycling program with a critical denaturation temperature (Tc of 81°C increased the sensitivity of the assay >10-fold for the majority of KRAS mutations. Results We compared the COLD-PCR enhanced melting curve method to melting curve analysis without COLD-PCR and to traditional Sanger sequencing. In a cohort of 61 formalin-fixed paraffin-embedded colorectal cancer specimens, 29/61 were classified as mutant and 28/61 as wild type across all methods. Importantly, 4/61 (6% were re-classified from wild type to mutant by the more sensitive COLD-PCR melting curve method. These 4 samples were confirmed to harbor clinically-significant KRAS mutations by COLD-PCR DNA sequencing. Five independent mixing studies using mutation-discordant pairs of cell lines and patient specimens demonstrated that the COLD-PCR enhanced melting curve assay could consistently detect down to 1% mutant DNA in a wild type background. Conclusions We have developed and validated an inexpensive, rapid, and highly sensitive clinical assay for KRAS mutations that is the first report of COLD-PCR combined with probe

  7. Automated kidney detection for 3D ultrasound using scan line searching

    Science.gov (United States)

    Noll, Matthias; Nadolny, Anne; Wesarg, Stefan

    2016-04-01

    Ultrasound (U/S) is a fast and non-expensive imaging modality that is used for the examination of various anatomical structures, e.g. the kidneys. One important task for automatic organ tracking or computer-aided diagnosis is the identification of the organ region. During this process the exact information about the transducer location and orientation is usually unavailable. This renders the implementation of such automatic methods exceedingly challenging. In this work we like to introduce a new automatic method for the detection of the kidney in 3D U/S images. This novel technique analyses the U/S image data along virtual scan lines. Here, characteristic texture changes when entering and leaving the symmetric tissue regions of the renal cortex are searched for. A subsequent feature accumulation along a second scan direction produces a 2D heat map of renal cortex candidates, from which the kidney location is extracted in two steps. First, the strongest candidate as well as its counterpart are extracted by heat map intensity ranking and renal cortex size analysis. This process exploits the heat map gap caused by the renal pelvis region. Substituting the renal pelvis detection with this combined cortex tissue feature increases the detection robustness. In contrast to model based methods that generate characteristic pattern matches, our method is simpler and therefore faster. An evaluation performed on 61 3D U/S data sets showed, that in 55 cases showing none or minor shadowing the kidney location could be correctly identified.

  8. Application of scanning laser Doppler vibrometry for delamination detection in composite structures

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    Kudela, Pawel; Wandowski, Tomasz; Malinowski, Pawel; Ostachowicz, Wieslaw

    2017-12-01

    In this paper application of scanning laser Doppler vibrometry for delamination detection in composite structures was presented. Delamination detection was based on a guided wave propagation method. In this papers results from numerical and experimental research were presented. In the case of numerical research, the Spectral Element Method (SEM) was utilized, in which a mesh was composed of 3D spectral elements. SEM model included also a piezoelectric transducer. In the experimental research guided waves were excited using the piezoelectric transducer whereas the sensing process was conducted using scanning laser Doppler vibrometer (SLDV). Analysis of guided wave propagation and its interaction with delamination was based on a full wavefield approach. Attention was focused on interactions of guided waves with delamination manifested by A0 mode reflection, A0 mode entrapment, and S0/A0 mode conversion. Delamination was simulated by a teflon insert located between plies of composite material. Results of interaction with symmetrically and nonsymmetrical placed delamination (in respect to the composite sample thickness) were presented. Moreover, the authors investigated different size of delaminations. Damage detection was based on a new signal processing algorithm proposed by the authors. In this approach the weighted RMS was utilized selectively. It means that the summation in RMS formula was performed only for a specially selected time instances. Results for simple composite panels, panel with honeycomb core, and real stiffened composite panel from the aircraft were presented.

  9. Combined frequency modulated atomic force microscopy and scanning tunneling microscopy detection for multi-tip scanning probe microscopy applications

    Science.gov (United States)

    Morawski, Ireneusz; Spiegelberg, Richard; Korte, Stefan; Voigtländer, Bert

    2015-12-01

    A method which allows scanning tunneling microscopy (STM) tip biasing independent of the sample bias during frequency modulated atomic force microscopy (AFM) operation is presented. The AFM sensor is supplied by an electronic circuit combining both a frequency shift signal and a tunneling current signal by means of an inductive coupling. This solution enables a control of the tip potential independent of the sample potential. Individual tip biasing is specifically important in order to implement multi-tip STM/AFM applications. An extensional quartz sensor (needle sensor) with a conductive tip is applied to record simultaneously topography and conductivity of the sample. The high resonance frequency of the needle sensor (1 MHz) allows scanning of a large area of the surface being investigated in a reasonably short time. A recipe for the amplitude calibration which is based only on the frequency shift signal and does not require the tip being in contact is presented. Additionally, we show spectral measurements of the mechanical vibration noise of the scanning system used in the investigations.

  10. High resolution surface scanning of Thick-GEM for single photo-electron detection

    Science.gov (United States)

    Hamar, G.; Varga, D.

    2012-12-01

    An optical system for high resolution scanning of TGEM UV photon detection systems is introduced. The structure exploits the combination of a single Au-coated TGEM under study, and an asymmetric MWPC (Close Cathode Chamber) as post-amplification stage. A pulsed UV LED source with emission down to 240 nm has been focused to a spot of 0.07 mm on the TGEM surface, and single photo-electron charge spectra has been recorded over selected two dimensional regions. This way, the TGEM gain (order of 10-100) and TGEM photo-electron detection efficiency is clearly separated, unlike in case of continuous illumination. The surface structure connected to the TGEM photon detection is well observable, including inefficiencies in the holes and at the symmetry points between holes. The detection efficiency as well as the gas gain are fluctuating from hole to hole. The gain is constant in the hexagon around any hole, pointing to the fact that the gain depends on hole geometry, and less on the position where the electron enters. The detection probability map strongly changes with the field strength above the TGEM surface, in relation to the change of the actual surface field configuration. The results can be confronted with position-dependent simulations of TGEM electron transfer and gas multiplication.

  11. EGFR and KRAS Gene Mutations in 754 Patients with Resectable Stage I-IIIa Non-small Cell Lung Cancer and Its Clinical Significance

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    Jing ZHAO

    2017-09-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR and KRAS gene are important driver genes of non-small cell lung cancer (NSCLC. The studies are mainly focused on detection of EGFR gene for advanced NSCLC, and the mutation feature of EGFR and KRAS gene in early NSCLC tissue is unknown. This study aims to investigate the mutations of EGFR and KRAS gene in NSCLC, and the relationship between the genotype and clinicopathologic features. Methods The hotspot mutations in EGFR and KRAS gene in 754 tissue samples of stage I-IIIa NSCLC from Department of Pathology, Peking Union Medical College Hospital were detected by modified amplification refractory mutation system (ARMS real-time PCR kit, and analyzed their correlation with clinical variables. Results The hotspot mutation rates in EGFR and KRAS were 34.5% and 13.1% respectively, and there were EGFR-KRAS double mutations in 3 samples. The mutation rate of EGFR was higher in females than that in males (39.5% vs 29.4%, P=0.076, significantly increased in adenocarcinomas (38.7% compared to that in the other forms of NSCLC (P<0.01, but still lower than that reported in some Asian studies of advanced adenocarcinoma (-50%. Meanwhile, the mutation rate of KRAS was remarkably higher in males than that in females (16.6% vs 9%, P=0.048, increased in adenocarcinomas compared to that in the other forms of NSCLC, but the difference was not significant (P=0.268. Samples harbored EGFR mutation were younger than those harbored KRAS mutation (P=0.031,5, and had significant difference in gender between the two groups (P<0.01. Conclusion The mutation rate of EGFR in stag I-IIIa NSCLC patients was lower than that in advanced NSCLC patients. And the percentage of the NSCLC patients with EGFR-KRAS double mutations is 0.9%.

  12. KRAS mutation testing in borderline ovarian tumors and low-grade ovarian carcinomas with a rapid, fully integrated molecular diagnostic system.

    Science.gov (United States)

    Sadlecki, Pawel; Antosik, Paulina; Grzanka, Dariusz; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

    2017-10-01

    Epithelial ovarian neoplasms are a heterogeneous group of tumors, including various malignancies with distinct clinicopathologic and molecular features. Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors. Implementation of targeted therapeutic strategies requires access to highly specific and highly sensitive diagnostic tests for rapid determination of mutation status. One candidate for such test is fully integrated, real-time polymerase chain reaction-based Idylla™ system for quick and simple detection of KRAS mutations in formaldehyde fixed-paraffin embedded tumor samples. The primary aim of this study was to verify whether fully integrated real-time polymerase chain reaction-based Idylla system may be useful in determination of KRAS mutation status in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 37 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland) between January 2009 and June 2012. Based on histopathological examination of surgical specimens, 30 lesions were classified as low-grade ovarian carcinomas and 7 as borderline ovarian tumors. Seven patients examined with Idylla KRAS Mutation Test tested positive for KRAS mutation. No statistically significant association was found between the incidence of KRAS mutations and histopathological type of ovarian tumors. Mean survival of the study subjects was 48.51 months (range 3-60 months). Presence of KRAS mutation did not exert a significant effect on the duration of survival in our series. Our findings suggest that Idylla KRAS Mutation Test may be a useful tool for rapid detection of KRAS mutations in ovarian tumor tissue.

  13. Computer-aided detection and quantification of cavitary tuberculosis from CT scans.

    Science.gov (United States)

    Xu, Ziyue; Bagci, Ulas; Kubler, Andre; Luna, Brian; Jain, Sanjay; Bishai, William R; Mollura, Daniel J

    2013-11-01

    To present a computer-aided detection tool for identifying, quantifying, and evaluating tuberculosis (TB) cavities in the infected lungs from computed tomography (CT) scans. The authors' proposed method is based on a novel shape-based automated detection algorithm on CT scans followed by a fuzzy connectedness (FC) delineation procedure. In order to assess interaction between cavities and airways, the authors first roughly identified air-filled structures (airway, cavities, esophagus, etc.) by thresholding over Hounsfield unit of CT image. Then, airway and cavity structure detection was conducted within the support vector machine classification algorithm. Once airway and cavities were detected automatically, the authors extracted airway tree using a hybrid multiscale approach based on novel affinity relations within the FC framework and segmented cavities using intensity-based FC algorithm. At final step, the authors refined airway structures within the local regions of FC with finer control. Cavity segmentation results were compared to the reference truths provided by expert radiologists and cavity formation was tracked longitudinally from serial CT scans through shape and volume information automatically determined through the authors' proposed system. Morphological evolution of the cavitary TB were analyzed accordingly with this process. Finally, the authors computed the minimum distance between cavity surface and nearby airway structures by using the linear time distance transform algorithm to explore potential role of airways in cavity formation and morphological evolution. The proposed methodology was qualitatively and quantitatively evaluated on pulmonary CT images of rabbits experimentally infected with TB, and multiple markers such as cavity volume, cavity surface area, minimum distance from cavity surface to the nearest bronchial-tree, and longitudinal change of these markers (namely, morphological evolution of cavities) were determined precisely. While

  14. SINGLE TREE DETECTION FROM AIRBORNE LASER SCANNING DATA USING A MARKED POINT PROCESS BASED METHOD

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    J. Zhang

    2013-05-01

    Full Text Available Tree detection and reconstruction is of great interest in large-scale city modelling. In this paper, we present a marked point process model to detect single trees from airborne laser scanning (ALS data. We consider single trees in ALS recovered canopy height model (CHM as a realization of point process of circles. Unlike traditional marked point process, we sample the model in a constraint configuration space by making use of image process techniques. A Gibbs energy is defined on the model, containing a data term which judge the fitness of the model with respect to the data, and prior term which incorporate the prior knowledge of object layouts. We search the optimal configuration through a steepest gradient descent algorithm. The presented hybrid framework was test on three forest plots and experiments show the effectiveness of the proposed method.

  15. Modeling and minimizing interference from corneal birefringence in retinal birefringence scanning for foveal fixation detection.

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    Irsch, Kristina; Gramatikov, Boris; Wu, Yi-Kai; Guyton, David

    2011-07-01

    Utilizing the measured corneal birefringence from a data set of 150 eyes of 75 human subjects, an algorithm and related computer program, based on Müller-Stokes matrix calculus, were developed in MATLAB for assessing the influence of corneal birefringence on retinal birefringence scanning (RBS) and for converging upon an optical/mechanical design using wave plates ("wave-plate-enhanced RBS") that allows foveal fixation detection essentially independently of corneal birefringence. The RBS computer model, and in particular the optimization algorithm, were verified with experimental human data using an available monocular RBS-based eye fixation monitor. Fixation detection using wave-plate-enhanced RBS is adaptable to less cooperative subjects, including young children at risk for developing amblyopia.

  16. Enhanced Ratio of Signals Enables Digital Mutation Scanning for Rare Allele Detection

    Science.gov (United States)

    Castellanos-Rizaldos, Elena; Paweletz, Cloud; Song, Chen; Oxnard, Geoffrey R.; Mamon, Harvey; Jänne, Pasi A.; Makrigiorgos, G. Mike

    2016-01-01

    The use of droplet digital PCR (ddPCR) for low-level DNA mutation detection in cancer, prenatal diagnosis, and infectious diseases is growing rapidly. However, although ddPCR has been implemented successfully for detection of rare mutations at pre-determined positions, no ddPCR adaptation for mutation scanning exists. Yet, frequently, clinically relevant mutations reside on multiple sequence positions in tumor suppressor genes or complex hotspot mutations in oncogenes. Here, we describe a combination of coamplification at lower denaturation temperature PCR (COLD-PCR) with ddPCR that enables digital mutation scanning within approximately 50-bp sections of a target amplicon. Two FAM/HEX-labeled hydrolysis probes matching the wild-type sequence are used during ddPCR. The ratio of FAM/HEX-positive droplets is constant when wild-type amplicons are amplified but deviates when mutations anywhere under the FAM or HEX probes are present. To enhance the change in FAM/HEX ratio, we employed COLD-PCR cycling conditions that enrich mutation-containing amplicons anywhere on the sequence. We validated COLD-ddPCR on multiple mutations in TP53 and in EGFR using serial mutation dilutions and cell-free circulating DNA samples, and demonstrate detection down to approximately 0.2% to 1.2% mutation abundance. COLD-ddPCR enables a simple, rapid, and robust two-fluorophore detection method for the identification of multiple mutations during ddPCR and potentially can identify unknown DNA variants present in the target sequence. PMID:25772705

  17. Birt-Hogg-Dube syndrome prospectively detected by review of chest computed tomography scans.

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    Hye Jung Park

    Full Text Available Birt-Hogg-Dube syndrome (BHD is a rare disorder caused by mutations in the gene that encodes folliculin (FLCN and is inherited in an autosomal dominant manner. BHD is commonly accompanied by fibrofolliculomas, renal tumors, multiple pulmonary cysts, and spontaneous pneumothorax. The aim of this study was to detect BHD prospectively in patients undergoing chest computed tomography (CT scans and to evaluate further the characteristics of BHD in Korea.We prospectively checked and reviewed the chest CT scans obtained for 10,883 patients at Gangnam Severance Hospital, Seoul, Korea, from June 1, 2015 to May 31, 2016. Seventeen patients met the study inclusion criteria and underwent screening for FLCN mutation to confirm BHD. We analyzed the characteristics of the patients confirmed to have BHD and those for a further 6 patients who had previously been described in Korea.Six (0.06% of the 10,883 patients reviewed were diagnosed with BHD. There was no difference in demographic or clinical features between the patients with BHD (n = 6 and those without BHD (n = 11. Pneumothorax was present in 50% of the patients with BHD but typical skin and renal lesions were absent. The maximum size of the cysts in the BHD group (median 39.4 mm; interquartile range [IQR] 11.4 mm was significantly larger than that in the non-BHD group (median 15.8 mm; IQR 7.8 mm; P = 0.001. Variable morphology was seen in 100.0% of the cysts in the BHD group but in only 18.2% of the cysts in the non-BHD group (P = 0.002. Nine (95% of the total of 12 Korean patients with BHD had experienced pneumothorax. Typical skin and renal lesions were present in 20.0% of patients with BHD.Our findings suggest that BHD can be detected if chest CT scans are read in detail.

  18. Noninvasive in vivo detection and quantification of Demodex mites by confocal laser scanning microscopy.

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    Sattler, E C; Maier, T; Hoffmann, V S; Hegyi, J; Ruzicka, T; Berking, C

    2012-11-01

    In many Demodex-associated skin diseases Demodex mites are present in abundance and seem to be at least partially pathogenic. So far all diagnostic approaches such as scraping or standardized superficial skin biopsy are (semi-)invasive and may cause discomfort to the patient. To see whether confocal laser scanning microscopy (CLSM) - a noninvasive method for the visualization of superficial skin layers - is able to detect and quantify D. folliculorum in facial skin of patients with rosacea. Twenty-five patients (34-72 years of age) with facial rosacea and 25 age- and sex-matched normal controls were examined by CLSM. Mosaics of 8 × 8 mm and 5 × 5 mm were created by scanning horizontal layers of lesional skin and quantification of mites per follicle and per area as well as follicles per area was performed. In all patients D. folliculorum could be detected by CLSM and presented as roundish or lengthy cone-shaped structures. CLSM allowed the quantification of Demodex mites and revealed significant differences (P Demodex mites noninvasively in facial skin of patients with rosacea. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  19. Detecting Changes in Forest Structure over Time with Bi-Temporal Terrestrial Laser Scanning Data

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    Timo Melkas

    2012-10-01

    Full Text Available Changes to stems caused by natural forces and timber harvesting constitute an essential input for many forestry-related applications and ecological studies, especially forestry inventories based on the use of permanent sample plots. Conventional field measurement is widely acknowledged as being time-consuming and labor-intensive. More automated and efficient alternatives or supportive methods are needed. Terrestrial laser scanning (TLS has been demonstrated to be a promising method in forestry field inventories. Nevertheless, the applicability of TLS in recording changes in the structure of forest plots has not been studied in detail. This paper presents a fully automated method for detecting changes in forest structure over time using bi-temporal TLS data. The developed method was tested on five densely populated forest plots including 137 trees and 50 harvested trees in point clouds. The present study demonstrated that 90 percent of tree stem changes could be automatically located from single-scan TLS data. These changes accounted for 92 percent of the changed basal area. The results indicate that the processing of TLS data collected at different times to detect tree stem changes can be fully automated.

  20. Scanning elastic scattering spectroscopy detects metastatic breast cancer in sentinel lymph nodes

    Science.gov (United States)

    Austwick, Martin R.; Clark, Benjamin; Mosse, Charles A.; Johnson, Kristie; Chicken, D. Wayne; Somasundaram, Santosh K.; Calabro, Katherine W.; Zhu, Ying; Falzon, Mary; Kocjan, Gabrijela; Fearn, Tom; Bown, Stephen G.; Bigio, Irving J.; Keshtgar, Mohammed R. S.

    2010-07-01

    A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic plate. Stepper motors raster-scanned a fiber-optic probe over the plate to interrogate the node's cut surface, creating a 20×20 grid of spectra. These spectra were analyzed to create a map of cancer risk across the node surface. Rules were developed to convert these maps to a prediction for the presence of cancer in the node. Using these analyses, a leave-one-out cross-validation to optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69% for detection of clinically relevant metastases (71% for macrometastases) and a specificity of 96%, comparable to literature results for touch imprint cytology, a standard technique for intraoperative diagnosis. ESS has the advantage of not requiring a pathologist to review the tissue sample.

  1. Defect Detection of Fiberglass Composite Laminates (FGCL) with Ultrasonic A-Scan Signal Measurement

    Science.gov (United States)

    Mahmod, M. F.; Abu Bakar, Elmi; Othman, A. R.

    2016-02-01

    Fiberglass composite laminates are widely used in many industries, due to its advantages of high specific strength and high specific modulus. Invisible defect such as delamination and inclusion may cause composite structural failure. Therefore, several research on ultrasonic testing for composite material defect detection have been done for the past few years. However, improper parameter setup may lead to significant error to determine the behavior of defects. In this paper, the intensive study on defect detection with ultrasonic single crystal immersion transducer has been conducted. In general, the defects detection thru acquired signal is determine the behavior of defects through the certain ultrasonic parameter setup such as sound velocity, pulse width, gain, sampling rate and transducer distance with specimen surface. Furthermore, an A-scan signal interpretation for FGCL defect detection is demonstrated and illustrated. This research is focusing on for FGCL with maximum thickness up to 10 mm in ambient temperature. The result shows an appropriate ultrasonic parameter will result better signal interpretation analysis.

  2. Automatic Detection of Small Single Trees in the Forest-Tundra Ecotone Using Airborne Laser Scanning

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    Nadja Stumberg

    2014-10-01

    Full Text Available A large proportion of Norway’s land area is occupied by the forest-tundra ecotone. The vegetation of this temperature-sensitive ecosystem between mountain forest and the alpine zone is expected to be highly affected by climate change and effective monitoring techniques are required. For the detection of such small pioneer trees, airborne laser scanning (ALS has been proposed as a useful tool employing laser height data. The objective of this study was to assess the capability of an unsupervised classification for automated monitoring programs of small individual trees using high-density ALS data. Field and ALS data were collected along a 1500 km long transect stretching from northern to southern Norway. Different laser and tree height thresholds were tested in various combinations within an unsupervised classification of tree and nontree raster cells employing different cell sizes. Suitable initial cell sizes for the exclusion of large treeless areas as well as an optimal cell size for tree cell detection were determined. High rates of successful tree cell detection involved high levels of commission error at lower laser height thresholds, however, exceeding the 20 cm laser height threshold, the rates of commission error decreased substantially with a still satisfying rate of successful tree cell detection.

  3. Detecting benzoyl peroxide in wheat flour by line-scan macro-scale Raman chemical imaging

    Science.gov (United States)

    Qin, Jianwei; Kim, Moon S.; Chao, Kuanglin; Gonzalez, Maria; Cho, Byoung-Kwan

    2017-05-01

    Excessive use of benzoyl peroxide (BPO, a bleaching agent) in wheat flour can destroy flour nutrients and cause diseases to consumers. A macro-scale Raman chemical imaging method was developed for direct detection of BPO mixed in the wheat flour. A 785 nm line laser was used in a line-scan Hyperspectral Raman imaging system. Raman images were collected from wheat flour mixed with BPO at eight concentrations (w/w) from 50 to 6,400 ppm. A sample holder (150×100×2 mm3) was used to present a thin layer (2 mm thick) of the powdered sample for image acquisition. A baseline correction method was used to correct the fluctuating fluorescence signals from the wheat flour. To isolate BPO particles from the flour background, a simple thresholding method was applied to the single-band fluorescence-free images at a unique Raman peak wavenumber (i.e., 1001 cm-1) preselected for the BPO detection. Chemical images were created to detect and map the BPO particles. Limit of detection for the BPO was estimated in the order of 50 ppm, which is on the same level with regulatory standards.

  4. Evaluating the performance of selection scans to detect selective sweeps in domestic dogs.

    Science.gov (United States)

    Schlamp, Florencia; van der Made, Julian; Stambler, Rebecca; Chesebrough, Lewis; Boyko, Adam R; Messer, Philipp W

    2016-01-01

    Selective breeding of dogs has resulted in repeated artificial selection on breed-specific morphological phenotypes. A number of quantitative trait loci associated with these phenotypes have been identified in genetic mapping studies. We analysed the population genomic signatures observed around the causal mutations for 12 of these loci in 25 dog breeds, for which we genotyped 25 individuals in each breed. By measuring the population frequencies of the causal mutations in each breed, we identified those breeds in which specific mutations most likely experienced positive selection. These instances were then used as positive controls for assessing the performance of popular statistics to detect selection from population genomic data. We found that artificial selection during dog domestication has left characteristic signatures in the haplotype and nucleotide polymorphism patterns around selected loci that can be detected in the genotype data from a single population sample. However, the sensitivity and accuracy at which such signatures were detected varied widely between loci, the particular statistic used and the choice of analysis parameters. We observed examples of both hard and soft selective sweeps and detected strong selective events that removed genetic diversity almost entirely over regions >10 Mbp. Our study demonstrates the power and limitations of selection scans in populations with high levels of linkage disequilibrium due to severe founder effects and recent population bottlenecks. © 2015 John Wiley & Sons Ltd.

  5. Impact of number of repeated scans on model observer performance for a low-contrast detection task in computed tomography.

    Science.gov (United States)

    Ma, Chi; Yu, Lifeng; Chen, Baiyu; Favazza, Christopher; Leng, Shuai; McCollough, Cynthia

    2016-04-01

    Channelized Hotelling observer (CHO) models have been shown to correlate well with human observers for several phantom-based detection/classification tasks in clinical computed tomography (CT). A large number of repeated scans were used to achieve an accurate estimate of the model's template. The purpose of this study is to investigate how the experimental and CHO model parameters affect the minimum required number of repeated scans. A phantom containing 21 low-contrast objects was scanned on a 128-slice CT scanner at three dose levels. Each scan was repeated 100 times. For each experimental configuration, the low-contrast detectability, quantified as the area under receiver operating characteristic curve, [Formula: see text], was calculated using a previously validated CHO with randomly selected subsets of scans, ranging from 10 to 100. Using [Formula: see text] from the 100 scans as the reference, the accuracy from a smaller number of scans was determined. Our results demonstrated that the minimum number of repeated scans increased when the radiation dose level decreased, object size and contrast level decreased, and the number of channels increased. As a general trend, it increased as the low-contrast detectability decreased. This study provides a basis for the experimental design of task-based image quality assessment in clinical CT using CHO.

  6. Clinical experience with the radioisotope varicocele scan as a screening method for the detection of subclinical varicoceles

    Energy Technology Data Exchange (ETDEWEB)

    Wheatley, J.K.; Fajman, W.A.; Witten, F.R.

    1982-07-01

    The association of varicoceles and subfertility has been well documented. Although varicoceles remain the most common surgically correctable cause of male infertility the diagnosis of small varicoceles remains a challenge. We evaluated 40 men with an isotope blood pooling scan. Seven volunteers served as either positive or negative controls. Complete correlation between physical findings and the isotope scan was found. The 6 patients with obvious clinical varicoceles and a stress pattern on semen analysis all had positive scans. The 18 patients with a stress pattern and who were clinically suspected of having a varicocele all had positive scans. Of 9 patients evaluated for infertility with a stress pattern but no clinical evidence of varicocele 6 had positive scans. We believe that the isotope scan will prove to be a useful procedure in the detection of nonpalpable varicoceles in selected subfertile men.

  7. The differentially mutational spectra of the APC, K-ras, and p53 genes in sporadic colorectal cancers from Taiwanese patients.

    Science.gov (United States)

    Wang, Jaw-Yuan; Hsieh, Jan-Sing; Lu, Chien-Yu; Yu, Fang-Jung; Wu, Jeng-Yih; Chen, Fang-Ming; Huang, Che-Jen; Lin, Shiu-Ru

    2007-12-01

    Adenomatous polyposis coli (APC), K-ras and p53 gene mutations are the most common genetic alterations present in colorectal cancer (CRC). The aim of this study was to analyze tumor mutation frequencies and spectra in a large cohort of Taiwanese patients with CRC. APC, K-ras, and p53 gene mutations in primary tumor tissues and their paired normal tissues of 123 CRC patients were detected by polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing. Of these 123 CRC patients, 43.1%, 44.7%, 35% of tumor tissue specimens presented mutations in APC, K-ras, and p53 genes, respectively. Overall, gene mutations in APC, K-ras and/or p53 were present in 78% (96/123) of tumor tissues. Among 96 CRC patients harboring gene mutations, 49 (51%) contained mutations of at least two different genes and 47 (49%) contained mutations of one gene only. The most common combination of gene mutations was APC and K-ras mutations (21.9%), followed by K-ras and p53 mutations (12.5%) and then APC and p53 mutations (10.4%). In addition, there were only 6.3% (6/96) of tumor tissues from CRC patients simultaneously containing mutations of APC, K-ras and p53 genes. The most common mutation spectrum of these genes was missense mutations, at a frequency of 38.8%, 92.7% and 70.5% for APC, K-ras and p53 genes, respectively. These data support that the frequencies and patterns of somatic mutation of the APC, Kras and p53 genes in CRCs are considerably variable and distinct among populations, for which the interaction between exogenous environmental factors and endogenous gene alterations may be important determinants.

  8. Kras mutations increase telomerase activity and targeting telomerase is a promising therapeutic strategy for Kras-mutant NSCLC

    OpenAIRE

    Liu, Weiran; Yin, Yuesong; Wang, Jun; Shi, Bowen; Zhang, Lianmin; Qian, Dong; Li, Chenguang; Zhang, Hua; Wang, Shengguang; Zhu, Jinfang; Gao, Liuwei; Zhang, Qiang; Jia, Bin; Hao, Ligang; Wang, Changli

    2016-01-01

    As shortened telomeres inhibit tumor formation and prolong life span in a KrasG12D mouse lung cancer model, we investigated the implications of telomerase in Kras-mutant NSCLC. We found that Kras mutations increased TERT (telomerase reverse transcriptase) mRNA expression and telomerase activity and telomere length in both immortalized bronchial epithelial cells (BEAS-2B) and lung adenocarcinoma cells (Calu-3). MEK inhibition led to reduced TERT expression and telomerase activity. Furthermore,...

  9. STREAMED VERTICAL RECTANGLE DETECTION IN TERRESTRIAL LASER SCANS FOR FACADE DATABASE PRODUCTION

    Directory of Open Access Journals (Sweden)

    J. Demantké

    2012-07-01

    Full Text Available A reliable and accurate facade database would be a major asset in applications such as localization of autonomous vehicles, registration and fine building modeling. Mobile mapping devices now provide the data required to create such a database, but efficient methods should be designed in order to tackle the enormous amount of data collected by such means (a million point per second for hours of acquisition. Another important limitation is the presence of numerous objects in urban scenes of many different types. This paper proposes a method that overcomes these two issues: – The facade detection algorithm is streamed: the data is processed in the order it was acquired. More precisely, the input data is split into overlapping blocks which are analysed in turn to extract facade parts. Close overlapping parts are then merged in order to recover the full facade rectangle. – The geometry of the neighborhood of each point is analysed to define a probability that the point belongs to a vertical planar patch. This probability is then injected in a RANdom SAmple Consensus (RANSAC algorithm both in the sampling step and in the hypothesis validation, in order to favour the most reliable candidates. This ensures much more robustness against outliers during the facade detection. This way, the main vertical rectangles are detected without any prior knowledge about the data. The only assumptions are that the facades are roughly planar and vertical. The method has been successfully tested on a large dataset in Paris. The facades are detected despite the presence of trees occluding large areas of some facades. The robustness and accuracy of the detected facade rectangles makes them useful for localization applications and for registration of other scans of the same city or of entire city models.

  10. A novel versatile microbiosensor for local hydrogen detection by means of scanning photoelectrochemical microscopy.

    Science.gov (United States)

    Zhao, Fangyuan; Conzuelo, Felipe; Hartmann, Volker; Li, Huaiguang; Stapf, Stefanie; Nowaczyk, Marc M; Rögner, Matthias; Plumeré, Nicolas; Lubitz, Wolfgang; Schuhmann, Wolfgang

    2017-08-15

    The development of a versatile microbiosensor for hydrogen detection is reported. Carbon-based microelectrodes were modified with a [NiFe]-hydrogenase embedded in a viologen-modified redox hydrogel for the fabrication of a sensitive hydrogen biosensor By integrating the microbiosensor in a scanning photoelectrochemical microscope, it was capable of serving simultaneously as local light source to initiate photo(bio)electrochemical reactions while acting as sensitive biosensor for the detection of hydrogen. A hydrogen evolution biocatalyst based on photosystem 1-platinum nanoparticle biocomplexes embedded into a specifically designed redox polymer was used as a model for proving the capability of the developed hydrogen biosensor for the detection of hydrogen upon localized illumination. The versatility and sensitivity of the proposed microbiosensor as probe tip allows simplification of the set-up used for the evaluation of complex electrochemical processes and the rapid investigation of local photoelectrocatalytic activity of biocatalysts towards light-induced hydrogen evolution. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. A new approach for using genome scans to detect recent positive selection in the human genome.

    Directory of Open Access Journals (Sweden)

    Kun Tang

    2007-07-01

    Full Text Available Genome-wide scanning for signals of recent positive selection is essential for a comprehensive and systematic understanding of human adaptation. Here, we present a genomic survey of recent local selective sweeps, especially aimed at those nearly or recently completed. A novel approach was developed for such signals, based on contrasting the extended haplotype homozygosity (EHH profiles between populations. We applied this method to the genome single nucleotide polymorphism (SNP data of both the International HapMap Project and Perlegen Sciences, and detected widespread signals of recent local selection across the genome, consisting of both complete and partial sweeps. A challenging problem of genomic scans of recent positive selection is to clearly distinguish selection from neutral effects, given the high sensitivity of the test statistics to departures from neutral demographic assumptions and the lack of a single, accurate neutral model of human history. We therefore developed a new procedure that is robust across a wide range of demographic and ascertainment models, one that indicates that certain portions of the genome clearly depart from neutrality. Simulations of positive selection showed that our tests have high power towards strong selection sweeps that have undergone fixation. Gene ontology analysis of the candidate regions revealed several new functional groups that might help explain some important interpopulation differences in phenotypic traits.

  12. Effective Detection of Sub-Surface Archeological Features from Laser Scanning Point Clouds and Imagery Data

    Science.gov (United States)

    Fryskowska, A.; Kedzierski, M.; Walczykowski, P.; Wierzbicki, D.; Delis, P.; Lada, A.

    2017-08-01

    The archaeological heritage is non-renewable, and any invasive research or other actions leading to the intervention of mechanical or chemical into the ground lead to the destruction of the archaeological site in whole or in part. For this reason, modern archeology is looking for alternative methods of non-destructive and non-invasive methods of new objects identification. The concept of aerial archeology is relation between the presence of the archaeological site in the particular localization, and the phenomena that in the same place can be observed on the terrain surface form airborne platform. One of the most appreciated, moreover, extremely precise, methods of such measurements is airborne laser scanning. In research airborne laser scanning point cloud with a density of 5 points/sq. m was used. Additionally unmanned aerial vehicle imagery data was acquired. Test area is located in central Europe. The preliminary verification of potentially microstructures localization was the creation of digital terrain and surface models. These models gave an information about the differences in elevation, as well as regular shapes and sizes that can be related to the former settlement/sub-surface feature. The paper presents the results of the detection of potentially sub-surface microstructure fields in the forestry area.

  13. EFFECTIVE DETECTION OF SUB-SURFACE ARCHEOLOGICAL FEATURES FROM LASER SCANNING POINT CLOUDS AND IMAGERY DATA

    Directory of Open Access Journals (Sweden)

    A. Fryskowska

    2017-08-01

    Full Text Available The archaeological heritage is non-renewable, and any invasive research or other actions leading to the intervention of mechanical or chemical into the ground lead to the destruction of the archaeological site in whole or in part. For this reason, modern archeology is looking for alternative methods of non-destructive and non-invasive methods of new objects identification. The concept of aerial archeology is relation between the presence of the archaeological site in the particular localization, and the phenomena that in the same place can be observed on the terrain surface form airborne platform. One of the most appreciated, moreover, extremely precise, methods of such measurements is airborne laser scanning. In research airborne laser scanning point cloud with a density of 5 points/sq. m was used. Additionally unmanned aerial vehicle imagery data was acquired. Test area is located in central Europe. The preliminary verification of potentially microstructures localization was the creation of digital terrain and surface models. These models gave an information about the differences in elevation, as well as regular shapes and sizes that can be related to the former settlement/sub-surface feature. The paper presents the results of the detection of potentially sub-surface microstructure fields in the forestry area.

  14. Epidermal Growth Factor Receptor and K-RAS status in two cohorts of squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Van Laethem Jean-Luc

    2010-05-01

    Full Text Available Abstract Background With the availability of effective anti-EGFR therapies for various solid malignancies, such as non-cell small lung cancer, colorectal cancer and squamous cell carcinoma of the head and neck, the knowledge of EGFR and K-RAS status becomes clinically important. The aim of this study was to analyse EGFR expression, EGFR gene copy number and EGFR and K-RAS mutations in two cohorts of squamous cell carcinomas, specifically anal canal and tonsil carcinomas. Methods Formalin fixed, paraffin-embedded tissues from anal and tonsil carcinoma were used. EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. The somatic status of the EGFR gene was investigated by PCR using primers specific for exons 18 through 21. For the K-RAS gene, PCR was performed using exon 2 specific primers. Results EGFR immunoreactivity was present in 36/43 (83.7% of anal canal and in 20/24 (83.3% of tonsil squamous cell carcinomas. EGFR amplification was absent in anal canal tumours (0/23, but could be identified in 4 of 24 tonsil tumours. From 38 anal canal specimens, 26 specimens were successfully analysed for exon 18, 30 for exon 19, 34 for exon 20 and 30 for exon 21. No EGFR mutations were found in the investigated samples. Thirty samples were sequenced for K-RAS exon 2 and no mutation was identified. From 24 tonsil specimens, 22 were successfully analysed for exon 18 and all 24 specimens for exon 19, 20 and 21. No EGFR mutations were found. Twenty-two samples were sequenced for K-RAS exon 2 and one mutation c.53C > A was identified. Conclusion EGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. EGFR amplification was seen in tonsil but not in anal canal carcinomas. In our investigated panel, only one mutation in the K-RAS gene of a tonsil squamous cell carcinoma was identified

  15. EN FACE VERSUS 12-LINE RADIAL OPTICAL COHERENCE TOMOGRAPHY SCAN PATTERNS FOR DETECTION OF MACULAR FLUID IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Adam, Murtaza K; Shahlaee, Abtin; Samara, Wasim A; Maguire, Joseph I; Ho, Allen C; Hsu, Jason

    2017-08-14

    To compare fluid detection of autosegmented en face to 12-line radial spectral domain optical coherence tomography scan patterns in neovascular age-related macular degeneration. Retrospective observational case series. Sixty-seven patients (94 eyes) with neovascular age-related macular degeneration underwent autosegmented en face optical coherence tomography (with associated 304-line raster scan) and 12-line radial scan patterns. Sensitivity and specificity of fluid detection for en face scan and 12-line radial scans were determined by combining radial and 304-line raster scans as a gold standard. Two hundred and fifty-eight en face and 12-line radial spectral domain optical coherence tomography scans were interpreted. Seventy-five scans (58.1%) had fluid, whereas 54 scans (41.9%) did not. En face scan pattern fluid detection sensitivity and specificity was 89.3% and 61.1%, respectively. Twelve-line radial scan pattern fluid detection sensitivity and specificity was 97.3% and 100%, respectively. The difference in fluid detection between scan patterns was statistically significant (P = 0.01). Decreased central macular thickness was associated with false-positive (P = 0.035) and false-negative (P = 0.01) fluid detection on en face scans. En face optical coherence tomography alone is not as sensitive or specific as the 12-line radial scan pattern in detecting fluid in neovascular age-related macular degeneration. En face scans should be corroborated with other optical coherence tomography protocols to guide clinical decision making.

  16. Scanning of Open Data for Detection of Emerging Organized Crime Threats

    DEFF Research Database (Denmark)

    Pastor Pastor, Raquel; Larsen, Henrik Legind

    2017-01-01

    In fighting organized crime, open data provide an important source for both detecting emerging threats, as well as forecasting future threats. This allows the police to plan their resources and capacity for countering the threats in due time to prevent it or at least to mitigate its effects....... A vital part of a system supporting the police analysts for this purpose is an efficient and effective system for scanning the open data providing information about the relevant factors in the environment. This chapter presents the ePOOLICE project, aimed at developing a solution, the “ePOOLICE system...... in deploying such systems. One of the outcomes from the end-user evaluation of the prototype was the desire to integrate internal data to support not only strategic, but also operational analysis and investigation....

  17. Detecting Distributed Scans Using High-Performance Query-DrivenVisualization

    Energy Technology Data Exchange (ETDEWEB)

    Stockinger, Kurt; Bethel, E. Wes; Campbell, Scott; Dart, Eli; Wu,Kesheng

    2006-09-01

    Modern forensic analytics applications, like network trafficanalysis, perform high-performance hypothesis testing, knowledgediscovery and data mining on very large datasets. One essential strategyto reduce the time required for these operations is to select only themost relevant data records for a given computation. In this paper, wepresent a set of parallel algorithms that demonstrate how an efficientselection mechanism -- bitmap indexing -- significantly speeds up acommon analysist ask, namely, computing conditional histogram on verylarge datasets. We present a thorough study of the performancecharacteristics of the parallel conditional histogram algorithms. Asacase study, we compute conditional histograms for detecting distributedscans hidden in a dataset consisting of approximately 2.5 billion networkconnection records. We show that these conditional histograms can becomputed on interactive timescale (i.e., in seconds). We also show how toprogressively modify the selection criteria to narrow the analysis andfind the sources of the distributed scans.

  18. Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation.

    Science.gov (United States)

    Kadota, Kyuichi; Yeh, Yi-Chen; D'Angelo, Sandra P; Moreira, Andre L; Kuk, Deborah; Sima, Camelia S; Riely, Gregory J; Arcila, Maria E; Kris, Mark G; Rusch, Valerie W; Adusumilli, Prasad S; Travis, William D

    2014-08-01

    Multiple reports indicate that epidermal growth factor receptor (EGFR) mutations are associated with lepidic-pattern lung adenocarcinoma and that KRAS mutations are associated with invasive mucinous adenocarcinoma. We sought to investigate the association between EGFR and KRAS mutations and specific morphologic characteristics, such as predominant histologic subtype and mucinous features. Clinical data for 864 patients with resected lung adenocarcinoma that underwent molecular testing for EGFR and KRAS mutations were collected. Histologic subtyping was performed according to the IASLC/ATS/ERS lung adenocarcinoma classification, with attention given to signet-ring cell feature and extracellular mucin. EGFR mutations were detected using a polymerase chain reaction-based sizing assay, KRAS mutations were detected using Sanger sequencing, and ALK expression was detected using immunohistochemistry. Invasive mucinous adenocarcinoma was associated with KRAS mutation (Pmutation, a pure mucinous pattern was more common than a mixed mucinous/nonmucinous pattern (P=0.002). Invasive mucinous adenocarcinoma was associated with KRAS transition mutations (G→A) but not transversion mutations (G→T or G→C) compared with nonmucinous tumors (P=0.009). The lepidic-predominant group was associated with EGFR mutation compared with nonlepidic-predominant tumors (P=0.011). Extracellular mucin was associated with KRAS mutation (Pmutation (P=0.517). ALK expression was associated with signet-ring cell feature (P=0.001) but not with extracellular mucin (P=0.089). Our study shows that histologic patterns of mucin in lung adenocarcinoma-including invasive mucinous adenocarcinoma and extracellular mucin-are associated with KRAS mutation.

  19. ANALYSIS OF MUTATIONS IN KRAS AND BRAF GENES IN COLORECTAL CANCER IN RUSSIAN PATIENTS

    Directory of Open Access Journals (Sweden)

    E. E. Pisareva

    2016-01-01

    Full Text Available Mutations in KRAS and BRAF genes in 80 colorectal cancer (CRC samples from Russian patients were tested using two methods: 1 allele-specific real-time PCR (as-rt PCR and 2 wild-type blocking PCR with Sanger sequencing (WTBS. Material and methods. Sections of fresh frozen or formalin-fixed paraffin embedded tumor tissue from 80 patients were used in the study. Tumor tissue content was determined on H&E stained sections. Samples were first tested by as-rtPCR for common mutations of the KRAS gene (G12C, G12S, G12R, G12V, G12D, G12A, G13D and mutations BRAFV600E. After that samples were evaluated in PCR with oligonucleotide blocking amplification of wild-type DNA for enrichment with mutant allele followed by Sanger sequencing of the PCR DNA (WTBS method. Results. In 5 (6.3 % cases samples had low tumor tissue content (<20 %. In reconstruction experiments both methods detected 1–5 % mutant allele. Mutations of KRAS and BRAF genes were found in 37 (46 % and 3 (3.8 % of the clinical cases, respectively. Classification in to wild-type and mutant samples by both methods was in agreement in 79 (98.8 % cases. A single case with rare mutation KRASG13R was detected by WTBS, but was missed by as-rtPCR since this mutation is not included in the test. Of note, KRAS mutations were detected by both tests in two cases with low tumor content. Two cases were found with multiple mutations: one with KRASG12V and G13D, and one with KRASG13D and BRAFV600E. Conclusion. The frequency of mutations in CRC was 46 % for mutations in the KRAS gene, and 3.8 % for the BRAF. We showed 98.8% agreement in KRAS mutation detection by sensitive Sanger sequencing and as-rt PCR. The data on the frequencies of mutations are in agreement with studies in other countries. This in the first study to discover CRC case with multiple mutations KRASG13D and BRAFV600E.

  20. BRAF, PIK3CA, and HER2 Oncogenic Alterations According to KRAS Mutation Status in Advanced Colorectal Cancers with Distant Metastasis.

    Directory of Open Access Journals (Sweden)

    Soo Kyung Nam

    Full Text Available Anti-EGFR antibody-based treatment is an important therapeutic strategy for advanced colorectal cancer (CRC; despite this, several mutations--including KRAS, BRAF, and PIK3CA mutations, and HER2 amplification--are associated with the mechanisms underlying the development of resistance to anti-EGFR therapy. The aim of our study was to investigate the frequencies and clinical implications of these genetic alterations in advanced CRC.KRAS, BRAF, and PIK3CA mutations were determined by Cobas real-time polymerase chain reaction (PCR in 191 advanced CRC patients with distant metastasis. Microsatellite instability (MSI status was determined by a fragmentation assay and HER2 amplification was assessed by silver in situ hybridization. In addition, KRAS mutations were investigated by the Sanger sequencing method in 97 of 191 CRC cases.Mutations in KRAS, BRAF, and PIK3CA were found in 104 (54.5%, 6 (3.1%, and 25 (13.1% cases of advanced CRC, respectively. MSI-high status and HER2 amplification were observed in 3 (1.6% and 16 (8.4% cases, respectively. PIK3CA mutations were more frequently found in KRAS mutant type (18.3% than KRAS wild type (6.9% (P = 0.020. In contrast, HER2 amplifications and BRAF mutations were associated with KRAS wild type with borderline significance (P = 0.052 and 0.094, respectively. In combined analyses with KRAS, BRAF and HER2 status, BRAF mutations or HER2 amplifications were associated with the worst prognosis in the wild type KRAS group (P = 0.004. When comparing the efficacy of detection methods, the results of real time PCR analysis revealed 56 of 97 (57.7% CRC cases with KRAS mutations, whereas Sanger sequencing revealed 49 cases (50.5%.KRAS mutations were found in 54.5% of advanced CRC patients. Our results support that subgrouping using PIK3CA and BRAF mutation or HER2 amplification status, in addition to KRAS mutation status, is helpful for managing advanced CRC patients.

  1. Data Handling and Validation in Automated Detection of Food Toxicants Using Full Scan GC-MS and LC-MS

    NARCIS (Netherlands)

    Mol, H.; Lommen, A.; Zomer, P.; Kamp, van der H.; Lee, van der M.; Gerssen, A.

    2010-01-01

    Generic methods based on chromatography with full scan MS detection are maturing. Progress has been made in the development of software for automated detection or identification of the analytes, but this still is the bottleneck inhibiting implementation for routine analysis. Validation of

  2. Comparison of KRAS Mutation Assessment in Tumor DNA and Circulating Free DNA in Plasma and Serum Samples

    Directory of Open Access Journals (Sweden)

    Shethah R. Morgan

    2012-01-01

    Full Text Available Testing for mutations in the KRAS oncogene for patients with metastatic colorectal cancer (mCRC is generally performed using DNA from formalin-fixed paraffin-embedded tumor tissue; however, access to specimens can be limited and analysis challenging. This study assessed the identification of KRAS mutations in circulating free DNA (cfDNA using a commercially available KRAS polymerase chain reaction (PCR kit. Matched plasma, serum and tumor samples were available from 71 patients with mCRC who had received prior therapy but whose disease progressed following therapy. Yields of cfDNA from plasma and serum samples were comparable. Analyses were successful in 70/71 plasma-extracted samples (specificity: 97%, sensitivity: 31% and 67/71 serum-extracted samples (specificity: 100%, sensitivity: 25%. This study demonstrates that KRAS mutations can be detected in cfDNA using a commercially available KRAS PCR kit, confirming cfDNA as a potential alternative source of tumor DNA in a diagnostic setting if access to archival tumor specimens is limited.

  3. Computational and biochemical characterization of two partially overlapping interfaces and multiple weak-affinity K-Ras dimers

    Science.gov (United States)

    Prakash, Priyanka; Sayyed-Ahmad, Abdallah; Cho, Kwang-Jin; Dolino, Drew M.; Chen, Wei; Li, Hongyang; Grant, Barry J.; Hancock, John F.; Gorfe, Alemayehu A.

    2017-01-01

    Recent studies found that membrane-bound K-Ras dimers are important for biological function. However, the structure and thermodynamic stability of these complexes remained unknown because they are hard to probe by conventional approaches. Combining data from a wide range of computational and experimental approaches, here we describe the structure, dynamics, energetics and mechanism of assembly of multiple K-Ras dimers. Utilizing a range of techniques for the detection of reactive surfaces, protein-protein docking and molecular simulations, we found that two largely polar and partially overlapping surfaces underlie the formation of multiple K-Ras dimers. For validation we used mutagenesis, electron microscopy and biochemical assays under non-denaturing conditions. We show that partial disruption of a predicted interface through charge reversal mutation of apposed residues reduces oligomerization while introduction of cysteines at these positions enhanced dimerization likely through the formation of an intermolecular disulfide bond. Free energy calculations indicated that K-Ras dimerization involves direct but weak protein-protein interactions in solution, consistent with the notion that dimerization is facilitated by membrane binding. Taken together, our atomically detailed analyses provide unique mechanistic insights into K-Ras dimer formation and membrane organization as well as the conformational fluctuations and equilibrium thermodynamics underlying these processes.

  4. Structural damage detection using higher-order finite elements and a scanning laser vibrometer

    Science.gov (United States)

    Jin, Si

    In contrast to conventional non-destructive evaluation methods, dynamics-based damage detection methods are capable of rapid integrity evaluation of large structures and have received considerable attention from aerospace, mechanical, and civil engineering communities in recent years. However, the identifiable damage size using dynamics-based methods is determined by the number of sensors used, level of measurement noise, accuracy of structural models, and signal processing techniques. In this thesis we study dynamics of structures with damage and then derive and experimentally verify new model-independent structural damage detection methods that can locate small damage to structures. To find sensitive damage detection parameters we develop a higher-order beam element that enforces the continuity of displacements, slopes, bending moments, and shear forces at all nodes, and a higher-order rectangular plate element that enforces the continuity of displacements, slopes, and bending and twisting moments at all nodes. These two elements are used to study the dynamics of beams and plates. Results show that high-order spatial derivatives of high-frequency modes are important sensitive parameters that can locate small structural damage. Unfortunately the most powerful and popular structural modeling technique, the finite element method, is not accurate in predicting high-frequency responses. Hence, a model-independent method using dynamic responses obtained from high density measurements is concluded to be the best approach. To increase measurement density and reduce noise a Polytec PI PSV-200 scanning laser vibrometer is used to provide non-contact, dense, and accurate measurements of structural vibration velocities. To avoid the use of structural models and to extract sensitive detection parameters from experimental data, a brand-new structural damage detection method named BED (Boundary-Effect Detection) is developed for pinpointing damage locations using Operational

  5. Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection.

    Science.gov (United States)

    Mwanza, Jean-Claude; Warren, Joshua L; Hochberg, Jessica T; Budenz, Donald L; Chang, Robert T; Ramulu, Pradeep Y

    2015-01-01

    To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. One hundred ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike's information criterion (AIC), and prediction confidence interval lengths. For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDx-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT×NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single-variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAP-FDT, and interaction GDx-TSNIT×NAP-FDT consistently provided better discriminating abilities for detecting early, moderate, and severe glaucoma than the best single-variable models. The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDx-TSNIT×NAP-FDT provides the best glaucoma prediction compared with all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared with using GDx or FDT alone.

  6. Quantitative Detection of Benzoyl Peroxide in Wheat Flour Using Line-Scan Macroscale Raman Chemical Imaging.

    Science.gov (United States)

    Qin, Jianwei; Kim, Moon S; Chao, Kuanglin; Gonzalez, Maria; Cho, Byoung-Kwan

    2017-11-01

    A high-throughput Raman chemical imaging method was developed for direct inspection of benzoyl peroxide (BPO) mixed in wheat flour. A 5 W, 785 nm line laser (240 mm long and 1 mm wide) was used as a Raman excitation source in a push-broom Raman imaging system. Hyperspectral Raman images were collected in a wavenumber range of 103-2881 cm-1 from dry wheat flour mixed with BPO at eight concentrations (w/w) from 50 to 6400 ppm. A sample holder with a sampling volume of 150 × 100 × 2 mm3 was used to present a thin layer (2 mm thick) of the powdered sample for line-scan image acquisition with a spatial resolution of 0.2 mm. A baseline correction method based on adaptive iteratively reweighted penalized least squares was used to remove the fluctuating fluorescence signals from the wheat flour. To isolate BPO particles from the flour background, a simple thresholding method was applied to the single-band fluorescence-free images at a unique Raman peak wavenumber (i.e., 1001 cm-1) preselected for the BPO detection. Chemical images were created to detect and map the BPO particles. Limit of detection for the BPO was estimated in the order of 50 ppm, which is on the same level with regulatory standards. Pixel concentrations were calculated from the percentages of the BPO pixels in the chemical images. High correlation was found between the pixel concentrations and the mass concentrations of the BPO, indicating that the Raman chemical imaging method can be used for quantitative detection of the BPO mixed in the wheat flour.

  7. Role of [{sup 18}F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Caicedo, Carlos; Garcia-Velloso, Maria Jose; Vigil Diaz, Carmen; Richter Echevarria, Jose Angel [University of Navarra, Nuclear Medicine Department, University Clinic of Navarra, Pamplona (Spain); Lozano, Maria Dolores; Labiano, Tania [University of Navarra, Pathology Department, University Clinic of Navarra, Pamplona (Spain); Lopez-Picazo, Jose Maria; Gurpide, Alfonso; Perez Gracia, Jose Luis [University of Navarra, Oncology Department, University Clinic of Navarra, Pamplona (Spain); Zulueta, Javier [University of Navarra, Pulmonology Department, University Clinic of Navarra, Pamplona (Spain)

    2014-11-15

    The tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [{sup 18}F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC. Between January 2005 and October 2011, 340 NSCLC patients were tested for KRAS and EGFR mutation status. We identified patients with stage III and IV disease who had undergone [{sup 18}F]FDG PET/CT scanning for initial staging. SUVpeak, SUVmax and SUVmean of the single hottest tumour lesions were calculated, and their association with KRAS and EGFR mutation status was assessed. A receiver operator characteristic (ROC) curve analysis and a multivariate analysis (including SUVmean, gender, age and AJCC stage) were performed to identify the potential value of [{sup 18}F]FDG PET/CT for predicting KRAS mutation. From 102 patients staged using [{sup 18}F]FDG PET/CT, 28 (27 %) had KRAS mutation (KRAS+), 22 (22 %) had EGFR mutation (EGFR+) and 52 (51 %) had wild-type KRAS and EGFR profiles (WT). KRAS+ patients showed significantly higher [{sup 18}F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; p < 0.001). No significant differences were observed in [{sup 18}F]FDG uptake between EGFR+ patients and WT patients. ROC curve analysis for KRAS mutation status discrimination yielded an area under the curve of 0.740 for SUVmean (p < 0.001). The multivariate analysis showed a sensitivity and specificity of 78.6 % and 62.2 %, respectively, and the AUC was 0.773. NSCLC patients with tumours harbouring KRAS mutations showed significantly higher [{sup 18}F]FDG uptake than WT patients, as assessed in terms of SUVpeak, SUVmax and SUVmean. A multivariate model based on age, gender, AJCC stage and SUVmean might be used as a predictive marker of KRAS mutation status in patients with stage III or IV NSCLC. (orig.)

  8. Design of Pixellated CMOS Photon Detector for Secondary Electron Detection in the Scanning Electron Microscope

    Directory of Open Access Journals (Sweden)

    Joon Huang Chuah

    2011-01-01

    Full Text Available This paper presents a novel method of detecting secondary electrons generated in the scanning electron microscope (SEM. The method suggests that the photomultiplier tube (PMT, traditionally used in the Everhart-Thornley (ET detector, is to be replaced with a configurable multipixel solid-state photon detector offering the advantages of smaller dimension, lower supply voltage and power requirements, and potentially cheaper product cost. The design of the proposed detector has been implemented using a standard 0.35 μm CMOS technology with optical enhancement. This microchip comprises main circuit constituents of an array of photodiodes connecting to respective noise-optimised transimpedance amplifiers (TIAs, a selector-combiner (SC circuit, and a postamplifier (PA. The design possesses the capability of detecting photons with low input optical power in the range of 1 nW with 100 μm × 100 μm sized photodiodes and achieves a total amplification of 180 dBΩ at the output.

  9. Galectin-3 mediates cross-talk between K-Ras and Let-7c tumor suppressor microRNA.

    Directory of Open Access Journals (Sweden)

    Ran Levy

    Full Text Available BACKGROUND: Galectin-3 (Gal-3 and active (GTP-bound K-Ras contribute to the malignant phenotype of many human tumors by increasing the rate of cell proliferation, survival, and migration. These Gal-3-mediated effects result from a selective binding to K-Ras.GTP, causing increased nanoclustering in the cell membrane and leading to robust Ras signaling. Regulation of the interactions between Gal-3 and active K-Ras is not fully understood. METHODS AND FINDINGS: To gain a better understanding of what regulates the critical interactions between these two proteins, we examined the role of Gal-3 in the regulation of K-Ras by using Gal-3-knockout mouse embryonic-fibroblasts (Gal-3-/- MEFs and/or Gal-3/Gal-1 double-knockout MEFs. We found that knockout of Gal-3 induced strong downregulation (∼60% of K-Ras and K-Ras.GTP. The downregulation was somewhat more marked in the double-knockout MEFs, in which we also detected robust inhibition(∼50% of ERK and Akt activation. These additional effects are probably attributable to inhibition of the weak interactions of K-Ras.GTP with Gal-1. Re-expression of Gal-3 reversed the phenotype of the Gal-3-/- MEFs and dramatically reduced the disappearance of K-Ras in the presence of cycloheximide to the levels seen in wild-type MEFs. Furthermore, phosphorylation of Gal-3 by casein kinase-1 (CK-1 induced translocation of Gal-3 from the nucleus to the cytoplasm and the plasma membrane, leading to K-Ras stabilization accompanied by downregulation of the tumor suppressor miRNA let-7c, known to negatively control K-Ras transcription. CONCLUSIONS: Our results suggest a novel cross-talk between Gal-3-mediated downregulation of let 7c microRNA (which in turn negatively regulates K-Ras transcription and elucidates the association among Gal-3 let-7c and K-Ras transcription/translation, cellular compartmentalization and activity.

  10. Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis

    DEFF Research Database (Denmark)

    Boppudi, S; Bögershausen, N; Hove, H B

    2016-01-01

    the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence...... than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report...

  11. Higher prevalence of KRAS mutations in colorectal cancer in Saudi ...

    African Journals Online (AJOL)

    KRAS mutation is widely accepted as a key factor in colorectal tumorigenesis. Although KRAS mutation is widely studied in CRC limited data are available about mutation rates and spectrum in CRC from developing countries like Saudi Arabia where epidemiological features of the disease are different. We studied ...

  12. KRAS testing on colo-rectal carcinoma cytological imprints.

    Science.gov (United States)

    Malapelle, Umberto; Bellevicine, Claudio; Russo, Anna; Salatiello, Maria; Palombini, Lucio; Troncone, Giancarlo

    2011-04-01

    Anti-EGFR monoclonal antibodies, cetuximab, and panitumumab, are administrated under the condition that advanced colo-rectal cancer (CRC) carries a wild-type KRAS gene. Thus, clinicians request pathologists to genotype KRAS before treatment. In the near future routine mutation testing at the same time of the surgery may be implemented. The reliability of a rapid KRAS testing on ex vivo cytological samples obtained by direct scraping of the colon tumour tissue is here evaluated. A consecutive series of 20 surgically resected, primary CRC specimens was analysed. Fresh tissue from CRC was scraped with a scalpel blade, smeared on uncoated glass slides, air-dried and Diff-Quik stained to ensure malignant cell presence. The same tissue area was also histologically processed. Exon 2 KRAS gene mutations were evaluated on both cytological and histological specimens by dideoxy sequencing and by the DxS KRAS Mutation Test Kit (DxS, Manchester, England). Data obtained on on imprint cytology and matched histological samples showed full concordance; however, the mutation frequency was slightly higher (35%) by the DxS KRAS Mutation Test Kit than by the dideoxy sequencing (30%). Thus, colon cancer imprint cytology sample is a reliable biospecimen for both dideoxy-sequencing and DxS KRAS Mutation Test Kit analysis and it may be useful to abbreviate the KRAS assay turnaround time. Copyright © 2010 Wiley-Liss, Inc.

  13. Incidental detection of adult polycystic kidney disease on routine bone scan

    Energy Technology Data Exchange (ETDEWEB)

    Axelrod, M.S.; Maayan, M.L.

    1989-04-01

    A routine bone scan performed on a 36-y old male incidentally demonstrated enlarged kidneys with multifocal areas of radionuclide concentration suggestive of polycystic kidneys. Further evaluation using ultrasonography, CT scan, and a /sup 99m/Tc-GHA renal scan confirmed the initial impression. The routine evaluation of the kidneys on a bone scan is emphasized as a simple method of identifying previously unsuspected renal structural abnormalities. (orig.).

  14. Field emission scanning electron microscopy (FE-SEM) as an approach for nanoparticle detection inside cells.

    Science.gov (United States)

    Havrdova, M; Polakova, K; Skopalik, J; Vujtek, M; Mokdad, A; Homolkova, M; Tucek, J; Nebesarova, J; Zboril, R

    2014-12-01

    When developing new nanoparticles for bio-applications, it is important to fully characterize the nanoparticle's behavior in biological systems. The most common techniques employed for mapping nanoparticles inside cells include transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). These techniques entail passing an electron beam through a thin specimen. STEM or TEM imaging is often used for the detection of nanoparticles inside cellular organelles. However, lengthy sample preparation is required (i.e., fixation, dehydration, drying, resin embedding, and cutting). In the present work, a new matrix (FTO glass) for biological samples was used and characterized by field emission scanning electron microscopy (FE-SEM) to generate images comparable to those obtained by TEM. Using FE-SEM, nanoparticle images were acquired inside endo/lysosomes without disruption of the cellular shape. Furthermore, the initial steps of nanoparticle incorporation into the cells were captured. In addition, the conductive FTO glass endowed the sample with high stability under the required accelerating voltage. Owing to these features of the sample, further analyses could be performed (material contrast and energy-dispersive X-ray spectroscopy (EDS)), which confirmed the presence of nanoparticles inside the cells. The results showed that FE-SEM can enable detailed characterization of nanoparticles in endosomes without the need for contrast staining or metal coating of the sample. Images showing the intracellular distribution of nanoparticles together with cellular morphology can give important information on the biocompatibility and demonstrate the potential of nanoparticle utilization in medicine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Prognostic and Predictive Roles of KRAS Mutation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Amanda K. Arrington

    2012-09-01

    Full Text Available The RAS gene family is among the most studied and best characterized of the known cancer-related genes. Of the three human ras isoforms, KRAS is the most frequently altered gene, with mutations occurring in 17%–25% of all cancers. In particular, approximately 30%–40% of colon cancers harbor a KRAS mutation. KRAS mutations in colon cancers have been associated with poorer survival and increased tumor aggressiveness. Additionally, KRAS mutations in colorectal cancer lead to resistance to select treatment strategies. In this review we examine the history of KRAS, its prognostic value in patients with colorectal cancer, and evidence supporting its predictive value in determining appropriate therapies for patients with colorectal cancer.

  16. Endogenous K-ras signaling in erythroid differentiation.

    Science.gov (United States)

    Zhang, Jing; Lodish, Harvey F

    2007-08-15

    K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines.

  17. Mutations of the KRAS oncogene in endometrial hyperplasia and carcinoma.

    Directory of Open Access Journals (Sweden)

    Wiesława Niklińska

    2009-05-01

    Full Text Available The aim of this study was to examine the prevalence and clinicopathological significance of KRAS point mutation in endometrial hyperplasia and carcinoma. We analysed KRAS in 11 cases of complex atypical hyperplasia and in 49 endometrial carcinomas using polymerase chain reaction associated with restriction fragment length polymorphism (PCR-RFPL. Point mutations at codon 12 of KRAS oncogene were identified in 7 of 49 (14,3% tumor specimens and in 2 of 11 (18,2% hyperplasias. No correlation was found between KRAS gene mutation and age at onset, histology, grade of differentiation and clinical stage. We conclude that KRAS mutation is a relatively common event in endometrial carcinogenesis, but with no prognostic value.

  18. Detection and Segmentation of Small Trees in the Forest-Tundra Ecotone Using Airborne Laser Scanning

    Directory of Open Access Journals (Sweden)

    Marius Hauglin

    2016-05-01

    Full Text Available Due to expected climate change and increased focus on forests as a potential carbon sink, it is of interest to map and monitor even marginal forests where trees exist close to their tolerance limits, such as small pioneer trees in the forest-tundra ecotone. Such small trees might indicate tree line migrations and expansion of the forests into treeless areas. Airborne laser scanning (ALS has been suggested and tested as a tool for this purpose and in the present study a novel procedure for identification and segmentation of small trees is proposed. The study was carried out in the Rollag municipality in southeastern Norway, where ALS data and field measurements of individual trees were acquired. The point density of the ALS data was eight points per m2, and the field tree heights ranged from 0.04 to 6.3 m, with a mean of 1.4 m. The proposed method is based on an allometric model relating field-measured tree height to crown diameter, and another model relating field-measured tree height to ALS-derived height. These models are calibrated with local field data. Using these simple models, every positive above-ground height derived from the ALS data can be related to a crown diameter, and by assuming a circular crown shape, this crown diameter can be extended to a crown segment. Applying this model to all ALS echoes with a positive above-ground height value yields an initial map of possible circular crown segments. The final crown segments were then derived by applying a set of simple rules to this initial “map” of segments. The resulting segments were validated by comparison with field-measured crown segments. Overall, 46% of the field-measured trees were successfully detected. The detection rate increased with tree size. For trees with height >3 m the detection rate was 80%. The relatively large detection errors were partly due to the inherent limitations in the ALS data; a substantial fraction of the smaller trees was hit by no or just a few

  19. Detection accuracy of proximal caries by phosphor plate and cone-beam computerized tomography images scanned with different resolutions.

    Science.gov (United States)

    Cheng, Jun-Ge; Zhang, Zhi-Ling; Wang, Xiao-Yan; Zhang, Zu-Yan; Ma, Xu-Chen; Li, Gang

    2012-08-01

    This study was carried out to assess whether the spatial resolution has an impact on the detection accuracy of proximal caries in flat panel CBCT (cone beam computerized tomography) images and if the detection accuracy can be improved by flat panel CBCT images scanned with high spatial resolution when compared to digital intraoral images. The CBCT test images of 45 non-restored human permanent teeth were respectively scanned with the ProMax 3D and the DCT Pro scanners at different resolutions. Digital images were obtained with a phosphor plate imaging system Digora Optime. Eight observers evaluated all the test images for carious lesion within the 90 proximal surfaces. With the histological examination serving as the reference standard, observer performances were evaluated by receiver operating characteristic (ROC) curves. The areas under the ROC curves were analyzed with two-way analysis of variance. No significant differences were found among the CBCT images and between CBCT and digital images when only proximal enamel caries was detected (p = 0.989). With respect to the detection of proximal dentinal caries, significant difference was found between CBCT and digital images (p proximal caries in flat panel CBCT images. The flat panel CBCT images scanned with high spatial resolution did not improve the detection accuracy of proximal enamel caries compared to digital intraoral images. CBCT images scanned with high spatial resolutions could not be used for proximal caries detection.

  20. Effect of the degree of liver inflammation on FibroScan detection

    Directory of Open Access Journals (Sweden)

    Fan LI

    2011-11-01

    Full Text Available Objective To observe the effect of the degree of liver inflammation on transient elastography(FibroScan detection value(FS.Methods A total of 282 patients with chronic hepatitis from 302 Hospital of PLA from April 2009 to December 2010 were enrolled in the current study.The patients were subjected to histologic examination of a liver biopsy and FibroScan detection.The patients were divided into two groups according to stage of fibrosis F0-2 and F3-4 to compare the FS values of the patients with different degrees of inflammation.The patients were divided into the G1-2 group and G3-4 group according to grade of histologic inflammation,and Receive Operating Characteristic(ROC curve were drawn for the two patient groups to diagnose liver cirrhosis using the FS values and to analyze the correlation between the FS value of patients with the different degrees of inflammation.Results Up to 115 patients had histologic inflammation grade(G1,109 patients had grade 2,54 had grade 3,and 4 patients had grade 4.Their FS values were 6.4(2.9,35.0,11.6(2.9,45.0,15.1(5.2,75.0,and 61.5(45.0,75.0,respectively.Significant differences were observed among the groups(P < 0.001,H=107.5.Among the patients in groups F0-2 and F3-4,the FS value increased with the degree of inflammation(P < 0.001.The area under the curve was 0.853 and 0.897 for the patients of G1-2 and G3-4 groups,respectively,using the FS value to diagnose liver cirrhosis.The FS threshold limit value was 17.7kPa and 18.7kPa,respectively.Conclusion Liver inflammation is one of the factors that affect FS values.The threshold limit for FS in diagnosing liver cirrhosis among patients with different degrees of liver inflammation varies.

  1. GNAS and KRAS mutations are common in intraductal papillary neoplasms of the bile duct.

    Directory of Open Access Journals (Sweden)

    Motoko Sasaki

    Full Text Available Intraductal papillary neoplasms of the bile duct (IPNB shows favorable prognosis and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN of the pancreas. Although activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of IPMNs of the pancreas, there have been few studies on GNAS mutations in IPNBs. This study investigates the status of GNAS and KRAS mutations and their association with clinicopathological factors in IPNBs. We examined the status of GNAS mutation at codon 201 and KRAS mutation at codon 12&13, degree of mucin production and immunohistochemical expressions of MUC mucin core proteins in 29 patients (M/F = 15/14 with IPNB in intrahepatic and perihilar bile ducts (perihilar IPNB and 6 patients (M/F = 5/1 with IPNB in distal bile ducts (distal IPNB. GNAS mutations and KRAS mutations were detected in 50% and 46.2% of IPNBs, respectively. There was no significant correlation between the status of GNAS mutation and clinicopathological factors in IPNBs, whereas, the status of KRAS mutation was significantly inversely correlated with the degree of MUC2 expression in IPNBs (p<0.05. All IPNBs with GNAS mutation only showed high-mucin production. Degree of mucin production was significantly higher in perihilar IPNBs than distal IPNBs (p<0.05. MUC2 and MUC5AC expression was significantly higher in IPNBs with high-mucin production than those with low-mucin production (p<0.01 and p<0.05, respectively. In conclusions, this study firstly disclosed frequent GNAS mutations in IPNBs, similarly to IPMNs. This may suggest a common histopathogenesis of IPNBs and IPMNs. The status of KRAS mutations was inversely correlated to MUC2 expression and this may suggest heterogeneous properties of IPNBs. IPNBs with high-mucin production are characterized by perihilar location and high expression of MUC2 and MUC5AC, irrespective of the status of GNAS and KRAS mutations.

  2. Diet, lifestyle and risk of K-ras mutation-positive and -negative colorectal adenomas.

    NARCIS (Netherlands)

    Wark, P.A.; Kuil, W. van der; Ploemacher, J.; Muijen, G.N.P. van; Mulder, C.J.J.; Weijenberg, M.P.; Kok, F.J.; Kampman, E.

    2006-01-01

    K-ras mutation-positive (K-ras+) and -negative (K-ras-) colorectal adenomas may differ clinically and pathologically. As environmental compounds may cause mutations in the growth-related K-ras oncogene or affect clonal selection depending on mutational status, we evaluated whether the aetiology of

  3. Diet, Lifestyle and risk of K-ras mutation-positive and -negative colorectal adenomas

    NARCIS (Netherlands)

    Wark, P.A.; Kuil, van der W.; Ploemacher, J.; Muijen, van G.N.P.; Mulder, Ch.J.J.; Weijenberg, M.P.; Kok, F.J.; Kampman, E.

    2006-01-01

    K-ras mutation-positive (K-ras+) and -negative (K-ras-) colorectal adenomas may differ clinically and pathologically. As environmental compounds may cause mutations in the growth-related K-ras oncogene or affect clonal selection depending on mutational status, we evaluated whether the aetiology of

  4. High Resolution Trichromatic Road Surface Scanning with a Line Scan Camera and Light Emitting Diode Lighting for Road-Kill Detection

    Directory of Open Access Journals (Sweden)

    Gil Lopes

    2016-04-01

    Full Text Available This paper presents a road surface scanning system that operates with a trichromatic line scan camera with light emitting diode (LED lighting achieving road surface resolution under a millimeter. It was part of a project named Roadkills—Intelligent systems for surveying mortality of amphibians in Portuguese roads, sponsored by the Portuguese Science and Technology Foundation. A trailer was developed in order to accommodate the complete system with standalone power generation, computer image capture and recording, controlled lighting to operate day or night without disturbance, incremental encoder with 5000 pulses per revolution attached to one of the trailer wheels, under a meter Global Positioning System (GPS localization, easy to utilize with any vehicle with a trailer towing system and focused on a complete low cost solution. The paper describes the system architecture of the developed prototype, its calibration procedure, the performed experimentation and some obtained results, along with a discussion and comparison with existing systems. Sustained operating trailer speeds of up to 30 km/h are achievable without loss of quality at 4096 pixels’ image width (1 m width of road surface with 250 µm/pixel resolution. Higher scanning speeds can be achieved by lowering the image resolution (120 km/h with 1 mm/pixel. Computer vision algorithms are under development to operate on the captured images in order to automatically detect road-kills of amphibians.

  5. Delamination detection by Multi-Level Wavelet Processing of Continuous Scanning Laser Doppler Vibrometry data

    Science.gov (United States)

    Chiariotti, P.; Martarelli, M.; Revel, G. M.

    2017-12-01

    A novel non-destructive testing procedure for delamination detection based on the exploitation of the simultaneous time and spatial sampling provided by Continuous Scanning Laser Doppler Vibrometry (CSLDV) and the feature extraction capability of Multi-Level wavelet-based processing is presented in this paper. The processing procedure consists in a multi-step approach. Once the optimal mother-wavelet is selected as the one maximizing the Energy to Shannon Entropy Ratio criterion among the mother-wavelet space, a pruning operation aiming at identifying the best combination of nodes inside the full-binary tree given by Wavelet Packet Decomposition (WPD) is performed. The pruning algorithm exploits, in double step way, a measure of the randomness of the point pattern distribution on the damage map space with an analysis of the energy concentration of the wavelet coefficients on those nodes provided by the first pruning operation. A combination of the point pattern distributions provided by each node of the ensemble node set from the pruning algorithm allows for setting a Damage Reliability Index associated to the final damage map. The effectiveness of the whole approach is proven on both simulated and real test cases. A sensitivity analysis related to the influence of noise on the CSLDV signal provided to the algorithm is also discussed, showing that the processing developed is robust enough to measurement noise. The method is promising: damages are well identified on different materials and for different damage-structure varieties.

  6. Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection

    Directory of Open Access Journals (Sweden)

    S. R. Alam

    2015-01-01

    Full Text Available Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO- enhanced magnetic resonance imaging (MRI can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2∗-weighted protocols. R2∗ values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2∗ values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36 versus 0.96 (0.92 to 1.04, P<0.01. R2∗ values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51 compared to native kidney (2.91 (1.11 to 6.46 P<0.05. Increased R2∗ signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.

  7. A new total body scanning system for automatic change detection in multiple pigmented skin lesions.

    Science.gov (United States)

    Korotkov, Konstantin; Quintana, Josep; Puig, Susana; Malvehy, Josep; Garcia, Rafael

    2015-01-01

    The detection of newly appearing and changing pigmented skin lesions (PSLs) is essential for timely diagnosis of cutaneous melanoma. Total body skin examination (TBSE) procedures, currently practiced for this purpose, can be extremely time-consuming for patients with numerous lesions. In addition, these procedures are prone to subjectivity when selecting PSLs for baseline image comparison, increasing the risk of missing a developing cancer. To address this issue, we propose a new photogrammetry-based total body scanning system allowing for skin surface image acquisition using cross-polarized light. Equipped with 21 high-resolution cameras and a turntable, this scanner automatically acquires a set of overlapping images, covering 85%-90% of the patient's skin surface. These images are used for the automated mapping of PSLs and their change estimation between explorations. The maps produced relate images of individual lesions with their locations on the patient's body, solving the body-to-image and image-to-image correspondence problem in TBSEs. Currently, the scanner is limited to patients with sparse body hair and, for a complete skin examination, the scalp, palms, soles and inner arms should be photographed manually. The initial tests of the scanner showed that it can be successfully applied for automated mapping and temporal monitoring of multiple lesions: PSLs relevant for follow-up were repeatedly mapped in several explorations. Moreover, during the baseline image comparison, all lesions with artificially induced changes were correctly identified as "evolved."

  8. PAVEMENT DISTRESS DETECTION WITH PICUCHA METHODOLOGY FOR AREA-SCAN CAMERAS AND DARK IMAGES

    Directory of Open Access Journals (Sweden)

    Reus Salini

    2017-04-01

    Full Text Available The PICture Unsupervised Classification with Human Analysis (PICUCHA refers to a hybrid human-artificial intelligence methodology for pavement distresses assessment. It combines the human flexibility to recognize patterns and features in images with the neural network ability to expand such recognition to large volumes of images. In this study, the PICUCHA performance was tested with images taken with area-scan cameras and flash light illumination over a pavement with dark textures. These images are particularly challenging for the analysis because of the lens distortion and non-homogeneous illumination, generating artificial joints that happened at random positions inside the image cells. The chosen images were previously analyzed by other software without success because of the dark coluor. The PICUCHA algorithms could analyze the images with no noticeable problem and without any image pre-processing, such as contrast or brightness adjustments. Because of the special procedure used by the pavement engineer for the key patterns description, the distresses detection accuracy of the PICUCHA for the particular image set could reach 100%.

  9. Line-scan Raman microscopy complements optical coherence tomography for tumor boundary detection

    Science.gov (United States)

    Sudheendran, Narendran; Qi, Ji; Young, Eric D.; Lazar, Alexander J.; Lev, Dina C.; Pollock, Raphael E.; Larin, Kirill V.; Shih, Wei-Chuan

    2014-10-01

    Current technique for tumor resection requires biopsy of the tumor region and histological confirmation before the surgeon can be certain that the entire tumor has been resected. This confirmation process is time consuming both for the surgeon and the patient and also requires sacrifice of healthy tissue, motivating the development of novel technologies which can enable real-time detection of tumor-healthy tissue boundary for faster and more efficient surgeries. In this study, the potential of combining structural information from optical coherence tomography (OCT) and molecular information from line-scan Raman microscopy (LSRM) for such an application is presented. The results show a clear presence of boundary between myxoid liposarcoma and normal fat which is easily identifiable both from structural and molecular information. In cases where structural images are indistinguishable, for example, in normal fat and well differentiated liposarcoma (WDLS) or gastrointestinal sarcoma tumor (GIST) and myxoma, distinct molecular spectra have been obtained. The results suggest LSRM can effectively complement OCT to tumor boundary demarcation with high specificity.

  10. Phase imaging and detection in pseudo-heterodyne scattering scanning near-field optical microscopy measurements.

    Science.gov (United States)

    Moreno, Camilo; Alda, Javier; Kinzel, Edward; Boreman, Glenn

    2017-02-01

    When considering the pseudo-heterodyne mode for detection of the modulus and phase of the near field from scattering scanning near-field optical microscopy (s-SNOM) measurements, processing only the modulus of the signal may produce an undesired constraint in the accessible values of the phase of the near field. A two-dimensional analysis of the signal provided by the data acquisition system makes it possible to obtain phase maps over the whole [0, 2π) range. This requires post-processing of the data to select the best coordinate system in which to represent the data along the direction of maximum variance. The analysis also provides a quantitative parameter describing how much of the total variance is included within the component selected for calculation of the modulus and phase of the near field. The dependence of the pseudo-heterodyne phase on the mean position of the reference mirror is analyzed, and the evolution of the global phase is extracted from the s-SNOM data. The results obtained from this technique compared well with the expected maps of the near-field phase obtained from simulations.

  11. Automatic fracture detection based on Terrestrial Laser Scanning data: A new method and case study

    Science.gov (United States)

    Cao, Ting; Xiao, Ancheng; Wu, Lei; Mao, Liguang

    2017-09-01

    Terrestrial Laser Scanning (TLS), widely known as light detection and ranging (LiDAR) technology, is increasingly used to obtain rapidly three-dimensional (3-D) geometry or highly detailed digital terrain models with millimetric point precision and accuracy. In this contribution, we proposed a simple and unbiased approach to identify fractures directly from 3-D surface model of natural outcrops generated from TLS data and thus acquire surface density, which can provide important supplement data for fracture related research. One outcrop from the Shizigou anticline in the Qaidam Basin (NW China) is taken as the case to validate the method and obtain optimal parameters, according to the references of surface density measured in the field and from the photos taken by high-resolution camera. The results show that with suitable parameters, the proposed method can identify most structural fractures quickly, providing a solution of extracting structural fractures from virtual outcrops based on TLS data. Furthermore, it will help a lot in analyzing the development of fractures and other related fields.

  12. KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study

    Directory of Open Access Journals (Sweden)

    Cerne Jasmina-Ziva

    2012-03-01

    Full Text Available Abstract Background A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370 disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics. Methods Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models. Results No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2 - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users. Conclusion Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis.

  13. ScanIndel: a hybrid framework for indel detection via gapped alignment, split reads and de novo assembly.

    Science.gov (United States)

    Yang, Rendong; Nelson, Andrew C; Henzler, Christine; Thyagarajan, Bharat; Silverstein, Kevin A T

    2015-12-07

    Comprehensive identification of insertions/deletions (indels) across the full size spectrum from second generation sequencing is challenging due to the relatively short read length inherent in the technology. Different indel calling methods exist but are limited in detection to specific sizes with varying accuracy and resolution. We present ScanIndel, an integrated framework for detecting indels with multiple heuristics including gapped alignment, split reads and de novo assembly. Using simulation data, we demonstrate ScanIndel's superior sensitivity and specificity relative to several state-of-the-art indel callers across various coverage levels and indel sizes. ScanIndel yields higher predictive accuracy with lower computational cost compared with existing tools for both targeted resequencing data from tumor specimens and high coverage whole-genome sequencing data from the human NIST standard NA12878. Thus, we anticipate ScanIndel will improve indel analysis in both clinical and research settings. ScanIndel is implemented in Python, and is freely available for academic use at https://github.com/cauyrd/ScanIndel.

  14. Can K-ras gene mutation be utilized as prognostic biomarker for colorectal cancer patients receiving chemotherapy? A meta-analysis and systematic review.

    Science.gov (United States)

    Rui, Yuan-Yi; Zhang, Dan; Zhou, Zong-Guang; Wang, Cun; Yang, Lie; Yu, Yong-Yang; Chen, Hai-Ning

    2013-01-01

    K-ras gene mutations were common in colorectal patients, but their relationship with prognosis was unclear. Verify prognostic differences between patient with and without mutant K-ras genes by reviewing the published evidence. Systematic reviews and data bases were searched for cohort/case-control studies of prognosis of colorectal cancer patients with detected K-ras mutations versus those without mutant K-ras genes, both of whom received chemotherapy. Number of patients, regimens of chemotherapy, and short-term or long-term survival rate (disease-free or overall) were extracted. Quality of studies was also evaluated. 7 studies of comparisons with a control group were identified. No association between K-ras gene status with neither short-term disease free-survival (OR=1.01, 95% CI, 0.73-1.38, P=0.97) nor overall survival (OR=1.06, 95% CI, 0.82-1.36, P=0.66) in CRC patients who received chemotherapy was indicated. Comparison of long-term survival between two groups also indicated no significant difference after heterogeneity was eliminated (OR=1.09, 95% CI, 0.85-1.40, P=0.49). K-ras gene mutations may not be a prognostic index for colorectal cancer patients who received chemotherapy.

  15. K-ras mutations in sinonasal cancers in relation to wood dust exposure

    DEFF Research Database (Denmark)

    Bornholdt, Jette; Hansen, Johnni; Steiniche, Torben

    2008-01-01

    as the most common and often related to wood dust exposure. CONCLUSION: Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-ras mutations were detected in 13% of adenocarcinomas. In this study and previously published studies of sinonasal cancer...... to be explanatory for the G-->A mutations, but combination of exposure to tobacco, wood dust, and possibly other occupational agents may be a more likely explanation. Overall, the study suggests a limited role for K-ras mutations in development of sinonasal cancer.......BACKGROUND: Cancer in the sinonasal tract is rare, but persons who have been occupationally exposed to wood dust have a substantially increased risk. It has been estimated that approximately 3.6 million workers are exposed to inhalable wood dust in EU. In previous small studies of this cancer, ras...

  16. An oligonucleotide-tagged microarray for routine diagnostics of colon cancer by genotyping KRAS mutations

    DEFF Research Database (Denmark)

    Liu, Yuliang; Guðnason, Haukur; Li, Yiping

    2014-01-01

    and therapeutic importance. In this study, KRAS gene fragments containing mutations in codon 12 were amplified by multiplex PCR using a 5'-Cy5-labeled reverse primer in combination with 3'-mutation-specific forward primers that were linked with four unique nucleotide-sequence tags at the 5'-end. The Cy5-labeled...... or spiked fecal samples. The immobilized tag-probes were stable under multiple thermal cycling treatments, allowing re-use of the tag-microarray and further optimization to solid PCR. Our results demonstrated that a novel oligonucleotide-tagged microarray system has been developed which would be suitable...... to be used for detection of KRAS mutations and clinical diagnosis of CRC....

  17. Detection of Ground Clutter from Weather Radar Using a Dual-Polarization and Dual-Scan Method

    Directory of Open Access Journals (Sweden)

    Mohammad-Hossein Golbon-Haghighi

    2016-06-01

    Full Text Available A novel dual-polarization and dual-scan (DPDS classification algorithm is developed for clutter detection in weather radar observations. Two consecutive scans of dual-polarization radar echoes are jointly processed to estimate auto- and cross-correlation functions. Discriminants are then defined and estimated in order to separate clutter from weather based on their physical and statistical properties. An optimal Bayesian classifier is used to make a decision on clutter presence from the estimated discriminant functions. The DPDS algorithm is applied to the data collected with the KOUN polarimetric radar and compared with the existing detection methods. It is shown that the DPDS algorithm yields a higher probability of detection and lower false alarm rate in clutter detection.

  18. The mutational spectrum of HRAS, KRAS, NRAS and FGFR3 genes in bladder cancer.

    Science.gov (United States)

    Ouerhani, Slah; Elgaaied, Amel Ben Ammar

    Bladder cancer is one of the most common cancers worldwide. A number of genetic and epigenetic alterations have been identified in bladder tumorigenesis, including activating mutations in fibroblast growth factor receptor 3 (FGFR3) and RAS family genes. In this study, we have analysed the mutational spectrum of FGFR3 and RAS genes (HRAS, NRAS and KRAS). We have also studied the relationship between mutations. A total of 234 patients with different stages and grades were included in the present study (58 superficial low-grade, 53 superficial high-grade and 123 muscle-invasive tumours). Mutations in exons 1 and 2 of HRAS, KRAS and NRAS genes were screened by PCR and direct sequencing. The hot spot mutations in exons 7, 10 and 15 of the FGFR3 oncogene were studied by multiplex PCR and the SNaP-shot protocol. Overall, 8.97% (21/234) of samples were mutant for one of the RAS genes. Among these mutations 47.61% were detected in KRAS, 33.33% in HRAS and only 19.04% most frequent RAS mutations were KRAS p.G12C and p.G12D. The correlation between RAS mutations and tumour subgroups does not report a statistical significant association (p=0.876). The FGFR3 mutations were detected in 31.19% (73/234) of bladder tumours and were associated with low stages and grades. The study of relationship between RAS and FGFR3 genes revealed that FGFR3 mutations were mutually exclusive with RAS ones (p=10(-4)). In conclusion we retain that activated RAS and FGFR3 do not appear to be drivers in bladder cancer but the mutually exclusive relationship between RAS and FGFR3 mutations indicates a possible clonal advantage of modified signaling via a common pathway.

  19. Improved detection and biopsy of solid liver lesions using pulse-inversion ultrasound scanning and contrast agent infusion

    DEFF Research Database (Denmark)

    Skjoldbye, B.; Pedersen, Morten Høgholm; Struckmann, J.

    2002-01-01

    The purpose of this study was to assess the ability of pulse-inversion ultrasound (US) scanning (PIUS), combined with an IV contrast agent, to detect malignant liver lesions and its impact on patient management (resectability). Additionally, to determine the feasibility of US-guided biopsy of new...

  20. The Role of Conventional Bronchoscopy in the Workup of Suspicious CT Scan Screen-Detected Pulmonary Nodules

    NARCIS (Netherlands)

    van't Westeinde, Susan C.; Horeweg, Nanda; Vernhout, Rene M.; Groen, Harry J. M.; Lammers, Jan-Willem J.; Weenink, Carla; Nackaerts, Kristiaan; Oudkerk, Matthijs; Mali, Willem; Thunnissen, Frederik B.; de Koning, Harry J.; van Klaveren, Rob J.

    Background: Up to 50% of the participants in CT scan lung cancer screening trials have at least one pulmonary nodule. To date, the role of conventional bronchoscopy in the workup of suspicious screen-detected pulmonary nodules is unknown. If a bronchoscopic evaluation could be eliminated, the

  1. The role of conventional bronchoscopy in the workup of suspicious CT scan screen-detected pulmonary nodules

    NARCIS (Netherlands)

    S.C. van 't Westeinde (Susan); N. Horeweg (Nanda); R. Vernhout (Rene); H.J.M. Groen (Henk); J.-W.J. Lammers (Jan-Willem); C. Weenink (Carla); K. Nackaerts (Kristiaan); M. Oudkerk (Matthijs); W.P. Mali (Willem); F.B.J.M. Thunnissen (Frederik); H.J. de Koning (Harry); R.J. van Klaveren (Rob)

    2012-01-01

    textabstractBackground: Up to 50% of the participants in CT scan lung cancer screening trials have at least one pulmonary nodule. To date, the role of conventional bronchoscopy in the workup of suspicious screen-detected pulmonary nodules is unknown. If a bronchoscopic evaluation could be

  2. Optimal experimental design for the detection of light atoms from high-resolution scanning transmission electron microscopy images

    NARCIS (Netherlands)

    Gonnissen, J.; De Backer, A.; Den Dekker, A.J.; Martinez, G.T.; Rosenauer, A.; Sijbers, J.; Van Aert, S.

    2014-01-01

    We report an innovative method to explore the optimal experimental settings to detect light atoms from scanning transmission electron microscopy (STEM) images. Since light elements play a key role in many technologically important materials, such as lithium-battery devices or hydrogen storage

  3. Early Detection of Brain Pathology Suggestive of Early AD Using Objective Evaluation of FDG-PET Scans

    Directory of Open Access Journals (Sweden)

    James C. Patterson

    2011-01-01

    Full Text Available The need for early detection of AD becomes critical as disease-modifying agents near the marketplace. Here, we present results from a study focused on improvement in detection of metabolic deficits related to neurodegenerative changes consistent with possible early AD with statistical evaluation of FDG-PET brain images. We followed 31 subjects at high risk or diagnosed with MCI/AD for 3 years. 15 met criteria for diagnosis of MCI, and five met criteria for AD. FDG-PET scans were completed at initiation and termination of the study. PET scans were read clinically and also evaluated objectively using Statistical Parametric Mapping (SPM. Using standard clinical evaluation of the FDG-PET scans, 11 subjects were detected, while 18 were detected using SPM evaluation. These preliminary results indicate that objective analyses may improve detection; however, early detection in at-risk normal subjects remains tentative. Several FDA-approved software packages are available that use objective analyses, thus the capacity exists for wider use of this method for MCI/AD.

  4. DETECTING SELECTION IN NATURAL POPULATIONS: MAKING SENSE OF GENOME SCANS AND TOWARDS ALTERNATIVE SOLUTIONS

    Science.gov (United States)

    Haasl, Ryan J.; Payseur, Bret A.

    2016-01-01

    Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome-scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example FST, cross-population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole-chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach. PMID:26224644

  5. Scanning laser polarimetry and optical coherence tomography for detection of retinal nerve fiber layer defects.

    Science.gov (United States)

    Oh, Jong-Hyun; Kim, Yong Yeon

    2009-09-01

    To compare the ability of scanning laser polarimetry with variable corneal compensation (GDx-VCC) and Stratus optical coherence tomography (OCT) to detect photographic retinal nerve fiber layer (RNFL) defects. This retrospective cross-sectional study included 45 eyes of 45 consecutive glaucoma patients with RNFL defects in red-free fundus photographs. The superior and inferior temporal quadrants in each eye were included for data analysis separately. The location and presence of RNFL defects seen in red-free fundus photographs were compared with those seen in GDx-VCC deviation maps and OCT RNFL analysis maps for each quadrant. Of the 90 quadrants (45 eyes), 31 (34%) had no apparent RNFL defects, 29 (32%) had focal RNFL defects, and 30 (33%) had diffuse RNFL defects in red-free fundus photographs. The highest agreement between GDx-VCC and red-free photography was 73% when we defined GDx-VCC RNFL defects as a cluster of three or more color-coded squares (p<5%) along the traveling line of the retinal nerve fiber in the GDx-VCC deviation map (kappa value, 0.388; 95% confidence interval (CI), 0.195 to 0.582). The highest agreement between OCT and red-free photography was 85% (kappa value, 0.666; 95% CI, 0.506 to 0.825) when a value of 5% outside the normal limit for the OCT analysis map was used as a cut-off value for OCT RNFL defects. According to the kappa values, the agreement between GDx-VCC deviation maps and red-free photography was poor, whereas the agreement between OCT analysis maps and red-free photography was good.

  6. Single ion impact detection and scanning probe aligned ion implantation for quantum bit formation

    Energy Technology Data Exchange (ETDEWEB)

    Weis, Christoph D.

    2011-10-04

    Quantum computing and quantum information processing is a promising path to replace classical information processing via conventional computers which are approaching fundamental physical limits. Instead of classical bits, quantum bits (qubits) are utilized for computing operations. Due to quantum mechanical phenomena such as superposition and entanglement, a completely different way of information processing is achieved, enabling enhanced performance for certain problem sets. Various proposals exist on how to realize a quantum bit. Among them are electron or nuclear spins of defect centers in solid state systems. Two such candidates with spin degree of freedom are single donor atoms in silicon and nitrogen vacancy (NV) defect centers in diamond. Both qubit candidates possess extraordinary qualities which makes them promising building blocks. Besides certain advantages, the qubits share the necessity to be placed precisely in their host materials and device structures. A commonly used method is to introduce the donor atoms into the substrate materials via ion implantation. For this, focused ion beam systems can be used, or collimation techniques as in this work. A broad ion beam hits the back of a scanning probe microscope (SPM) cantilever with incorporated apertures. The high resolution imaging capabilities of the SPM allows the non destructive location of device areas and the alignment of the cantilever and thus collimated ion beam spot to the desired implant locations. In this work, this technique is explored, applied and pushed forward to meet necessary precision requirements. The alignment of the ion beam to surface features, which are sensitive to ion impacts and thus act as detectors, is demonstrated. The technique is also used to create NV center arrays in diamond substrates. Further, single ion impacts into silicon device structures are detected which enables deliberate single ion doping.

  7. Novel Automatic Detection of Pleura and B-lines (Comet-Tail Artifacts) on In-Vivo Lung Ultrasound Scans

    DEFF Research Database (Denmark)

    Moshavegh, Ramin; Hansen, Kristoffer Lindskov; Møller-Sørensen, Hasse

    2016-01-01

    images. The pleural line is first segmented on each image and then the B-line artifacts spreading down from the pleural line are detected and overlayed on the image. The resulting 300 images showed that the mean lateral distance between B-lines detected on images acquired from patients decreased by 20......This paper presents a novel automatic method for detection of B-lines (comet-tail artifacts) in lung ultrasound scans. B-lines are the most commonly used artifacts for analyzing the pulmonary edema. They appear as laser-like vertical beams, which arise from the pleural line and spread down without...

  8. A Low Cost, Electronically Scanned Array (ESA) Antenna Technology for Aviation Hazard Detection and Avoidance Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed project will investigate the feasibility of utilizing ThinKom's low cost electronically scanned array (ESA) antenna concepts to enable affordable...

  9. Development of a scanning micro-pulse lidar for aerosol and cloud detection

    Science.gov (United States)

    Chen, Chao; Wang, Zhangjun; Meng, Xiangqian; Qu, Junle; Du, Libin; Li, Xianxin; Lv, Bin; Kabanov, V. V.

    2014-11-01

    A scanning micro-pulse lidar (MPL) was developed by Institute of Oceanographic Instrumentation, Shandong Academy of Sciences, which can be used for routine observations of optical properties, temporal and spatial variation of atmospheric aerosol and cloud in the lower troposphere. In addition to the optical system design, the design of 3 dimensional (3-D) scanning system controlled by servo motors is analyzed, including servo motor selection and mechanical design. Through the measurements in Qingdao, it is proved that 3-D scanning system can control the lidar azimuth/elevation scanning with high precision. The lidar has good performance and can provide time-height indication (THI), range-height indication (RHI) and plane-position indication (PPI) of lidar signals which can well reflect the temporal and spatial variation of atmospheric aerosol.

  10. Quantitative detection of gold nanoparticles on individual, unstained cancer cells by Scanning Electron Microscopy

    NARCIS (Netherlands)

    Hartsuiker, Liesbeth; van Es, Peter; Petersen, Wilhelmina; van Leeuwen, Ton; Terstappen, Leonardus Wendelinus Mathias Marie; Otto, Cornelis

    2011-01-01

    Gold nanoparticles are rapidly emerging for use in biomedical applications. Characterization of the interaction and delivery of nanoparticles to cells through microscopy is important. Scanning electron microscopes have the intrinsic resolution to visualize gold nanoparticles on cells. A novel sample

  11. Characterization of mutations and loss of heterozygosity of p53 and K-ras2 in pancreatic cancer cell lines by immobilized polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Edwards Jeremy

    2003-07-01

    Full Text Available Abstract Background The identification of known mutations in a cell population is important for clinical applications and basic cancer research. In this work an immobilized form of the polymerase chain reaction, referred to as polony technology, was used to detect mutations as well as gene deletions, resulting in loss of heterozygosity (LOH, in cancer cell lines. Specifically, the mutational hotspots in p53, namely codons 175, 245, 248, 249, 273, and 282, and K-ras2, codons 12, 13 and 61, were genotyped in the pancreatic cell line, Panc-1. In addition LOH analysis was also performed for these same two genes in Panc-1 by quantifying the relative gene copy number of p53 and K-ras2. Results Using polony technology, Panc-1 was determined to possess only one copy of p53, which possessed a mutation in codon 273, and two copies of K-ras2, one wildtype and one with a mutation in codon 12. To further demonstrate the general approach of this method, polonies were also used to detect K-ras2 mutations in the pancreatic cell lines, AsPc-1 and CAPAN-1. Conclusions In conclusion, we have developed an assay that can detect mutations in hotspots of p53 and K-ras2 as well as diagnose LOH in these same genes.

  12. Outcome of fetuses with short femur length detected at second trimester malformation scan - a national survey

    DEFF Research Database (Denmark)

    Mathiesen, Jonathan Michael; Aksglaede, Lise; Skibsted, Lillian

    2014-01-01

    To assess the relationship between fetal femur diaphysis length (FL) below the 5th percentile at the second trimester scan and pregnancy outcome, in a population where more than 90 % of women attend first trimester screening.......To assess the relationship between fetal femur diaphysis length (FL) below the 5th percentile at the second trimester scan and pregnancy outcome, in a population where more than 90 % of women attend first trimester screening....

  13. Signal Processing and Its Effect on Scanning Efficiencies for a Field Instrument for Detecting Low-energy Radiation.

    Science.gov (United States)

    Marianno, Craig M

    2015-07-01

    Signal processing within a radiation detector affects detection efficiency. Currently, organizations such as private industry, the U.S. Navy, Army, and Air Force are coupling some detector systems with data collection devices to survey large land areas for radioactive contamination. As detector technology has advanced and analog data collection has turned to digital, signal processing is becoming prevalent in some instruments. Using a NIST traceable (241)Am source, detection efficiency for a field instrument for detecting low-energy radiation (FIDLER) was examined for both a static and scanning mode. Experimental results were compared to Monte Carlo-generated efficiencies. Stationary data compared nicely to the theoretical results. Conversely, scanning detection efficiencies were considerably different from their theoretical counterparts. As speed increased, differences in detection efficiency approached two orders of magnitude. To account for these differences, a quasi time-dependent Monte Carlo simulation was created mimicking the signal processing undertaken by the FIDLER detection system. By including signal processing, experimental results fell within the bounds of the Monte Carlo-generated efficiencies, thus demonstrating the negative effects of such processing on detection efficiencies.

  14. Scanning of Open Data for Detection of Emerging Organized Crime Threats—The ePOOLICE Project

    DEFF Research Database (Denmark)

    Larsen, Henrik Legind

    2017-01-01

    In fighting organized crime, open data provide an important source for both detecting emerging threats, as well as forecasting future threats. This allows the police to plan their resources and capacity for countering the threats in due time to prevent it or at least to mitigate its effects....... A vital part of a system supporting the police analysts for this purpose is an efficient and effective system for scanning the open data providing information about the relevant factors in the environment. This chapter presents the ePOOLICE project, aimed at developing a solution, the “ePOOLICE system......”, for such a scanning system. Through a prototype demonstrated with use cases, the project provided a proof of concept of an efficient and effective environmental scanning system as part of the early warning system for discovering emerging, as well as likely future, organized crime threats. Main elements...

  15. Comparison of EGFR and KRAS Status between Primary Non-small Cell Lung Cancer and Corresponding Metastases: A Systematic Review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Chengbo HAN

    2010-09-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR and KRAS status were particularly critical for the choice of first-line targeted therapy of non-small cell lung cancer (NSCLC, while the primary tumor and metastases might be different in the EGFR and KRAS gene status. The aim of this pooled analysis is to compare EGFR and KRAS status in matching primary NSCLC and metastases and further to guide clinical practice. Methods Systematic computerized searches of the Pubmed and Medline databases (up to May 10, 2010 meeting specified search criteria were performed, followed by a further screening according to inclusive and exclusive criteria. Results Fourteen articles were selected into the final meta-analysis with paired primary and metastatic cases of 598. Expression level of EGFR protein and mutation frequency of KRAS gene in primary tumors were higher than that in metastases, relative risk (RR=1.13 (95%CI: 0.98-1.31, P=0.09 and RR=1.39 (95%CI: 0.95-2.03, P=0.09, respectively. EGFR gene copy number in metastases was higher than that in primary tumor, RR=0.74 (95%CI: 0.53-1.02, P=0.06. There was no statistically significant difference of EGFR mutation frequency in primary tumors and metastases (P=0.31. The discordant rate in primary and metastases was 17.09% for EGFR mutation, 27.07% for EGFR amplification, 27.84% for EGFR protein expression and 25.91% for KRAS mutation. Conclusion The systematic analysis showed that the EGFR mutation status in primary lung cancer and corresponding metastases was more stable than KRAS gene. KRAS mutation in primary lung cancerous foci seems to better reflect systemically cancerous genetic characteristics of KRAS gene. Determination of KRAS gene status based merely on metastatic foci might lead to more resistant selections of EGFR tyrosine kinase inhibitor (TKI therapy. Combined detection of EGFR and KRAS mutation from primary NSCLC foci might serve as a better predictive biomarker for anti-EGFR targeted

  16. Bio markers and Anti-EGFR therapies for Krads wild-type tumors in metastatic colorectal cancer patients; Biomarcadores y terapeutica ANTI-EGFR en el cancer colorrectal metastasico en pacientes con K-Ras no mutado

    Energy Technology Data Exchange (ETDEWEB)

    Diaz Rubio Garcia, E.

    2009-07-01

    The natural history of metastasis colorectal cancer has being clearly modified in terms of response rate, time to progression and overall survival, once the anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have emerged in combination with the standard cytotoxic chemotherapy (FOLFOX and FOLFIRI). However, the benefit from cetuximab and panitumumab is only confined to KRAS-wild type (KRAS-wt) colorectal tumors, while KRAS mutated tumors do not respond to these drugs. The 65 % of colorectal tumors are KRAS-wt tumors, but efficacy of antiEGFR therapies is detected only in 60-70 % of these KRAS-wt tumors. Other biomarkers and molecular pathways must be involved in the response of the antiEGFR therapies for the KRAS-wt colorectal tumors, such as the EGFR ligands, the EGFR-phosphorilated levels, the number of EGFR copies, the status of the KRAS effected B-RAF and the alternative intracellular signaling pathways PIK3CA/PTEN/AKT and JAK/STAT. A battery of these biomarkers is needed to select the most sensitive patients to the antiEGFR therapies. This pattern may represent a novel favorable cost-effectiveness tool to develop tailored treatments. A review of these biomarkers and molecular pathways, involved in the antiEGFR therapies response, is performed. (Author) 68 refs.

  17. Let-7 Sensitizes KRAS Mutant Tumor Cells to Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Xin Dai

    Full Text Available KRAS is the most commonly mutated oncogene in human cancers and is associated with poor prognosis and drug resistance. Let-7 is a family of tumor suppressor microRNAs that are frequently suppressed in solid tumors, where KRAS mutations are highly prevalent. In this study, we investigated the potential use of let-7 as a chemosensitizer. We found that let-7b repletion selectively sensitized KRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type KRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEK/ERK and PI3K/AKT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in KRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of β-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of KRAS mutant tumors.

  18. Detectability of cerebral aneurysms and surrounding vessels by three-dimensional evaluation using helical scanning CT (HES-CT)

    Energy Technology Data Exchange (ETDEWEB)

    Ogura, Yuko; Katada, Kazuhiro; Sano, Hirotoshi; Kato, Yoko; Kanno, Tetsuo; Takeshita, Gen; Koga, Sukehiko (Fujita Health Univ., Toyoake, Aichi (Japan))

    1994-09-01

    Helical scanning CT (HES-CT) is a new technique to enable high-speed volumetric data acquisition. We have applied HES-CT to the diagnosis of cerebral vascular diseases. In our experience, the relationship between the scanning parameters of HES-CT and image quality was complex and reciprocal, so that optimization of the parameters according to the clinical demands was essential. We compared HES-CT with conventional cerebral angiography to determine the detectability of the aneurysm and surrounding vessels, and sought the optimal parameters to delineate small vessels. All aneurysms were detected in multiplanar reconstruction (MPR) images. The smallest one was 3 x 4 mm. MPR images were found to have some advantages over conventional cerebral angiography in delineation of intracranial aneurysms: (1) scanning was over in a short time (30 s), (2) the relationship between the aneurysm and surrounding vessels was easily recognized, (3) the diameter of the neck could be measured, because the neck of the aneurysm and parent artery could be imaged on the same plane without overlapping another vessel, (4) calcified lesions on the aneurysmal wall were detected, and (5) HES-CT was done safety without arterial puncture. However, the detectability of unknown aneurysm was less than the detectability of known aneurysm in MPR images. The 180deg interpolation algorithm and 1 mm slice were effective in detecting small vessels. However, vessels with a diameter less than 1 mm could not be detected by HES-CT. HES-CT was considered to be useful as a supplementary examination to conventional angiography for the diagnosis of intracranial aneurysms. (author).

  19. Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma.

    Science.gov (United States)

    Ohba, Taro; Toyokawa, Gouji; Osoegawa, Atsushi; Hirai, Fumihiko; Yamaguchi, Masafumi; Taguchi, Ken-Ichi; Seto, Takashi; Takenoyama, Mitsuhiro; Ichinose, Yukito; Sugio, Kenji

    2016-09-01

    The EGFR, K-ras, EML4-ALK, and BRAF genes are oncogenic drivers of lung adenocarcinoma. We conducted this study to analyze the mutations of these genes in stage I adenocarcinoma. The subjects of this retrospective study were 256 patients with resected stage I lung adenocarcinoma. We analyzed mutations of the EGFR, K-ras, and BRAF genes, and the EML4-ALK fusion gene. We also assessed disease-free survival (DFS) to evaluate the prognostic value and overall survival (OS) to evaluate the predictive value of treatment after recurrence. Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes were detected in 120 (46.8 %), 14 (5.5 %), 6 (2.3 %), and 2 (0.8 %) of the 256 tumors. Two tumors had double mutations (0.8 %). The incidence of EGFR mutations was significantly higher in women than in men. The EML4-ALK fusion gene was detected only in younger patients. The DFS and OS of the K-ras mutant group were significantly worse than those of the EGFR mutant group, the EML4-ALK fusion gene group, and the wild-type group. Six of the seven patients with the EML4-ALK fusion gene are still alive without recurrent disease. In patients with stage I adenocarcinoma, mutation of the K-ras gene was a poor prognostic factor for recurrence. The presence of a mutation of the EGFR or EML4-ALK gene was not a prognostic factor.

  20. Signal Processing Variables for Optimization of Flaw Detection in Composites Using Ultrasonic Guided Wave Scanning

    Science.gov (United States)

    Roth, Don J.; Cosgriff, Laura M.; Martin, Richard E.; Teemer, LeTarrie

    2004-01-01

    This study analyzes the effect of signal processing variables on the ability of the ultrasonic guided wave scan method at NASA Glenn Research Center to distinguish various flaw conditions in ceramic matrix composites samples. In the ultrasonic guided wave scan method, several time- and frequency-domain parameters are calculated from the ultrasonic guided wave signal at each scan location to form images. The parameters include power spectral density, centroid mean time, total energy (zeroth moment), centroid frequency, and ultrasonic decay rate. A number of signal processing variables are available to the user when calculating these parameters. These signal processing variables include 1) the time portion of the time-domain waveform processed, 2) integration type for the properties requiring integrations, 3) bounded versus unbounded integrations, 4) power spectral density window type, 5) and the number of time segments chosen if using the short-time fourier transform to calculate ultrasonic decay rate. Flaw conditions examined included delamination, cracking, and density variation.

  1. Concurrent Targeting of KRAS and AKT by MiR-4689 Is a Novel Treatment Against Mutant KRAS Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Masayuki Hiraki

    2015-01-01

    Full Text Available KRAS mutations are a major cause of drug resistance to molecular-targeted therapies. Aberrant epidermal growth factor receptor (EGFR signaling may cause dysregulation of microRNA (miRNA and gene regulatory networks, which leads to cancer initiation and progression. To address the functional relevance of miRNAs in mutant KRAS cancers, we transfected exogenous KRASG12V into human embryonic kidney 293 and MRC5 cells with wild-type KRAS and BRAF genes, and we comprehensively profiled the dysregulated miRNAs. The result showed that mature miRNA oligonucleotide (miR-4689, one of the significantly down-regulated miRNAs in KRASG12V overexpressed cells, was found to exhibit a potent growth-inhibitory and proapoptotic effect both in vitro and in vivo. miR-4689 expression was significantly down-regulated in cancer tissues compared to normal mucosa, and it was particularly decreased in mutant KRAS CRC tissues. miR-4689 directly targets v-ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS and v-akt murine thymoma viral oncogene homolog 1(AKT1, key components of two major branches in EGFR pathway, suggesting KRAS overdrives this signaling pathway through inhibition of miR-4689. Overall, this study provided additional evidence that mutant KRAS functions as a broad regulator of the EGFR signaling cascade by inhibiting miR-4689, which negatively regulates both RAS/mitogen-activated protein kinase (MAPK and phosphoinositide 3-kinase (PI3K/AKT pathways. These activities indicated that miR-4689 may be a promising therapeutic agent in mutant KRAS CRC.

  2. Hotspot detection using space-time scan statistics on children under five years of age in Depok

    Science.gov (United States)

    Verdiana, Miranti; Widyaningsih, Yekti

    2017-03-01

    Some problems that affect the health level in Depok is the high malnutrition rates from year to year and the more spread infectious and non-communicable diseases in some areas. Children under five years old is a vulnerable part of population to get the malnutrition and diseases. Based on this reason, it is important to observe the location and time, where and when, malnutrition in Depok happened in high intensity. To obtain the location and time of the hotspots of malnutrition and diseases that attack children under five years old, space-time scan statistics method can be used. Space-time scan statistic is a hotspot detection method, where the area and time of information and time are taken into account simultaneously in detecting the hotspots. This method detects a hotspot with a cylindrical scanning window: the cylindrical pedestal describes the area, and the height of cylinder describe the time. Cylinders formed is a hotspot candidate that may occur, which require testing of hypotheses, whether a cylinder can be summed up as a hotspot. Hotspot detection in this study carried out by forming a combination of several variables. Some combination of variables provides hotspot detection results that tend to be the same, so as to form groups (clusters). In the case of infant health level in Depok city, Beji health care center region in 2011-2012 is a hotspot. According to the combination of the variables used in the detection of hotspots, Beji health care center is most frequently as a hotspot. Hopefully the local government can take the right policy to improve the health level of children under five in the city of Depok.

  3. Performance and Cost Efficiency of KRAS Mutation Testing for Metastatic Colorectal Cancer in Routine Diagnosis: The MOKAECM Study, a Nationwide Experience

    Science.gov (United States)

    Chatellier, Gilles; Côté, Jean-François; Pages, Jean-Christophe; de Fraipont, Florence; Boyer, Jean-Christophe; Merlio, Jean Philippe; Morel, Alain; Gorisse, Marie-Claude; de Cremoux, Patricia; Leroy, Karen; Milano, Gérard; Ouafik, L’Houcine; Merlin, Jean-Louis; Le Corre, Delphine; Aucouturier, Pascaline; Sabourin, Jean-Christophe; Nowak, Frédérique; Frebourg, Thierry; Emile, Jean-François; Durand-Zaleski, Isabelle; Laurent-Puig, Pierre

    2013-01-01

    Purpose Rapid advances in the understanding of cancer biology have transformed drug development thus leading to the approval of targeted therapies and to the development of molecular tests to select patients that will respond to treatments. KRAS status has emerged as a negative predictor of clinical benefit from anti-EGFR antibodies in colorectal cancer, and anti-EGFR antibodies use was limited to KRAS wild type tumors. In order to ensure wide access to tumor molecular profiling, the French National Cancer Institute (INCa) has set up a national network of 28 regional molecular genetics centers. Concurrently, a nationwide external quality assessment for KRAS testing (MOKAECM) was granted to analyze reproducibility and costs. Methods 96 cell-line DNAs and 24 DNA samples from paraffin embedded tumor tissues were sent to 40 French laboratories. A total of 5448 KRAS results were collected and analyzed and a micro-costing study was performed on sites for 5 common methods by an independent team of health economists. Results This work provided a baseline picture of the accuracy and reliability of KRAS analysis in routine testing conditions at a nationwide level. Inter-laboratory Kappa values were >0.8 for KRAS results despite differences detection methods and the use of in-house technologies. Specificity was excellent with only one false positive in 1128 FFPE data, and sensitivity was higher for targeted techniques as compared to Sanger sequencing based methods that were dependent upon local expertise. Estimated reagent costs per patient ranged from €5.5 to €19.0. Conclusion The INCa has set-up a network of public laboratories dedicated to molecular oncology tests. Our results showed almost perfect agreements in KRAS testing at a nationwide level despite different testing methods ensuring a cost-effective equal access to personalized colorectal cancer treatment. PMID:23935912

  4. Performance and cost efficiency of KRAS mutation testing for metastatic colorectal cancer in routine diagnosis: the MOKAECM study, a nationwide experience.

    Directory of Open Access Journals (Sweden)

    Hélène Blons

    Full Text Available PURPOSE: Rapid advances in the understanding of cancer biology have transformed drug development thus leading to the approval of targeted therapies and to the development of molecular tests to select patients that will respond to treatments. KRAS status has emerged as a negative predictor of clinical benefit from anti-EGFR antibodies in colorectal cancer, and anti-EGFR antibodies use was limited to KRAS wild type tumors. In order to ensure wide access to tumor molecular profiling, the French National Cancer Institute (INCa has set up a national network of 28 regional molecular genetics centers. Concurrently, a nationwide external quality assessment for KRAS testing (MOKAECM was granted to analyze reproducibility and costs. METHODS: 96 cell-line DNAs and 24 DNA samples from paraffin embedded tumor tissues were sent to 40 French laboratories. A total of 5448 KRAS results were collected and analyzed and a micro-costing study was performed on sites for 5 common methods by an independent team of health economists. RESULTS: This work provided a baseline picture of the accuracy and reliability of KRAS analysis in routine testing conditions at a nationwide level. Inter-laboratory Kappa values were >0.8 for KRAS results despite differences detection methods and the use of in-house technologies. Specificity was excellent with only one false positive in 1128 FFPE data, and sensitivity was higher for targeted techniques as compared to Sanger sequencing based methods that were dependent upon local expertise. Estimated reagent costs per patient ranged from €5.5 to €19.0. CONCLUSION: The INCa has set-up a network of public laboratories dedicated to molecular oncology tests. Our results showed almost perfect agreements in KRAS testing at a nationwide level despite different testing methods ensuring a cost-effective equal access to personalized colorectal cancer treatment.

  5. Novel automatic detection of pleura and B-lines (comet-tail artifacts) on in vivo lung ultrasound scans

    Science.gov (United States)

    Moshavegh, Ramin; Hansen, Kristoffer Lindskov; Møller Sørensen, Hasse; Hemmsen, Martin Christian; Ewertsen, Caroline; Nielsen, Michael Bachmann; Jensen, Jørgen Arendt

    2016-04-01

    This paper presents a novel automatic method for detection of B-lines (comet-tail artifacts) in lung ultrasound scans. B-lines are the most commonly used artifacts for analyzing the pulmonary edema. They appear as laser-like vertical beams, which arise from the pleural line and spread down without fading to the edge of the screen. An increase in their number is associated with presence of edema. All the scans used in this study were acquired using a BK3000 ultrasound scanner (BK Ultrasound, Denmark) driving a 192-element 5:5 MHz wide linear transducer (10L2W, BK Ultrasound). The dynamic received focus technique was employed to generate the sequences. Six subjects, among those three patients after major surgery and three normal subjects, were scanned once and Six ultrasound sequences each containing 50 frames were acquired. The proposed algorithm was applied to all 300 in-vivo lung ultrasound images. The pleural line is first segmented on each image and then the B-line artifacts spreading down from the pleural line are detected and overlayed on the image. The resulting 300 images showed that the mean lateral distance between B-lines detected on images acquired from patients decreased by 20% in compare with that of normal subjects. Therefore, the method can be used as the basis of a method of automatically and qualitatively characterizing the distribution of B-lines.

  6. Field emission scanning electron microscopy (FE-SEM) as an approach for nanoparticle detection inside cells

    Czech Academy of Sciences Publication Activity Database

    Havrdová, M.; Poláková, K.; Skopalík, J.; Vůjtek, M.; Mokdad, A.; Homolková, M.; Tuček, J.; Nebesářová, Jana; Zbořil, R.

    2014-01-01

    Roč. 67, DEC 2014 (2014), s. 149-154 ISSN 0968-4328 Institutional support: RVO:60077344 Keywords : Field emission scanning electronmicroscopy (FE-SEM) * Stem cells * Iron oxide nanoparticles * Cellular morphology * Endosomes * Cell uptake Subject RIV: FD - Oncology ; Hematology Impact factor: 1.988, year: 2014

  7. Detection of sunflower oil in extra virgin olive oil by fast differential scanning calorimetry

    NARCIS (Netherlands)

    Wetten, I.A.; Herwaarden, A.W.; Splinter, R.; Boerrigter-Eenling, R.; Ruth, van S.M.

    2015-01-01

    Extra virgin olive oil (EVOO) is an economically valuable product, due to its high quality and premium price. Therefore it is vulnerable for adulteration by means of the addition of cheaper vegetable oils. Differential scanning calorimetry (DSC) has been suggested as a fast technique for the

  8. Roller-transducer scanning of wooden pallet parts for defect detection

    Science.gov (United States)

    Mohammed F. Kabir; Daniel L. Schmoldt; Mark E. Schafer

    2001-01-01

    Ultrasonic scanning experiments were conducted on two species of pallet deckboards using rolling transducers in a pitch-catch arrangement. Sound and unsound knots, cross grain, bark pockets, holes, splits, decay, and wane were characterized using several ultrasound parameters. Almost all parameters displayed sensitivity to defects distinctly from clear wood regions—...

  9. Bladder cancer detection in patients with gross haematuria: Computed tomography urography with enhancement-triggered scan versus flexible cystoscopy.

    Science.gov (United States)

    Helenius, Malin; Brekkan, Einar; Dahlman, Pär; Lönnemark, Maria; Magnusson, Anders

    2015-01-01

    Computed tomography urography (CTU) can be used to direct further investigation of patients if the bladder tumour detection rate is high. The aim of this study was to compare a CTU protocol including an enhancement-triggered scan and flexible cystoscopy for detecting bladder tumours. Patients with gross haematuria undergoing CTU during 2005-2008 were included. For patients younger than 50 years the CTU protocol included unenhanced, enhancement-triggered corticomedullary, and excretory phases. Patients older than 50 years followed the same protocol plus a nephrographic phase. The entire urinary tract was examined in all phases. Of 435 patients, 55 patients were diagnosed with bladder tumour. CTU detected bladder tumour in 48 patients (87%). Five CTU examination reports were false positive. With CTU, sensitivity for finding bladder tumour was 0.87, specificity 0.99, positive predictive value (PPV) 0.91 and negative predictive value (NPV) 0.98. Cystoscopy detected bladder tumour in 48 patients (87%) and had one false-positive finding, resulting in sensitivity of 0.87, specificity 1.0, PPV 0.98 and NPV 0.98. The detection rate of bladder tumours for the CTU protocol including an enhancement-triggered scan was high and comparable to flexible cystoscopy. Hence, this protocol could be used to assess the bladder as the primary investigation and direct further investigation of the patient.

  10. Evaluation of Intraductal Ultrasonography, Endoscopic Brush Cytology and K-ras, P53 Gene Mutation in the Early Diagnosis of Malignant Bile Duct Stricture.

    Science.gov (United States)

    Huang, Ping; Zhang, Hao; Zhang, Xiao-Feng; Zhang, Xiao; Lyu, Wen; Fan, Zhen

    2015-07-20

    In qualitative diagnosis of bile duct stenosis, single diagnostic measure is difficult to make a correct diagnosis, to combine several diagnostic techniques may be helpful to make an accurate diagnosis. The aim of this study was to evaluate the value of intraductal ultrasonography (IDUS), endoscopic brush cytology and K-ras, P53 gene mutation in the early diagnosis of malignant biliary stricture. From February 2012 to February 2013, 84 patients with suspected malignant biliary stricture were performed IDUS firstly, then endoscopic brush cytology and finally K-ras, P53 gene mutation detection, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of all above ways were evaluated and compared. Of 84 patients, 52 cases were ultimately diagnosed malignant biliary stenosis; of which, 9 cases had no recurrence or metastasis to other organs after radical operation during the follow-up period. IDUS combined with brush cytology and K-ras + P53 gene mutation detection had obvious advantage in the sensitivity, accuracy and negative predictive value than any other joint detection and single detection (the advantage was more significant compared with IDUS + brush cytology or any single detection P ras and IDUS + brush cytology or IDUS (P ras (P > 0.05). IDUS combined with brush cytology and K-ras, P53 gene mutation detection is better than the separate detection and contribute to the early diagnosis of malignant biliary stricture. Its more widespread use is recommended.

  11. KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis.

    Science.gov (United States)

    Lohinai, Zoltan; Klikovits, Thomas; Moldvay, Judit; Ostoros, Gyula; Raso, Erzsebet; Timar, Jozsef; Fabian, Katalin; Kovalszky, Ilona; Kenessey, István; Aigner, Clemens; Renyi-Vamos, Ferenc; Klepetko, Walter; Dome, Balazs; Hegedus, Balazs

    2017-01-04

    Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17.4%), brain (16.8%), pleura (15.6%) and liver (11%). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p = 0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17% (p < 0.001) and 16% (p = 0.02) vs 33%, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRAS-wild-type vs KRAS-mutant; median OS 9.7 v 3.7 months; HR, 0.49; 95% CI, 0.31 to 0.79; p  = 0.003). Our study suggests that KRAS mutation frequency in LADC patients shows a metastatic site dependent variation and, moreover, that the presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases.

  12. A surface-scanning coil detector for real-time, in-situ detection of bacteria on fresh food surfaces.

    Science.gov (United States)

    Chai, Yating; Horikawa, Shin; Li, Suiqiong; Wikle, Howard C; Chin, Bryan A

    2013-12-15

    Proof-in-principle of a new surface-scanning coil detector has been demonstrated. This new coil detector excites and measures the resonant frequency of free-standing magnetoelastic (ME) biosensors that may now be placed outside the coil boundaries. With this coil design, the biosensors are no longer required to be placed inside the coil before frequency measurement. Hence, this new coil enables bacterial pathogens to be detected on fresh food surfaces in real-time and in-situ. The new coil measurement technique was demonstrated using an E2 phage-coated ME biosensor to detect Salmonella typhimurium on tomato surfaces. Real-time, in-situ detection was achieved with a limit of detection (LOD) statistically determined to be lower than 1.5×10(3) CFU/mm(2) with a confidence level of difference higher than 95% (p<0.05). Copyright © 2013 Elsevier B.V. All rights reserved.

  13. The development of the line-scan image recognition algorithm for the detection of frass on mature tomatoes

    Science.gov (United States)

    Yang, Chun-Chieh; Kim, Moon S.; Millner, Pat; Chao, Kuanglin; Chan, Diane E.

    2012-05-01

    In this research, a multispectral algorithm derived from hyperspectral line-scan fluorescence imaging under violet LED excitation was developed for the detection of frass contamination on mature tomatoes. The algorithm utilized the fluorescence intensities at two wavebands, 664 nm and 690 nm, for computation of the simple ratio function for effective detection of frass contamination. The contamination spots were created on the tomato surfaces using four concentrations of aqueous frass dilutions. The algorithms could detect more than 99% of the 0.2 g/ml and 0.1 g/ml frass contamination spots and successfully differentiated these spots from clean tomato surfaces. The results demonstrated that the simple multispectral fluorescence imaging algorithms based on violet LED excitation can be appropriate to detect frass on tomatoes in high-speed post-harvest processing lines.

  14. Molecular Characterization of KRAS, BRAF, and EGFR Genes in Cases with Prostatic Adenocarcinoma; Reporting Bioinformatics Description and Recurrent Mutations.

    Science.gov (United States)

    Salmaninejad, Arash; Ghadami, Shirin; Dizaji, Majid Zaki; Golchehre, Zahra; Estiar, Mehrdad Asghari; Zamani, Mohammad Reza; Ebrahimzadeh-Vesal, Reza; Nowroozi, Mohammad Reza; Shakoori, Abbas

    2015-01-01

    Prostate cancer is one of the most common cancers which develops by mutations and/or other genetic alterations in specific genes. Regarding the previous studies in literature predominant mutations take place in KRAS, BRAF, and EGFR genes in special types of cancers. In this research, we attempt to identify the prevalence and significant role of the possible mutations in EGFR exons 18-21, KRAS codon 12, 13, and 61, and BRAF codon 600 mutations in tumoral tissue specimens from patients with prostatic adenocarcinoma. Furthermore, in this research, it has been attempted to investigate the molecular characteristics of these genes in terms of bioinformatic aspects. A total of 35 prostatic adenocarcinoma fresh tissue samples, enriched in neoplastic cells, were obtained from the Cancer Institute of Iran. The presence of mutations at codons 12, 13 and 61 of KRAS, codon 600 of BRAF and EGFR exons 18-21 were determined by direct Sanger sequencing. To evaluate the molecular features, structure, and post-translation modification of those genes, a bioinformatics survey was performed using the SWISS-MODEL (http://swissmodel.expasy.org) and NetPhos 2.0 (http://www.cbs.dtu.dk/services/NetPhos/) Server. Also, using bioinformatics software, the phylogeny tree of the mutations was drawn. Mutations of codons 12 and 13 of KRAS were found in 2 of the 35 prostatic adenocarcinomas. Two cases carried homozygous mutations on exon 2 in codon 12 (G12V) and codon 13 (G13D). Also, no mutation was detected at BRAF codon 600 and EGFR exons 18-21 in any of the samples. Based on the group of patients with prostate adenocarcinoma, our research shows that the mutations in codons 12 and 13 of KRAS are the most common in prostate carcinomas. Noting these results and the molecular pathway of this gene, there is a possible more perceptible role for this gene in the pathogenesis of prostatic carcinoma. However, according to our finding, as in previous studies, the role of BRAF and EGFR gene mutations in

  15. Presence of activating KRAS mutations correlates significantly with expression of tumour suppressor genes DCN and TPM1 in colorectal cancer.

    Science.gov (United States)

    Mlakar, Vid; Berginc, Gasper; Volavsek, Metka; Stor, Zdravko; Rems, Miran; Glavac, Damjan

    2009-08-13

    Despite identification of the major genes and pathways involved in the development of colorectal cancer (CRC), it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that lead towards CRC. Therefore we wanted to improve our understanding of the genetic mechanisms of CRC development. We used microarrays to identify novel genes involved in the development of CRC. Real time PCR was used for mRNA expression as well as to search for chromosomal abnormalities within candidate genes. The correlation between the expression obtained by real time PCR and the presence of the KRAS mutation was investigated. We detected significant previously undescribed underexpression in CRC for genes SLC26A3, TPM1 and DCN, with a suggested tumour suppressor role. We also describe the correlation between TPM1 and DCN expression and the presence of KRAS mutations in CRC. When searching for chromosomal abnormalities, we found deletion of the TPM1 gene in one case of CRC, but no deletions of DCN and SLC26A3 were found. Our study provides further evidence of decreased mRNA expression of three important tumour suppressor genes in cases of CRC, thus implicating them in the development of this type of cancer. Moreover, we found underexpression of the TPM1 gene in a case of CRCs without KRAS mutations, showing that TPM1 might serve as an alternative path of development of CRC. This downregulation could in some cases be mediated by deletion of the TPM1 gene. On the other hand, the correlation of DCN underexpression with the presence of KRAS mutations suggests that DCN expression is affected by the presence of activating KRAS mutations, lowering the amount of the important tumour suppressor protein decorin.

  16. Diagnostic value of saccoradiculography and of cat scan to detect stenosis of the lumbar canal

    Energy Technology Data Exchange (ETDEWEB)

    Arrault, I.; Benoist, M.; Rocolle, J.; Busson, J.; Lassale, B.; Deburge, A.

    1987-10-01

    Radiculographic X-rays and CAT scans of 60 patients operated on for stenosis of the lumbar canal were analysed separately and retrospectively by rheumatologists, a radiologist and surgeons working jointly, without knowledge of findings revealed by surgery. Comparison of findings with a detailed surgical report reveals that in the case of central lumbar canal stenosis, CAT scan provides a higher degree of reliability (72%) in diagnosis than does radiculography (56%). With lateral stenosis of the lateral cleft, reliability of both tests is identical (62%). The diagnostic deficiencies of these two examinations are discussed as well as diagnostic criteria employed and possible avenues of research. Currently, in the case of stenosis of the lumbar canal, it is still necessary to perform both of these examinations in combination and to accept the fact that, in certain cases, only one of the two tests reveals the stenosis, to be able to attain a preoperative rate of correct diagnosis greater than 80%.

  17. Phase Error Caused by Speed Mismatch Analysis in the Line-Scan Defect Detection by Using Fourier Transform Technique

    Directory of Open Access Journals (Sweden)

    Eryi Hu

    2015-01-01

    Full Text Available The phase error caused by the speed mismatch issue is researched in the line-scan images capturing 3D profile measurement. The experimental system is constructed by a line-scan CCD camera, an object moving device, a digital fringe pattern projector, and a personal computer. In the experiment procedure, the detected object is moving relative to the image capturing system by using a motorized translation stage in a stable velocity. The digital fringe pattern is projected onto the detected object, and then the deformed patterns are captured and recorded in the computer. The object surface profile can be calculated by the Fourier transform profilometry. However, the moving speed mismatch error will still exist in most of the engineering application occasion even after an image system calibration. When the moving speed of the detected object is faster than the expected value, the captured image will be compressed in the moving direction of the detected object. In order to overcome this kind of measurement error, an image recovering algorithm is proposed to reconstruct the original compressed image. Thus, the phase values can be extracted much more accurately by the reconstructed images. And then, the phase error distribution caused by the speed mismatch is analyzed by the simulation and experimental methods.

  18. Intra-tumoral Heterogeneity of KRAS and BRAF Mutation Status in Patients with Advanced Colorectal Cancer (aCRC and Cost-Effectiveness of Multiple Sample Testing

    Directory of Open Access Journals (Sweden)

    Susan D. Richman

    2011-01-01

    Full Text Available KRAS mutation status is established as a predictive biomarker of benefit from anti-EGFr therapies. Mutations are normally assessed using DNA extracted from one formalin-fixed, paraffin-embedded (FFPE tumor block. We assessed heterogeneity of KRAS and BRAF mutation status intra-tumorally (multiple blocks from the same primary tumor. We also investigated the utility and efficiency of genotyping a ‘DNA cocktail’ prepared from multiple blocks. We studied 68 consenting patients in two randomized clinical trials. DNA was extracted, from ≥2 primary tumor FFPE blocks per patient. DNA was genotyped by pyrosequencing for KRAS codons 12, 13 and 61 and BRAF codon 600. In patients with heterogeneous mutation status, DNA cocktails were prepared and genotyped. Among 69 primary tumors in 68 patients, 7 (10.1% showed intratumoral heterogeneity; 5 (7.2% at KRAS codons 12, 13 and 2 (2.9% at BRAF codon 600. In patients displaying heterogeneity, the relevant KRAS or BRAF mutation was also identified in ‘DNA cocktail’ samples when including DNA from mutant and wild-type blocks. Heterogeneity is uncommon but not insignificant. Testing DNA from a single block will wrongly assign wild-type status to 10% patients. Testing more than one block, or preferably preparation of a ‘DNA cocktail’ from two or more tumor blocks, improves mutation detection at minimal extra cost.

  19. An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer.

    Science.gov (United States)

    Vallejo, Adrian; Perurena, Naiara; Guruceaga, Elisabet; Mazur, Pawel K; Martinez-Canarias, Susana; Zandueta, Carolina; Valencia, Karmele; Arricibita, Andrea; Gwinn, Dana; Sayles, Leanne C; Chuang, Chen-Hua; Guembe, Laura; Bailey, Peter; Chang, David K; Biankin, Andrew; Ponz-Sarvise, Mariano; Andersen, Jesper B; Khatri, Purvesh; Bozec, Aline; Sweet-Cordero, E Alejandro; Sage, Julien; Lecanda, Fernando; Vicent, Silve

    2017-02-21

    KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. Furthermore, FOSL1 genetic inhibition is detrimental to both KRAS-driven tumour types. Mechanistically, FOSL1 links the KRAS oncogene to components of the mitotic machinery, a pathway previously postulated to function orthogonally to oncogenic KRAS. FOSL1 targets include AURKA, whose inhibition impairs viability of mutant KRAS cells. Lastly, combination of AURKA and MEK inhibitors induces a deleterious effect on mutant KRAS cells. Our findings unveil KRAS downstream effectors that provide opportunities to treat KRAS-driven cancers.

  20. An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer

    Science.gov (United States)

    Vallejo, Adrian; Perurena, Naiara; Guruceaga, Elisabet; Mazur, Pawel K.; Martinez-Canarias, Susana; Zandueta, Carolina; Valencia, Karmele; Arricibita, Andrea; Gwinn, Dana; Sayles, Leanne C.; Chuang, Chen-Hua; Guembe, Laura; Bailey, Peter; Chang, David K.; Biankin, Andrew; Ponz-Sarvise, Mariano; Andersen, Jesper B.; Khatri, Purvesh; Bozec, Aline; Sweet-Cordero, E. Alejandro; Sage, Julien; Lecanda, Fernando; Vicent, Silve

    2017-01-01

    KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. Furthermore, FOSL1 genetic inhibition is detrimental to both KRAS-driven tumour types. Mechanistically, FOSL1 links the KRAS oncogene to components of the mitotic machinery, a pathway previously postulated to function orthogonally to oncogenic KRAS. FOSL1 targets include AURKA, whose inhibition impairs viability of mutant KRAS cells. Lastly, combination of AURKA and MEK inhibitors induces a deleterious effect on mutant KRAS cells. Our findings unveil KRAS downstream effectors that provide opportunities to treat KRAS-driven cancers. PMID:28220783

  1. Automated detection and quantification of micronodules in thoracic CT scans to identify subjects at risk for silicosis

    Science.gov (United States)

    Jacobs, C.; Opdam, S. H. T. T.; van Rikxoort, E. M.; Mets, O. M.; Rooyackers, J.; de Jong, P. A.; Prokop, M.; van Ginneken, B.

    2014-03-01

    Silica dust-exposed individuals are at high risk of developing silicosis, a fatal and incurable lung disease. The presence of disseminated micronodules on thoracic CT is the radiological hallmark of silicosis but locating micronodules, to identify subjects at risk, is tedious for human observers. We present a computer-aided detection scheme to automatically find micronodules and quantify micronodule load. The system used lung segmentation, template matching, and a supervised classification scheme. The system achieved a promising sensitivity of 84% at an average of 8.4 false positive marks per scan. In an independent data set of 54 CT scans in which we defined four risk categories, the CAD system automatically classified 83% of subjects correctly, and obtained a weighted kappa of 0.76.

  2. Roller-transducer scanning of wooden pallet parts for defect detection

    Science.gov (United States)

    Kabir, M. F.; Schmoldt, D. L.; Schafer, M. E.

    2001-04-01

    Ultrasonic scanning experiments were conducted on two species of pallet deckboards using rolling transducers in a pitch-catch arrangement. Sound and unsound knots, cross grain, bark pockets, holes, splits, decay, and wane were characterized using several ultrasound parameters. Almost all parameters displayed sensitivity to defects distinctly from clear wood regions—being greatest for unsound knots, bark pockets, decay, holes, splits, and less for sound knots and cross grain. This study supports our conjecture that on-line inspection of wooden pallet parts is possible using rolling-transducer ultrasonic inspection.

  3. Panitumumab Use in Metastatic Colorectal Cancer and Patterns of KRAS Testing: Results from a Europe-Wide Physician Survey and Medical Records Review.

    Directory of Open Access Journals (Sweden)

    Jörg Trojan

    Full Text Available From 2008-2013, the European indication for panitumumab required that patients' tumor KRAS exon 2 mutation status was known prior to starting treatment. To evaluate physician awareness of panitumumab prescribing information and how physicians prescribe panitumumab in patients with metastatic colorectal cancer (mCRC, two European multi-country, cross-sectional, observational studies were initiated in 2012: a physician survey and a medical records review. The first two out of three planned rounds for each study are reported.The primary objective in the physician survey was to estimate the prevalence of KRAS testing, and in the medical records review, it was to evaluate the effect of test results on patterns of panitumumab use. The medical records review study also included a pathologists' survey.In the physician survey, nearly all oncologists (299/301 were aware of the correct panitumumab indication and the need to test patients' tumor KRAS status before treatment with panitumumab. Nearly all oncologists (283/301 had in the past 6 months of clinical practice administered panitumumab correctly to mCRC patients with wild-type KRAS status. In the medical records review, 97.5% of participating oncologists (77/79 conducted a KRAS test for all of their patients prior to prescribing panitumumab. Four patients (1.3% did not have tumor KRAS mutation status tested prior to starting panitumumab treatment. Approximately one-quarter of patients (85/306 were treated with panitumumab and concurrent oxaliplatin-containing chemotherapy; of these, 83/85 had confirmed wild-type KRAS status prior to starting panitumumab treatment. All 56 referred laboratories that participated used a Conformité Européenne-marked or otherwise validated KRAS detection method, and nearly all (55/56 participated in a quality assurance scheme.There was a high level of knowledge amongst oncologists around panitumumab prescribing information and the need to test and confirm patients

  4. Panitumumab Use in Metastatic Colorectal Cancer and Patterns of KRAS Testing: Results from a Europe-Wide Physician Survey and Medical Records Review.

    Science.gov (United States)

    Trojan, Jörg; Mineur, Laurent; Tomášek, Jiří; Rouleau, Etienne; Fabian, Pavel; de Maglio, Giovanna; García-Alfonso, Pilar; Aprile, Giuseppe; Taylor, Aliki; Kafatos, George; Downey, Gerald; Terwey, Jan-Henrik; van Krieken, J Han

    2015-01-01

    From 2008-2013, the European indication for panitumumab required that patients' tumor KRAS exon 2 mutation status was known prior to starting treatment. To evaluate physician awareness of panitumumab prescribing information and how physicians prescribe panitumumab in patients with metastatic colorectal cancer (mCRC), two European multi-country, cross-sectional, observational studies were initiated in 2012: a physician survey and a medical records review. The first two out of three planned rounds for each study are reported. The primary objective in the physician survey was to estimate the prevalence of KRAS testing, and in the medical records review, it was to evaluate the effect of test results on patterns of panitumumab use. The medical records review study also included a pathologists' survey. In the physician survey, nearly all oncologists (299/301) were aware of the correct panitumumab indication and the need to test patients' tumor KRAS status before treatment with panitumumab. Nearly all oncologists (283/301) had in the past 6 months of clinical practice administered panitumumab correctly to mCRC patients with wild-type KRAS status. In the medical records review, 97.5% of participating oncologists (77/79) conducted a KRAS test for all of their patients prior to prescribing panitumumab. Four patients (1.3%) did not have tumor KRAS mutation status tested prior to starting panitumumab treatment. Approximately one-quarter of patients (85/306) were treated with panitumumab and concurrent oxaliplatin-containing chemotherapy; of these, 83/85 had confirmed wild-type KRAS status prior to starting panitumumab treatment. All 56 referred laboratories that participated used a Conformité Européenne-marked or otherwise validated KRAS detection method, and nearly all (55/56) participated in a quality assurance scheme. There was a high level of knowledge amongst oncologists around panitumumab prescribing information and the need to test and confirm patients' tumors as

  5. Ossification defects detected in CT scans represent early osteochondrosis in the distal femur of piglets.

    Science.gov (United States)

    Olstad, Kristin; Kongsro, Jørgen; Grindflek, Eli; Dolvik, Nils Ivar

    2014-08-01

    The purpose of the current study was to validate the use of CT for selection against osteochondrosis in pigs by calculating positive predictive value and comparing it to the positive predictive value of macroscopic evaluation, using histological examination as the reference standard. Eighteen male, hereditarily osteochondrosis-predisposed piglets underwent terminal examination at biweekly intervals from the ages of 82-180 days old, including CT scanning, macroscopic, and histological evaluation of the left distal femur. Areas of ischemic chondronecrosis (osteochondrosis) were confirmed in histological sections from 44/56 macroscopically suspected lesions, resulting in a positive predictive value of 79% (95% CI: 67-84%). Suspected lesions, that is; focal, radiolucent defects in the ossification front in CT scans corresponded to areas of ischemic chondronecrosis in 36/36 histologically examined lesions, resulting in a positive predictive value of 100% (95% CI: 90-100%). CT was superior to macroscopic evaluation for diagnosis of early stages of osteochondrosis in the distal femur of piglets. The current histologically validated observations can potentially be extrapolated to diagnostic monitoring of juvenile osteochondritis dissecans in children, or to animal models of human juvenile articular cartilage injury and repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. AB029. The clinical significance of RigiScan plus detection

    OpenAIRE

    Gao, Bing; Mu, Hongtao; Zhang, Zhichao; Yuan, Yiming; Peng, Jing; Xin, Zhongcheng; Guo, Yinglu

    2016-01-01

    Erectile dysfunction (ED) is a common disease in male outpatient service, the penis hardness testing of ED in the clinical diagnosis has important significance, past some detection methods, such as nocturnal penile tumescence monitoring (NPT) due to time-consuming is not easy in outpatient service and a vasodilator agent intervention tests such as color Doppler detection due to the injection of drugs in the penis is difficult for patients to accept. In 1965 night rapid eye movement sleep phas...

  7. Coronary Calcium Scan

    Science.gov (United States)

    ... Back To Health Topics / Coronary Calcium Scan Coronary Calcium Scan Also known as Calcium Scan Test A coronary calcium scan is a CT scan of your heart that detects and measures the amount of calcium in the walls of your coronary arteries. Overview ...

  8. Detecting central fixation by means of artificial neural networks in a pediatric vision screener using retinal birefringence scanning.

    Science.gov (United States)

    Gramatikov, Boris I

    2017-04-27

    Reliable detection of central fixation and eye alignment is essential in the diagnosis of amblyopia ("lazy eye"), which can lead to blindness. Our lab has developed and reported earlier a pediatric vision screener that performs scanning of the retina around the fovea and analyzes changes in the polarization state of light as the scan progresses. Depending on the direction of gaze and the instrument design, the screener produces several signal frequencies that can be utilized in the detection of central fixation. The objective of this study was to compare artificial neural networks with classical statistical methods, with respect to their ability to detect central fixation reliably. A classical feedforward, pattern recognition, two-layer neural network architecture was used, consisting of one hidden layer and one output layer. The network has four inputs, representing normalized spectral powers at four signal frequencies generated during retinal birefringence scanning. The hidden layer contains four neurons. The output suggests presence or absence of central fixation. Backpropagation was used to train the network, using the gradient descent algorithm and the cross-entropy error as the performance function. The network was trained, validated and tested on a set of controlled calibration data obtained from 600 measurements from ten eyes in a previous study, and was additionally tested on a clinical set of 78 eyes, independently diagnosed by an ophthalmologist. In the first part of this study, a neural network was designed around the calibration set. With a proper architecture and training, the network provided performance that was comparable to classical statistical methods, allowing perfect separation between the central and paracentral fixation data, with both the sensitivity and the specificity of the instrument being 100%. In the second part of the study, the neural network was applied to the clinical data. It allowed reliable separation between normal subjects

  9. Automated Fovea Detection in Spectral Domain Optical Coherence Tomography Scans of Exudative Macular Disease

    Directory of Open Access Journals (Sweden)

    Jing Wu

    2016-01-01

    Full Text Available In macular spectral domain optical coherence tomography (SD-OCT volumes, detection of the foveal center is required for accurate and reproducible follow-up studies, structure function correlation, and measurement grid positioning. However, disease can cause severe obscuring or deformation of the fovea, thus presenting a major challenge in automated detection. We propose a fully automated fovea detection algorithm to extract the fovea position in SD-OCT volumes of eyes with exudative maculopathy. The fovea is classified into 3 main appearances to both specify the detection algorithm used and reduce computational complexity. Based on foveal type classification, the fovea position is computed based on retinal nerve fiber layer thickness. Mean absolute distance between system and clinical expert annotated fovea positions from a dataset comprised of 240 SD-OCT volumes was 162.3 µm in cystoid macular edema and 262 µm in nAMD. The presented method has cross-vendor functionality, while demonstrating accurate and reliable performance close to typical expert interobserver agreement. The automatically detected fovea positions may be used as landmarks for intra- and cross-patient registration and to create a joint reference frame for extraction of spatiotemporal features in “big data.” Furthermore, reliable analyses of retinal thickness, as well as retinal structure function correlation, may be facilitated.

  10. LASER SCANNING APPLICATION FOR DETECTION OF HUMAN POSTURE DISTORTION DURING MASS EXAMINATIONS

    Directory of Open Access Journals (Sweden)

    R. L. Voinov

    2014-03-01

    Full Text Available Identification of human posture distortion in the early stages is an important task, which makes it possible to adjust the onset of the disease with just exercise and without the use of drugs. Existing methods for monitoring of human posture assessment do not meet modern requirements for speed of data acquisition and processing. Real time evaluation of human posture distortion in static and dynamic modes is possible by using a laser scanner. The paper deals with a three-dimensional laser scanning method for determining human posture. The device designed on the basis of its examination gives the possibility for real-time static and dynamic modes. Characteristic feature of the laser scanner is the presence of automated servo rotatable measuring head in two planes (vertical and horizontal with a density of up to tens of measurement points per square centimeter.

  11. Modern Detection of Prostate Cancer's Bone Metastasis: Is the Bone Scan Era Over?

    Directory of Open Access Journals (Sweden)

    Bertrand Tombal

    2012-01-01

    Full Text Available Prostate cancer cells have an exquisite tropism for bone, which clinically translates into the highest rate of bone metastases amongst male cancers. Although in the latest years there has been an active development of new “bone targeted” therapies, modern diagnostic techniques for bone metastases still relies mostly on 99mTc bone scanning (BS and plain X-ray. BS dramatically lacks specificity and sensitivity. Recent publications using modern imaging technologies have clearly pinpointed that BS grossly underestimates the true prevalence of bone metastasis. In addition BS does not allow tumour measurement and is, therefore, not appropriate to monitor response to therapy. This might be extremely important in patients harbouring high-risk localized disease that are eventually candidate for local therapy. Here we reviewed what are the emerging imaging strategies that are likely to supplant BS and to what extent they can be used in the clinic already.

  12. Obstacle avoidance, visual detection performance, and eye-scanning behavior of glaucoma patients in a driving simulator: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Rocío Prado Vega

    Full Text Available The objective of this study was to evaluate differences in driving performance, visual detection performance, and eye-scanning behavior between glaucoma patients and control participants without glaucoma. Glaucoma patients (n = 23 and control participants (n = 12 completed four 5-min driving sessions in a simulator. The participants were instructed to maintain the car in the right lane of a two-lane highway while their speed was automatically maintained at 100 km/h. Additional tasks per session were: Session 1: none, Session 2: verbalization of projected letters, Session 3: avoidance of static obstacles, and Session 4: combined letter verbalization and avoidance of static obstacles. Eye-scanning behavior was recorded with an eye-tracker. Results showed no statistically significant differences between patients and control participants for lane keeping, obstacle avoidance, and eye-scanning behavior. Steering activity, number of missed letters, and letter reaction time were significantly higher for glaucoma patients than for control participants. In conclusion, glaucoma patients were able to avoid objects and maintain a nominal lane keeping performance, but applied more steering input than control participants, and were more likely than control participants to miss peripherally projected stimuli. The eye-tracking results suggest that glaucoma patients did not use extra visual search to compensate for their visual field loss. Limitations of the study, such as small sample size, are discussed.

  13. The use of the temporal scan statistic to detect methicillin-resistant Staphylococcus aureus clusters in a community hospital.

    Science.gov (United States)

    Faires, Meredith C; Pearl, David L; Ciccotelli, William A; Berke, Olaf; Reid-Smith, Richard J; Weese, J Scott

    2014-07-08

    In healthcare facilities, conventional surveillance techniques using rule-based guidelines may result in under- or over-reporting of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks, as these guidelines are generally unvalidated. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting MRSA clusters, validate clusters using molecular techniques and hospital records, and determine significant differences in the rate of MRSA cases using regression models. Patients admitted to a community hospital between August 2006 and February 2011, and identified with MRSA>48 hours following hospital admission, were included in this study. Between March 2010 and February 2011, MRSA specimens were obtained for spa typing. MRSA clusters were investigated using a retrospective temporal scan statistic. Tests were conducted on a monthly scale and significant clusters were compared to MRSA outbreaks identified by hospital personnel. Associations between the rate of MRSA cases and the variables year, month, and season were investigated using a negative binomial regression model. During the study period, 735 MRSA cases were identified and 167 MRSA isolates were spa typed. Nine different spa types were identified with spa type 2/t002 (88.6%) the most prevalent. The temporal scan statistic identified significant MRSA clusters at the hospital (n=2), service (n=16), and ward (n=10) levels (P ≤ 0.05). Seven clusters were concordant with nine MRSA outbreaks identified by hospital staff. For the remaining clusters, seven events may have been equivalent to true outbreaks and six clusters demonstrated possible transmission events. The regression analysis indicated years 2009-2011, compared to 2006, and months March and April, compared to January, were associated with an increase in the rate of MRSA cases (P ≤ 0.05). The application of the temporal scan statistic identified several MRSA clusters that were not detected by hospital

  14. Detection of circulating tumour cells in peripheral blood with an automated scanning fluorescence microscope.

    Science.gov (United States)

    Ntouroupi, T G; Ashraf, S Q; McGregor, S B; Turney, B W; Seppo, A; Kim, Y; Wang, X; Kilpatrick, M W; Tsipouras, P; Tafas, T; Bodmer, W F

    2008-09-02

    We have developed an automated, highly sensitive and specific method for identifying and enumerating circulating tumour cells (CTCs) in the blood. Blood samples from 10 prostate, 25 colorectal and 4 ovarian cancer patients were analysed. Eleven healthy donors and seven men with elevated serum prostate-specific antigen (PSA) levels but no evidence of malignancy served as controls. Spiking experiments with cancer cell lines were performed to estimate recovery yield. Isolation was performed either by density gradient centrifugation or by filtration, and the CTCs were labelled with monoclonal antibodies against cytokeratins 7/8 and either AUA1 (against EpCam) or anti-PSA. The slides were analysed with the Ikoniscope robotic fluorescence microscope imaging system. Spiking experiments showed that less than one epithelial cell per millilitre of blood could be detected, and that fluorescence in situ hybridisation (FISH) could identify chromosomal abnormalities in these cells. No positive cells were detected in the 11 healthy control samples. Circulating tumour cells were detected in 23 out of 25 colorectal, 10 out of 10 prostate and 4 out of 4 ovarian cancer patients. Five samples (three colorectal and two ovarian) were analysed by FISH for chromosomes 7 and 8 combined and all had significantly more than four dots per cell. We have demonstrated an Ikoniscope based relatively simple and rapid procedure for the clear-cut identification of CTCs. The method has considerable promise for screening, early detection of recurrence and evaluation of treatment response for a wide variety of carcinomas.

  15. Time-resolved detection of surface plasmon polaritons with a scanning tunneling microscope

    DEFF Research Database (Denmark)

    Keil, Ulrich Dieter Felix; Ha, T.; Jensen, Jacob Riis

    1998-01-01

    We present the time-resolved detection of surface plasmon polaritons with an STM. The results indicate that the time resolved signal is due to rectification of coherently superimposed plasmon voltages. The comparison with differential reflectivity measurements shows that the tip itself influences...

  16. Bag-of-visual-phrases and hierarchical deep models for traffic sign detection and recognition in mobile laser scanning data

    Science.gov (United States)

    Yu, Yongtao; Li, Jonathan; Wen, Chenglu; Guan, Haiyan; Luo, Huan; Wang, Cheng

    2016-03-01

    This paper presents a novel algorithm for detection and recognition of traffic signs in mobile laser scanning (MLS) data for intelligent transportation-related applications. The traffic sign detection task is accomplished based on 3-D point clouds by using bag-of-visual-phrases representations; whereas the recognition task is achieved based on 2-D images by using a Gaussian-Bernoulli deep Boltzmann machine-based hierarchical classifier. To exploit high-order feature encodings of feature regions, a deep Boltzmann machine-based feature encoder is constructed. For detecting traffic signs in 3-D point clouds, the proposed algorithm achieves an average recall, precision, quality, and F-score of 0.956, 0.946, 0.907, and 0.951, respectively, on the four selected MLS datasets. For on-image traffic sign recognition, a recognition accuracy of 97.54% is achieved by using the proposed hierarchical classifier. Comparative studies with the existing traffic sign detection and recognition methods demonstrate that our algorithm obtains promising, reliable, and high performance in both detecting traffic signs in 3-D point clouds and recognizing traffic signs on 2-D images.

  17. An exploratory study to detect Ménière’s disease in conventional MRI scans using radiomics

    Directory of Open Access Journals (Sweden)

    E. L. van den Burg

    2016-11-01

    radiomics approach on high resolution T2 weighted MRI scans of the labyrinth. Further research should be aimed at validating these results and translating them in a potential clinical diagnostic method to detect Ménière’s disease in MRI scans.

  18. A new microarray substrate for ultra-sensitive genotyping of KRAS and BRAF gene variants in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Silvia Galbiati

    Full Text Available Molecular diagnostics of human cancers may increase accuracy in prognosis, facilitate the selection of the optimal therapeutic regimen, improve patient outcome, reduce costs of treatment and favour development of personalized approaches to patient care. Moreover sensitivity and specificity are fundamental characteristics of any diagnostic method. We developed a highly sensitive microarray for the detection of common KRAS and BRAF oncogenic mutations. In colorectal cancer, KRAS and BRAF mutations have been shown to identify a cluster of patients that does not respond to anti-EGFR therapies; the identification of these mutations is therefore clinically extremely important. To verify the technical characteristics of the microarray system for the correct identification of the KRAS mutational status at the two hotspot codons 12 and 13 and of the BRAF(V600E mutation in colorectal tumor, we selected 75 samples previously characterized by conventional and CO-amplification at Lower Denaturation temperature-PCR (COLD-PCR followed by High Resolution Melting analysis and direct sequencing. Among these samples, 60 were collected during surgery and immediately steeped in RNAlater while the 15 remainders were formalin-fixed and paraffin-embedded (FFPE tissues. The detection limit of the proposed method was different for the 7 KRAS mutations tested and for the V600E BRAF mutation. In particular, the microarray system has been able to detect a minimum of about 0.01% of mutated alleles in a background of wild-type DNA. A blind validation displayed complete concordance of results. The excellent agreement of the results showed that the new microarray substrate is highly specific in assigning the correct genotype without any enrichment strategy.

  19. Hyperspectral reflectance and fluorescence line-scan imaging system for online detection of fecal contamination on apples

    Science.gov (United States)

    Kim, Moon S.; Cho, Byoung-Kwan; Yang, Chun-Chieh; Chao, Kaunglin; Lefcourt, Alan M.; Chen, Yud-Ren

    2006-10-01

    We have developed nondestructive opto-electronic imaging techniques for rapid assessment of safety and wholesomeness of foods. A recently developed fast hyperspectral line-scan imaging system integrated with a commercial apple-sorting machine was evaluated for rapid detection of animal feces matter on apples. Apples obtained from a local orchard were artificially contaminated with cow feces. For the online trial, hyperspectral images with 60 spectral channels, reflectance in the visible to near infrared regions and fluorescence emissions with UV-A excitation, were acquired from apples moving at a processing sorting-line speed of three apples per second. Reflectance and fluorescence imaging required a passive light source, and each method used independent continuous wave (CW) light sources. In this paper, integration of the hyperspectral imaging system with the commercial applesorting machine and preliminary results for detection of fecal contamination on apples, mainly based on the fluorescence method, are presented.

  20. Automated terrestrial laser scanning with near-real-time change detection - monitoring of the Séchilienne landslide

    Science.gov (United States)

    Kromer, Ryan A.; Abellán, Antonio; Hutchinson, D. Jean; Lato, Matt; Chanut, Marie-Aurelie; Dubois, Laurent; Jaboyedoff, Michel

    2017-05-01

    We present an automated terrestrial laser scanning (ATLS) system with automatic near-real-time change detection processing. The ATLS system was tested on the Séchilienne landslide in France for a 6-week period with data collected at 30 min intervals. The purpose of developing the system was to fill the gap of high-temporal-resolution TLS monitoring studies of earth surface processes and to offer a cost-effective, light, portable alternative to ground-based interferometric synthetic aperture radar (GB-InSAR) deformation monitoring. During the study, we detected the flux of talus, displacement of the landslide and pre-failure deformation of discrete rockfall events. Additionally, we found the ATLS system to be an effective tool in monitoring landslide and rockfall processes despite missing points due to poor atmospheric conditions or rainfall. Furthermore, such a system has the potential to help us better understand a wide variety of slope processes at high levels of temporal detail.

  1. Detection of Progressive Retinal Nerve Fiber Layer Loss in Glaucoma Using Scanning Laser Polarimetry with Variable Corneal Compensation

    Science.gov (United States)

    Medeiros, Felipe A.; Alencar, Luciana M.; Zangwill, Linda M.; Bowd, Christopher; Vizzeri, Gianmarco; Sample, Pamela A.; Weinreb, Robert N.

    2010-01-01

    Purpose To evaluate the ability of scanning laser polarimetry with variable corneal compensation to detect progressive retinal nerve fiber layer (RNFL) loss in glaucoma patients and patients suspected of having the disease. Methods This was an observational cohort study that included 335 eyes of 195 patients. Images were obtained annually with the GDx VCC scanning laser polarimeter, along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. The median follow-up time was 3.94 years. Progression was determined using commercial software for SAP and by masked assessment of optic disc stereophotographs performed by expert graders. Random coefficient models were used to evaluate the relationship between RNFL thickness measurements over time and progression as determined by SAP and/or stereophotographs. Results From the 335 eyes, 34 (10%) showed progression over time by stereophotographs and/or SAP. Average GDx VCC measurements decreased significantly over time for both progressors as well as non-progressors. However, the rate of decline was significantly higher in the progressing group (−0.70 μm/year) compared to the non-progressing group (−0.14 μm/year; P = 0.001). Black race and male sex were significantly associated with higher rates of RNFL loss during follow-up. Conclusions The GDx VCC scanning laser polarimeter was able to identify longitudinal RNFL loss in eyes that showed progression in optic disc stereophotographs and/or visual fields. These findings suggest that this technology could be useful to detect and monitor progressive disease in patients with established diagnosis of glaucoma or suspected of having the disease. PMID:19029038

  2. Automatic Scanning Detection for Characterization of Dome-Related Seismic Swarms at Mount St. Helens and their Evolution Through Time

    Science.gov (United States)

    MacCarthy, J. K.; Rowe, C. A.

    2005-12-01

    Using the waveform data for Mount St. Helens from October 2004 through April, 2005 available from the IRIS DMC, as well as a special data set including the accelerometer that recorded eleven days of activity on the whaleback dome of St. Helens during February, 2005, we have modified a waveform cross-correlation algorithm previously applied for event clustering and repicking into a correlation scanning detector. This tool is being developed for implementation during routine volcano monitoring, as a means of identifying, characterizing and locating repeating swarm events and quantifying their seismic energy release. Application of the scanning detector to St. Helens data reveals stable swarm-type activity over periods with cross-correlation values exceeding 0.8 for 25 days, within which the repeating events slowly evolve over time. Waveforms show high correlation when as much as 60 s of coda is included in the correlation, suggesting very stable source and path characteristics. We present analysis of waveform evolution and event location stability as determined through the detection and automatic repicking and relocation of correlated events. Evolving seismic waveform characteristics are compared to available information about the ongoing eruption sequence to investigate the correspondence among such observables as deformation, volatile flux (both magmagenic and meteoric), estimated dome volume or magma flux and overall energy partitioning. The correlation-detection tool shows promise for real-time implementation, with the potential to greatly reduce analyst workload and augment on-the-fly characterizations already provided by such routine monitoring tools as RSAM and SSAM.

  3. Moving Object Detection Using Scanning Camera on a High-Precision Intelligent Holder

    Directory of Open Access Journals (Sweden)

    Shuoyang Chen

    2016-10-01

    Full Text Available During the process of moving object detection in an intelligent visual surveillance system, a scenario with complex background is sure to appear. The traditional methods, such as “frame difference” and “optical flow”, may not able to deal with the problem very well. In such scenarios, we use a modified algorithm to do the background modeling work. In this paper, we use edge detection to get an edge difference image just to enhance the ability of resistance illumination variation. Then we use a “multi-block temporal-analyzing LBP (Local Binary Pattern” algorithm to do the segmentation. In the end, a connected component is used to locate the object. We also produce a hardware platform, the core of which consists of the DSP (Digital Signal Processor and FPGA (Field Programmable Gate Array platforms and the high-precision intelligent holder.

  4. P53, MAPK, topoisomerase II alpha and Ki67 immunohistochemical expression and KRAS/BRAF mutation in ovarian serous carcinomas

    Directory of Open Access Journals (Sweden)

    Sundov Dinka

    2013-02-01

    Full Text Available Abstract Background We investigated the immunohistochemical expression of p53, MAPK, topoisomerase II alpha (topoII alpha and Ki67 in ovarian serous carcinomas (OSCs along with mutational analysis for KRAS and BRAF. Methods Eighty one cases of OSCs were reviewed and examined immunohistochemically using antibodies against p53, MAPK, topoII alpha and Ki67. Staining was evaluated as a percentage of immunopositive cells with cut-off levels at 10% for p53 and topoII alpha, and 5% for MAPK. The Ki67 immunoexpression was assessed by means of Olympus Image Analysis System as a percentage of immunopositive cells in 1000 tumor cells. KRAS and BRAF mutational analysis was performed on 73 available microdissected samples. Results Of 81 cases of OSCs 13.6% were of low-grade and 86.4% were of high-grade morphology. In the high-grade group there was a significantly higher immunoexpression of p53 (P P = 0.001, with Ki67 median 56.5 vs. 19 in low-grade group (P P = 0.003. MAPK positive immunostaining was detected in 63.6% of low-grade vs. 17.1% of high-grade OSCs. The frequency of KRAS mutation was significantly higher in low-grade as compared to high-grade group (P = 0.006. None of the samples had BRAF mutation. In addition, we detected positive MAPK immunoexpression in 13/59 samples with wild-type KRAS, suggesting that activation of MAPK pathway is not ultimately related either to KRAS or BRAF mutation. Seven morphologically high-grade samples (11.7% showed both KRAS mutation and p53 immunopositivity. Conclusions Although this study is limited by its humble number of low-grade samples, our data fit the proposed dualistic pathway of ovarian carcinogenesis. Mutational analysis for KRAS and BRAF discloses some possible interactions between different tumorigenic pathways of low- and high-grade carcinomas. Immunohistochemical staining for MAPK was not sufficiently sensitive, nor specific, to precisely predict the KRAS mutation. However, it appears

  5. Multidimensional slit-scan detection of bladder cancer. Preliminary clinical results.

    Science.gov (United States)

    Wheeless, L L; Berkan, T K; Patten, S F; Reeder, J E; Robinson, R D; Eldidi, M M; Hulbert, W C; Frank, I N

    1986-03-01

    A multidimensional slit-scan flow system was developed for the automated recognition of abnormal cells derived from cancer of the uterine cervix and its precursors. It provides great sensitivity in both its ability to recognize cellular abnormality and to deal with the myriad potential causes of false alarms in an automated flow system. While its initial application was the automated recognition of the spectrum of neoplasia in gynecologic cytology samples, a preliminary study was carried out using specimens obtained from the urinary bladder. Cellular material was collected by bladder irrigation and stained with the fluorochrome acridine orange. One hundred fifty-three bladder irrigation specimens, including 115 abnormal specimens containing cells derived from neoplastic lesions of the bladder epithelium, were analyzed. For the purposes of this study, abnormal specimens from the urinary bladder included specimens containing cells derived from the following lesions of the urothelium: dysplasia (atypical hyperplasia), carcinoma-in-situ, and transitional cell carcinoma, grades 1-3. Approximately 50,000 cells were analyzed for most specimens. Of the 38 presumed normal specimens (specimens containing only normal urothelial components), four were instrument classified abnormal. For the 69 specimens containing cells derived from transitional cell carcinoma, grade 1, 1-2, 2, 66 were correctly classified as abnormal while three were classified as normal.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Magnetic Resonance Angiography and Doppler Scanning for Detecting Atherosclerotic Renal Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Yee-Yung Ng

    2010-06-01

    Conclusion: RDS might still be the diagnostic procedure of choice for screening outpatients for ARAS because it is inexpensive, convenient, able to detect severity, and avoids the use of contrast media. When RDS is negative in aged people who have smoked longer than 20 years, with coronary artery disease or serum creatinine > 4 mg/dL, MRA is recommended for further evaluation of ARAS.

  7. An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer

    DEFF Research Database (Denmark)

    Vallejo, Adrian; Perurena, Naiara; Guruceaga, Elisabet

    2017-01-01

    KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report...... the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. Furthermore, FOSL1 genetic inhibition......, combination of AURKA and MEK inhibitors induces a deleterious effect on mutant KRAS cells. Our findings unveil KRAS downstream effectors that provide opportunities to treat KRAS-driven cancers....

  8. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?

    Directory of Open Access Journals (Sweden)

    Schmitt Fernando

    2008-09-01

    Full Text Available Abstract Background BRAF, KRAS and PIK3CA mutations are frequently found in sporadic colorectal cancer (CRC. In contrast to KRAS and PIK3CA mutations, BRAF mutations are associated with tumours harbouring CpG Island methylation phenotype (CIMP, MLH1 methylation and microsatellite instability (MSI. We aimed at determine the frequency of KRAS, BRAF and PIK3CA mutations in the process of colorectal tumourigenesis using a series of colorectal polyps and carcinomas. In the series of polyps CIMP, MLH1 methylation and MSI were also studied. Methods Mutation analyses were performed by PCR/sequencing. Bisulfite treated DNA was used to study CIMP and MLH1 methylation. MSI was detected by pentaplex PCR and Genescan analysis of quasimonomorphic mononucleotide repeats. Chi Square test and Fisher's Exact test were used to perform association studies. Results KRAS, PIK3CA or BRAF occur in 71% of polyps and were mutually exclusive. KRAS mutations occur in 35% of polyps. PIK3CA was found in one of the polyps. V600E BRAF mutations occur in 29% of cases, all of them classified as serrated adenoma. CIMP phenotype occurred in 25% of the polyps and all were mutated for BRAF. MLH1 methylation was not detected and all the polyps were microsatellite stable. The comparison between the frequency of oncogenic mutations in polyps and CRC (MSI and MSS lead us to demonstrate that KRAS and PIK3CA are likely to precede both types of CRC. BRAF mutations are likely to precede MSI carcinomas since the frequency found in serrated polyps is similar to what is found in MSI CRC (P = 0.9112, but statistically different from what is found in microsatellite stable (MSS tumours (P = 0.0191. Conclusion Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis. Further, we show that BRAF mutations occur in association with CIMP phenotype in colorectal

  9. Comparison of the prevalence of KRAS-LCS6 polymorphism (rs61764370) within different tumour types (colorectal, breast, non-small cell lung cancer and brain tumours). A study of the Czech population.

    Science.gov (United States)

    Uvirova, Magdalena; Simova, Jarmila; Kubova, Barbora; Dvorackova, Nina; Tomaskova, Hana; Sedivcova, Monika; Dite, Petr

    2015-09-01

    A germline SNP (rs61764370) is located in a let-7 complementary site (LCS6) in the 3'UTR of KRAS oncogene, and it was found to alter the binding capability of the mature let-7 microRNA to the KRAS mRNA. The aim of the study was to evaluate the frequency of the KRAS-LCS6 variant allele in different cancer types that included patients with colorectal cancer (CRC), breast cancer (BC), non-small cell lung cancer (NSCLC) and brain tumour patient subgroups from the Czech Republic. The occurrence of this genetic variant was correlated with the presence of selected somatic mutations representing predictive biomarkers in the respective tumours. DNA of tumour tissues was isolated from 428 colorectal cancer samples, 311 non-small cell lung cancer samples, 195 breast cancer samples and 151 samples with brain tumour. Analysis of SNP (rs61764370) was performed by the PCR+RFLP method and direct sequencing. KRAS, BRAF and EGFR mutation status was assessed using real-time PCR. The status of the HER2 gene was assessed using the FISH method. The KRAS-LCS6 TG genotype has been detected in 16.4% (32/195) of breast cancer cases (in HER2 positive breast cancer 3.3%, in HER2 negative breast cancer 20.1%), in 12.4% (53/428) of CRC cases (KRAS/BRAF wild type CRC in 10.6%, KRAS mutant CRC in 10.1%, BRAF V600E mutant CRC in 18.5%), in 13.2% (41/311) of NSCLC samples, (EGFR mutant NSCLC patients in 8%, EGFR wild type NSCLC in 12.9%), and 17.9% (27/151) of brain tumour cases. The KRAS-LCS6 TG genotype was not significantly different across the studied tumours. In our study, the GG genotype has not been found among the cancer samples. Based on the findings, it is concluded that the occurrence of the KRAS-LCS6 TG genotype was statistically significantly different in association with status of the HER2 gene in breast cancer. Furthermore, significant association between the mutation status of analysed somatic variants in genes of the EGFR signalling pathway (KRAS, BRAF, EGFR) and the KRAS-LCS6

  10. Reconstruction of the Magnetkoepfl rockfall event - Detecting rock fall release zones using terrestrial laser scanning, Hohe Tauern, Austria

    Science.gov (United States)

    Hartmeyer, I.; Keuschnig, M.; Delleske, R.; Schrott, L.

    2012-04-01

    Instability of rock faces in high mountain areas is an important risk factor for man and infrastructure, particularly within the context of climate change. Numerous rock fall events in the European Alps suggest an increasing occurrence of mass movements due to rising temperatures in recent years. Within the MOREXPERT project ('Monitoring Expert System for Hazardous Rock Walls') a new long-term monitoring site for mass movement and permafrost interaction has been initiated in the Austrian Alps. The study area is located at the Kitzsteinhorn (Hohe Tauern), a particularly interesting site for the investigation of glacier retreat and potential permafrost degradation and their respective consequences for the stability of alpine rock faces. To detect and quantify changes occurring at the terrain surface an extensive terrestrial laser scanning (TLS) monitoring campaign was started in 2011. TLS creates three-dimensional high-resolution images of the scanned area allowing precise quantification of changes in geometry and volume in steep rock faces over distances of up to several hundreds of meters. Within the TLS monitoring campaign at the Kitzsteinhorn a large number of differently dimensioned rock faces is examined (varying size, slope inclination etc.). Scanned areas include the Kitzsteinhorn northwest and south face, the Magnetkoepfl east face as well as a couple of small rock faces in the vicinity of the summit station. During the night from August 27th to August 28th 2011 a rock fall event was documented by employees of the cable car company. The release zone could not immediately be detected. The east face of the Magnetkoepfl covers approximately 70 meters in height and about 200 meters in width. It is made up of calcareous mica-schist and displays an abundance of well-developed joint sets with large joint apertures. Meteorological data from a weather station located at the same altitude (2.950m) and just 500m away from the release zone show that the rock fall event

  11. Comparative genome scan detects host-related divergent selection in the grasshopper Hesperotettix viridis.

    Science.gov (United States)

    Apple, Jennifer L; Grace, Tony; Joern, Anthony; St Amand, Paul; Wisely, Samantha M

    2010-09-01

    In this study, we used a comparative genome scan to examine patterns of population differentiation with respect to host plant use in Hesperotettix viridis, a Nearctic oligophagous grasshopper locally specialized on various Asteraceae including Solidago, Gutierrezia, and Ericameria. We identified amplified fragment length polymorphism (AFLP) loci with significantly elevated F(ST) (outlier loci) in multiple different-host and same-host comparisons of populations while controlling for geographic distance. By comparing the number and identities of outlier loci in different-host vs. same-host comparisons, we found evidence of host plant-related divergent selection for some population comparisons (Solidago- vs. Gutierrezia-feeders), while other comparisons (Ericameria- vs. Gutierrezia-feeders) failed to demonstrate a strong role for host association in population differentiation. In comparisons of Solidago- vs. Gutierrezia-feeding populations, a relatively high number of outlier loci observed repeatedly in different-host comparisons (35% of all outliers and 2.7% of all 625 AFLP loci) indicated a significant role for host-related selection in contributing to overall genomic differentiation in this grasshopper. Mitochondrial DNA sequence data revealed a star-shaped phylogeny with no host- or geography-related structure, low nucleotide diversity, and high haplotype diversity, suggesting a recent population expansion. mtDNA data do not suggest a long period of isolation in separate glacial refugia but are instead more compatible with a single glacial refugium and more recent divergence in host use. Our study adds to research documenting heterogeneity in differentiation across the genome as a consequence of divergent natural selection, a phenomenon that may occur as part of the process of ecological speciation. © 2010 Blackwell Publishing Ltd.

  12. Mediastinal lymph node detection on thoracic CT scans using spatial prior from multi-atlas label fusion

    Science.gov (United States)

    Liu, Jiamin; Zhao, Jocelyn; Hoffman, Joanne; Yao, Jianhua; Zhang, Weidong; Turkbey, Evrim B.; Wang, Shijun; Kim, Christine; Summers, Ronald M.

    2014-03-01

    Lymph nodes play an important role in clinical practice but detection is challenging due to low contrast surrounding structures and variable size and shape. We propose a fully automatic method for mediastinal lymph node detection on thoracic CT scans. First, lungs are automatically segmented to locate the mediastinum region. Shape features by Hessian analysis, local scale, and circular transformation are computed at each voxel. Spatial prior distribution is determined based on the identification of multiple anatomical structures (esophagus, aortic arch, heart, etc.) by using multi-atlas label fusion. Shape features and spatial prior are then integrated for lymph node detection. The detected candidates are segmented by curve evolution. Characteristic features are calculated on the segmented lymph nodes and support vector machine is utilized for classification and false positive reduction. We applied our method to 20 patients with 62 enlarged mediastinal lymph nodes. The system achieved a significant improvement with 80% sensitivity at 8 false positives per patient with spatial prior compared to 45% sensitivity at 8 false positives per patient without a spatial prior.

  13. Incidental musculoskeletal lesions detected on abdomnopelvic CT scans: A pictorial essay

    Energy Technology Data Exchange (ETDEWEB)

    Song, Eun Jee; Ryu, Kyung Nam; Park, Ji Seon [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Jin, Wook; Park, So Young [Dept. of Radiology, Kyung Hee University Hospital at Gangdong Hospital, Seoul (Korea, Republic of)

    2015-02-15

    Various musculoskeletal findings incidentally detected on abdominopelvic computed tomography (CT) images have risen with the increasing use of abdominopelvic CT; however, it is not uncommon for radiologists to overlook the musculoskeletal system when they examine abdominopelvic CT images. Some musculoskeletal lesions may have more clinical significance than abdominopelvic lesions, although most lesions are of little to no significance. Many osseous lesions can be diagnosed using the bone window setting and reconstructed images. The purpose of this article was to review the wide variety of musculoskeletal lesions depicted on abdominopelvic CT images and to emphasize the use of the bone window setting.

  14. Automated lesion detection on MRI scans using combined unsupervised and supervised methods.

    Science.gov (United States)

    Guo, Dazhou; Fridriksson, Julius; Fillmore, Paul; Rorden, Christopher; Yu, Hongkai; Zheng, Kang; Wang, Song

    2015-10-30

    Accurate and precise detection of brain lesions on MR images (MRI) is paramount for accurately relating lesion location to impaired behavior. In this paper, we present a novel method to automatically detect brain lesions from a T1-weighted 3D MRI. The proposed method combines the advantages of both unsupervised and supervised methods. First, unsupervised methods perform a unified segmentation normalization to warp images from the native space into a standard space and to generate probability maps for different tissue types, e.g., gray matter, white matter and fluid. This allows us to construct an initial lesion probability map by comparing the normalized MRI to healthy control subjects. Then, we perform non-rigid and reversible atlas-based registration to refine the probability maps of gray matter, white matter, external CSF, ventricle, and lesions. These probability maps are combined with the normalized MRI to construct three types of features, with which we use supervised methods to train three support vector machine (SVM) classifiers for a combined classifier. Finally, the combined classifier is used to accomplish lesion detection. We tested this method using T1-weighted MRIs from 60 in-house stroke patients. Using leave-one-out cross validation, the proposed method can achieve an average Dice coefficient of 73.1% when compared to lesion maps hand-delineated by trained neurologists. Furthermore, we tested the proposed method on the T1-weighted MRIs in the MICCAI BRATS 2012 dataset. The proposed method can achieve an average Dice coefficient of 66.5% in comparison to the expert annotated tumor maps provided in MICCAI BRATS 2012 dataset. In addition, on these two test datasets, the proposed method shows competitive performance to three state-of-the-art methods, including Stamatakis et al., Seghier et al., and Sanjuan et al. In this paper, we introduced a novel automated procedure for lesion detection from T1-weighted MRIs by combining both an unsupervised and a

  15. Genome Scan Detects Quantitative Trait Loci Affecting Female Fertility Traits in Danish and Swedish Holstein Cattle

    DEFF Research Database (Denmark)

    Höglund, Johanna Karolina; Guldbrandtsen, B; Su, G

    2009-01-01

    microsatellite markers. Single trait breeding values were used for 12 traits relating to female fertility and female reproductive disorders. Data were analyzed by least squares regression analysis within and across families. Twenty-six QTL were detected on 17 different chromosomes. The best evidence was found......Data from the joint Nordic breeding value prediction for Danish and Swedish Holstein grandsire families were used to locate quantitative trait loci (QTL) for female fertility traits in Danish and Swedish Holstein cattle. Up to 36 Holstein grandsires with over 2,000 sons were genotyped for 416...

  16. Two-dimensional radial laser scanning for circular marker detection and external mobile robot tracking.

    Science.gov (United States)

    Teixidó, Mercè; Pallejà, Tomàs; Font, Davinia; Tresanchez, Marcel; Moreno, Javier; Palacín, Jordi

    2012-11-28

    This paper presents the use of an external fixed two-dimensional laser scanner to detect cylindrical targets attached to moving devices, such as a mobile robot. This proposal is based on the detection of circular markers in the raw data provided by the laser scanner by applying an algorithm for outlier avoidance and a least-squares circular fitting. Some experiments have been developed to empirically validate the proposal with different cylindrical targets in order to estimate the location and tracking errors achieved, which are generally less than 20 mm in the area covered by the laser sensor. As a result of the validation experiments, several error maps have been obtained in order to give an estimate of the uncertainty of any location computed. This proposal has been validated with a medium-sized mobile robot with an attached cylindrical target (diameter 200 mm). The trajectory of the mobile robot was estimated with an average location error of less than 15 mm, and the real location error in each individual circular fitting was similar to the error estimated with the obtained error maps. The radial area covered in this validation experiment was up to 10 m, a value that depends on the radius of the cylindrical target and the radial density of the distance range points provided by the laser scanner but this area can be increased by combining the information of additional external laser scanners.

  17. Online platform for applying space–time scan statistics for prospectively detecting emerging hot spots of dengue fever

    Directory of Open Access Journals (Sweden)

    Chien-Chou Chen

    2016-11-01

    Full Text Available Abstract Background Cases of dengue fever have increased in areas of Southeast Asia in recent years. Taiwan hit a record-high 42,856 cases in 2015, with the majority in southern Tainan and Kaohsiung Cities. Leveraging spatial statistics and geo-visualization techniques, we aim to design an online analytical tool for local public health workers to prospectively identify ongoing hot spots of dengue fever weekly at the village level. Methods A total of 57,516 confirmed cases of dengue fever in 2014 and 2015 were obtained from the Taiwan Centers for Disease Control (TCDC. Incorporating demographic information as covariates with cumulative cases (365 days in a discrete Poisson model, we iteratively applied space–time scan statistics by SaTScan software to detect the currently active cluster of dengue fever (reported as relative risk in each village of Tainan and Kaohsiung every week. A village with a relative risk >1 and p value <0.05 was identified as a dengue-epidemic area. Assuming an ongoing transmission might continuously spread for two consecutive weeks, we estimated the sensitivity and specificity for detecting outbreaks by comparing the scan-based classification (dengue-epidemic vs. dengue-free village with the true cumulative case numbers from the TCDC’s surveillance statistics. Results Among the 1648 villages in Tainan and Kaohsiung, the overall sensitivity for detecting outbreaks increases as case numbers grow in a total of 92 weekly simulations. The specificity for detecting outbreaks behaves inversely, compared to the sensitivity. On average, the mean sensitivity and specificity of 2-week hot spot detection were 0.615 and 0.891 respectively (p value <0.001 for the covariate adjustment model, as the maximum spatial and temporal windows were specified as 50% of the total population at risk and 28 days. Dengue-epidemic villages were visualized and explored in an interactive map. Conclusions We designed an online analytical tool for

  18. Burden of subclinical heart and lung disease detected on thoracic CT scans of HIV patients on HAART

    Directory of Open Access Journals (Sweden)

    Stefano Zona

    2014-11-01

    -infected individuals even in non-smokers. Reduced CD4 count (hence severity of HIV infection may be an important risk factor for chronic lung and heart disease. Thoracic CT scans may provide an excellent screening tool to detect MLHD in HIV-infected patients.

  19. Scanning seismic intrusion detection method and apparatus. [monitoring unwanted subterranean entry and departure

    Science.gov (United States)

    Lee, R. D. (Inventor)

    1983-01-01

    An intrusion monitoring system includes an array of seismic sensors, such as geophones, arranged along a perimeter to be monitored for unauthorized intrusion as by surface movement or tunneling. Two wires lead from each sensor to a central monitoring station. The central monitoring station has three modes of operation. In a first mode of operation, the output of all of the seismic sensors is summed into a receiver for amplification and detection. When the amplitude of the summed signals exceeds a certain predetermined threshold value an alarm is sounded. In a second mode of operation, the individual output signals from the sensors are multiplexed into the receiver for sequentially interrogating each of the sensors.

  20. KRAS mutational concordance between primary and metastatic colorectal adenocarcinoma

    Science.gov (United States)

    PALIOGIANNIS, PANAGIOTIS; COSSU, ANTONIO; TANDA, FRANCESCO; PALMIERI, GIUSEPPE; PALOMBA, GRAZIA

    2014-01-01

    KRAS mutation analysis is commonly performed on tissue samples obtained from primary colorectal cancers (CRCs). The metastatic lesions of CRC are usually considered as qualitatively similar or even identical to the primary tumors. The aim of this study was to evaluate the spectrum and distribution of KRAS mutations in a large collection of CRCs, while also evaluating the concordance of primary and metastatic lesions among available paired specimens from the same patients. A total of 729 patients with histologically confirmed advanced CRC at the University Hospital and Local Health Unit (Sassari, Italy) were included. Clinical and pathological features were obtained from medical records and/or pathology reports. Formalin-fixed, paraffin-embedded tissue samples were used for mutation analysis. Genomic DNA was isolated using a standard protocol; the coding sequence and splice junctions of exons 2 and 3 in the KRAS gene were screened by direct automated sequencing. Overall, 219 (30%) KRAS mutations were found; 208 (30.1%) were identified in the 690 primary tumors and 11 (28.2%) in the 39 metastatic tissue samples. Among the 31 (4.3%) patients who had paired samples of primary CRC and synchronous or asynchronous metastases, 28 (90.3%) showed consistent mutation patterns between the primary tumors and metastatic lesions. In one case, an additive mutation (Q61L) was found in the metastatic tissue, while two other discrepant cases exhibited a different mutation distribution; Q61H in the primitive lesion and G13V in the metastatic lesion in one case, and a mutated primary tumor (Q61L) and wild-type metastasis in another case. The results of this study confirm that a high concordance exists between the results of KRAS mutation analysis performed in primitive and metastatic CRCs; independent subclones may be generated in a limited amount of patients. PMID:25202344

  1. AN ENERGY-BASED APPROACH FOR DETECTION AND CHARACTERIZATION OF SUBTLE ENTITIES WITHIN LASER SCANNING POINT-CLOUDS

    Directory of Open Access Journals (Sweden)

    R. Arav

    2016-06-01

    Full Text Available Airborne laser scans present an optimal tool to describe geomorphological features in natural environments. However, a challenge arises in the detection of such phenomena, as they are embedded in the topography, tend to blend into their surroundings and leave only a subtle signature within the data. Most object-recognition studies address mainly urban environments and follow a general pipeline where the data are partitioned into segments with uniform properties. These approaches are restricted to man-made domain and are capable to handle limited features that answer a well-defined geometric form. As natural environments present a more complex set of features, the common interpretation of the data is still manual at large. In this paper, we propose a data-aware detection scheme, unbound to specific domains or shapes. We define the recognition question as an energy optimization problem, solved by variational means. Our approach, based on the level-set method, characterizes geometrically local surfaces within the data, and uses these characteristics as potential field for minimization. The main advantage here is that it allows topological changes of the evolving curves, such as merging and breaking. We demonstrate the proposed methodology on the detection of collapse sinkholes.

  2. A voting-based statistical cylinder detection framework applied to fallen tree mapping in terrestrial laser scanning point clouds

    Science.gov (United States)

    Polewski, Przemyslaw; Yao, Wei; Heurich, Marco; Krzystek, Peter; Stilla, Uwe

    2017-07-01

    This paper introduces a statistical framework for detecting cylindrical shapes in dense point clouds. We target the application of mapping fallen trees in datasets obtained through terrestrial laser scanning. This is a challenging task due to the presence of ground vegetation, standing trees, DTM artifacts, as well as the fragmentation of dead trees into non-collinear segments. Our method shares the concept of voting in parameter space with the generalized Hough transform, however two of its significant drawbacks are improved upon. First, the need to generate samples on the shape's surface is eliminated. Instead, pairs of nearby input points lying on the surface cast a vote for the cylinder's parameters based on the intrinsic geometric properties of cylindrical shapes. Second, no discretization of the parameter space is required: the voting is carried out in continuous space by means of constructing a kernel density estimator and obtaining its local maxima, using automatic, data-driven kernel bandwidth selection. Furthermore, we show how the detected cylindrical primitives can be efficiently merged to obtain object-level (entire tree) semantic information using graph-cut segmentation and a tailored dynamic algorithm for eliminating cylinder redundancy. Experiments were performed on 3 plots from the Bavarian Forest National Park, with ground truth obtained through visual inspection of the point clouds. It was found that relative to sample consensus (SAC) cylinder fitting, the proposed voting framework can improve the detection completeness by up to 10 percentage points while maintaining the correctness rate.

  3. Beyond KRAS mutation status: influence of KRAS copy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Mekenkamp Leonie JM

    2012-07-01

    Full Text Available Abstract Background KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor (EGFR antibodies in metastatic colorectal cancer (mCRC. Novel predictive markers are required to further improve the selection of patients for this treatment. We assessed the influence of modification of KRAS by gene copy number aberration (CNA and microRNAs (miRNAs in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab. Methods Formalin-fixed paraffin-embedded primary tumour tissue was used from 34 mCRC patients in a phase III trial, who were selected based upon their good (n = 17 or poor (n = 17 progression-free survival (PFS upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene copy number at the KRAS locus was assessed using high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR. Results Copy number loss of the KRAS locus was observed in the tumour of 5 patients who were all good responders including patients with a KRAS mutation. Copy number gains in two wild-type KRAS tumours were associated with a poor PFS. In KRAS mutated tumours increased miR-200b and decreased miR-143 expression were associated with a good PFS. In wild-type KRAS patients, miRNA expression did not correlate with PFS in a multivariate model. Conclusions Our results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS might further optimize the selection of mCRC eligible for anti-EGFR therapy.

  4. Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Al-Kzayer, Lika'a Fasih Y; Sakashita, Kazuo; Al-Jadiry, Mazin Faisal; Al-Hadad, Salma Abbas; Ghali, Hasanein Habeeb; Uyen, Le T N; Liu, Tingting; Matsuda, Kazuyuki; Abdulkadhim, Jaafar M H; Al-Shujairi, Tariq Abadi; Matti, Zead Ismael I K; Sughayer, Maher A; Rihani, Rawad; Madanat, Faris F; Inoshita, Toshi; Kamata, Minoru; Koike, Kenichi

    2015-12-01

    KRAS and NRAS gene mutations are frequently observed in childhood leukemia. The objective of this study was to determine the frequency of RAS mutations and the association between RAS mutations and other genetic aberrations in Arab Asian children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Diagnostic samples of 485 patients (RAS mutations were detected in 86/318 (27%) of ALL cases and 35/167 (21%) of AML cases. The frequency of NRAS mutation was similar to that of KRAS mutation in ALL. Two RAS mutations were detected in nine patients. Among 264 Iraqi patients with ALL, RAS mutation was significantly associated with lower initial white blood cell count. Of 57 patients with chimeric transcripts, only two patients with either TEL-AML1 or E2A-PBX1 had KRAS mutation. The frequency of NRAS mutation was four times higher than that of KRAS mutation in AML. FAB-M4 and M5 subsets were associated with RAS mutation. Among 134 Iraqi patients with AML, 18 patients had RAS mutations and other genetic aberrations. In particular, 9 of 25 (36%) with MLL-rearrangement had RAS mutations. The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement. © 2015 Wiley Periodicals, Inc.

  5. Detection of Vertical Pole-Like Objects in a Road Environment Using Vehicle-Based Laser Scanning Data

    Directory of Open Access Journals (Sweden)

    Harri Kaartinen

    2010-02-01

    Full Text Available Accurate road environment information is needed in applications such as road maintenance and virtual 3D city modelling. Vehicle-based laser scanning (VLS can produce dense point clouds from large areas efficiently from which the road and its environment can be modelled in detail. Pole-like objects such as traffic signs, lamp posts and tree trunks are an important part of road environments. An automatic method was developed for the extraction of pole-like objects from VLS data. The method was able to find 77.7% of the poles which were found by a manual investigation of the data. Correctness of the detection was 81.0%.

  6. The experiment to detect equivalent optical path difference in independent double aperture interference light path based on step scanning method

    Science.gov (United States)

    Wang, Chaoyan; Chen, Xin-yang; Zheng, Lixin; Ding, Yuanyuan

    2014-11-01

    Fringe test is the method which can detect the relative optical path difference in optical synthetic aperture telescope array. To get to the interference fringes, the two beams of light in the meeting point must be within the coherence length. Step scanning method is within its coherence length, selecting a specific step, changing one-way's optical path of both by changing position of micro displacement actuator. At the same time, every fringe pattern can be recorded. The process of fringe patterns is from appearing to clear to disappearing. Firstly, a particular pixel is selected. Then, we keep tract of the intensity of every picture in the same position. From the intensity change, the best position of relative optical path difference can be made sure. The best position of relative optical path difference is also the position of the clearest fringe. The wavelength of the infrared source is 1290nm and the bandwidth is 63.6nm. In this experiment, the coherence length of infrared source is detected by cube reflection experiment. The coherence length is 30μm by data collection and data processing, and that result of 30μm is less different from the 26μm of theoretical calculated. In order to further test the relative optical path of optical synthetic aperture using step scanning method, the infrared source is placed into optical route of optical synthesis aperture telescope double aperture. The precision position of actuator can be obtained when the fringe is the clearest. By the experiment, we found that the actuating step affects the degree of precision of equivalent optical path. The smaller step size, the more accurate position. But the smaller the step length, means that more steps within the coherence length measurement and the longer time.

  7. Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- but not BRAF+ colorectal cancer.

    Science.gov (United States)

    Jayasekara, Harindra; MacInnis, Robert J; Williamson, Elizabeth J; Hodge, Allison M; Clendenning, Mark; Rosty, Christophe; Walters, Rhiannon; Room, Robin; Southey, Melissa C; Jenkins, Mark A; Milne, Roger L; Hopper, John L; Giles, Graham G; Buchanan, Daniel D; English, Dallas R

    2017-04-01

    Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 38,149 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose-dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow-up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04-1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (phomogeneity  = 0.02). Alcohol intake was associated with increased risks of KRAS+ (HR = 1.07, 95% CI: 1.00-1.15) and BRAF-/KRAS- (HR = 1.05, 95% CI: 1.00-1.11) but not BRAF+ tumors (HR = 0.89, 95% CI: 0.78-1.01; phomogeneity  = 0.01). Alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- tumors originating via specific molecular pathways including the traditional adenoma-carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma-carcinoma pathway. © 2016 UICC.

  8. Biomarkers predicting resistance to epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer with wild-type KRAS

    Directory of Open Access Journals (Sweden)

    Liu J

    2016-01-01

    Full Text Available Jiang Liu,* Jing Hu,* Lei Cheng, Wei Ren, Mi Yang, Baorui Liu, Li Xie, Xiaoping Qian The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: EGFR pathway is an important therapeutic target in human tumors, including metastatic colorectal cancer (mCRC. The advent of EGFR-targeted monoclonal antibodies panitumumab and cetuximab has generated promise for the treatment of mCRC and has largely improved patients’ progression-free survival (PFS and overall survival (OS. However, treatment with anti-EGFR monoclonal antibodies is only effective in a subset of mCRC patients with wild-type KRAS. This indicates that there are other factors affecting the efficacy of anti-EGFR monoclonal antibodies. Existing studies have demonstrated that among colorectal cancer patients with wild-type KRAS, harboring mutations of BRAF, PIK3CA, NRAS, or PTEN-null may demonstrate resistance to anti-EGFR-targeted therapy, and biomarkers detection can provide better-personalized treatment for mCRC patients. How to identify and reverse the secondary resistance to anti-EGFR monoclonal antibody therapy is also another great challenge to improve the anti-EGFR efficacy in wild-type KRAS mCRC patients. Finally, both of the molecular mechanisms of response and acquired resistance would be important for the directions of future research. This review focuses on how to further improve the predictive value of anti-EGFR therapies and how to also try and avoid futile treatment for wild-type KRAS colorectal cancer patients. Keywords: colorectal cancer, EGFR, BRAF, RAS, cetuximab, panitumumab

  9. Mutations of the EGFR and K-ras genes in resected stage I lung adenocarcinoma and their clinical significance.

    Science.gov (United States)

    Ohba, Taro; Toyokawa, Gouji; Kometani, Takuro; Nosaki, Kaname; Hirai, Fumihiko; Yamaguchi, Masafumi; Hamatake, Motoharu; Seto, Takashi; Ichinose, Yukito; Sugio, Kenji

    2014-03-01

    This study retrospectively assessed the mutations of the epidermal growth factor receptor (EGFR) and K-ras genes and their clinical significance in patients with resected stage I adenocarcinomas. A total of 354 patients with resected lung adenocarcinomas were included, and 256 patients with stage I disease were analyzed for the prognostic and predictive value of these mutations. Mutations of EGFR and K-ras genes were detected in 149 (41.1 %) and 23 (6.4 %) of all tumors, and in 122 (47.6 %) and 14 (5.5 %) of stage I tumors, respectively. There were no significant differences in the disease-free survival (DFS) and overall survival (OS) between the EGFR-mutant and wild-type groups. However, the DFS and OS were significantly shorter in patients with K-ras mutations than in those without (5-year DFS: 50.8 vs. 76.9 %, 5-year OS: 70.0 vs. 86.6 %, p ras mutations were an independent poor prognostic factor. Twenty-four of the 41 patients with recurrent disease after surgery were treated with an EGFR-TKI. Fifteen EGFR-mutant patients treated with an EGFR-TKI had a better prognosis than did the nine EGFR-wild-type patients. The presence of an EGFR gene mutation was a predictive factor for the response to EGFR-TKI treatment in patients with resected stage I adenocarcinoma, but was not a prognostic factor. The presence of a K-ras gene mutation was a poor prognostic factor.

  10. 454 next generation-sequencing outperforms allele-specific PCR, Sanger sequencing, and pyrosequencing for routine KRAS mutation analysis of formalin-fixed, paraffin-embedded samples

    Science.gov (United States)

    Altimari, Annalisa; de Biase, Dario; De Maglio, Giovanna; Gruppioni, Elisa; Capizzi, Elisa; Degiovanni, Alessio; D’Errico, Antonia; Pession, Annalisa; Pizzolitto, Stefano; Fiorentino, Michelangelo; Tallini, Giovanni

    2013-01-01

    Detection of KRAS mutations in archival pathology samples is critical for therapeutic appropriateness of anti-EGFR monoclonal antibodies in colorectal cancer. We compared the sensitivity, specificity, and accuracy of Sanger sequencing, ARMS-Scorpion (TheraScreen®) real-time polymerase chain reaction (PCR), pyrosequencing, chip array hybridization, and 454 next-generation sequencing to assess KRAS codon 12 and 13 mutations in 60 nonconsecutive selected cases of colorectal cancer. Twenty of the 60 cases were detected as wild-type KRAS by all methods with 100% specificity. Among the 40 mutated cases, 13 were discrepant with at least one method. The sensitivity was 85%, 90%, 93%, and 92%, and the accuracy was 90%, 93%, 95%, and 95% for Sanger sequencing, TheraScreen real-time PCR, pyrosequencing, and chip array hybridization, respectively. The main limitation of Sanger sequencing was its low analytical sensitivity, whereas TheraScreen real-time PCR, pyrosequencing, and chip array hybridization showed higher sensitivity but suffered from the limitations of predesigned assays. Concordance between the methods was k = 0.79 for Sanger sequencing and k > 0.85 for the other techniques. Tumor cell enrichment correlated significantly with the abundance of KRAS-mutated deoxyribonucleic acid (DNA), evaluated as ΔCt for TheraScreen real-time PCR (P = 0.03), percentage of mutation for pyrosequencing (P = 0.001), ratio for chip array hybridization (P = 0.003), and percentage of mutation for 454 next-generation sequencing (P = 0.004). Also, 454 next-generation sequencing showed the best cross correlation for quantification of mutation abundance compared with all the other methods (P < 0.001). Our comparison showed the superiority of next-generation sequencing over the other techniques in terms of sensitivity and specificity. Next-generation sequencing will replace Sanger sequencing as the reference technique for diagnostic detection of KRAS mutation in archival tumor tissues. PMID

  11. KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Lin Lin

    Full Text Available Molecular biomarkers to determine the effectiveness of targeted therapies in cancer treatment have been widely adopted in colorectal cancer (CRC, but those to predict chemotherapy sensitivity remain poorly defined. We tested our hypothesis that KRAS mutation may be a predictor of oxaliplatin sensitivity in CRC. KRAS was knocked-down in KRAS-mutant CRC cells (DLD-1(G13D and SW480(G12V by small interfering RNAs (siRNA and overexpressed in KRAS-wild-type CRC cells (COLO320DM by KRAS-mutant vectors to generate paired CRC cells. These paired CRC cells were tested by oxaliplatin, irinotecan and 5FU to determine the change in drug sensitivity by MTT assay and flow cytometry. Reasons for sensitivity alteration were further determined by western blot and real-time quantitative reverse transcriptase polymerase chain reaction (qRT -PCR. In KRAS-wild-type CRC cells (COLO320DM, KRAS overexpression by mutant vectors caused excision repair cross-complementation group 1 (ERCC1 downregulation in protein and mRNA levels, and enhanced oxaliplatin sensitivity. In contrast, in KRAS-mutant CRC cells (DLD-1(G13D and SW480(G12V, KRAS knocked-down by KRAS-siRNA led to ERCC1 upregulation and increased oxaliplatin resistance. The sensitivity of irinotecan and 5FU had not changed in the paired CRC cells. To validate ERCC1 as a predictor of sensitivity for oxaliplatin, ERCC1 was knocked-down by siRNA in KRAS-wild-type CRC cells, which restored oxaliplatin sensitivity. In contrast, ERCC1 was overexpressed by ERCC1-expressing vectors in KRAS-mutant CRC cells, and caused oxaliplatin resistance. Overall, our findings suggest that KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells by the mechanism of ERCC1 downregulation.

  12. Peripheral lung adenocarcinomas with KRAS mutations are more likely to invade visceral pleura.

    Science.gov (United States)

    Raparia, Kirtee; Villa, Celina; Raj, Rishi; Cagle, Philip T

    2015-02-01

    Kirsten-RAS (KRAS) mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas and are associated with poorer prognosis. To investigate the relationship of KRAS mutation status to the histologic subtype of adenocarcinoma according to the recent classification, patient demographics, tumor size, predominant histologic subtype, nodal status, and visceral pleural invasion, in an attempt to uncover the reason for the worse prognosis associated with KRAS mutation. A total of 187 consecutive resected lung adenocarcinomas from our institution from 2008 to 2011 that were diagnosed according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification and screened for KRAS mutations were included in the study. A total of 32% of the adenocarcinomas harbored the KRAS mutation. The median age in the KRAS mutation group was 69 years (range, 43-86 years), and male to female ratio was 1:2.3. The proportion of heavy smokers was significantly higher in tumors with KRAS mutation compared with wild type (83% versus 62%; P = .01). A total of 27% of tumors with KRAS mutation had pleural invasion versus 11% of tumors without KRAS mutation (P = .009). A total of 59 tumor samples were positive for KRAS mutation (25 for G12C, 14 for G12A, 8 for G12V, 7 for G12D, 3 for G12S, and 1 for G12T), and only 3 tumors harbored codon 13 mutations (G13C). Two tumors had double mutations. KRAS mutations are more common in heavy smokers, and lung adenocarcinomas with KRAS mutation are more likely to invade the visceral pleura. Increased frequency of visceral pleural invasion may explain in part the worse prognosis associated with KRAS mutations.

  13. Evaluation of intrapleural contrast-enhanced abdominal pelvic CT-scan in detecting diaphragm injury in stable patients with thoraco-abdominal stab wound: a preliminary study.

    Science.gov (United States)

    Abbasy, Hamid Reza; Panahi, Farzad; Sefidbakht, Sepideh; Akrami, Majid; Paydar, Shahram; Mirhashemi, Sedighe; Bolandparvaz, Shahram; Asaadi, Kambiz; Salahi, Roohollah

    2012-09-01

    Many of the patients with thoraco-abdominal stab wound remain asymptomatic; in this regard, previous studies reported that 7-48% of asymptomatic patients had diaphragm injury (DI). Thoracoscopy or multidetector computed tomography (MDCT) scan is the best method to detect DI. We aimed to evaluate the role of CT scan with intrapleural contrast to rule out DI in stable thoraco-abdominal stab wounds. In a prospective study, we evaluated all haemodynamically stable patients with thoraco-abdominal stab wound, from October 2009 to 2010. Exclusion criteria included patients who needed emergency thoracotomy or laparotomy, those who were haemodynamically unstable and those with blunt trauma or gunshot injury. In the CT-scan department, 500 cc of diluted meglumine diatrozate was transfused into the pleural space via a chest tube and the CT scan was performed from the dome of the diaphragm to the pelvic cavity. In the second step, all patients were taken for thoracoscopy within 24h after admission. The CT-scan slide was considered positive if one of the following signs was found: (1) the diaphragm was obviously injured as seen in CT-scan slides and (2) contrast agent was seen in the peritoneal cavity. Sensitivity and specificity were calculated for CT scan and thoracoscopy. Four out of 40 patients had DI according to thoracoscopy. CT scan with intrapleural contrast predicted diaphragmatic injury correctly in all four patients. Considering thoracoscopy as the gold-standard method, the CT scan had two false-positive cases. The sensitivity of the intrapleural-contrast CT scan was 100% and its specificity was 94.4%. Our study showed that CT scan with intrapleural contrast can be an acceptable approach to rule out DI and limit the use of thoracoscopy for final diagnosis and repair of DI in cases with suspicious or positive CT-scan results, especially in trauma centres with high load of trauma patients and little accessible equipment. Copyright © 2011 Elsevier Ltd. All rights

  14. SonoNet: Real-Time Detection and Localisation of Fetal Standard Scan Planes in Freehand Ultrasound.

    Science.gov (United States)

    Baumgartner, Christian F; Kamnitsas, Konstantinos; Matthew, Jacqueline; Fletcher, Tara P; Smith, Sandra; Koch, Lisa M; Kainz, Bernhard; Rueckert, Daniel

    2017-11-01

    Identifying and interpreting fetal standard scan planes during 2-D ultrasound mid-pregnancy examinations are highly complex tasks, which require years of training. Apart from guiding the probe to the correct location, it can be equally difficult for a non-expert to identify relevant structures within the image. Automatic image processing can provide tools to help experienced as well as inexperienced operators with these tasks. In this paper, we propose a novel method based on convolutional neural networks, which can automatically detect 13 fetal standard views in freehand 2-D ultrasound data as well as provide a localization of the fetal structures via a bounding box. An important contribution is that the network learns to localize the target anatomy using weak supervision based on image-level labels only. The network architecture is designed to operate in real-time while providing optimal output for the localization task. We present results for real-time annotation, retrospective frame retrieval from saved videos, and localization on a very large and challenging dataset consisting of images and video recordings of full clinical anomaly screenings. We found that the proposed method achieved an average F1-score of 0.798 in a realistic classification experiment modeling real-time detection, and obtained a 90.09% accuracy for retrospective frame retrieval. Moreover, an accuracy of 77.8% was achieved on the localization task.

  15. Detecting element specific electrons from a single cobalt nanocluster with synchrotron x-ray scanning tunneling microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kersell, Heath; Shirato, Nozomi; Cummings, Marvin; Chang, Hao; Miller, Dean; Rosenmann, Daniel; Hla, Saw-Wai; Rose, Volker

    2017-09-04

    We use a nanofabricated scanning tunneling microscope tip as a detector to investigate local X-ray induced tunneling and electron emission from a single cobalt nanocluster on a Au(111) surface. The tip-detector is positioned a few angstroms above the nanocluster, and ramping the incident X-ray energy across the Co photoabsorption K-edge enables the detection of element specific electrons. Atomic-scale spatial dependent changes in the X-ray absorption cross section are directly measured by taking the X-ray induced current as a function of X-ray energy. From the measured sample and tip currents, element specific X-ray induced current components can be separated and thereby the corresponding yields for the X-ray induced processes of the single cobalt nanocluster can be determined. The detection of element specific synchrotron X-ray induced electrons of a single nanocluster opens a new avenue for materials characterization on a one particle at-a-time basis.

  16. Wavelet entropy and directed acyclic graph support vector machine for detection of patients with unilateral hearing loss in MRI scanning

    Directory of Open Access Journals (Sweden)

    Shuihua Wang

    2016-10-01

    Full Text Available (Aim Sensorineural hearing loss (SNHL is correlated to many neurodegenerative disease. Now more and more computer vision based methods are using to detect it in an automatic way. (Materials We have in total 49 subjects, scanned by 3.0T MRI (Siemens Medical Solutions, Erlangen, Germany. The subjects contain 14 patients with right-sided hearing loss (RHL, 15 patients with left-sided hearing loss (LHL, and 20 healthy controls (HC. (Method We treat this as a three-class classification problem: RHL, LHL, and HC. Wavelet entropy (WE was selected from the magnetic resonance images of each subjects, and then submitted to a directed acyclic graph support vector machine (DAG-SVM. (Results The 10 repetition results of 10-fold cross validation shows 3-level decomposition will yield an overall accuracy of 95.10% for this three-class classification problem, higher than feedforward neural network, decision tree, and naive Bayesian classifier. (Conclusions This computer-aided diagnosis system is promising. We hope this study can attract more computer vision method for detecting hearing loss.

  17. Automated terrestrial laser scanning with near-real-time change detection – monitoring of the Séchilienne landslide

    Directory of Open Access Journals (Sweden)

    R. A. Kromer

    2017-05-01

    Full Text Available We present an automated terrestrial laser scanning (ATLS system with automatic near-real-time change detection processing. The ATLS system was tested on the Séchilienne landslide in France for a 6-week period with data collected at 30 min intervals. The purpose of developing the system was to fill the gap of high-temporal-resolution TLS monitoring studies of earth surface processes and to offer a cost-effective, light, portable alternative to ground-based interferometric synthetic aperture radar (GB-InSAR deformation monitoring. During the study, we detected the flux of talus, displacement of the landslide and pre-failure deformation of discrete rockfall events. Additionally, we found the ATLS system to be an effective tool in monitoring landslide and rockfall processes despite missing points due to poor atmospheric conditions or rainfall. Furthermore, such a system has the potential to help us better understand a wide variety of slope processes at high levels of temporal detail.

  18. Damage detection in composite panels based on mode-converted Lamb waves sensed using 3D laser scanning vibrometer

    Science.gov (United States)

    Pieczonka, Łukasz; Ambroziński, Łukasz; Staszewski, Wiesław J.; Barnoncel, David; Pérès, Patrick

    2017-12-01

    This paper introduces damage identification approach based on guided ultrasonic waves and 3D laser Doppler vibrometry. The method is based on the fact that the symmetric and antisymmetric Lamb wave modes differ in amplitude of the in-plane and out-of-plane vibrations. Moreover, the modes differ also in group velocities and normally they are well separated in time. For a given time window both modes can occur simultaneously only close to the wave source or to a defect that leads to mode conversion. By making the comparison between the in-plane and out-of-plane wave vector components the detection of mode conversion is possible, allowing for superior and reliable damage detection. Experimental verification of the proposed damage identification procedure is performed on fuel tank elements of Reusable Launch Vehicles designed for space exploration. Lamb waves are excited using low-profile, surface-bonded piezoceramic transducers and 3D scanning laser Doppler vibrometer is used to characterize the Lamb wave propagation field. The paper presents theoretical background of the proposed damage identification technique as well as experimental arrangements and results.

  19. Localization of proteins in paint cross-sections by scanning electrochemical microscopy as an alternative immunochemical detection technique

    Energy Technology Data Exchange (ETDEWEB)

    Sciutto, Giorgia; Prati, Silvia [Microchemistry and Microscopy Art Diagnostic Laboratory, University of Bologna, Via Guaccimanni 42, Ravenna 48121 (Italy); Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi, Bologna 2 40126 (Italy); Mazzeo, Rocco, E-mail: rocco.mazzeo@unibo.it [Microchemistry and Microscopy Art Diagnostic Laboratory, University of Bologna, Via Guaccimanni 42, Ravenna 48121 (Italy); Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi, Bologna 2 40126 (Italy); Zangheri, Martina; Roda, Aldo; Bardini, Luca; Valenti, Giovanni; Rapino, Stefania [Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi, Bologna 2 40126 (Italy); Marcaccio, Massimo, E-mail: massimo.marcaccio@unibo.it [Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi, Bologna 2 40126 (Italy)

    2014-06-01

    Highlights: • Advanced immuno-electrochemical detection of proteins in paint samples by SECM. • Analysis performed directly on cross-section with high spatial resolution. • Identification of HRP catalytic activity for a selective location of analyte. • Satisfactory results were obtained for aged real samples. • The way forward for an extensive application of SECM in conservation science is shown. - Abstract: The qualitative identification of proteinaceous substances, as well as their location within a complex paint stratigraphy, is one of the most challenging issues in the characterization of painting materials. Nevertheless, information on paint components represent a crucial task for studies concerning both the ancient painting techniques adopted and the state of conservation, being fundamental investigations for the selection of appropriate conservation actions. The present research was aimed at developing a new detection approach for the immunochemical localization of ovalbumin in paint cross-sections based on the use of scanning electrochemical microscopy (SECM). The immunochemical analyses were performed using an anti-ovalbumin primary antibody and a secondary antibody labelled with horseradish peroxidase (HRP). SECM measurements were performed in feedback mode using benzoquinone (BQ)/hydroquinone (H{sub 2}Q) redox couple. In presence of hydrogen peroxide (H{sub 2}O{sub 2}), HRP catalyzes the re-oxidation of H{sub 2}Q to BQ and the increment of BQ concentration in correspondence of the target protein was detected by SECM through the electrochemical reduction of the regenerated BQ at the microelectrode. Indeed, the localization of ovalbumin was possible thanks to a clear discrimination of SECM currents, achieved by the comparison of the measurements recorded before and after H{sub 2}O{sub 2} administration, based on the HRP on/off approach. The method was evaluated both on samples from standard mocks-up and on a historical sample, collected from a

  20. Wavelet Entropy and Directed Acyclic Graph Support Vector Machine for Detection of Patients with Unilateral Hearing Loss in MRI Scanning.

    Science.gov (United States)

    Wang, Shuihua; Yang, Ming; Du, Sidan; Yang, Jiquan; Liu, Bin; Gorriz, Juan M; Ramírez, Javier; Yuan, Ti-Fei; Zhang, Yudong

    2016-01-01

    Highlights We develop computer-aided diagnosis system for unilateral hearing loss detection in structural magnetic resonance imaging.Wavelet entropy is introduced to extract image global features from brain images. Directed acyclic graph is employed to endow support vector machine an ability to handle multi-class problems.The developed computer-aided diagnosis system achieves an overall accuracy of 95.1% for this three-class problem of differentiating left-sided and right-sided hearing loss from healthy controls. Aim: Sensorineural hearing loss (SNHL) is correlated to many neurodegenerative disease. Now more and more computer vision based methods are using to detect it in an automatic way. Materials: We have in total 49 subjects, scanned by 3.0T MRI (Siemens Medical Solutions, Erlangen, Germany). The subjects contain 14 patients with right-sided hearing loss (RHL), 15 patients with left-sided hearing loss (LHL), and 20 healthy controls (HC). Method: We treat this as a three-class classification problem: RHL, LHL, and HC. Wavelet entropy (WE) was selected from the magnetic resonance images of each subjects, and then submitted to a directed acyclic graph support vector machine (DAG-SVM). Results: The 10 repetition results of 10-fold cross validation shows 3-level decomposition will yield an overall accuracy of 95.10% for this three-class classification problem, higher than feedforward neural network, decision tree, and naive Bayesian classifier. Conclusions: This computer-aided diagnosis system is promising. We hope this study can attract more computer vision method for detecting hearing loss.

  1. Design of small molecules that compete with nucleotide binding to an engineered oncogenic KRAS allele.

    Science.gov (United States)

    Zhang, Yan; Larraufie, Mare-Helene; Musavi, Leila; Akkiraju, Hemanth; Brown, Lewis M; Stockwell, Brent R

    2018-01-09

    RAS mutations are found in 30% of all human cancers, with KRAS the most frequently mutated among the three RAS isoforms (KRAS, NRAS, HRAS). However, directly targeting oncogenic KRAS with small molecules in the nucleotide-binding site has been difficult due to the high affinity of KRAS for GDP and GTP. We designed an engineered allele of KRAS, and a covalent inhibitor that competes for GTP and GDP. This ligand-receptor combination demonstrates that the high affinity of GTP/GDP for RAS proteins can be overcome with a covalent inhibitor and a suitably engineered binding site. The covalent inhibitor irreversibly modifies the protein at the engineered nucleotide binding site and is able to compete with GDP and GTP. This provides a new tool for studying KRAS function and suggests strategies for targeting the nucleotide-binding site of oncogenic RAS proteins.

  2. Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts

    Science.gov (United States)

    Li, S; Li, L; Zhu, Y; Huang, C; Qin, Y; Liu, H; Ren-Heidenreich, L; Shi, B; Ren, H; Chu, X; Kang, J; Wang, W; Xu, J; Tang, K; Yang, H; Zheng, Y; He, J; Yu, G; Liang, N

    2014-01-01

    Background: Determining the somatic mutations of epidermal growth factor receptor (EGFR)-pathway networks is the key to effective treatment for non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs).The somatic mutation frequencies and their association with gender, smoking history and histology was analysed and reported in this study. Methods: Five thousand one hundred and twenty-five NSCLC patients' pathology samples were collected, and EGFR, KRAS, BRAF and PIK3CA mutations were detected by multiplex testing. The mutation status of EGFR, KRAS, BRAF and PIK3CA and their association with gender, age, smoking history and histological type were evaluated by appropriate statistical analysis. Results: EGFR, KRAS, BRAF and PIK3CA mutation rates revealed 36.2%, 8.4%, 0.5% and 3.3%, respectively, across the 5125 pathology samples. For the first time, evidence of KRAS mutations were detected in two female, non-smoking patients, age 5 and 14, with NSCLC. Furthermore, we identified 153 double and coexisting mutations and 7 triple mutations. Interestingly, the second drug-resistant mutations, T790M or E545K, were found in 44 samples from patients who had never received TKI treatments. Conclusions: EGFR exons 19, 20 and 21, and BRAF mutations tend to happen in females and non-smokers, whereas KRAS mutations were more inclined to males and smokers. Activating and resistant mutations to EGFR-TKI drugs can coexist and ‘second drug-resistant mutations', T790M or E545K, may be primary mutations in some patients. These results will help oncologists to decide candidates for mutation testing and EGFR-TKI treatment. PMID:24743704

  3. Automatic Detection and Classification of Pole-Like Objects for Urban Cartography Using Mobile Laser Scanning Data

    Directory of Open Access Journals (Sweden)

    Celestino Ordóñez

    2017-06-01

    Full Text Available Mobile laser scanning (MLS is a modern and powerful technology capable of obtaining massive point clouds of objects in a short period of time. Although this technology is nowadays being widely applied in urban cartography and 3D city modelling, it has some drawbacks that need to be avoided in order to strengthen it. One of the most important shortcomings of MLS data is concerned with the fact that it provides an unstructured dataset whose processing is very time-consuming. Consequently, there is a growing interest in developing algorithms for the automatic extraction of useful information from MLS point clouds. This work is focused on establishing a methodology and developing an algorithm to detect pole-like objects and classify them into several categories using MLS datasets. The developed procedure starts with the discretization of the point cloud by means of a voxelization, in order to simplify and reduce the processing time in the segmentation process. In turn, a heuristic segmentation algorithm was developed to detect pole-like objects in the MLS point cloud. Finally, two supervised classification algorithms, linear discriminant analysis and support vector machines, were used to distinguish between the different types of poles in the point cloud. The predictors are the principal component eigenvalues obtained from the Cartesian coordinates of the laser points, the range of the Z coordinate, and some shape-related indexes. The performance of the method was tested in an urban area with 123 poles of different categories. Very encouraging results were obtained, since the accuracy rate was over 90%.

  4. Glaucoma progression detection by retinal nerve fiber layer measurement using scanning laser polarimetry: event and trend analysis.

    Science.gov (United States)

    Moon, Byung Gil; Sung, Kyung Rim; Cho, Jung Woo; Kang, Sung Yong; Yun, Sung-Cheol; Na, Jung Hwa; Lee, Youngrok; Kook, Michael S

    2012-06-01

    To evaluate the use of scanning laser polarimetry (SLP, GDx VCC) to measure the retinal nerve fiber layer (RNFL) thickness in order to evaluate the progression of glaucoma. Test-retest measurement variability was determined in 47 glaucomatous eyes. One eye each from 152 glaucomatous patients with at least 4 years of follow-up was enrolled. Visual field (VF) loss progression was determined by both event analysis (EA, Humphrey guided progression analysis) and trend analysis (TA, linear regression analysis of the visual field index). SLP progression was defined as a reduction of RNFL exceeding the predetermined repeatability coefficient in three consecutive exams, as compared to the baseline measure (EA). The slope of RNFL thickness change over time was determined by linear regression analysis (TA). Twenty-two eyes (14.5%) progressed according to the VF EA, 16 (10.5%) by VF TA, 37 (24.3%) by SLP EA and 19 (12.5%) by SLP TA. Agreement between VF and SLP progression was poor in both EA and TA (VF EA vs. SLP EA, k = 0.110; VF TA vs. SLP TA, k = 0.129). The mean (±standard deviation) progression rate of RNFL thickness as measured by SLP TA did not significantly differ between VF EA progressors and non-progressors (-0.224 ± 0.148 µm/yr vs. -0.218 ± 0.151 µm/yr, p = 0.874). SLP TA and EA showed similar levels of sensitivity when VF progression was considered as the reference standard. RNFL thickness as measurement by SLP was shown to be capable of detecting glaucoma progression. Both EA and TA of SLP showed poor agreement with VF outcomes in detecting glaucoma progression.

  5. Automatic Detection and Classification of Pole-Like Objects for Urban Cartography Using Mobile Laser Scanning Data.

    Science.gov (United States)

    Ordóñez, Celestino; Cabo, Carlos; Sanz-Ablanedo, Enoc

    2017-06-22

    Mobile laser scanning (MLS) is a modern and powerful technology capable of obtaining massive point clouds of objects in a short period of time. Although this technology is nowadays being widely applied in urban cartography and 3D city modelling, it has some drawbacks that need to be avoided in order to strengthen it. One of the most important shortcomings of MLS data is concerned with the fact that it provides an unstructured dataset whose processing is very time-consuming. Consequently, there is a growing interest in developing algorithms for the automatic extraction of useful information from MLS point clouds. This work is focused on establishing a methodology and developing an algorithm to detect pole-like objects and classify them into several categories using MLS datasets. The developed procedure starts with the discretization of the point cloud by means of a voxelization, in order to simplify and reduce the processing time in the segmentation process. In turn, a heuristic segmentation algorithm was developed to detect pole-like objects in the MLS point cloud. Finally, two supervised classification algorithms, linear discriminant analysis and support vector machines, were used to distinguish between the different types of poles in the point cloud. The predictors are the principal component eigenvalues obtained from the Cartesian coordinates of the laser points, the range of the Z coordinate, and some shape-related indexes. The performance of the method was tested in an urban area with 123 poles of different categories. Very encouraging results were obtained, since the accuracy rate was over 90%.

  6. Online platform for applying space-time scan statistics for prospectively detecting emerging hot spots of dengue fever.

    Science.gov (United States)

    Chen, Chien-Chou; Teng, Yung-Chu; Lin, Bo-Cheng; Fan, I-Chun; Chan, Ta-Chien

    2016-11-25

    Cases of dengue fever have increased in areas of Southeast Asia in recent years. Taiwan hit a record-high 42,856 cases in 2015, with the majority in southern Tainan and Kaohsiung Cities. Leveraging spatial statistics and geo-visualization techniques, we aim to design an online analytical tool for local public health workers to prospectively identify ongoing hot spots of dengue fever weekly at the village level. A total of 57,516 confirmed cases of dengue fever in 2014 and 2015 were obtained from the Taiwan Centers for Disease Control (TCDC). Incorporating demographic information as covariates with cumulative cases (365 days) in a discrete Poisson model, we iteratively applied space-time scan statistics by SaTScan software to detect the currently active cluster of dengue fever (reported as relative risk) in each village of Tainan and Kaohsiung every week. A village with a relative risk >1 and p value dengue fever transmission on a weekly basis at the village level by using the routine surveillance data.

  7. Thin-layer chromatography with UV-scanning detection for quantitative analysis of coal-derived products

    Energy Technology Data Exchange (ETDEWEB)

    Vela, J.; Cebolla, V.L.; Membrado, L.; Ferrando, A.C. [University of Zaragoza, Zaragoza (Spain). Dept. of Analytical Chemistry

    1998-07-01

    Quantitative analysis of hydrocarbon groups (HGTA) is important in the characterization of products derived from coal conversion. The heaviest products are usually analyzed by thin-layer chromatography with flame-ionization detection (TLC-FID). TLC with ultraviolet (UV) scanning densitometry was investigated as an alternative to TLC-FID for the rapid determination of aromatic, polar, and noneluted compounds in coal-derived products. The results obtained show that TLC-UV is adequate in terms of speed, repeatability, and quantitative analysis, and furnishes results similar to those obtained by TLC-FID. Preparative TLC enables isolation of fractions suitable for preparative purposes and is less time-consuming (hours rather than days) than LC methods. Rapid calibration of TLC-UV is possible by use of fractions isolated by preparative TLC (derived from the actual fossil fuels to be analyzed) as external standards. A method of fast internal calibration has been tested for hydrocarbon group-type analysis. Direct acquisition of UV spectra from the separated peaks can be used to determine whether this method of calibration is applicable to the sample.

  8. Detection of macrophage activity in atherosclerosis in vivo using multichannel, high-resolution laser scanning fluorescence microscopy

    Science.gov (United States)

    Pande, Ashvin N.; Kohler, Rainer; Aikawa, Elena; Weissleder, Ralph; Jaffer, Farouc

    2006-03-01

    Molecular and cellular mechanisms of atherogenesis and its treatment are largely being unraveled by in vitro techniques. We describe methodology to directly image macrophage cell activity in vivo in a murine model of atherosclerosis using laser scanning fluorescence microscopy (LSFM) and a macrophage-targeted, near-infrared fluorescent (NIRF) magnetofluorescent nanoparticle (MFNP). Atherosclerotic apolipoprotein E deficient (apoE -/-) mice (n=10) are injected with MFNP or 0.9% saline, and wild-type mice (n=4) are injected with MFNP as additional controls. After 24 h, common carotid arteries are surgically exposed and prepared for LSFM. Multichannel LSFM of MFNP-enhanced carotid atheroma (5×5-µm in-plane resolution) shows a strong focal NIRF signal, with a plaque target-to-background ratio of 3.9+/-1.8. Minimal NIRF signal is observed in control mice. Spectrally resolved indocyanine green (ICG) fluorescence angiograms confirm the intravascular location of atheroma. On ex vivo fluorescence reflectance imaging, greater NIRF plaque signal is seen in apoE -/- MFNP mice compared to controls (p<0.01). The NIRF signal correlates well with immunostained macrophages, both by stained surface area (r=0.77) and macrophage number (r=0.86). The validated experimental methodology thus establishes a platform for investigating macrophage activity in atherosclerosis in vivo, and has implications for the detection of clinical vulnerable plaques.

  9. [Relationship between EGFR and KRAS mutations and prognosis in Chinese patients with non-small cell lung cancer: a mutation analysis with real-time polymerase chain reaction using scorpion amplification refractory mutation system].

    Science.gov (United States)

    Gao, Jie; Chen, Jia-qi; Zhang, Li; Liang, Zhi-yong

    2012-10-01

    To investigate the gene mutation of EGFR and KRAS in Chinese patients with non-small cell lung cancer (NSCLC), and to analyze the relationship between the gene mutations and the clinicopathological features and EGFR-TKI efficiency. EGFR mutation was detected in 120 patients and KRAS mutation in 104 patients with NSCLC in Peking Union Medical College Hospital from March 2009 to December 2010, and the correlation of the gene mutations with the clinicopathological features and EGFR-TKI efficiency was analyzed in the study. EGFR mutation was detected in 44 of 120 (36.7%) patients with NSCLC, in which three types of EGFR gene mutations were found: deletion in exon 19, exon 21 L858R (2573T > G) and Exon 21 L861Q (2582T > A) mutations. There were 29(24.2%) patients with EGFR exon 19 deletion, 14 (11.7%) patients with EGFR exon 21 L858R mutation and one (0.8%) with EGFR exon 21 L861Q mutation in the patients. All the mutations were single point mutations, and no multiple points mutations detected. EGFR mutation rate of bronchioloalveolar carcinoma and adenocarcinoma were higher than that of non-adenocarcinoma (P = 0.009). EGFR mutation rate was higher in female patients or patients without smoking history than male patients or patients with smoking history (P = 0.014, P = 0.001, respectively) in NSCLC patients. EGFR mutation rate was higher in patients without smoking history or patients with well-differentiated carcinoma than patients with smoking history or patients with moderately-and poorly-differentiated carcinoma (P = 0.008, P = 0.018, respectively). There was no difference in prognosis and EGFR-TKI treatment response rate between EGFR mutation patients and EGFR wild-type patients. Nine (8.7%) patients with KRAS mutation were detected in 104 NSCLC patients. There were four types of KRAS gene mutations detected: KRAS Gly12Ala (GGT > GCT), KRAS Gly12Arg (GGT > CGT), KRAS Gly12Val (GGT > GTT) and KRAS Gly12Cys (GGT > TGT). There were 4 patients with Cys mutation, 2 with

  10. Sensitivity of /sup 67/Ga-scanning in sarcoidosis: Detection of biopsy proven pulmonary lesions radiographically undetectable

    Energy Technology Data Exchange (ETDEWEB)

    Beaumont, D.; Herry, J.Y.; Le Cloirec, J.; Le Jeune, J.J.; de Labarthe, B.

    1982-01-01

    Three cases are reported in which gallium-67 citrate scanning disclosed the presence of pulmonary sarcoid lesions, which were confirmed by open lung biopsy. In all three cases the chest radiograph showed no evidence of pulmonary parenchymal leisons. The present report provides evidence that the gallium-67 scan is more sensitive than radiography in disclosing sarcoid lesions of the lung parenchyma. The scan is useful in the management of sarcoidosis, as it shows progressions or remissions of disease more reliably than chest radiographs.

  11. The detection and influence of food soils on microorganisms on stainless steel using scanning electron microscopy and epifluorescence microscopy.

    Science.gov (United States)

    Whitehead, Kathryn A; Smith, Lindsay A; Verran, Joanna

    2010-07-31

    A range of food soils and components (complex [meat extract, fish extract, and cottage cheese extract]; oils [cholesterol, fish oil, and mixed fatty acids]; proteins [bovine serum albumin (BSA), fish peptones, and casein]; and carbohydrates [glycogen, starch, and lactose]) were deposited onto 304 2B finish stainless steel surfaces at different concentrations (10-0.001%). Scanning electron microscopy (SEM) and epifluorescence microscopy were used to visualise the cell and food soil distribution across the surface. Epifluorescence microscopy was also used to quantify the percentage of a field covered by cells or soil. At 10% concentration, most soils, with the exception of BSA and fish peptone were easily visualised using SEM, presenting differences in gross soil morphology and distribution. When soil was stained with acridine orange and visualised by epifluorescence microscopy, the limit of detection of the method varied between soils, but some (meat, cottage cheese and glycogen) were detected at the lowest concentrations used (0.001%). The decrease in soil concentration did not always relate to the surface coverage measurement. When 10% food soil was applied to a surface with Escherichia coli and compared, cell attachment differed depending on the nature of the soil. The highest percentage coverage of cells was observed on surfaces with fish extract and related products (fish peptone and fish oil), followed by carbohydrates, meat extract/meat protein, cottage cheese/casein and the least to the oils (cholesterol and mixed fatty acids). Cells could not be clearly observed in the presence of some food soils using SEM. Findings demonstrate that food soils heterogeneously covered stainless steel surfaces in differing patterns. The pattern and amount of cell attachment was related to food soil type rather than to the amount of food soil detected. This work demonstrates that in the study of conditioning film and cell retention on the hygienic properties of surfaces, SEM

  12. Computed tomography scan to detect traumatic arthrotomies and identify periarticular wounds not requiring surgical intervention: an improvement over the saline load test.

    Science.gov (United States)

    Konda, Sanjit R; Davidovitch, Roy I; Egol, Kenneth A

    2013-09-01

    To report our experience with computed tomography (CT) scans to detect traumatic arthrotomies of the knee (TAK) joint based on the presence of intra-articular air. Retrospective review. Level I trauma center. Sixty-two consecutive patients (63 knees) underwent a CT scan of the knee in the emergency department and had a minimum of 14 days follow-up. Cohort of 37 patients (37 knees) from the original 62 patients who underwent a saline load test (SLT). CT scan and SLT. Positive traumatic arthrotomy of the knee (+TAK) was defined as operating room (OR) confirmation of an arthrotomy or no intra-articular air on CT scan (-iaCT) (and -SLT if performed) with follow-up revealing a septic knee. Periarticular wound equivalent to no traumatic arthrotomy (pw = (-TAK)) was defined as OR evaluation revealing no arthrotomy or -iaCT (and -SLT if performed) with follow-up revealing no septic knee. All 32 knees with intra-articular air on CT scan (+iaCT) had OR confirmation of a TAK and none of these patients had a knee infection at a mean follow-up of 140.0 ± 279.6 days. None of the 31 patients with -iaCT had a knee infection at a mean follow-up of 291.0 ± 548.1 days. Based on these results, the sensitivity and specificity of the CT scan to detect +TAK and pw = (-TAK) was 100%. In a subgroup of 37 patients that received both a CT scan and the conventional SLT, the sensitivity and specificity of the CT scan was 100% compared with 92% for the SLT (P wounds that do not require surgical intervention and should be considered a valid diagnostic test in the appropriate clinical setting. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

  13. High definition colonoscopy combined with i-Scan is superior in the detection of colorectal neoplasias compared with standard video colonoscopy: a prospective randomized controlled trial.

    Science.gov (United States)

    Hoffman, A; Sar, F; Goetz, M; Tresch, A; Mudter, J; Biesterfeld, S; Galle, P R; Neurath, M F; Kiesslich, R

    2010-10-01

    Colonoscopy is the accepted gold standard for the detection of colorectal cancer. The aim of the current study was to prospectively compare high definition plus (HD+) colonoscopy with I-Scan functionality (electronic staining) vs. standard video colonoscopy. The primary endpoint was the detection of patients having colon cancer or at least one adenoma. A total of 220 patients due to undergo screening colonoscopy, postpolypectomy surveillance or with a positive occult blood test were randomized in a 1 : 1 ratio to undergo HD+ colonoscopy in conjunction with I-Scan surface enhancement (90i series, Pentax, Tokyo, Japan) or standard video colonoscopy (EC-3870FZK, Pentax). Detected colorectal lesions were judged according to type, location, and size. Lesions were characterized in the HD+ group by using further I-Scan functionality (p- and v-modes) to analyze pattern and vessel architecture. Histology was predicted and biopsies or resections were performed on all identified lesions. HD+ colonoscopy with I-Scan functionality detected significantly more patients with colorectal neoplasia (38 %) compared with standard resolution endoscopy (13 %) (200 patients finally analyzed; 100 per arm). Significantly more neoplastic (adenomatous and cancerous) lesions and more flat adenomas could be detected using high definition endoscopy with surface enhancement. Final histology could be predicted with high accuracy (98.6 %) within the HD+ group. HD+ colonoscopy with I-Scan is superior to standard video colonoscopy in detecting patients with colorectal neoplasia based on this prospective, randomized, controlled trial. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Identification of Differentially Expressed K-Ras Transcript Variants in Patients With Leiomyoma.

    Science.gov (United States)

    Zolfaghari, Nooshin; Shahbazi, Shirin; Torfeh, Mahnaz; Khorasani, Maryam; Hashemi, Mehrdad; Mahdian, Reza

    2017-10-01

    Molecular studies have demonstrated a wide range of gene expression variations in uterine leiomyoma. The rat sarcoma virus/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase (RAS/RAF/MAPK) is the crucial cellular pathway in transmitting external signals into nucleus. Deregulation of this pathway contributes to excessive cell proliferation and tumorigenesis. The present study aims to investigate the expression profile of the K-Ras transcripts in tissue samples from patients with leiomyoma. The patients were leiomyoma cases who had no mutation in mediator complex subunit 12 ( MED12) gene. A quantitative approach has been applied to determine the difference in the expression of the 2 main K-Ras messenger RNA (mRNA) variants. The comparison between gene expression levels in leiomyoma and normal myometrium group was performed using relative expression software tool. The expression of K-Ras4B gene was upregulated in leiomyoma group ( P = .016), suggesting the involvement of K-Ras4B in the disease pathogenesis. Pairwise comparison of the K-Ras4B expression between each leiomyoma tissue and its matched adjacent normal myometrium revealed gene upregulation in 68% of the cases. The expression of K-Ras4A mRNA was relatively upregulated in leiomyoma group ( P = .030). In addition, the mean expression of K-Ras4A gene in leiomyoma tissues relative to normal samples was 4.475 (95% confidence interval: 0.10-20.42; standard error: 0.53-12.67). In total, 58% of the cases showed more than 2-fold increase in K-Ras4A gene expression. Our results demonstrated increased expression of both K-Ras mRNA splicing variants in leiomyoma tissue. However, the ultimate result of KRAS expression on leiomyoma development depends on the overall KRAS isoform balance and, consequently, on activated signaling pathways.

  15. Nearest Neighbor Averaging and its Effect on the Critical Level and Minimum Detectable Concentration for Scanning Radiological Survey Instruments that Perform Facility Release Surveys.

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Sean Donovan; Beall, Patrick S; Miller, Mark L

    2014-08-01

    Through the SNL New Mexico Small Business Assistance (NMSBA) program, several Sandia engineers worked with the Environmental Restoration Group (ERG) Inc. to verify and validate a novel algorithm used to determine the scanning Critical Level (L c ) and Minimum Detectable Concentration (MDC) (or Minimum Detectable Areal Activity) for the 102F scanning system. Through the use of Monte Carlo statistical simulations the algorithm mathematically demonstrates accuracy in determining the L c and MDC when a nearest-neighbor averaging (NNA) technique was used. To empirically validate this approach, SNL prepared several spiked sources and ran a test with the ERG 102F instrument on a bare concrete floor known to have no radiological contamination other than background naturally occurring radioactive material (NORM). The tests conclude that the NNA technique increases the sensitivity (decreases the L c and MDC) for high-density data maps that are obtained by scanning radiological survey instruments.

  16. Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Sørensen, Morten; Pallisgaard, Niels

    2013-01-01

    Background. Patients with chemotherapy refractory metastatic colorectal cancer and KRAS mutations have no effective treatment option. The present study evaluated the efficacy of temsirolimus in chemotherapy refractory mCRC with KRAS mutations. Furthermore, we wanted to investigate if resistance...

  17. Detection of urinary stones at reduced radiation exposure: a phantom study comparing computed radiography and a low-dose digital radiography linear slit scanning system

    Science.gov (United States)

    Szucs-Farkas, Zsolt; Chakraborty, D. P.; Thoeny, Harriet C.; Loupatatzis, Christos; Vock, Peter; Harald, Bonel

    2010-01-01

    Objective In this experimental study we assessed the diagnostic performance of linear slit scanning radiography (LSSR) compared to conventional computed radiography (CR) in the detection of urinary calculi in an anthropomorphic phantom imitating patients weighing approximately 58 to 88 kg. Conclusion Compared to computed radiography, LSSR is superior in the detection of urinary stones and may be used for pretreatment localization and follow-up at a lower patient exposure. PMID:19457787

  18. Gene therapy of pancreatic cancer targeting the K-Ras oncogene.

    Science.gov (United States)

    Lisiansky, V; Naumov, I; Shapira, S; Kazanov, D; Starr, A; Arber, N; Kraus, S

    2012-12-01

    Ras mutations are present in ∼95% of pancreatic cancer (PC) cases leading to increased proliferation and apoptosis resistance. The aim of this study is to selectively kill Ras-transformed cells by overexpressing the pro-apoptotic protein, p53 upregulated modulator of apoptosis (PUMA) under a Ras-responsive promoter. Colo357, Panc1 and MiaPaca, PC cell lines harboring K-Ras mutations, normal rat IEC18 enterocytes, and their K-Ras transformed R1 counterparts, were tested. We constructed adenoviral vectors containing the PUMA gene downstream to: (1) Four or five repetitive Ras-responsive elements (Ad-PY4/PY5-PUMA) and (2) a negative control (Ad-SV40-PUMA). Cell viability was estimated by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis was evaluated by FACS. In vivo potency of the adenoviruses was evaluated in athymic nude mice. Infection with Ad-PY4/PY5-PUMA markedly inhibited cell growth (∼40-50%), and apoptosis was detected in all cells with high Ras activity, whereas IEC18 cells remained unaffected. The control vector, Ad-SV40-PUMA, did not induce any cell death. Selective and high expression of PUMA was detected in Ad-PY4-PUMA-infected cells. In vivo, Ad-PY4-PUMA inhibited by ∼35% the growth of established tumors compared with the Ad-SV40-PUMA. Selective overexpression of PUMA efficiently inhibits the growth of Ras-transformed cells while sparing the normal ones. This treatment modality may become a useful, effective and safe approach to selectively target Ras-mutated tumor cells.

  19. The use of indium-111 labeled platelet scanning for the detection of asymptomatic deep venous thrombosis in a high risk population

    Energy Technology Data Exchange (ETDEWEB)

    Siegel, R.S.; Rae, J.L.; Ryan, N.L.; Edwards, C.; Fortune, W.P.; Lewis, R.J.; Reba, R.C. (George Washington Univ. Medical Center, Washington, DC (USA))

    1989-11-01

    Five hundred indium-111 labeled platelet imaging studies (387 donor and 113 autologous) were performed postoperatively in 473 patients who had undergone total hip replacement, total knee replacement, or internal fixation of a hip fracture to detect occult deep venous thrombosis. All patients had been anticoagulated prophylactically with aspirin, warfarin sodium (Coumadin), or dextran. Thirty-four possible cases of proximal deep venous thrombosis were identified in 28 asymptomatic patients. To verify the scan results, 31 venograms were performed in 25 patients (three refused). In 21 of 31 cases, totally occlusive thrombi were detected; in 5 cases, partially occlusive thrombi were detected; in 5 cases, no thrombus was seen. No patient who had a negative scan nor any patient who had a verified positive scan (and received appropriate heparin therapy) subsequently developed symptoms or signs of pulmonary embolism. One hundred forty-one indium study patients also underwent Doppler ultrasonography/impedance plethysmography (Doppler/IPG) as a comparative non-invasive technique. In 137 cases, the results of the indium study and Doppler/IPG studies were congruent. The indium study had no false negative results that were detected by Doppler/IPG. No patient had any clinically evident toxicity. These results suggest that indium-111 labeled platelet scanning is a safe, noninvasive means for identifying DVT in high risk patients.

  20. Hot-spot detection and calibration of a scanning thermal probe with a noise thermometry gold wire sample

    NARCIS (Netherlands)

    Gaitas, A.; Wolgast, S.; Covington, E.; Kurdak, C.

    2013-01-01

    Measuring the temperature profile of a nanoscale sample using scanning thermal microscopy is challenging due to a scanning probe's non-uniform heating. In order to address this challenge, we have developed a calibration sample consisting of a 1-?m wide gold wire, which can be heated electrically by

  1. Relative value of thallium-201 and iodine-131 scans in the detection of recurrence or distant metastasis of well differentiated thyroid carcinoma.

    Science.gov (United States)

    Lin, J D; Kao, P F; Weng, H F; Lu, W T; Huang, M J

    1998-07-01

    Radioactive iodine (131I) has been found to be more sensitive and more specific than thallium-201 for the detection of distant metastases and thyroid remnants in the neck in cases of well-differentiated thyroid carcinoma. 201Tl has been deemed particularly useful in localizing metastases or recurrence in patients with a negative 131I scan and abnormal levels of serum thyroglobulin (Tg). This study aimed to: (1) determine the value of 201Tl imaging in localizing metastases or recurrence in patients with well-differentiated thyroid carcinoma, and (2) evaluate the false-positive and false-negative results of 131I and 201Tl scintigraphy. Sixty-two thyroid remnant ablated patients who underwent simultaneous postoperative 201Tl and 131I scans and and serum Tg determinations were evaluated. Fifty patients had papillary thyroid carcinomas and 12 had follicular thyroid carcinomas. 201Tl imaging was performed before the 131I studies. Of the 62 patients who underwent 201Tl imaging studies, 24 were found to have positive results, with local recurrence or distant metastases. Patients with positive results in the 201Tl imaging studies tended to be older, were mor often male, had higher Tg levels and had a higher recurrence rate. Of these 24 patients, ten had negative diagnostic or therapeutic 131I scans. Concurrently, serum Tg levels were less than 5 ng/ml in five of these ten patients. Three patients were deemed false positive by 201Tl scans; one had a parotid tumour, one a periodontal abscess and one lung metastasis. Among the 38 patients with negative 201Tl scans, 11 had positive findings on 131I scans. Three had distant metastases: two with lung metastases and one with bone metastases. Patients with false-positive results on 131I scans included those with biliary tract stones, ovarian cysts, and breast secretion. Of the 27 patients with negative 201Tl and 131I scans, 15 had elevated serum Tg levels. Among these, local recurrence followed by lung metastases was manifested in

  2. Relative value of thallium-201 and iodine-131 scans in the detection of recurrence or distant metastasis of well differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jen-Der; Weng Hsiao-Fen; Lu Wen-Tsoung [Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital (Taiwan, Province of China); Kao Pan-Fu; Huang Miau-Ju [Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taiwan (Taiwan, Province of China)

    1998-07-01

    Radioactive iodine ({sup 131}I) has been found to be more sensitive and more specific than thallium-201 for the detection of distant metastases and thyroid remnants in the neck in cases of well-differentiated thyroid carcinoma. {sup 201}Tl has been deemed particularly useful in localizing metastases or recurrence in patients with a negative {sup 131}I scan and abnormal levels of serum thyroglobulin (Tg). This study aimed to: (1) determine the value of {sup 201}Tl imaging in localizing metastases or recurrence in patients with well-differentiated thyroid carcinoma, and (2) evaluate the false-positive and false-negative results of {sup 131}I and {sup 201}Tl scintigraphy. Sixty-two thyroid remnant ablated patients who underwent simultaneous postoperative {sup 201}Tl and {sup 131}I scans and and serum Tg determinations were evaluated. Fifty patients had papillary thyroid carcinomas and 12 had follicular thyroid carcinomas. {sup 201}Tl imaging was performed before the {sup 131}I studies. Of the 62 patients who underwent {sup 201}Tl imaging studies, 24 were found to have positive results, with local recurrence or distant metastases. Patients with positive results in the {sup 201}Tl imaging studies tended to be older, were mor often male, had higher Tg levels and had a higher recurrence rate. Of these 24 patients, ten had negative diagnostic or therapeutic {sup 131}I scans. Concurrently, serum Tg levels were less than 5 ng/ml in five of these ten patients. Three patients were deemed false positive by {sup 201}Tl scans; one had a parotid tumour, one a periodontal abscess and one lung metastasis. Among the 38 patients with negative {sup 201}Tl scans, 11 had positive findings on {sup 131}I scans. Three had distant metastases: two with lung metastases and one with bone metastases. Patients with false-positive results on {sup 131}I scans included those with biliary tract stones, ovarian cysts, and breast secretion. Of the 27 patients with negative {sup 201}Tl and {sup 131}I

  3. Detection of cervical cancer biomarker patterns in blood plasma and urine by differential scanning calorimetry and mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Nichola C Garbett

    Full Text Available Improved methods for the accurate identification of both the presence and severity of cervical intraepithelial neoplasia (CIN and extent of spread of invasive carcinomas of the cervix (IC are needed. Differential scanning calorimetry (DSC has recently been shown to detect specific changes in the thermal behavior of blood plasma proteins in several diseases. This methodology is being explored to provide a complementary approach for screening of cervical disease. The present study evaluated the utility of DSC in differentiating between healthy controls, increasing severity of CIN and early and advanced IC. Significant discrimination was apparent relative to the extent of disease with no clear effect of demographic factors such as age, ethnicity, smoking status and parity. Of most clinical relevance, there was strong differentiation of CIN from healthy controls and IC, and amongst patients with IC between FIGO Stage I and advanced cancer. The observed disease-specific changes in DSC profiles (thermograms were hypothesized to reflect differential expression of disease biomarkers that subsequently bound to and affected the thermal behavior of the most abundant plasma proteins. The effect of interacting biomarkers can be inferred from the modulation of thermograms but cannot be directly identified by DSC. To investigate the nature of the proposed interactions, mass spectrometry (MS analyses were employed. Quantitative assessment of the low molecular weight protein fragments of plasma and urine samples revealed a small list of peptides whose abundance was correlated with the extent of cervical disease, with the most striking plasma peptidome data supporting the interactome theory of peptide portioning to abundant plasma proteins. The combined DSC and MS approach in this study was successful in identifying unique biomarker signatures for cervical cancer and demonstrated the utility of DSC plasma profiles as a complementary diagnostic tool to evaluate

  4. Detection of airbag impact-induced cone photoreceptor damage by adaptive optics scanning laser ophthalmoscopy: a case report.

    Science.gov (United States)

    Kaizu, Yoshihiro; Nakao, Shintaro; Yamaguchi, Muneo; Murakami, Yusuke; Salehi-Had, Hani; Ishibashi, Tatsuro

    2016-07-08

    The purpose of this study was to report a case of traumatic maculopathy with para-central visual field defects following an impact by airbag deployment using adaptive optics scanning laser ophthalmoscopy (AO-SLO). A 51-year-old man was involved in a motor vehicular accident and his left eye was struck by the deployed airbag, resulting in a para-central scotoma. The patient underwent a full ophthalmologic examination, spectral-domain optical coherence tomography (SD-OCT), and imaging with prototype AO-SLO systems (Canon Inc.) at 14 and 22 months after the injury. Images focused on the photoreceptor layer were recorded in the foveal area, and a montage of AO-SLO images was created. On AO-SLO, focal dark areas could be observed in the left eye at 14 months after the injury. The analysis showed that the cone mosaic (cone density, 16503/mm(2); ratio of hexagonal Voronoi domain, 36.3 %; average nearest-neighbor distance (NND)/expected NND, 0.606) was disordered compared with the normal area of the same eye (cone density, 24821/mm(2); ratio of hexagonal Voronoi domain, 44.1 %; average NND/expected NND, 0.739). The cone defect area corresponded to the area of the scotoma. A second AO-SLO was performed on the patient at 22 months after the injury and although there were still areas with reduced cone reflectivity, partial improvement of cone mosaic was detected by AO-SLO at this time point. Partial recovery of damaged cone photoreceptors following closed globe blunt ocular trauma can be documented using AO-SLO longitudinal tracking.

  5. 454 next generation-sequencing outperforms allele-specific PCR, Sanger sequencing, and pyrosequencing for routine KRAS mutation analysis of formalin-fixed, paraffin-embedded samples

    Directory of Open Access Journals (Sweden)

    Altimari A

    2013-08-01

    Full Text Available Annalisa Altimari,1,* Dario de Biase,2,* Giovanna De Maglio,3 Elisa Gruppioni,1 Elisa Capizzi,1 Alessio Degiovanni,1 Antonia D'Errico,1 Annalisa Pession,2 Stefano Pizzolitto,3 Michelangelo Fiorentino,1,# Giovanni Tallini2,#1Laboratory of Molecular Oncologic and Transplantation Pathology, S. Orsola-Malpighi Hospital, Bologna, 2Laboratory of Molecular Pathology, Anatomic Pathology, Bellaria Hospital, Bologna, 3Department of Pathology, S. Maria della Misericordia Hospital, Udine, Italy*These authors contributed equally to this work #These authors share senior authorshipAbstract: Detection of KRAS mutations in archival pathology samples is critical for therapeutic appropriateness of anti-EGFR monoclonal antibodies in colorectal cancer. We compared the sensitivity, specificity, and accuracy of Sanger sequencing, ARMS-Scorpion (TheraScreen® real-time polymerase chain reaction (PCR, pyrosequencing, chip array hybridization, and 454 next-generation sequencing to assess KRAS codon 12 and 13 mutations in 60 nonconsecutive selected cases of colorectal cancer. Twenty of the 60 cases were detected as wild-type KRAS by all methods with 100% specificity. Among the 40 mutated cases, 13 were discrepant with at least one method. The sensitivity was 85%, 90%, 93%, and 92%, and the accuracy was 90%, 93%, 95%, and 95% for Sanger sequencing, TheraScreen real-time PCR, pyrosequencing, and chip array hybridization, respectively. The main limitation of Sanger sequencing was its low analytical sensitivity, whereas TheraScreen real-time PCR, pyrosequencing, and chip array hybridization showed higher sensitivity but suffered from the limitations of predesigned assays. Concordance between the methods was k = 0.79 for Sanger sequencing and k > 0.85 for the other techniques. Tumor cell enrichment correlated significantly with the abundance of KRAS-mutated deoxyribonucleic acid (DNA, evaluated as ΔCt for TheraScreen real-time PCR (P = 0.03, percentage of mutation for

  6. Detection of morphological changes in cliff face surrounding a waterfall using terrestrial laser scanning and unmanned aerial system

    Science.gov (United States)

    Hayakawa, Yuichi S.; Obanawa, Hiroyuki

    2015-04-01

    Waterfall or bedrock knickpoint appears as an erosional front in bedrock rivers forming deep v-shaped valley downstream. Following the rapid fluvial erosion of waterfall, rockfalls and gravita-tional collapses often occur in surrounding steep cliffs. Although morphological changes of such steep cliffs are sometimes visually observed, quantitative and precise measurements of their spatio-temporal distribution have been limited due to the difficulties in direct access to such cliffs if with classical measurement methods. However, for the clarification of geomorphological processes oc-curring in the cliffs, multi-temporal mapping of the cliff face at a high resolution is necessary. Re-mote sensing approaches are therefore suitable for the topographic measurements and detection of changes in such inaccessible cliffs. To achieve accurate topographic mapping of cliffs around a wa-terfall, here we perform multi-temporal terrestrial laser scanning (TLS), as well as structure-from-motion multi-view stereo (SfM-MVS) photogrammetry based on unmanned aerial system (UAS). The study site is Kegon Falls in central Japan, having a vertical drop of surface water from top of its overhanging cliff, as well as groundwater outflows from its lower portions. The bedrock is composed of alternate layers of andesite lava and conglomerates. Minor rockfalls in the cliffs are often ob-served by local people. The latest major rockfall occurred in 1986, causing ca. 8-m upstream propa-gation of the waterfall lip. This provides a good opportunity to examine the changes in the surround-ing cliffs following the waterfall recession. Multi-time point clouds were obtained by TLS measure-ment over years, and the three-dimensional changes of the rock surface were detected, uncovering the locus of small rockfalls and gully developments. Erosion seems particularly frequent in relatively weak the conglomerates layer, whereas small rockfalls seems to have occurred in the andesite layers. Also, shadows in the

  7. Reduced HRAS G12V-Driven Tumorigenesis of Cell Lines Expressing KRAS C118S.

    Directory of Open Access Journals (Sweden)

    Lu Huang

    Full Text Available In many different human cancers, one of the HRAS, NRAS, or KRAS genes in the RAS family of small GTPases acquires an oncogenic mutation that renders the encoded protein constitutively GTP-bound and thereby active, which is well established to promote tumorigenesis. In addition to oncogenic mutations, accumulating evidence suggests that the wild-type isoforms may also be activated and contribute to oncogenic RAS-driven tumorigenesis. In this regard, redox-dependent reactions with cysteine 118 (C118 have been found to promote activation of wild-type HRAS and NRAS. We sought to determine if this residue is also important for the activation of wild-type KRAS and promotion of tumorigenesis. Thus, we mutated C118 to serine (C118S in wild-type KRAS to block redox-dependent reactions at this site. We now report that this mutation reduced the level of GTP-bound KRAS and impaired RAS signaling stimulated by the growth factor EGF. With regards to tumorigenesis, we also report that oncogenic HRAS-transformed human cells in which endogenous KRAS was knocked down and replaced with KRASC118S exhibited reduced xenograft tumor growth, as did oncogenic HRAS-transformed KrasC118S/C118S murine cells in which the C118S mutation was knocked into the endogenous Kras gene. Taken together, these data suggest a role for redox-dependent activation of wild-type KRAS through C118 in oncogenic HRAS-driven tumorigenesis.

  8. KRAS and MAPK1 Gene Amplification in Type II Ovarian Carcinomas

    Directory of Open Access Journals (Sweden)

    Noriyuki Ishikawa

    2013-07-01

    Full Text Available In this study, we examined the clinical significance of KRAS and MAPK1 amplification and assessed whether these amplified genes were potential therapeutic targets in type II ovarian carcinoma. Using fluorescence in situ hybridization, immunohistochemistry, and retrospectively collected clinical data, KRAS and MAPK1 amplifications were identified in 9 (13.2% and 5 (7.4% of 68 type II ovarian carcinoma tissue samples, respectively. Interestingly, co-amplification of KRAS and MAPK1 seemed to be absent in the type II ovarian carcinomas tested, except one case. Active phospho-ERK1/2 was identified in 26 (38.2% out of 68 type II ovarian carcinomas and did not correlate with KRAS or MAPK1 amplification. There was no significant relationship between KRAS amplification and overall or progression-free survival in patients with type II ovarian carcinoma. However, patients with MAPK1 amplification had significantly poorer progression-free survival than patients without MAPK1 amplification. Moreover, type II ovarian carcinoma cells with concomitant KRAS amplification and mutation exhibited dramatic growth reduction following treatment with the MEK inhibitor PD0325901. These findings indicate that KRAS/MAPK1 amplification is critical for the growth of a subset of type II ovarian carcinomas. Additionally, RAS/RAF/MEK/ERK pathway-targeted therapy may benefit selected patients with type II ovarian carcinoma harboring KRAS/MAPK1 amplifications.

  9. Evaluation of the ScanRDI(R) as a Rapid Alternative to the Pharmacopoeial Sterility Test Method: Comparison of the Limits of Detection.

    Science.gov (United States)

    Smith, Ron; Von Tress, Mark; Tubb, Cheyenne; Vanhaecke, Erwin

    2010-01-01

    Two sterility test methods, the ScanRDI® rapid sterility test and the United States Pharmacopeia/European Pharmacopoeia/Japanese Pharmacopoeia (USP/EP/JP) compendial sterility test, were compared with respect to the limits of detection for the presence of viable microorganisms in aqueous solutions at low inoculation levels. The ScanRDI® system employs a combination of direct fluorescent labeling techniques and solid-phase laser scanning cytometry to rapidly enumerate viable microorganisms from aqueous samples, whereas the compendial sterility test is a qualitative, growth-based method that uses a visual assessment of turbidity to indicate microbial contamination. Eight microorganisms were evaluated, seven compendial microorganisms (Clostridium sporogenes, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Aspergillus niger, Candida albicans) and the Gram-positive anaerobe Propionibacterium acnes. The number of viable organisms was estimated using the ScanRDI® method and the conventional sterility test method using most probable number methodology. The mean difference between the methods was computed and 95% confidence intervals around the mean difference were estimated. The ScanRDI® method was found to be numerically superior and statistically non-inferior to the compendial (USP/EP/JP) sterility test with respect to the limits of detection for all organisms tested.

  10. Detection of lacunar infarction in brain CT-scans: No evidence of bias from accompanying patient information

    Energy Technology Data Exchange (ETDEWEB)

    Bonke, B.; Knippenberg, F.C.E. van; Duivenvoorden, H.J.; Koudstaal, P.J.; Dijkstra, G.; Hilligersberg, R. van; Kappelle, L.J.

    1989-05-01

    Interobserver agreement in assessing brain CT-scans is, in general, high. The extent, however, to which such agreement is caused by bias through knowledge of other clinical details remains uncertain. The hypothesis that observers are somehow prejudiced before assessing ambiguous, CT-scans in this particular situation was tested. Sixteen neurologists and 16 radiologists volunteered to interpret two ambiguous brain CT-scans, with regard to the presence or absence of a lacunar infarct in the region of the internal capsule. The scans were accompanied by 'patient' information that was or was not suggestive of a stroke. These scans were camouflaged by a variety of other scans, to be assessed in the same way, to mask the purpose of the study. I was assumed that the observers, in their assessments of the scans, would somehow let their ratings of the likelihood of a lacunar infarction in or near the internal capsule be subject to the accompanying information. Results showed lower ratings produced by neurologists (i.e., less likelihood of an infarction) than by radiologists in the majority of all assessments, but no bias by the accompanying information.

  11. Structural dataset for the fast-exchanging KRAS G13D

    Directory of Open Access Journals (Sweden)

    Jia Lu

    2015-12-01

    Full Text Available Cancers bearing the KRAS G13D mutation are notable for their distinct clinical behavior relative to other oncogenic KRAS mutations. We hypothesized that primary biochemical or biophysical properties of KRAS G13D might contribute to these clinical observations and as part of our study undertook structural studies using x-ray crystallography. In this data article we discuss several x-ray diffraction datasets that yielded structures of oncogenic KRAS mutants including a high resolution (1.13 Å structure of KRAS G13D. The datasets are typical for high resolution x-ray diffraction data and allow the construction of atomic resolution, three dimensional structural models with high confidence. This data can be correlated with biochemical information such as defects in substrate binding kinetics, GTPase activities and interactions with the RAS effector RAF kinase.

  12. Change detection studies of Sagar Island, India, using Indian Remote Sensing Satellite 1C linear imaging self-scan sensor III data

    Digital Repository Service at National Institute of Oceanography (India)

    DineshKumar, P.K.; Gopinath, G.; Laluraj, C.M.; Seralathan, P.; Mitra, D.

    Research 23 6 1498–1502 West Palm Beach, Florida November 2007 Change Detection Studies of Sagar Island, India, using Indian Remote Sensing Satellite 1C Linear Imaging Self-Scan Sensor III Data P.K. Dinesh Kumar † , Girish Gopinath ‡ , C.M. Laluraj † , P...-Scan Sensor III data. Journal of Coastal Research, 23(6), 1498–1502. West Palm Beach (Florida), ISSN 0749-0208. The coastal zone of Sagar Island, India, is subjected to various cyclic and random processes that continuously modify the region. The shoreline...

  13. [miR-143 inhibits cell proliferation through targeted regulating the expression of K-ras gene in HeLa cells].

    Science.gov (United States)

    Qin, H X; Cui, H K; Pan, Y; Hu, R L; Zhu, L H; Wang, S J

    2016-12-23

    Objective: To explore the effect of microRNA miR-143 on the proliferation of cervical cancer HeLa cells through targeted regulating the expression of K-ras gene. Methods: The luciferase report carrier containing wild type 3'-UTR of K-ras gene (K-ras-wt) or mutated 3'-UTR of the K-ras (K-ras-mut) were co-transfected with iR-143 mimic into the HeLa cells respectively, and the targeting effect of miR-143 in the transfectants was verified by the dual luciferase report system. HeLa cells were also transfected with miR-143 mimic (miR-143 mimic group), mimic control (negative control group), and miR-143 mimic plus K-ras gene (miR-143 mimic+ K-ras group), respectively. The expression of miR-143 in the transfected HeLa cells was detected by real-time PCR (RT-PCR), and the expression of K-ras protein was detected by Western blot. The cell proliferation activity of each group was examined by MTT assay. In addition, human cervical cancer tissue samples (n=5) and cervical intraepithelial neoplasia tissue samples (n=5) were also examined for the expression of miR-143 and K-ras protein by RT-PCR and Western blot, respectively. Results: The luciferase report assay showed that co-transfection with miR-143 mimic decreased the luciferase activity of the K-ras-wt significantly, but did not inhibit the luciferase activity of the K-ras-mut. The expression of miR-143 in the HeLa cells transfected with miR-143 mimic was significantly higher than that in the HeLa cells transfected with the mimic control (3.31±0.45 vs 0.97±0.22, Pras group was also significantly lower than the control group (Pras protein in the miR-143 mimic group, the negative control group and the miR-143 mimic+ K-ras group were lowest, moderate, and highest, respectively (115.27±34.08, 521.36±41.89, and 706.52±89.44, all Pras protein expression in the cervical cancer group was significantly higher than that in the cervical intraepithelial neoplasia group (584.39±72.34 vs. 114.23±25.82, Pras gene. In human cervical

  14. Detection of airbag impact-induced cone photoreceptor damage by adaptive optics scanning laser ophthalmoscopy: a case report

    National Research Council Canada - National Science Library

    Kaizu, Yoshihiro; Nakao, Shintaro; Yamaguchi, Muneo; Murakami, Yusuke; Salehi-Had, Hani; Ishibashi, Tatsuro

    2016-01-01

    The purpose of this study was to report a case of traumatic maculopathy with para-central visual field defects following an impact by airbag deployment using adaptive optics scanning laser ophthalmoscopy (AO-SLO...

  15. Comparison of the novel quantitative ARMS assay and an enriched PCR-ASO assay for K-ras mutations with conventional cytology on endobiliary brush cytology from 312 consecutive extrahepatic biliary stenoses.

    NARCIS (Netherlands)

    Heek, N.T. van; Clayton, S.J.; Sturm, P.D.J.; Walker, J.; Gouma, D.J.; Noorduyn, L.A.; Offerhaus, G.J.; Fox, J.C.

    2005-01-01

    BACKGROUND: Extrahepatic biliary stenosis (EBS) has malignant and benign causes. Patients with EBS are at risk of having or developing malignancy. Accurate diagnostic tests for early detection and surveillance are needed. The sensitivity of biliary cytology for malignancy is low. K-ras mutation

  16. Comparison of the novel quantitative ARMS assay and an enriched PCR-ASO assay for K-ras mutations with conventional cytology on endobiliary brush cytology from 312 consecutive extrahepatic biliary stenoses

    NARCIS (Netherlands)

    van Heek, N. T.; Clayton, S. J.; Sturm, P. D. J.; Walker, J.; Gouma, D. J.; Noorduyn, L. A.; Offerhaus, G. J. A.; Fox, J. C.

    2005-01-01

    Background: Extrahepatic biliary stenosis (EBS) has malignant and benign causes. Patients with EBS are at risk of having or developing malignancy. Accurate diagnostic tests for early detection and surveillance are needed. The sensitivity of biliary cytology for malignancy is low. K-ras mutation

  17. Results-based management - Developing one's key results areas (KRAs).

    Science.gov (United States)

    Kansal, Om Prakash; Goel, Sonu

    2015-01-01

    In spite of aspiring to be a good manager, we public health experts fail to evaluate ourselves against our personal and professional goals. The Key Result Areas (KRAs) or key performance indicators (KPIs) help us in setting our operational (day-to-day) and/or strategic (long-term) goals followed by grading ourselves at different times of our careers. These shall help in assessing our strengths and weaknesses. The weakest KRA should set the maximum extent to which one should use his/her skills and abilities to have the greatest impact on his/her career.

  18. Diagnostic performance of digital breast tomosynthesis with a wide scan angle compared to full-field digital mammography for the detection and characterization of microcalcifications

    Energy Technology Data Exchange (ETDEWEB)

    Clauser, Paola, E-mail: paola.clauser@meduniwien.ac.at [Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Nagl, Georg [Department for Radiology and Interventional Radiology, Landesklinikum Horn, Spitalgasse 10, 3580 Horn (Austria); Helbich, Thomas H., E-mail: thomas.helbich@meduniwien.ac.at [Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Pinker-Domenig, Katja [Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Weber, Michael [Department of Biomedical Imaging and Image-Guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Kapetas, Panagiotis; Bernathova, Maria; Baltzer, Pascal A.T. [Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

    2016-12-15

    Highlights: • Wide scan-angle DBT alone shows a high detection rate for microcalcifications. • DBT and FFDM can characterize microcalcifications at a comparable level. • Characterization is influenced by reader and by lesion type (benign vs malignant). • DBT might be used as a stand-alone technique for the assessment of microcalcifications. - Abstract: Objectives: To assess the diagnostic performance of digital breast tomosynthesis (DBT), with a wide scan-angle, compared to full-field digital mammography (FFDM), for the detection and characterization of microcalcifications. Methods: IRB approval was obtained for this retrospective study. We selected 150 FFDM and DBT (50 benign and 50 malignant histologically verified microcalcifications, 50 cases classified as BI-RADS 1). Four radiologists evaluated, in separate sessions and blinded to patients’ history and histology, the presence of microcalcifications. Cases with microcalcifications were assessed for visibility, characteristics, and grade of suspicion using BI-RADS categories. Detection rate and diagnostic performance were calculated. Visibility, lesions’ characteristics and reading time were analysed. Results: Detection rate and visibility were good for both FFDM and DBT, without intra-reader differences (P = 0.510). Inter-reader differences were detected (P < 0.018). Only two lesions were not detected by any reader on either FFDM or DBT. Diagnostic performance with DBT was as good as that of FFDM, but a significant inter-reader difference was found (P = 0.041). High inter-reader variability in the use of the descriptors was found. Reading time for DBT was almost twice that for FFDM (44 and 25 s, respectively). Conclusion: Wide scan-angle DBT enabled the detection and characterization of microcalcifications with no significant differences from FFDM. Inter-reader variability was seen.

  19. Spectrum of EGFR gene copy number changes and KRAS gene mutation status in Korean triple negative breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Yoonjung Kim

    Full Text Available Anti-epidermal growth factor receptor (EGFR therapy has been tried in triple negative breast cancer (TNBC patients without evaluation of molecular and clinical predictors in several randomized clinical studies. Only fewer than 20% of metastatic TNBCs showed response to anti-EGFR therapy. In order to increase the overall response rate, first step would be to classify TNBC into good or poor responders according to oncogenic mutation profiles. This study provides the molecular characteristics of TNBCs including EGFR gene copy number changes and mutation status of EGFR and KRAS gene in Korean TNBC patients. Mutation analysis for EGFR, KRAS, BRAF and TP53 from a total of 105 TNBC tissue samples was performed by direct sequencing, peptide nucleic acid-mediated PCR clamping method and real-time PCR. Copy number changes of EGFR gene were evaluated using multiplex ligation-dependent probe amplification. Out of all 105 TNBCs, 15.2% (16/105 showed EGFR copy number changes. Among them, increased or decreased EGFR copy number was detected in 13 (5 single copy gain, 2 amplification and 4 high-copy number amplification and 3 cases (3 hemizygous deletion, respectively. The mutation frequencies of KRAS, EGFR and TP53 gene were 1.9% (G12V and G12D, 1.0% (exon 19 del and 31.4%, respectively. There was no BRAF V600E mutation found. Future studies are needed to evaluate the clinical outcomes of TNBC patients who undergo anti-EGFR therapy according to the genetic status of EGFR.

  20. Nuclear Scans

    Science.gov (United States)

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  1. Fast scanning tomosynthesis for the detection of pulmonary nodules: diagnostic performance compared with chest radiography, using multidetector-row computed tomography as the reference.

    Science.gov (United States)

    Yamada, Yoshitake; Jinzaki, Masahiro; Hasegawa, Ichiro; Shiomi, Eisuke; Sugiura, Hiroaki; Abe, Takayuki; Sato, Yuji; Kuribayashi, Sachio; Ogawa, Kenji

    2011-08-01

    : To evaluate the diagnostic performance of fast scanning tomosynthesis in comparison with that of chest radiography for the detection of pulmonary nodules, using multidetector-row computed tomography (MDCT) as the reference, and to assess the association of the true-positive fraction (TPF) with the size, CT attenuation value, and location of the nodules. : The institutional review board approved this study, and written informed consent was obtained from all patients. Fifty-seven patients with and 59 without pulmonary nodules underwent chest MDCT, fast scanning tomosynthesis, and radiography. The images of tomosynthesis and radiography were randomly read by 3 blinded radiologists; MDCT served as the reference standard. Free-response receiver-operating characteristic (FROC) and receiver-operating characteristic (ROC) analyses, Cochran-Armitage trend or Fisher exact test, a conditional logistic regression model, and McNemar test were used. : Both FROC and ROC analyses revealed significantly better performance (P performance of fast scanning tomosynthesis for the detection of pulmonary nodules was significantly superior to that of radiography. The TPF was affected by the size, CT attenuation value, and location of the nodule, in both fast scanning tomosynthesis and radiography.

  2. Hypoxia activates the K-ras proto-oncogene to stimulate angiogenesis and inhibit apoptosis in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Min Zeng

    2010-06-01

    Full Text Available The KRAS proto-oncogene plays a key role in the development of many human tumors and is commonly activated by somatic mutation or signaling through specific growth factor receptors. However, the interaction between the micro-environment and K-ras activity has not been defined. Hypoxia invariably develops as tumors outgrow their supply of oxygen. A series of well-orchestrated cellular adaptations occur that stimulate angiogenesis and enhance survival of the tumor in hypoxic conditions. Our previous studies demonstrated that mutant KRAS alleles can interact with hypoxia to induce vascular endothelial growth factor (VEGF in colon cancer. We sought to determine whether similar hypoxic responses are also present in tumors without a KRAS mutation. Hypoxia consistently increased the levels of activated, GTP-bound K-ras in colon cancer cell lines with a wild-type KRAS gene, and this depended upon the activation of c-Src. Inhibition of c-Src by PP2 treatment or siRNA knockdown blocked the hypoxic activation of K-ras. This activation of K-ras did not depend upon EGFR and resulted in the phosphorylation of Akt and induction of VEGF expression. In addition, activation of K-ras significantly blocked apoptosis in hypoxic conditions. These studies reveal a unique adaptive mechanism in hypoxia that activates K-ras signaling in the absence of a mutant KRAS oncogene.

  3. Intraoperative iodinated contrast swallow with CT-scan delayed control for detection of early complications in laparoscopic gastric bypass: A case series of 260 cases

    Directory of Open Access Journals (Sweden)

    Vincenzo Consalvo, M.D.

    2017-01-01

    Conclusions: This study gives a contribute to the existing issue of fast track in bariatric surgery for the early diagnosis of complications and patients' readmission or non-discharge. In conclusion, the use of intraoperative iodinated water soluble contrast swallow and abdominal CT-scan at 48 h was a safe and accurate test in order to detect and treat any potential early surgical complication in LRYGB.

  4. Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning.

    Science.gov (United States)

    Hosgood, H Dean; Pao, William; Rothman, Nathaniel; Hu, Wei; Pan, Yumei Helen; Kuchinsky, Kyle; Jones, Kirk D; Xu, Jun; Vermeulen, Roel; Simko, Jeff; Lan, Qing

    2013-11-01

    Lung cancer in never smokers, which has been partially attributed to household solid fuel use (i.e., coal), is etiologically and clinically different from lung cancer attributed to tobacco smoking. To explore the spectrum of driver mutations among lung cancer tissues from never smokers, specifically in a population where high lung cancer rates have been attributed to indoor air pollution from domestic coal use, multiplexed assays were used to detect >40 point mutations, insertions, and deletions (EGFR, KRAS, BRAF, HER2, NRAS, PIK3CA, MEK1, AKT1, and PTEN) among the lung tumors of confirmed never smoking females from Xuanwei, China [32 adenocarcinomas (ADCs), 7 squamous cell carcinomas (SCCs), 1 adenosquamous carcinoma (ADSC)]. EGFR mutations were detected in 35% of tumors. 46% of these involved EGFR exon 18 G719X, while 14% were exon 21 L858R mutations. KRAS mutations, all of which were G12C_34G>T, were observed in 15% of tumors. EGFR and KRAS mutations were mutually exclusive, and no mutations were observed in the other tested genes. Most point mutations were transversions and were also found in tumors from patients who used coal in their homes. Our high mutation frequencies in EGFR exon 18 and KRAS and low mutation frequency in EGFR exon 21 are strikingly divergent from those in other smoking and never smoking populations from Asia. Given that our subjects live in a region where coal is typically burned indoors, our findings provide new insights into the pathogenesis of lung cancer among never smoking females exposed to indoor air pollution from coal. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Diagnostic value of the FHIT and p16 mRNA loss and the K-ras gene mutation in pleural fluids for malignant pleural effusion.

    Science.gov (United States)

    Li, Jian; Bao, Qian-Lei; Wang, Yi; Hu, Yi-Ming; Chen, Ping

    2013-01-01

    Inactivation of the tumor suppressor genes and activation of oncogenes are involved in the development of cancer. The aim of this study was to evaluate the diagnostic value of the fragile histidine triad (FHIT) and p16 mRNA loss and the K-ras gene mutation in distinguishing malignant from benign pleural effusion. A total of 50 patients with malignant pleural effusion and 30 patients with benign pleural effusion were enrolled in this study. All pleural fluid specimens were evaluated in parallel by cytology, reverse transcriptase-PCR for the loss of FHIT and p16 mRNA, and PCR-SSCP (single-stranded conformation polymorphism) for the mutation of K-ras gene. The detection rates of FHIT and p16 mRNA loss were significantly higher in malignant than in benign pleural effusion (P ras mutations were more frequent in malignant than benign pleural effusion (P = 0.006). The sensitivity and specificity were 58% and 93% for FHIT loss, 48% and 90% for p16 loss, and 44% and 87% for the K-ras mutation, respectively. In combined evaluation with both FHIT and p16 loss, the sensitivity was 68%, and specificity was 90%. The combination of the three molecular markers reached 74% sensitivity, whereas the combined use of the cytology and the three markers increased the diagnostic yield of the former by 38%. More than one third of cytology negative malignant pleural effusion could be identified by at least one of the three markers. These results suggest that the detection of FHIT and p16 mRNA loss and the k-ras gene mutation in pleural fluid could be helpful adjunct to cytology in the diagnosis of malignant pleural effusion.

  6. KRAS, YAP, and obesity in pancreatic cancer: a signaling network with multiple loops.

    Science.gov (United States)

    Eibl, Guido; Rozengurt, Enrique

    2017-10-24

    Pancreatic ductal adenocarcinoma (PDAC) continues to be a lethal disease with no efficacious treatment modalities. The incidence of PDAC is expected to increase, at least partially because of the obesity epidemic. Increased efforts to prevent or intercept this disease are clearly needed. Mutations in KRAS are initiating events in pancreatic carcinogenesis supported by genetically engineered mouse models of the disease. However, oncogenic KRAS is not entirely sufficient for the development of fully invasive PDAC. Additional genetic mutations and/or environmental, nutritional, and metabolic stressors, e.g. inflammation and obesity, are required for efficient PDAC formation with activation of KRAS downstream effectors. Multiple factors "upstream" of KRAS associated with obesity, including insulin resistance, inflammation, changes in gut microbiota and GI peptides, can enhance/modulate downstream signals. Multiple signaling networks and feedback loops "downstream" of KRAS have been described that respond to obesogenic diets. We propose that KRAS mutations potentiate a signaling network that is promoted by environmental factors. Specifically, we envisage that KRAS mutations increase the intensity and duration of the growth-promoting signaling network. As the transcriptional activator YAP plays a critical role in the network, we conclude that the rationale for targeting the network (at different points), e.g. with FDA approved drugs such as statins and metformin, is therefore compelling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Nitrative and oxidative DNA damage caused by K-ras mutation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Shiho [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science (Japan); Saito, Hiromitsu; Suzuki, Noboru [Department of Animal Genomics, Mie University Life Science Research Center (Japan); Ma, Ning [Faculty of Health Science, Suzuka University of Medical Science (Japan); Hiraku, Yusuke; Murata, Mariko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine (Japan); Kawanishi, Shosuke, E-mail: kawanisi@suzuka-u.ac.jp [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science (Japan)

    2011-09-23

    Highlights: {yields} Mutated K-ras in transgenic mice caused nitrative DNA damage, 8-nitroguanine. {yields} The mutagenic 8-nitroguanine seemed to be generated by iNOS via Ras-MAPK signal. {yields} Mutated K-ras produces additional mutagenic lesions, as a new oncogenic role. -- Abstract: Ras mutation is important for carcinogenesis. Carcinogenesis consists of multi-step process with mutations in several genes. We investigated the role of DNA damage in carcinogenesis initiated by K-ras mutation, using conditional transgenic mice. Immunohistochemical analysis revealed that mutagenic 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) were apparently formed in adenocarcinoma caused by mutated K-ras. 8-Nitroguanine was co-localized with iNOS, eNOS, NF-{kappa}B, IKK, MAPK, MEK, and mutated K-ras, suggesting that oncogenic K-ras causes additional DNA damage via signaling pathway involving these molecules. It is noteworthy that K-ras mutation mediates not only cell over-proliferation but also the accumulation of mutagenic DNA lesions, leading to carcinogenesis.

  8. High-stage urachal adenocarcinoma can be associated with microsatellite instability and KRAS mutations.

    Science.gov (United States)

    Sirintrapun, S Joseph; Ward, Martha; Woo, Jennifer; Cimic, Adela

    2014-02-01

    Urachal adenocarcinoma (UAC) is a rare tumor of the urinary bladder, which can show intestinal, mucinous, and signet ring cell histology. The morphology is similar to that of colorectal adenocarcinoma (CAC). Microsatellite instability (MSI), KRAS, and BRAF have been more extensively studied in CAC. What is not known is whether UAC in its morphologic similarity to CAC could show immunohistochemical features of MSI along with KRAS- and BRAF-activating mutations. A retrospective review of institutional archives for UAC cases found 7 cases, all of which were high stage. Most (6/7) of our UAC cases showed evidence of MSI or mutations of KRAS. No cases showed a BRAF mutation at codon 600. Of the cases that demonstrated MSI, 1 showed mutS homolog 2 and mutS homolog 6 loss, and 2 showed PMS2 (postmeiotic segregation increased 2) loss. Of the remaining 4 cases, 3 showed KRAS mutations at codon 12. Our UAC series showed mutual exclusivity of MSI and KRAS mutations. Furthermore, our UAC cases with KRAS mutations showed markedly better overall survival (mean, 101.7 versus 6.5 months; P = .035). Thus, our study justifies ancillary testing for MSI and KRAS in UAC, particularly when there is high-stage and mucinous histology, but a larger multi-institutional accruement of UAC cases is necessary to further validate our novel findings. © 2014.

  9. Ezh2 Acts as a Tumor Suppressor in Kras-driven Lung Adenocarcinoma.

    Science.gov (United States)

    Wang, Yanxiao; Hou, Ning; Cheng, Xuan; Zhang, Jishuai; Tan, Xiaohong; Zhang, Chong; Tang, Yuling; Teng, Yan; Yang, Xiao

    2017-01-01

    Previous studies have suggested that enhancer zeste homolog 2 (Ezh2), a histone methyltransferase subunit of polycomb repressive complex 2 (PRC2), acts as an oncogene in lung adenocarcinoma (ADC) development. However, we found that in human lung ADC samples, deletion and mutations of EZH2 were also frequently present, with 14% of patients harboring loss-of-function EZH2 alterations. To explore the effect of Ezh2 loss on lung tumor formation, lung epithelial Ezh2 gene was deleted in Kras-driven lung ADC mouse model. Unexpectedly, Ezh2 loss dramatically promoted Kras-driven ADC formation. Kras(G12D/+);Ezh2(fl/fl) mice exhibited shorter lifespan, more tumor lesions and higher tumor burden than Kras(G12D/+) mice, suggesting the tumor-suppressive role of Ezh2 in Kras-driven ADCs. Mechanistically, Ezh2 loss amplified Akt and ERK activation through de-repressing its target insulin-like growth factor 1 (Igf1). Additionally, Ezh2 loss cooperated with Kras mutation to exacerbate the inflammatory response, as shown by massive macrophage and neutrophil infiltrates, as well as a marked increase in tumor-associated cytokines such as IL-6 and TNF-α. Taken together, our findings revealed the tumor suppressive function of Ezh2 in Kras-driven ADCs, underlining the importance of revaluating the application of EZH2 inhibitors in a variety of cancers.

  10. Molecular interaction between K-Ras and H-REV107 in the Ras signaling pathway.

    Science.gov (United States)

    Han, Chang Woo; Jeong, Mi Suk; Jang, Se Bok

    2017-09-16

    Ras proteins are small GTPases that serve as master moderators of a large number of signaling pathways involved in various cellular processes. Activating mutations in Ras are found in about one-third of cancers. H-REV107, a K-Ras binding protein, plays an important role in determining K-Ras function. H-REV107 is a member of the HREV107 family of class II tumor suppressor genes and a growth inhibitory Ras target gene that suppresses cellular growth, differentiation, and apoptosis. Expression of H-REV107 was strongly reduced in about 50% of human carcinoma cell lines. However, the specific molecular mechanism by which H-REV107 inhibits Ras is still unknown. In the present study, we suggest that H-REV107 forms a strong complex with activating oncogenic mutation Q61H K-Ras from various biochemical binding assays and modeled structures. In addition, the interaction sites between K-Ras and H-REV107 were predicted based on homology modeling. Here, we found that some structure-based mutants of the K-Ras disrupted the complex formation with H-REV107. Finally, a novel molecular mechanism describing K-Ras and H-REV107 binding is suggested and insights into new K-Ras effector target drugs are provided. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. KRAS mutational status as a predictor of epidermal growth factor receptor inhibitor efficacy in colorectal cancer.

    Science.gov (United States)

    Baynes, Roy D; Gansert, Jennifer

    2009-01-01

    Inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated promising potential in the treatment of advanced colorectal cancer. However, a proportion of patients do not respond to therapy with EGFR inhibitors, and therefore, there has been interest in identifying those patients most likely to benefit from therapy with these agents. KRAS, a member of the RAS family of signaling proteins, plays an important role in EGFR-mediated regulation of cellular proliferation and survival. Although there is still some debate regarding the prognostic importance of KRAS mutations in patients with metastatic colorectal cancer, several recent phase 2 and 3 studies have identified the presence of mutations at codons 12 and 13 of KRAS as predictors of poor response to the anti-EGFR monoclonal antibodies panitumumab and cetuximab. Patients with wild-type KRAS were found to have significantly better progression-free survival, overall survival, and/or objective response rate compared with patients harboring KRAS mutations. As a result, there has been growing interest in the development of KRAS mutational status as a biomarker for predicting patient response to EGFR-targeted therapy. Screening colorectal tumors for the absence of KRAS mutations may help identify patients most likely to benefit from anti-EGFR therapies.

  12. KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay

    Directory of Open Access Journals (Sweden)

    Reinthaller Alexander

    2009-04-01

    Full Text Available Abstract Background Mutations in the KRAS gene are one of the most frequent genetic abnormalities in ovarian carcinoma. They are of renewed interest as new epidermal growth factor receptor (EGFR-targeted therapies are being investigated for use in ovarian carcinoma. As KRAS mutations are associated with poor response and resistance to EGFR-targeting drugs, this study was conducted to obtain more information on the spectrum of KRAS mutations in ovarian carcinoma. Methods The presence of KRAS mutations in codon 12 and 13 was analyzed in frozen and formalin-fixed paraffin-embedded (FFPE tissue with a low density biochip platform. 381 malignant (29 borderline malignancy, 270 primary carcinomas, and 82 recurrent carcinomas and 22 benign tissue samples from a total of 394 patients were examined. KRAS mutational status of each sample was correlated with dignity, FIGO stage, grade, histology, and survival. Results KRAS mutations were found in 60 (15% samples with 58 samples deriving from malignant tissue and 2 samples deriving from benign tissue. In 55 (92% samples codon 12 was found to be mutated. Frozen and FFPE samples concurred with respect to KRAS mutation status. Conclusion KRAS mutation is a common event in ovarian cancer primarily in carcinomas of lower grade, lower FIGO stage, and mucinous histotype. The KRAS mutational status is no prognostic factor for patients treated with standard therapy. However, in line with experience from colorectal cancer and non-small-cell-lung cancer (NSCLC, it may be important for prediction of response to EGFR-targeted therapies.

  13. [Clinical relevance of the K-ras oncogene in colorectal cancer: experience in a Mexican population].

    Science.gov (United States)

    Cabrera-Mendoza, F; Gainza-Lagunes, S; Castañeda-Andrade, I; Castro-Zárate, A

    2014-01-01

    Colorectal cancer is frequent in the developed countries, with a cancer-specific mortality rate of 33%. Different biomarkers are associated with overall survival and the prediction of monoclonal treatment effectiveness. The presence of mutations in the K-ras oncogene alters the response to target therapy with cetuximab and could be an independent prognostic factor. To analyze the difference in survival between patients with mutated K-ras and those with K-ras wild-type status. Thirty-one clinical records were retrospectively analyzed of patients presenting with colorectal cancer that underwent K-ras sequencing through real-time polymerase chain reaction within the time frame of 2009 to 2012 at the Hospital de Alta Especialidad de Veracruz of the Instituto para la Salud y Seguridad Social de los Trabajadores del Estado (HAEV-ISSSTE). Survival analysis for patients with and without K-ras mutation was performed using the Kaplan Meier method. Contrast of covariates was performed using logarithmic transformations. No statistically significant difference was found in relation to survival in the patients with mutated K-ras vs. those with K-ras wild-type (P=.416), nor were significant differences found when analyzing the covariants and survival in the patients with mutated K-ras: ECOG scale (P=.221); age (less than, equal to or greater than 65years, P=.441); clinical stage according to the AJCC (P=.057), and primary lesion site (P=.614). No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature. Further studies that include both a larger number of patients and those receiving monoclonal treatment, need to be conducted. There were only 5 patients in the present study that received cetuximab, resulting in a misleading analysis. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  14. A new method to detect air leakage in a patient with pneumothorax using saline solution and multidetector-row spiral CT scan.

    Science.gov (United States)

    Nakanishi, Kozo; Shimotakahara, Akihiro; Asato, Yuko; Ishihara, Toshihiro

    2013-09-01

    The purpose of this study was to establish a new CT scan method to show signs of air leakage and to detect the point of the lung leak in patients with spontaneous pneumothorax by using saline solution and phonation. Eleven patients with spontaneous pneumothorax who had a chest tube placed and underwent an operation because of continuing air leakage were studied. After a plain chest CT scan was performed, 0.9% saline was injected into the affected pleural cavity. A CT scan was acquired again while the patient vocalized continuously. The CT images were evaluated by two thoracic surgeons. All patients underwent video-assisted thoracoscopic surgery to confirm their points of leakage and were treated for spontaneous pneumothorax. Bubble shadows were seen in nine of 11 cases. In seven of those nine cases, multiple bubbles formed foam or wave shadows. These cases had a small pleural fistula. In the other two cases with a large fistula, air-fluid level in bulla and ground-glass attenuation areas were seen in the pulmonary parenchyma. In all 11 cases, some air-leakage signs were seen on CT scan, and a culprit lesion was presumed to exist by analyzing CT imaging findings and confirming with a surgical air-leak test. With a saline injection and vocalization, CT scan could demonstrate air-leak signs in patients with spontaneous pneumothorax. This method does not require contrast medium, special instruments, or high skill and, thus, is a novel and useful examination to detect the culprit lesion in pneumothorax.

  15. Development and Validation of the Suprathreshold Stochastic Resonance-Based Image Processing Method for the Detection of Abdomino-pelvic Tumor on PET/CT Scans.

    Science.gov (United States)

    Saroha, Kartik; Pandey, Anil Kumar; Sharma, Param Dev; Behera, Abhishek; Patel, Chetan; Bal, Chandrashekhar; Kumar, Rakesh

    2017-01-01

    The detection of abdomino-pelvic tumors embedded in or nearby radioactive urine containing 18F-FDG activity is a challenging task on PET/CT scan. In this study, we propose and validate the suprathreshold stochastic resonance-based image processing method for the detection of these tumors. The method consists of the addition of noise to the input image, and then thresholding it that creates one frame of intermediate image. One hundred such frames were generated and averaged to get the final image. The method was implemented using MATLAB R2013b on a personal computer. Noisy image was generated using random Poisson variates corresponding to each pixel of the input image. In order to verify the method, 30 sets of pre-diuretic and its corresponding post-diuretic PET/CT scan images (25 tumor images and 5 control images with no tumor) were included. For each sets of pre-diuretic image (input image), 26 images (at threshold values equal to mean counts multiplied by a constant factor ranging from 1.0 to 2.6 with increment step of 0.1) were created and visually inspected, and the image that most closely matched with the gold standard (corresponding post-diuretic image) was selected as the final output image. These images were further evaluated by two nuclear medicine physicians. In 22 out of 25 images, tumor was successfully detected. In five control images, no false positives were reported. Thus, the empirical probability of detection of abdomino-pelvic tumors evaluates to 0.88. The proposed method was able to detect abdomino-pelvic tumors on pre-diuretic PET/CT scan with a high probability of success and no false positives.

  16. The effects of slice thickness and radiation dose level variations on computer-aided diagnosis (CAD) nodule detection performance in pediatric chest CT scans

    Science.gov (United States)

    Emaminejad, Nastaran; Lo, Pechin; Ghahremani, Shahnaz; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael F.

    2017-03-01

    For pediatric oncology patients, CT scans are performed to assess treatment response and disease progression. CAD may be used to detect lung nodules which would reflect metastatic disease. The purpose of this study was to investigate the effects of reducing radiation dose and varying slice thickness on CAD performance in the detection of solid lung nodules in pediatric patients. The dataset consisted of CT scans of 58 pediatric chest cases, from which 7 cases had lung nodules detected by radiologist, and a total of 28 nodules were marked. For each case, the original raw data (sinogram data) was collected and a noise addition model was used to simulate reduced-dose scans of 50%, 25% and 10% of the original dose. In addition, the original and reduced-dose raw data were reconstructed at slice thicknesses of 1.5 and 3 mm using a medium sharp (B45) kernel; the result was eight datasets (4 dose levels x 2 thicknesses) for each case An in-house CAD tool was applied on all reconstructed scans, and results were compared with the radiologist's markings. Patient level mean sensitivities at 3mm thickness were 24%, 26%, 25%, 27%, and at 1.5 mm thickness were 23%, 29%, 35%, 36% for 10%, 25%, 50%, and 100% dose level, respectively. Mean FP numbers were 1.5, 0.9, 0.8, 0.7 at 3 mm and 11.4, 3.5, 2.8, 2.8 at 1.5 mm thickness for 10%, 25%, 50%, and 100% dose level respectively. CAD sensitivity did not change with dose level for 3mm thickness, but did change with dose for 1.5 mm. False Positives increased at low dose levels where noise values were high.

  17. High-Speed Scanning Interferometer Using CMOS Image Sensor and FPGA Based on Multifrequency Phase-Tracking Detection

    Science.gov (United States)

    Ohara, Tetsuo

    2012-01-01

    A sub-aperture stitching optical interferometer can provide a cost-effective solution for an in situ metrology tool for large optics; however, the currently available technologies are not suitable for high-speed and real-time continuous scan. NanoWave s SPPE (Scanning Probe Position Encoder) has been proven to exhibit excellent stability and sub-nanometer precision with a large dynamic range. This same technology can transform many optical interferometers into real-time subnanometer precision tools with only minor modification. The proposed field-programmable gate array (FPGA) signal processing concept, coupled with a new-generation, high-speed, mega-pixel CMOS (complementary metal-oxide semiconductor) image sensor, enables high speed (>1 m/s) and real-time continuous surface profiling that is insensitive to variation of pixel sensitivity and/or optical transmission/reflection. This is especially useful for large optics surface profiling.

  18. SonoNet: Real-Time Detection and Localisation of Fetal Standard Scan Planes in Freehand Ultrasound

    OpenAIRE

    Baumgartner, Christian F.; Kamnitsas, Konstantinos; Matthew, Jacqueline; Fletcher, Tara P.; Smith, Sandra; Koch, Lisa M.; Kainz, Bernhard; Rueckert, Daniel

    2016-01-01

    Identifying and interpreting fetal standard scan planes during 2D ultrasound mid-pregnancy examinations are highly complex tasks which require years of training. Apart from guiding the probe to the correct location, it can be equally difficult for a non-expert to identify relevant structures within the image. Automatic image processing can provide tools to help experienced as well as inexperienced operators with these tasks. In this paper, we propose a novel method based on convolutional neur...

  19. K-RAS mutations indicating primary resistance to crizotinib in ALK-rearranged adenocarcinomas of the lung: Report of two cases and review of the literature.

    Science.gov (United States)

    Mengoli, Maria Cecilia; Barbieri, Fausto; Bertolini, Federica; Tiseo, Marcello; Rossi, Giulio

    2016-03-01

    The paradigm of mutually exclusive alterations among oncogenic drivers in non-small-cell lung cancer (NSCLC) is challenged by the increasing evidence of detection of two or more driver alterations in the same tumor using highly-sensitive molecular assays. We report here two cases of ALK-rearranged adenocarcinomas harboring concomitant exon 2 K-RAS mutations (G13D and Q61H). The patients, a 49-year-old smoker man and a 59-year-old non-smoking woman, experienced a rapid disease progression and primary resistance to crizotinib. Search for similar cases in the literature reveals that concomitant K-RAS mutations and ALK rearrangement occur in a subset of NSCLC and seems to lead to resistance to crizotinib. Among 8 similar cases receiving crizotinib previously reported (4 in first line and 4 in second line), 1 had a partial response, 1 stable disease and 6 disease progression. One patient still had progression disease when switching to ceritinib. At the end, K-RAS mutations seem to represent a negative predictive marker in ALK-rearranged adenocarcinomas treated with ALK inhibitor. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Mutations of KRAS, NRAS, BRAF, EGFR, and PIK3CA genes in urachal carcinoma: Occurence and prognostic significance.

    Science.gov (United States)

    Módos, Orsolya; Reis, Henning; Niedworok, Christian; Rübben, Herbert; Szendröi, Attila; Szász, Marcell A; Tímár, József; Baghy, Kornélia; Kovalszky, Ilona; Golabek, Tomasz; Chlosta, Piotr; Okon, Krzysztof; Peyronnet, Benoit; Mathieu, Romain; Shariat, Shahrokh F; Hollósi, Péter; Nyirády, Péter; Szarvas, Tibor

    2016-06-28

    Targeted therapy represents an attractive alternative for rare tumors such as urachal carcinoma (UrC). The aim of this study was to assess the mutations of the most commonly affected 5 genes in the targetable EGFR-pathway in UrC and comapre their frequencies to those of found in urothelial and colorectal cancer. Mutational hot-spots of selected genes were tested in 22 UrC samples by pyrosequencing. Mutational patterns were compared to those published for colorectal and urothelial cancers. Furthermore, we sought correlations between mutations and clinicopathological and follow-up data. We found 11 mutations in 10 of 22 (45%) patients. The most frequently mutated gene was KRAS (27%) followed by BRAF (18%) and NRAS (5%), while no mutations were detected in the EGFR and PIK3CA genes. No correlation was found between the mutation status and clinicopathological parameters (Sheldon/Mayo stage, tumor grade, metastases). Furthermore, none of the mutations correlated with progression-free or overall survival. The mutation pattern of UrC is more similar to colorectal than to urothelial cancer. However, the mutation characteristics of UrC seems to be unique suggesting that clinical decision-making for UrC cannot be simply adopted from urothelial or colorectal carcinoma. The high occurence of EGFR-pathway mutations warrants the testing for KRAS and BRAF mutations when considering anti-EGFR therapy in UrC.

  1. The prognostic impact of K-RAS mutations in adult acute myeloid leukemia patients treated with high-dose cytarabine

    Directory of Open Access Journals (Sweden)

    Ahmad EI

    2011-07-01

    Full Text Available Ebtesam I Ahmad, Heba H Gawish, Nashwa MA Al Azizi, Ashraf M ElhefniClinical Pathology Department, Hematology and Oncology Unit of Internal Medicine Department, Faculty of Medicine, Zagazig University, Sharkia, EgyptBackground: Activating point mutation of the RAS gene has been generally accepted as an oncogenic event in a variety of malignancies. It represents one of the most common genetic alterations in acute myeloid leukemia (AML. However, little is known about its clinical relevance in the treatment outcome for this leukemia.Objective: This study aimed to clarify the biologic and prognostic impact of K-RAS mutations in relation to the dose of cytarabine (ara-C used in postinduction consolidation chemotherapy in adult AML patients.Patients and methods: The study comprised of 71 de novo AML patients with male/female ratio 1.4:1; their ages ranged from 21–59 years with a median of 37 years. They were subjected to full clinical evaluation, routine laboratory investigations, cytogenetic studies by G-banding (Giemsa staining, and K-RAS mutation detection using real-time polymerase chain reaction. The patients were randomized into two groups according to the ara-C dose used in consolidation treatment, the high the dose ara-C (HDAC group receiving 400 mg ara-C and-low-dose ara-C (LDAC group receiving 100 mg ara-C; they were followed over a period of five years.Results: Mutations in the K-RAS gene (mutRAS were detected in 23 patients (32% with the remaining 48 patients (68% having wild-type RAS (wtRAS. The percent of blast cells was significantly lower in mutRAS compared to wtRAS patients (P ≤ 0.001 while M4 subtype of AML and Inv(16 frequencies were significantly higher in mutRAS compared to wtRAS patients (P = 0.015 and (P = 0.003, respectively. The patients were followed up for a median of 43 months (range 11–57 months. There was no significant difference in overall survival (OS between mutRAS and wtRAS (P = 0.326. Within the mut

  2. Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

    Directory of Open Access Journals (Sweden)

    David Smith

    2013-03-01

    Full Text Available Background: Drug adverse event (AE signal detection using the Gamma Poisson Shrinker (GPS is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan. Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds.

  3. KRAS (G12D Cooperates with AML1/ETO to Initiate a Mouse Model Mimicking Human Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-01-01

    Full Text Available Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML, suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d. Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-. Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

  4. Benford's Law based detection of latent fingerprint forgeries on the example of artificial sweat printed fingerprints captured by confocal laser scanning microscopes

    Science.gov (United States)

    Hildebrandt, Mario; Dittmann, Jana

    2015-03-01

    The possibility of forging latent fingerprints at crime scenes is known for a long time. Ever since it has been stated that an expert is capable of recognizing the presence of multiple identical latent prints as an indicator towards forgeries. With the possibility of printing fingerprint patterns to arbitrary surfaces using affordable ink- jet printers equipped with artificial sweat, it is rather simple to create a multitude of fingerprints with slight variations to avoid raising any suspicion. Such artificially printed fingerprints are often hard to detect during the analysis procedure. Moreover, the visibility of particular detection properties might be decreased depending on the utilized enhancement and acquisition technique. In previous work primarily such detection properties are used in combination with non-destructive high resolution sensory and pattern recognition techniques to detect fingerprint forgeries. In this paper we apply Benford's Law in the spatial domain to differentiate between real latent fingerprints and printed fingerprints. This technique has been successfully applied in media forensics to detect image manipulations. We use the differences between Benford's Law and the distribution of the most significant digit of the intensity and topography data from a confocal laser scanning microscope as features for a pattern recognition based detection of printed fingerprints. Our evaluation based on 3000 printed and 3000 latent print samples shows a very good detection performance of up to 98.85% using WEKA's Bagging classifier in a 10-fold stratified cross-validation.

  5. A cross-sectional study examining the expression of splice variants K-RAS4A and K-RAS4B in advanced non-small-cell lung cancer patients.

    Science.gov (United States)

    Aran, Veronica; Masson Domingues, Pedro; Carvalho de Macedo, Fabiane; Moreira de Sousa, Carlos Augusto; Caldas Montella, Tatiane; de Souza Accioly, Maria Theresa; Ferreira, Carlos Gil

    2018-02-01

    Mammalian cells differently express 4 RAS isoforms: H-RAS, N-RAS, K-RAS4A and K-RAS4B, which are important in promoting oncogenic processes when mutated. In lung cancer, the K-RAS isoform is the most frequently altered RAS protein, being also a difficult therapeutic target. Interestingly, there are two K-RAS splice variants (K-RAS4A and K-RAS4B) and little is known about the role of K-RAS4A. Most studies targeting K-RAS, or analysing it as a prognostic factor, have not taken into account the two isoforms. Consequently, the in-depth investigation of them is needed. The present study analysed 98 specimens from advanced non-small cell lung cancer (NSCLC) adenocarcinoma patients originated from Brazil. The alterations present in K-RAS at the DNA level (Sanger sequencing) as well as the expression of the splicing isoforms at the RNA (qRT-PCR) and protein levels (immunohistochemistry analysis), were evaluated. Possible associations between clinicopathological features and the molecular findings were also investigated. Our results showed that in the non-smoking population, the cancer incidence was higher among women. In contrast, in smokers and former smokers, the incidence was higher among men. Regarding sequencing results, 10.5% of valid samples presented mutations in exon 2, being all wild-type for exon 3, and the most frequently occurring base change was the transversion G → T. Our qRT-PCR and immunohistochemical analysis showed that both, K-RAS4A and K-RAS4B, were differently expressed in NSCLC tumour samples. For example, tumour specimens showed higher K-RAS4A mRNA expression in relation to commercial normal lung control than did K-RAS4B. In addition, K-RAS4B protein expression was frequently stronger than K-RAS4A in the patients analysed. Our results highlight the differential expression of K-RAS4A and K-RAS4B in advanced adenocarcinoma NSCLC patients and underline the need to further clarify the enigma behind their biological significance in various cancer

  6. A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

    Directory of Open Access Journals (Sweden)

    Grace R. Anderson

    2017-07-01

    Full Text Available Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription. Furthermore, these screens revealed secondary genetic modifiers of sensitivity, yielding a SRC inhibitor-based combination therapy for KRAS/PIK3CA double-mutant colorectal cancers (CRCs with clinical potential. Surprisingly, acquired resistance to combinations of growth signaling pathway inhibitors develops rapidly following treatment, but by targeting signaling feedback or apoptotic priming, it is possible to construct three-drug combinations that greatly delay its emergence.

  7. Intensity-Stabilized Fast-Scanned Direct Absorption Spectroscopy Instrumentation Based on a Distributed Feedback Laser with Detection Sensitivity down to 4 × 10−6

    Directory of Open Access Journals (Sweden)

    Gang Zhao

    2016-09-01

    Full Text Available A novel, intensity-stabilized, fast-scanned, direct absorption spectroscopy (IS-FS-DAS instrumentation, based on a distributed feedback (DFB diode laser, is developed. A fiber-coupled polarization rotator and a fiber-coupled polarizer are used to stabilize the intensity of the laser, which significantly reduces its relative intensity noise (RIN. The influence of white noise is reduced by fast scanning over the spectral feature (at 1 kHz, followed by averaging. By combining these two noise-reducing techniques, it is demonstrated that direct absorption spectroscopy (DAS can be swiftly performed down to a limit of detection (LOD (1σ of 4 × 10−6, which opens up a number of new applications.

  8. Feedback-induced voltage change of a Vertical-Cavity Surface-Emitting Laser as an active detection system for miniature optical scanning probe microscopes.

    Science.gov (United States)

    Heinis, Dominique; Gorecki, Christophe; Bargiel, Sylwester; Cretin, Bernard

    2006-04-17

    We propose a novel detection technique for scanning probe microscopy based on the measuring of the feedback-induced voltage change of 780-nm VCSEL operating at constant current in far-field regime when we modulate mechanically the length of a coupled-cavity generating the feedback conditions. The voltage change of the VCSEL is produced by light back reflected from the sample to the laser cavity. Two-dimensional image probing is successfully demonstrated with high temporal resolution, offering a viable solution for miniature parallel scanning probe optical microscopes, such as confocal microscope, where the use of a photodetector is avoided. This approach opens the possibility to perform imaging tasks in a low cost and hand-held miniature device with much improved effective-space.

  9. Unusual metastatic sites from renal cell carcinoma detected by 18F-FDG PET/CT scan.

    Science.gov (United States)

    Aurangabadkar, Hrushikesh; Ali, Zakir

    2013-12-01

    Here we describe 2 cases of renal cell carcinoma where we found the unusual metastatic sites from renal cell carcinoma on 18F-FDG PET/CT scans in post-radical nephrectomy status. The first case resolves the venous migration of the tumor as a malignant thrombus arising from a remnant stump of the left renal vein, passing through hemiazygos vein further into the azygos vein and finally into the superior vena cava just before entering into the right atrium. The second case demonstrated extensive skeletal muscle deposits involving the muscles of the trunk as well as upper and lower extremities.

  10. Hand-held synchronous scan spectrometer for in situ and immediate detection of live/dead bacteria ratio

    Science.gov (United States)

    Li, Runze; Goswami, Umang; Walck, Matthew; Khan, Kasfia; Chen, Jie; Cesario, Thomas C.; Rentzepis, Peter M.

    2017-11-01

    The design, construction, and operation of a hand-held synchronously scanned, excitation-emission, double monochromator spectrometer is described. Data show that it is possible to record and display within minutes the fluorescence spectra and ratio of live/dead bacteria in situ. Excitation emission matrix contour plots display clearly bacteria fluorescence spectra before and after UV inactivation, respectively. The separation of the fluorescence band maxima of molecular components, such as tryptophan, tyrosine, and DNA, may be distinguished in the diffused fluorescence spectra of bacteria and mixtures.

  11. Incidental detection of a pseudoaneurysm at an amputation stump in a Tc-99m HMPAO labeled leukocyte scan

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Myung Hee; Jeong, Hwan Jeong; Lim, Seok Tae [Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2007-08-15

    A 20-year-old man underwent a Tc-99m HMPAO labeled leukocyte scan for the evaluation of an infection at the stump of an AK amputation, which was conducted due to an open communicated fracture of the left lower leg. Blood-flow and blood-pool images demonstrated a pseudoaneurysm with a focus of intense activity medial to the stump, and centered within a large photopenic defect by surrounding hematoma. Delayed image obtained at 3 hours post-injection showed persistent intense and slight increased activity. Contrast angiography confirmed the presence of a pseudoaneurysm arising from a branch of the left superficial femoral artery.

  12. Cost effectiveness of the addition of a comprehensive CT scan to the abdomen and pelvis for the detection of cancer after unprovoked venous thromboembolism.

    Science.gov (United States)

    Coyle, Kathryn; Carrier, Marc; Lazo-Langner, Alejandro; Shivakumar, Sudeep; Zarychanski, Ryan; Tagalakis, Vicky; Solymoss, Susan; Routhier, Nathalie; Douketis, James; Coyle, Douglas

    2017-03-01

    Unprovoked venous thromboembolism (VTE) can be the first manifestation of cancer. It is unclear if extensive screening for occult cancer including a comprehensive computed tomography (CT) scan of the abdomen/pelvis is cost-effective in this patient population. To assess the health care related costs, number of missed cancer cases and health related utility values of a limited screening strategy with and without the addition of a comprehensive CT scan of the abdomen/pelvis and to identify to what extent testing should be done in these circumstances to allow early detection of occult cancers. Cost effectiveness analysis using data that was collected alongside the SOME randomized controlled trial which compared an extensive occult cancer screening including a CT of the abdomen/pelvis to a more limited screening strategy in patients with a first unprovoked VTE, was used for the current analyses. Analyses were conducted with a one-year time horizon from a Canadian health care perspective. Primary analysis was based on complete cases, with sensitivity analysis using appropriate multiple imputation methods to account for missing data. Data from a total of 854 patients with a first unprovoked VTE were included in these analyses. The addition of a comprehensive CT scan was associated with higher costs ($551 CDN) with no improvement in utility values or number of missed cancers. Results were consistent when adopting multiple imputation methods. The addition of a comprehensive CT scan of the abdomen/pelvis for the screening of occult cancer in patients with unprovoked VTE is not cost effective, as it is both more costly and not more effective in detecting occult cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Preoperative F-18-FDG PET for the detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma patients with negative I-131 whole body scans

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Urn, Sang Moo; Cheon, Gi Jeong; Choi, Chang Woon; Lee, Byeong Cheol; Lee, Guk Haeng; Lee, Yong Sik; Shim, Youn Sang [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2007-07-01

    We evaluated the diagnostic performance of FDG-PET for the detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma patients with negative I-131 scan. All patients had total thyroidectomy and following I-131 ablation therapy. In the follow-up period, FDG-PET showed suspected cervical lymph nodes metastases and neck dissection was performed within 3 months after FDG-PET. It had shown for all patients the negative I-131 scan within 3 months before FDG-PET or negative I-131 scan during the period of cervical lymph nodes metastases suspected on the basis of FDG-PET, CT, or ultrasonography until the latest FDG-PET. Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 19 papillary thyroid carcinoma patients. Serum Tg, TSH, and Tg antibody levels at the time of latest I-131 scan were reviewed. The size of lymph node was measured by preoperative CT or ultrasonography. In 45 cervical lymph node groups dissected, 31 lymph node groups revealed metastasis. The sensitivity and specificity of FDG-PET for metastasis were 74.2% (23 of 31) and 50.0% (7 of 14), respectively. Except for patients with elevated Tg antibody levels, all patients showed the elevated serum Tg levels than normal limits at the TSH of =30uIU/ml. 8 lesions without suspected metastatic findings on FDG-PET revealed metastasis (false negative), and none of them exceeded 8mm in size (4 to 8mm, median= 6mm). On the other hand, 23 true positive lesions on FDG-PET were variable in size (6 to 17mm, median=9mm). FDG-PET is suitable for the detection of metastatic cervical lymph nodes in patients with recurrent papillary thyroid carcinoma. However, false positive or false negative should be considered according to the size of lymph node.

  14. Concurrent mutation in exons 1 and 2 of the K-ras oncogene in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Fiorella Guadagni

    2012-01-01

    Full Text Available The K-ras gene is frequently mutated in colorectal cancer and has been associated with tumor initiation and progression; approximately 90% of the activating mutations are found in codons 12 and 13 of exon 1 and just under 5% in codon 61 located in exon 2. These mutations determine single aminoacidic substitutions in the GTPase pocket leading to a block of the GTP hydrolytic activity of the K-ras p21 protein, and therefore to its constitutive activation. Point mutations in sites of the K-ras gene, other than codons 12, 13 and 61, and other types of genetic alterations, may occur in a minority of cases, such as in the less frequent cases of double mutations in the K-ras gene. However, all mutations in this gene, even those which occur in non-canonical sites or double mutations, are relevant oncogenic alterations in colorectal cancer and may underlie K-ras pathway hyperactivation. In the present study, we report the case of a patient with colorectal cancer presenting a concurrent point mutation in exons 1 and 2 of the K-ras gene, a GGT to TGT substitution (Glycine to Cysteine at codon 12, and a GAC to AAC substitution (Aspartic Acid to Asparagine at codon 57. In addition, we found in the same patient’s sample a silent polymorphism at codon 11 (Ala11Ala of exon 1. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 729–733

  15. Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy

    Directory of Open Access Journals (Sweden)

    Li Kuiyuan

    2009-04-01

    Full Text Available Abstract Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS status has emerged as a predictor of response to epidermal growth factor receptor (EGFR targeted therapies. In this article, we will discuss targeted therapies for colorectal cancers (CRC based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients with colorectal cancer whose tumor has an activating mutation in KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should now become a standard practice that any patients being considered for EGFR targeted therapies have their tumors tested for KRAS status and only those with wild-type KRAS being offered such therapies.

  16. RAF Suppression Synergizes with MEK Inhibition in KRAS Mutant Cancer Cells

    Directory of Open Access Journals (Sweden)

    Simona Lamba

    2014-09-01

    Full Text Available KRAS is the most frequently mutated oncogene in human cancer, yet no therapies are available to treat KRAS mutant cancers. We used two independent reverse genetic approaches to identify components of the RAS-signaling pathways required for growth of KRAS mutant tumors. Small interfering RNA (siRNA screening of 37 KRAS mutant colorectal cancer cell lines showed that RAF1 suppression was synthetic lethal with MEK inhibition. An unbiased kinome short hairpin RNA (shRNA-based screen confirmed this synthetic lethal interaction in colorectal as well as in lung cancer cells bearing KRAS mutations. Compounds targeting RAF kinases can reverse resistance to the MEK inhibitor selumetinib. MEK inhibition induces RAS activation and BRAF-RAF1 dimerization and sustains MEK-ERK signaling, which is responsible for intrinsic resistance to selumetinib. Prolonged dual blockade of RAF and MEK leads to persistent ERK suppression and efficiently induces apoptosis. Our data underlie the relevance of developing combinatorial regimens of drugs targeting the RAF-MEK pathway in KRAS mutant tumors.

  17. Prognostic and Predictive Value of RAS Gene Mutations in Colorectal Cancer: Moving Beyond KRAS Exon 2.

    Science.gov (United States)

    Boeckx, Nele; Peeters, Marc; Van Camp, Guy; Pauwels, Patrick; Op de Beeck, Ken; Deschoolmeester, Vanessa

    2015-10-01

    The advent of anti-EGFR (epidermal growth factor receptor) therapy resulted in significant progress in the treatment of metastatic colorectal cancer patients. However, many patients do not respond to this therapy or develop acquired resistance within a few months after the start of treatment. Since 2008, anti-EGFR therapy is restricted to KRAS wild-type patients as it has been shown that KRAS exon 2-mutated patients do not respond to this therapy. Still, up to 60 % of KRAS exon 2 wild-type patients show primary resistance to this treatment. Recently, several studies investigating the predictive and prognostic role of RAS mutations other than in KRAS exon 2 demonstrated that patients with these mutations are not responding to therapy. However, the role of these mutations has long been questioned as The National Comprehensive Cancer Network Guidelines in Oncology and the European Medicines Agency indications had already been changed in order to restrict anti-EGFR therapy to all RAS wild-type colorectal cancer patients, while the Food and Drug Administration guidelines remained unchanged. Recently, the Food and Drug Administration guidelines have also been changed, which implies the importance of RAS mutations beyond KRAS exon 2 in colorectal cancer. In this review, we discuss the most important studies regarding the predictive and prognostic role of RAS mutations other than in KRAS exon 2 in order to demonstrate the importance of these RAS mutations in patients with metastatic colorectal cancer treated with anti-EGFR therapy.

  18. Evaluation of KRAS Gene Mutations in Metastatic Colorectal Cancer Patients in Kermanshah Province.

    Science.gov (United States)

    Amirifard, Nasrin; Sadeghi, Edris; Farshchian, Negin; Haghparast, Abbas; Choubsaz, Mansour

    2016-01-01

    Worldwide, colorectal cancer (CRC) is reported to be the fourth most common cancer in men and the third most common in women. KRAS is a protooncogene located on the short arm of chromosome 12. The aim of this study was to evaluate the KRAS oncogene and its relationship it with clinicopathologic features in 33 Kurdish patients. Metastatic CRC between 2012 and 2016 that came to Imam Reza hospital, Kermanshah province, Iran, were analysed for KRAS mutations using allele specific PCR primers and pyrosequencing. Correlations between variables was analyzed in PASW SPSS and overall survival curves were plotted in Graph Pad prism 5. The mean age for them at diagnosis was 51.5±12.6 years (range, 2276 years). Among the 33 patients that were sequenced, 12 samples in the KRAS gene had a nucleotide change, 11 in codon 12 and 1 in codon 13.There was no significant relationship between the mutation and clinical and pathological aspects of the disease. Knowledge of the KRAS status can help in decisionmaking to treat metastatic colorectal cancer patients more efficiently and increase survival. However, many Kurdish people due to economic problems are not able to do this valuable genetic test. In addition, we need more careful research of KRAS oncogene at the molecular level in young populations with more patients.

  19. Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Mei; Lu, Jia; Li, Lianbo; Feru, Frederic; Quan, Chunshan; Gero, Thomas W.; Ficarro, Scott B.; Xiong, Yuan; Ambrogio, Chiara; Paranal, Raymond M.; Catalano, Marco; Shao, Jay; Wong, Kwok-Kin; Marto, Jarrod A.; Fischer, Eric S.; Jänne, Pasi A.; Scott, David A.; Westover, Kenneth D.; Gray, Nathanael S. (DFCI); (UTSMC); (Harvard-Med); (NYUSM)

    2017-08-01

    Targeted covalent small molecules have shown promise for cancers driven by KRAS G12C. Allosteric compounds that access an inducible pocket formed by movement of a dynamic structural element in KRAS, switch II, have been reported, but these compounds require further optimization to enable their advancement into clinical development. We demonstrate that covalent quinazoline-based switch II pocket (SIIP) compounds effectively suppress GTP loading of KRAS G12C, MAPK phosphorylation, and the growth of cancer cells harboring G12C. Notably we find that adding an amide substituent to the quinazoline scaffold allows additional interactions with KRAS G12C, and remarkably increases the labeling efficiency, potency, and selectivity of KRAS G12C inhibitors. Structural studies using X-ray crystallography reveal a new conformation of SIIP and key interactions made by substituents located at the quinazoline 2-, 4-, and 7-positions. Optimized lead compounds in the quinazoline series selectively inhibit KRAS G12C-dependent signaling and cancer cell growth at sub-micromolar concentrations.

  20. Renal scan

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003790.htm Renal scan To use the sharing features on this ... anaphylaxis . Alternative Names Renogram; Kidney scan Images Kidney anatomy Kidney - blood and urine flow References Chernecky CC, ...

  1. Step-scan T cell-based differential Fourier transform infrared photoacoustic spectroscopy (DFTIR-PAS) for detection of ambient air contaminants

    Science.gov (United States)

    Liu, Lixian; Mandelis, Andreas; Huan, Huiting; Melnikov, Alexander

    2016-10-01

    A step-scan differential Fourier transform infrared photoacoustic spectroscopy (DFTIR-PAS) using a commercial FTIR spectrometer was developed theoretically and experimentally for air contaminant monitoring. The configuration comprises two identical, small-size and low-resonance-frequency T cells satisfying the conflicting requirements of low chopping frequency and limited space in the sample compartment. Carbon dioxide (CO2) IR absorption spectra were used to demonstrate the capability of the DFTIR-PAS method to detect ambient pollutants. A linear amplitude response to CO2 concentrations from 100 to 10,000 ppmv was observed, leading to a theoretical detection limit of 2 ppmv. The differential mode was able to suppress the coherent noise, thereby imparting the DFTIR-PAS method with a better signal-to-noise ratio and lower theoretical detection limit than the single mode. The results indicate that it is possible to use step-scan DFTIR-PAS with T cells as a quantitative method for high sensitivity analysis of ambient contaminants.

  2. A scan statistic for binary outcome based on hypergeometric probability model, with an application to detecting spatial clusters of Japanese encephalitis.

    Science.gov (United States)

    Zhao, Xing; Zhou, Xiao-Hua; Feng, Zijian; Guo, Pengfei; He, Hongyan; Zhang, Tao; Duan, Lei; Li, Xiaosong

    2013-01-01

    As a useful tool for geographical cluster detection of events, the spatial scan statistic is widely applied in many fields and plays an increasingly important role. The classic version of the spatial scan statistic for the binary outcome is developed by Kulldorff, based on the Bernoulli or the Poisson probability model. In this paper, we apply the Hypergeometric probability model to construct the likelihood function under the null hypothesis. Compared with existing methods, the likelihood function under the null hypothesis is an alternative and indirect method to identify the potential cluster, and the test statistic is the extreme value of the likelihood function. Similar with Kulldorff's methods, we adopt Monte Carlo test for the test of significance. Both methods are applied for detecting spatial clusters of Japanese encephalitis in Sichuan province, China, in 2009, and the detected clusters are identical. Through a simulation to independent benchmark data, it is indicated that the test statistic based on the Hypergeometric model outweighs Kulldorff's statistics for clusters of high population density or large size; otherwise Kulldorff's statistics are superior.

  3. Detection of heavy metals released at the sediment/water interface by combining Anodic Stripping Voltammetry (ASV) and Scanning Electrochemical Microscopy (SECM) measurements

    Science.gov (United States)

    Daniele, S.; Ciani, I.; Bragato, C.; Baldo, M. A.

    2003-05-01

    Hemisphere mercury microelectrodes are investigated in combine anodic stripping voltammetry (ASV) and scanning electrochemical microscopy (SECM) experiments for the detection of heavy metal ions at the solid/solution interface of a sediment sample. Relatively large anodic stripping peaks due to lead are monitored at μm distances from the solid particles, while, under the same experimental conditions, no or lower ASV peaks are found in the bulk solution. This suggests that diffusion gradients at sediment/water interface is monitored. This method, therefore, offers a new possibility for investigating on spatial differences of immobilization and remobilization processes of heavy metals at sediment/water interfaces.

  4. Frequency-Modulated Magneto-Acoustic Detection and Imaging: Challenges, Experimental Procedures, and B-Scan Images

    CERN Document Server

    Aliroteh, Miaad S; Arbabian, Amin

    2016-01-01

    Magneto-acoustic tomography combines near-field radio-frequency (RF) and ultrasound with the aim of creating a safe, high resolution, high contrast hybrid imaging technique. We present continuous-wave magneto-acoustic imaging techniques, which improve SNR and/or reduce the required peak-to-average excitation power ratio, to make further integration and larger fields of view feasible. This method relies on the coherency between RF excitation and the resulting ultrasound generated through Lorentz force interactions, which was confirmed by our previous work. We provide detailed methodology, clarify the details of experiments, and explain how the presence of magneto-acoustic phenomenon was verified. An example magneto-acoustic B-scan image is acquired in order to illustrate the capability of magneto-acoustic tomography in highlighting boundaries where electrical conductivity alters, such as between different tissues.

  5. KRAS Protein Stability Is Regulated through SMURF2: UBCH5 Complex-Mediated β-TrCP1 Degradation

    Directory of Open Access Journals (Sweden)

    Shirish Shukla

    2014-02-01

    Full Text Available Attempts to target mutant KRAS have been unsuccessful. Here, we report the identification of Smad ubiquitination regulatory factor 2 (SMURF2 and UBCH5 as a critical E3:E2 complex maintaining KRAS protein stability. Loss of SMURF2 either by small interfering RNA/short hairpin RNA (siRNA/shRNA or by overexpression of a catalytically inactive mutant causes KRAS degradation, whereas overexpression of wild-type SMURF2 enhances KRAS stability. Importantly, mutant KRAS is more susceptible to SMURF2 loss where protein half-life decreases from >12 hours in control siRNA-treated cells to <3 hours on Smurf2 silencing, whereas only marginal differences were noted for wild-type protein. This loss of mutant KRAS could be rescued by overexpressing a siRNA-resistant wild-type SMURF2. Our data further show that SMURF2 monoubiquitinates UBCH5 at lysine 144 to form an active complex required for efficient degradation of a RAS-family E3, β-transducing repeat containing protein 1 (β-TrCP1. Conversely, β-TrCP1 is accumulated on SMURF2 loss, leading to increased KRAS degradation. Therefore, as expected, β-TrCP1 knockdown following Smurf2 siRNA treatment rescues mutant KRAS loss. Further, we identify two conserved proline (P residues in UBCH5 critical for SMURF2 interaction; mutation of either of these P to alanine also destabilizes KRAS. As a proof of principle, we demonstrate that Smurf2 silencing reduces the clonogenic survival in vitro and prolongs tumor latency in vivo in cancer cells including mutant KRAS-driven tumors. Taken together, we show that SMURF2:UBCH5 complex is critical in maintaining KRAS protein stability and propose that targeting such complex may be a unique strategy to degrade mutant KRAS to kill cancer cells.

  6. Microsatellite instability, KRAS mutations and cellular distribution of TRAIL-receptors in early stage colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Lydia Kriegl

    Full Text Available BACKGROUND: The fact that the receptors for the TNF-related apoptosis inducing ligand (TRAIL are almost invariably expressed in colorectal cancer (CRC represents the rationale for the employment of TRAIL-receptors targeting compounds for the therapy of patients affected by this tumor. Yet, first reports on the use of these bioactive agents provided disappointing results. We therefore hypothesized that loss of membrane-bound TRAIL-R might be a feature of some CRC and that the evaluation of membrane staining rather than that of the overall expression of TRAIL-R might predict the response to TRAIL-R targeting compounds in this tumor. AIM AND METHODS: Thus, we evaluated the immunofluorescence pattern of TRAIL-receptors and E-cadherin to assess the fraction of membrane-bound TRAIL-receptors in 231 selected patients with early-stage CRC undergoing surgical treatment only. Moreover, we investigated whether membrane staining for TRAIL-receptors as well as the presence of KRAS mutations or of microsatellite instability (MSI had an effect on survival and thus a prognostic effect. RESULTS: As expected, almost all CRC samples stained positive for TRAIL-R1 and 2. Instead, membrane staining for these receptors was positive in only 71% and 16% of samples respectively. No correlation between KRAS mutation status or MSI-phenotype and prognosis could be detected. TRAIL-R1 staining intensity correlated with survival in univariate analysis, but only membranous staining of TRAIL-R1 and TRAIL-R2 on cell membranes was an independent predictor of survival (cox multivariate analysis: TRAIL-R1: p = 0.019, RR 2.06[1.12-3.77]; TRAIL-R2: p = 0.033, RR 3.63[1.11-11.84]. CONCLUSIONS: In contrast to the current assumptions, loss of membrane staining for TRAIL-receptors is a common feature of early stage CRC which supersedes the prognostic significance of their staining intensity. Failure to achieve therapeutic effects in recent clinical trials using TRAIL-receptors targeting

  7. Lead identification for the K-Ras protein: virtual screening and combinatorial fragment-based approaches

    Directory of Open Access Journals (Sweden)

    Pathan AAK

    2016-05-01

    Full Text Available Akbar Ali Khan Pathan,1,2,* Bhavana Panthi,3,* Zahid Khan,1 Purushotham Reddy Koppula,4–6 Mohammed Saud Alanazi,1 Sachchidanand,3 Narasimha Reddy Parine,1 Mukesh Chourasia3,* 1Genome Research Chair (GRC, Department of Biochemistry, College of Science, King Saud University, 2Integrated Gulf Biosystems, Riyadh, Kingdom of Saudi Arabia; 3Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Hajipur, India; 4Department of Internal Medicine, School of Medicine, 5Harry S. Truman Memorial Veterans Affairs Hospital, 6Department of Radiology, School of Medicine, Columbia, MO, USA *These authors contributed equally to this work Objective: Kirsten rat sarcoma (K-Ras protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods: In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results: Interestingly, the designed compounds exhibit a binding preference for the

  8. Association between clinicopathological features and survival in patients with primary and paired metastatic colorectal cancer and KRAS mutation

    Directory of Open Access Journals (Sweden)

    Pang X

    2017-05-01

    Full Text Available Xue-Lian Pang,* Qiao-Xin Li,* Zhi-Ping Ma, Yi Shi, Yu-Qing Ma, Xin-Xia Li, Wen-Li Cui, Wei Zhang Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: The KRAS gene mutation is involved in several types of tumors. However, the potential role of the KRAS mutation in human primary and paired metastatic colorectal cancer (CRC among different nationalities is poorly understood. In the present study, we assessed the relationship between KRAS mutation status and overall survival (OS and disease-free survival (DFS in 230 patients with primary and paired metastatic CRC. The KRAS mutation rate in primary CRC tissue was 43.0% (99/230, which was higher than in paired metastatic CRC, which was 31.9% (23/72; P<0.001. Clinicopathologically, the KRAS gene mutation rate was higher in tumors that had infiltrated more deeply (T3, T4 and in lymph node (LN metastases (N1/N2 (P=0.029 and P=0.010, respectively. The KRAS gene status did not differ between the Han and Uyghur nationalities in both primary and metastatic CRC. In 72 paired cases, the KRAS mutation rate in primary CRC was significantly higher than in metastatic CRC (P<0.001 and in metastatic CRC that had infiltrated more deeply (T3, T4 (P=0.034. In the metastatic cases, the KRAS gene mutation rate was higher in patients aged over 65 years (P=0.035. Specifically, KRAS mutation was correlated with a poorer OS and DFS (P=0.004 and P=0.029, respectively. In our study, 35 patients with wild-type KRAS who received cetuximab targeted therapy had a better DFS than patients with mutant KRAS (P=0.029. The results of the current study demonstrate that the KRAS status is significantly associated with infiltrating LN metastases and the TNM stage in primary CRC. In addition, the results show that the KRAS mutation is significantly more common in primary tumors than in paired metastatic CRC, and

  9. Frequency and clinical significance of previously undetected incidental findings detected on computed tomography simulation scans for breast cancer patients.

    Science.gov (United States)

    Nakamura, Naoki; Tsunoda, Hiroko; Takahashi, Osamu; Kikuchi, Mari; Honda, Satoshi; Shikama, Naoto; Akahane, Keiko; Sekiguchi, Kenji

    2012-11-01

    To determine the frequency and clinical significance of previously undetected incidental findings found on computed tomography (CT) simulation images for breast cancer patients. All CT simulation images were first interpreted prospectively by radiation oncologists and then double-checked by diagnostic radiologists. The official reports of CT simulation images for 881 consecutive postoperative breast cancer patients from 2009 to 2010 were retrospectively reviewed. Potentially important incidental findings (PIIFs) were defined as any previously undetected benign or malignancy-related findings requiring further medical follow-up or investigation. For all patients in whom a PIIF was detected, we reviewed the clinical records to determine the clinical significance of the PIIF. If the findings from the additional studies prompted by a PIIF required a change in management, the PIIF was also recorded as a clinically important incidental finding (CIIF). There were a total of 57 (6%) PIIFs. The 57 patients in whom a PIIF was detected were followed for a median of 17 months (range, 3-26). Six cases of CIIFs (0.7% of total) were detected. Of the six CIIFs, three (50%) cases had not been noted by the radiation oncologist until the diagnostic radiologist detected the finding. On multivariate analysis, previous CT examination was an independent predictor for PIIF (p = 0.04). Patients who had not previously received chest CT examinations within 1 year had a statistically significantly higher risk of PIIF than those who had received CT examinations within 6 months (odds ratio, 3.54; 95% confidence interval, 1.32-9.50; p = 0.01). The rate of incidental findings prompting a change in management was low. However, radiation oncologists appear to have some difficulty in detecting incidental findings that require a change in management. Considering cost, it may be reasonable that routine interpretations are given to those who have not received previous chest CT examinations within 1 year

  10. KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Young; Shim, Eun Kyung [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Yeo, Hyun Yang [Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Hong, Yong Sang [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Tae Won [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jee Hyun [Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Im, Seock-Ah [Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Kyung Hae [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Chang, Hee Jin, E-mail: heejincmd@yahoo.com [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2013-01-01

    Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with

  11. Loosening of the total knee arthroplasty: detection by radionuclide bone scanning. [/sup 99m/Tc-methylene diphosphonate

    Energy Technology Data Exchange (ETDEWEB)

    Hunter, J.C. (Univ. of California, San Francisco); Hattner, R.S.; Murray, W.R.; Genant, H.K.

    1980-07-01

    Pain after total knee arthroplasty is a common clinical problem in orthopedics, and prosthetic loosening, often requiring surgical revision, is usually the etiology. Since standard clinical and radiographic diagnostic measures have not proven totally satisfactory, a study of the utility of bone scintigraphy to assess stability of the knee prosthesis was done. Thirty-five patients with 39 prostheses were studied. Seventeen patients with 21 total knee arthroplasties served as controls and were asymptomatic, were stable at surgery, or improved with conservative management. Eighteen knees in 18 symptomatic patients composed the experimental group. Of these, 11 knees were loose at surgery and seven have had surgery recommended. Scintigrams of the knees were obtained using /sup 99m/Tc-MDP, and ranked 0-3 corresponding to increasingly abnormal localization by three observers. Highly significant differences were observed between the abnormal and control groups (p<0.001). Reciprocal changes in sensitivity and specificity with increasingly stringent criteria were shown. While it is apparent that the bone scan cannot be used as the sole diagnostic method for evaluation of prosthetic stability, it does seem to be a useful adjunct along with clinical criteria and radiographic studies.

  12. Wavelet Entropy and Directed Acyclic Graph Support Vector Machine for Detection of Patients with Unilateral Hearing Loss in MRI Scanning

    OpenAIRE

    Wang, Shuihua; Yang, Ming; Du, Sidan; Yang, Jiquan; Liu, Bin; Gorriz, Juan M.; Ramírez, Javier; Yuan, Ti-Fei; Zhang, Yudong

    2016-01-01

    Highlights We develop computer-aided diagnosis system for unilateral hearing loss detection in structural magnetic resonance imaging. Wavelet entropy is introduced to extract image global features from brain images. Directed acyclic graph is employed to endow support vector machine an ability to handle multi-class problems. The developed computer-aided diagnosis system achieves an overall accuracy of 95.1% for this three-class problem of differentiating left-sided and right-sided he...

  13. Evaluation of computerized detection of pulmonary embolism in independent data sets of computed tomographic pulmonary angiographic (CTPA) scans

    Science.gov (United States)

    Zhou, Chuan; Chan, Heang-Ping; Sahiner, Berkman; Hadjiiski, Lubomir M.; Chughtai, Aamer; Patel, Smita; Wei, Jun; Cascade, Philip N.; Kazerooni, Ella A.

    2009-02-01

    Computed tomographic pulmonary angiography (CTPA) has been reported to be an effective means for clinical diagnosis of pulmonary embolism (PE). We are developing a computer-aided diagnosis (CAD) system for assisting radiologists in detection of pulmonary embolism in CTPA images. The pulmonary vessel tree is extracted based on the analysis of eigenvalues of Hessian matrices at multiple scales followed by 3D hierarchical EM segmentation. A multiprescreening method is designed to identify suspicious PEs along the extracted vessels. A linear discriminant analysis (LDA) classifier with feature selection is then used to reduce false positives (FPs). Two data sets of 59 and 69 CTPA PE cases were randomly selected from patient files at the University of Michigan (UM) and the PIOPED II study, respectively, and used as independent training and test sets. The PEs that were identified by three experienced thoracic radiologists were used as the gold standard. The detection performance of the CAD system was assessed by free response receiver operating characteristic analysis. The results indicated that our PE detection system can achieve a sensitivity of 80% at 18.9 FPs/case on the PIOPED cases when the LDA classifier was trained with the UM cases. The test sensitivity with the UM cases is 80% at 22.6 FPs/cases when the LDA classifier was trained with the PIOPED cases.

  14. Maintenance of acinar cell organization is critical to preventing Kras-induced acinar-ductal metaplasia.

    Science.gov (United States)

    Shi, G; DiRenzo, D; Qu, C; Barney, D; Miley, D; Konieczny, S F

    2013-04-11

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers owing to a number of characteristics including difficulty in establishing early diagnosis and the absence of effective therapeutic regimens. A large number of genetic alterations have been ascribed to PDAC with mutations in the KRAS2 proto-oncogene thought to be an early event in the progression of disease. Recent lineage-tracing studies have shown that acinar cells expressing mutant Kras(G12D) are induced to transdifferentiate, generating duct-like cells through a process known as acinar-ductal metaplasia (ADM). ADM lesions then convert to precancerous pancreatic intraepithelial neoplasia (PanIN) that progresses to PDAC over time. Thus, understanding the earliest events involved in ADM/PanIN formation would provide much needed information on the molecular pathways that are instrumental in initiating this disease. As studying the transition of acinar cells to metaplastic ductal cells in vivo is complicated by analysis of the entire organ, an in vitro three dimensional (3D) culture system was used to model ADM outside the animal. Kras(G12D)-expressing acinar cells rapidly underwent ADM in 3D culture, forming ductal cysts that silenced acinar genes and activated duct genes, characteristics associated with in vivo ADM/PanIN lesions. Analysis of downstream KRAS signaling events established a critical importance for the Raf/MEK/ERK pathway in ADM induction. In addition, forced expression of the acinar-restricted transcription factor Mist1, which is critical to acinar cell organization, significantly attenuated Kras(G12D)-induced ADM/PanIN formation. These results suggest that maintaining MIST1 activity in Kras(G12D)-expressing acinar cells can partially mitigate the transformation activity of oncogenic KRAS. Future therapeutics that target both the MAPK pathway and Mist1 transcriptional networks may show promising efficacy in combating this deadly disease.

  15. Oncogene-induced senescence underlies the mutual exclusive nature of oncogenic KRAS and BRAF.

    Science.gov (United States)

    Cisowski, J; Sayin, V I; Liu, M; Karlsson, C; Bergo, M O

    2016-03-10

    KRAS and BRAF are among the most commonly mutated oncogenes in human cancer that contribute to tumorigenesis in both distinct and overlapping tissues. However, KRAS and BRAF mutations are mutually exclusive; they never occur in the same tumor cell. The reason for the mutual exclusivity is unknown, but there are several possibilities. The two mutations could be functionally redundant and not create a selective advantage to tumor cells. Alternatively, they could be deleterious for the tumor cell and induce apoptosis or senescence. To distinguish between these possibilities, we activated the expression of BRAF(V600E) and KRAS(G12D) from their endogenous promoters in mouse lungs. Although the tumor-forming ability of BRAF(V600E) was higher than KRAS(G12D), KRAS(G12D) tumors were larger and more advanced. Coactivation of BRAF(V600E) and KRAS(G12D) markedly reduced lung tumor numbers and overall tumor burden compared with activation of BRAF(V600E) alone. Moreover, several tumors expressed only one oncogene, suggesting negative selection against expression of both. Similarly, expression of both oncogenes in mouse embryonic fibroblasts essentially stopped proliferation. The expression of both oncogenes hyperactivated the MEK-ERK-cyclin D pathway but reduced proliferation by increasing the production of p15, p16 and p19 proteins encoded by the Ink4/Arf locus and thereby increased senescence-associated β-galactosidase-positive cells. The data suggest that coexpression of BRAF(V600E) and KRAS(G12D) in early tumorigenesis leads to negative selection due to oncogene-induced senescence.

  16. K-RAS and N-RAS mutations in testicular germ cell tumors

    Directory of Open Access Journals (Sweden)

    Bekir Muhammet Hacioglu

    2017-05-01

    Full Text Available Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55% pure seminoma cases and 19 (45% non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen. In total, a RAS mutation was present in 12 patients (27%: 7 seminoma (29% and 5 non-seminoma cases (26% [p = 0.55]. A K-RAS mutation was present in 4 pure seminoma tumors (16% and 3 non-seminoma tumors (15% [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16% and 3 non-seminoma tumors (15% [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.

  17. Path scanning for the detection of anomalous subgraphs and use of DNS requests and host agents for anomaly/change detection and network situational awareness

    Energy Technology Data Exchange (ETDEWEB)

    Neil, Joshua Charles; Fisk, Michael Edward; Brugh, Alexander William; Hash, Curtis Lee; Storlie, Curtis Byron; Uphoff, Benjamin; Kent, Alexander

    2017-11-21

    A system, apparatus, computer-readable medium, and computer-implemented method are provided for detecting anomalous behavior in a network. Historical parameters of the network are determined in order to determine normal activity levels. A plurality of paths in the network are enumerated as part of a graph representing the network, where each computing system in the network may be a node in the graph and the sequence of connections between two computing systems may be a directed edge in the graph. A statistical model is applied to the plurality of paths in the graph on a sliding window basis to detect anomalous behavior. Data collected by a Unified Host Collection Agent ("UHCA") may also be used to detect anomalous behavior.

  18. Scanning laser polarimetry and spectral domain optical coherence tomography for the detection of retinal changes in Parkinson's disease.

    Science.gov (United States)

    Stemplewitz, Birthe; Keserü, Matthias; Bittersohl, Diana; Buhmann, Carsten; Skevas, Christos; Richard, Gisbert; Hassenstein, Andrea

    2015-12-01

    Whether retinal degeneration is part of the degenerative processes in patients with Parkinson's disease (PD) is still unclear. This cross-sectional study was undertaken to compare the retinal morphology of patients with PD and healthy controls using spectral domain optical coherence tomography (SD-OCT) and scanning laser polarimetry (SLP). Both eyes of patients with PD (n = 108) and healthy controls (n = 165) were examined using SD-OCT and SLP on the same day. Data on the thickness of the retinal nerve fibre layer (RNFL) of all quadrants and the macular area were acquired by OCT (Cirrus, Zeiss). The SLP device (Glaucoma diagnostics (GDx), Zeiss) measured the RNFL and calculated the nerve fibre index (NFI). All patients and probands were checked for concomitant ocular disorders by an ophthalmologist. Visual acuity, intraocular pressure (IOP), objective refraction and the anterior and posterior segment were assessed. Patients with PD showed a reduced macular volume and a reduced central subfield thickness in OCT examinations. The RNFL in the different quadrants did not differ significantly from that of controls. SLP data showed a reduced average RNFL thickness, a decreased thickness of the inferior quadrant and an increase of the NFI in patients with PD. PD may be associated with reduced thickness and volume of the macula and a reduced thickness of the RNFL in the inferior quadrant of the retina. Investigations using SD-OCT and SLP revealed distinct but significant differences between patients with PD and healthy controls. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Modelling cave flow hydraulics in the Notranjski Kras, Slovenia

    Science.gov (United States)

    Kaufmann, Georg; Gabrovsek, Franci

    2015-04-01

    The Notranjski Kras region is a karst region in western Slovenia, developed in Cretaceous limestone. The region is characterised by hilly relief, with peaks reaching 1300 m elevation. Several well-developed cave systems drain the karst aquifer, providing preferential flow pathes along two sections: The Pivka River, which sinks into Postojnska Jama and reappears in Planinska Jama, and the Stržen and Cerkniščica rivers, which sink into Karlovica Jama, flow through Zelške Jama and Tkalca Jama and also reappear in Planinska Jama. Both sub-surface flow pathes merge in Planinska Jama, providing water for the Unica river. The Unica river leaves Planinska Jama via a large karst srping and passes through Planinsko Polje, disappearing again through two groups of ponors, finally emerging in the Ljubljanka Springs at around 300 m asl. The sub-surface flow path through the Postojnska Jama cave system has been monitored with 7 stations distributed along the flow path, monitoring stage and temperature. We have used the stage data to model flow through the cave system with the program package SWMM, simulating the active parts of Postojnska Jama with simplified geometry. From the comparison of stage observations and predictions, we identified key sections in the cave, which control the sub-surface flow, such as passage constrictions, sumps and by-passes. Using a formal inverse procedure, we determined the geometry of this key sections by fitting predicted to observed stages, and we achieved a very high degree of correlation.

  20. Fever Screening and Detection of Febrile Arrivals at an International Airport in Korea: Association among Self-reported Fever, Infrared Thermal Camera Scanning, and Tympanic Temperature.

    Science.gov (United States)

    Cho, Kyung Sook; Yoon, Jangho

    2014-01-01

    The purpose of this research was to measure fever prevalence and the effectiveness of a fever screening procedure in detecting febrile arrivals at an international airport in Korea. Data were retrieved from arrivals' health declaration forms and questionnaires for febrile arrivals at an international airport collected by a national quarantine station during the year 2012. Self-reported health declaration forms were returned by 355,887 arrivals (61% of the total arrivals). Of these, 608 symptomatic arrivals (0.2%) including 6 febrile arrivals were analyzed. Fever prevalence at an international airport in Korea was 0.002%. Self-reported fever was significantly positively associated with tympanic temperature (pcamera temperature (36.83°C) and tympanic (or ear) temperature (38.14°C) was not statistically significant. The findings imply that a procedure for mass detection of fever such as self-reported questionnaires and thermal camera scanning may serve as an effective tool for detecting febrile arrivals at quarantine stations. Future research can benefit from looking at the sensitivity, specificity, positive predictive value, and negative predictive value of the entry screening system. The purpose of this research was to measure fever prevalence and the effectiveness of a fever screening procedure in detecting febrile arrivals at an international airport in Korea. Data were retrieved from arrivals’ health declaration forms and questionnaires for febrile arrivals at an international airport collected by a national quarantine station during the year 2012. Self-reported health declaration forms were returned by 355,887 arrivals (61% of the total arrivals). Of these, 608 symptomatic arrivals (0.2%) including 6 febrile arrivals were analyzed. Fever prevalence at an international airport in Korea was 0.002%. Self-reported fever was significantly positively associated with tympanic temperature (pcamera temperature (36.83°C) and tympanic (or ear) temperature (38.14

  1. Measurement of effective detective quantum efficiency for a photon counting scanning mammography system and comparison with two flat panel full-field digital mammography systems

    Science.gov (United States)

    Wood, Tim J.; Moore, Craig S.; Saunderson, John R.; Beavis, Andrew W.

    2018-01-01

    Effective detective quantum efficiency (eDQE) describes the resolution and noise properties of an imaging system along with scatter and primary transmission, all measured under clinically appropriate conditions. Effective dose efficiency (eDE) is the eDQE normalised to mean glandular dose and has been proposed as a useful metric for the optimisation of clinical imaging systems. The aim of this study was to develop a methodology for measuring eDQE and eDE on a Philips microdose mammography (MDM) L30 photon counting scanning system, and to compare performance with two conventional flat panel systems. A custom made lead-blocker was manufactured to enable the accurate determination of dose measurements, and modulation transfer functions were determined free-in-air at heights of 2, 4 and 6 cm above the breast support platform. eDQE were calculated for a Philips MDM L30, Hologic Dimensions and Siemens Inspiration digital mammography system for 2, 4 and 6 cm thick poly(methyl methacrylate) (PMMA). The beam qualities (target/filter and kilovoltage) assessed were those selected by the automatic exposure control, and anti-scatter grids were used where available. Measurements of eDQE demonstrate significant differences in performance between the slit- and scan-directions for the photon counting imaging system. MTF has been shown to be the limiting factor in the scan-direction, which results in a rapid fall in eDQE at mid-to-high spatial frequencies. A comparison with two flat panel mammography systems demonstrates that this may limit image quality for small details, such as micro-calcifications, which correlates with a more conventional image quality assessment with the CDMAM phantom. eDE has shown the scanning photon counting system offers superior performance for low spatial frequencies, which will be important for the detection of large low contrast masses. Both eDQE and eDE are proposed as useful metrics that should enable optimisation of the Philips MDM L30.

  2. Staging PET-CT Scanning Provides Superior Detection of Lymph Nodes and Distant Metastases than Traditional Imaging in Locally Advanced Breast Cancer.

    Science.gov (United States)

    Garg, Pankaj Kumar; Deo, Suryanarayana V S; Kumar, Rakesh; Shukla, Nootan Kumar; Thulkar, Sanjay; Gogia, Ajay; Sharma, Daya Nand; Mathur, Sandeep R

    2016-08-01

    This study was designed to evaluate the role of a single 18-FDG positron emission tomography and computed tomography (PET-CT) scan in comparison to multiple organ-directed conventional investigations (CI) as a staging tool in locally advanced breast cancer (LABC) to detect regional and distant metastasis. All eligible patients were subjected to CI (chest X-ray, abdominal sonography, and bone scintigraphy) followed by a single 18-FDG PET-CT scan. Standard imaging criteria were used for diagnosis of metastasis. Histopathological confirmation was undertaken for suspicious lesions. An exploratory analysis was done to assess the impact of PET-CT on the staging of LABC and how it resulted in a change in management. The study included 79 patients of LABC. PET-CT detected distant metastasis in 36 (45.5 %) patients while CI could identify distant metastasis in 20 (25.3 %) patients. Two of the 36 patients in whom PET-CT detected distant metastasis were false positive. Overall PET-CT upstaged the disease in 38 (48.1 %) patients as compared to CI: stage III to stage IV migration in 14 (17.7 %) patients due to identification of additional sites of distant metastasis, and within stage III upstaging in 24 (30.3 %) patients due to identification of additional regional lymphadenopathy. PET-CT led to a change in management plan in 14 (17.7 %) patients. PET-CT has a role in identifying additional sites of regional lymphadenopathy and distant metastasis to upstage the disease in a significant number of LABC patients in comparison to CI; this would help in accurate staging, selecting optimal treatment, and better prognostication of disease.

  3. Comparing Two Methods of Surface Change Detection on an Evolving Thermokarst Using High-Temporal-Frequency Terrestrial Laser Scanning, Selawik River, Alaska

    Directory of Open Access Journals (Sweden)

    Theodore B. Barnhart

    2013-05-01

    Full Text Available Terrestrial laser scanners (TLS allow large and complex landforms to be rapidly surveyed at previously unattainable point densities. Many change detection methods have been employed to make use of these rich data sets, including cloud to mesh (C2M comparisons and Multiscale Model to Model Cloud Comparison (M3C2. Rather than use simulated point cloud data, we utilized a 58 scan TLS survey data set of the Selawik retrogressive thaw slump (RTS to compare C2M and M3C2. The Selawik RTS is a rapidly evolving permafrost degradation feature in northwest Alaska that presents challenging survey conditions and a unique opportunity to compare change detection methods in a difficult surveying environment. Additionally, this study considers several error analysis techniques, investigates the spatial variability of topographic change across the feature and explores visualization techniques that enable the analysis of this spatiotemporal data set. C2M reports a higher magnitude of topographic change over short periods of time (~12 h and reports a lower magnitude of topographic change over long periods of time (~four weeks when compared to M3C2. We found that M3C2 provides a better accounting of the sources of uncertainty in TLS change detection than C2M, because it considers the uncertainty due to surface roughness and scan registration. We also found that localized areas of the RTS do not always approximate the overall retreat of the feature and show considerable spatial variability during inclement weather; however, when averaged together, the spatial subsets approximate the retreat of the entire feature. New data visualization techniques are explored to leverage temporally and spatially continuous data sets. Spatially binning the data into vertical strips along the headwall reduced the spatial complexity of the data and revealed spatiotemporal patterns of change.

  4. Relationship of KRAS and PIK3CA gene mutation in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Fan-Bao Yao; Qian-Yi Kuang; Xi Fu; Shi-Yao Huang

    2016-01-01

    Objective:To analyze the relationship between KRAS/PIK3CA gene mutation and clinicopathologic characteristics such as gender, age, tumor location, pathological pattern, histological grade, TNM stage and lymph node metastasis, especially the relationship with distant metastasis of colorectal cancer.Methods:A total of94 cases of colorectal cancer samples surgically resected in Gastrointestinal Surgery Department of our hospital from January 2012 to August 2015 were collected, DNA was extracted and then KRAS and PIK3CA gene sequencing was carried out; their clinicopathologic characteristics (gender, age, tumor location, pathological pattern, histological grade, TNM stage, lymph node metastasis and distant metastasis) were analyzed, the relationship between KRAS/PIK3CA gene mutation and above factors, especially distant metastasis was analyzed, and statistical analysis processing was conducted; patients received 3-year follow-up, distant metastasis and recurrence were observed, and the number of their cases was counted, statistically analyzed and processed.Results:KRAS gene mutation was not associated with gender, age, tumor location, pathological pattern and histological grade, and significantly associated with distant metastasis, lymph node metastasis and TNM stage; PIK3CA was not associated with gender, age, tumor location, pathological pattern and histological grade, and associated with TNM stage, lymph node metastasis and distant metastasis; 7 cases (7.4%) were with mutation of both KRAS and PIK3CA (double positive), and 55 cases (57.4%) were with no mutation at all (double negative); in double positive cases, 5 cases were with distant metastasis, metastasis rate was 71.4% and higher than that of double negative (16/55, 29.1%), and there were statistical differences; it was found in follow-up that metastasis rate of KRAS mutant type was higher than that of wild type, and differences were statistically significant; recurrence rates of KRAS and PIK3CA mutant type

  5. Cooperative scans

    NARCIS (Netherlands)

    M. Zukowski (Marcin); P.A. Boncz (Peter); M.L. Kersten (Martin)

    2004-01-01

    textabstractData mining, information retrieval and other application areas exhibit a query load with multiple concurrent queries touching a large fraction of a relation. This leads to individual query plans based on a table scan or large index scan. The implementation of this access path in most

  6. Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma.

    Science.gov (United States)

    McFadden, David G; Politi, Katerina; Bhutkar, Arjun; Chen, Frances K; Song, Xiaoling; Pirun, Mono; Santiago, Philip M; Kim-Kiselak, Caroline; Platt, James T; Lee, Emily; Hodges, Emily; Rosebrock, Adam P; Bronson, Roderick T; Socci, Nicholas D; Hannon, Gregory J; Jacks, Tyler; Varmus, Harold

    2016-10-18

    Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity.

  7. EVI1 oncogene promotes KRAS pathway through suppression of microRNA-96 in pancreatic carcinogenesis.

    Science.gov (United States)

    Tanaka, M; Suzuki, H I; Shibahara, J; Kunita, A; Isagawa, T; Yoshimi, A; Kurokawa, M; Miyazono, K; Aburatani, H; Ishikawa, S; Fukayama, M

    2014-05-08

    Despite frequent KRAS mutation, the early molecular mechanisms of pancreatic ductal adenocarcinoma (PDAC) development have not been fully elucidated. By tracking a potential regulator of another feature of PDAC precursors, acquisition of foregut or gastric epithelial gene signature, we herein report that aberrant overexpression of ecotropic viral integration site 1 (EVI1) oncoprotein, which is usually absent in normal pancreatic duct, is a widespread marker across the full spectrum of human PDAC precursors and PDAC. In pancreatic cancer cells, EVI1 depletion caused remarkable inhibition of cell growth and migration, indicating its oncogenic roles. Importantly, we found that EVI1 upregulated KRAS expression through suppression of a potent KRAS suppressor, miR-96, in pancreatic cancer cells. Collectively, the present findings suggest that EVI1 overexpression and KRAS mutation converge on activation of the KRAS pathway in early phases of pancreatic carcinogenesis and propose EVI1 and/or miR-96 as early markers and therapeutic targets in this dismal disease.

  8. Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Phuoc T Tran

    Full Text Available KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with Kras(G12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy.

  9. Mutant K-RAS Promotes Invasion and Metastasis in Pancreatic Cancer Through GTPase Signaling Pathways

    Science.gov (United States)

    Padavano, Julianna; Henkhaus, Rebecca S; Chen, Hwudaurw; Skovan, Bethany A; Cui, Haiyan; Ignatenko, Natalia A

    2015-01-01

    Pancreatic ductal adenocarcinoma is one of the most aggressive malignancies, characterized by the local invasion into surrounding tissues and early metastasis to distant organs. Oncogenic mutations of the K-RAS gene occur in more than 90% of human pancreatic cancers. The goal of this study was to investigate the functional significance and downstream effectors of mutant K-RAS oncogene in the pancreatic cancer invasion and metastasis. We applied the homologous recombination technique to stably disrupt K-RAS oncogene in the human pancreatic cell line MiaPaCa-2, which carries the mutant K-RASG12C oncogene in both alleles. Using in vitro assays, we found that clones with disrupted mutant K-RAS gene exhibited low RAS activity, reduced growth rates, increased sensitivity to the apoptosis inducing agents, and suppressed motility and invasiveness. In vivo assays showed that clones with decreased RAS activity had reduced tumor formation ability in mouse xenograft model and increased survival rates in the mouse orthotopic pancreatic cancer model. We further examined molecular pathways downstream of mutant K-RAS and identified RhoA GTP activating protein 5, caveolin-1, and RAS-like small GTPase A (RalA) as key effector molecules, which control mutant K-RAS-dependent migration and invasion in MiaPaCa-2 cells. Our study provides rational for targeting RhoA and RalA GTPase signaling pathways for inhibition of pancreatic cancer metastasis. PMID:26512205

  10. Clinical utility of KRAS status in circulating plasma DNA compared to archival tumour tissue from patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor therapy

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Pallisgaard, Niels; Appelt, Ane Lindegaard

    2015-01-01

    in patients from metastatic colorectal cancer (mCRC) prior to anti-epidermal growth factor receptor (anti-EGFR) therapy. Secondly, we investigated the concentration of total cfDNA in relation to clinical outcome. PATIENTS AND METHODS: Patients were resistant to 5-FU, oxaliplatin and irinotecan and treated......BACKGROUND: Circulating cell-free DNA (cfDNA) in plasma is a mixture of DNA from malignant and normal cells, and can be used as a liquid biopsy to detect and quantify tumour specific mutations e.g. KRAS. We investigated the clinical value of KRAS mutations when detected in plasma compared to tumour...... an additional prognostic effect. CONCLUSION: The value of clinically relevant mutations could be improved by performing the analysis on circulation plasma DNA rather than archival tumour tissue....

  11. Sensitivity of post treatment positron emission tomography/computed tomography to detect inter-fractional range variations in scanned ion beam therapy.

    Science.gov (United States)

    Handrack, Josefine; Tessonnier, Thomas; Chen, Wenjing; Liebl, Jakob; Debus, Jürgen; Bauer, Julia; Parodi, Katia

    2017-11-01

    Ion therapy, especially with modern scanning beam delivery, offers very sharp dose gradients for highly conformal cancer treatment. However, it is very sensitive to uncertainties of tissue stopping properties as well as to anatomical changes and setup errors, making range verification highly desirable. To this end, positron emission tomography (PET) can be used to measure decay products of β + -emitters created in interactions inside the patient. This work investigates the sensitivity of post treatment PET/CT (computed tomography) to detect inter-fractional range variations. Fourteen patients of different indication underwent PET/CT monitoring after selected treatment fractions with scanned proton or carbon ion beams. In addition to PET/CT measurements, PET and dose distributions were simulated on different co-registered CT data. Pairs of PET data were then analyzed in terms of longitudinal shifts along the beam path, as surrogate of inter-fractional range deviations. These findings were compared to changes of dose-volume-histogram indexes and corresponding dose as well as CT shifts to disentangle the origin of possible PET shifts. Biological washout modeling (PET simulations) and low (ions) were the main limitations for clinical treatment verification. For two selected cases, the benefit of improved washout modeling based on organ segmentation could be demonstrated. Overall, inter-fractional range shifts up to ±3 mm could be deduced from both PET measurements and simulations, and found well correlated (typically within 1.8 mm) to anatomical changes derived from CT scans, in agreement with dose data. Despite known limitations of post treatment PET/CT imaging, this work indicates its potential for assessing inter-fractional changes and points to future developments for improved PET-based treatment verification.

  12. FLIM and FCS detection in laser-scanning microscopes: increased efficiency by GaAsP hybrid detectors.

    Science.gov (United States)

    Becker, W; Su, B; Holub, O; Weisshart, K

    2011-09-01

    Photon counting detectors currently used in fluorescence lifetime microscopy have a number of deficiencies that result in less-than-ideal signal-to-noise ratio of the lifetimes obtained: either the quantum efficiency is unsatisfactory or the active area is too small, and afterpulsing or tails in the temporal response contribute to overall timing inaccuracy. We have therefore developed a new FLIM detector based on a GaAsP hybrid photomultiplier. Compared with conventional PMTs and SPADs, GaAsP hybrid detectors have a number of advantages: The detection quantum efficiency reaches or surpasses the efficiency of fast SPADs, and the active area is on the order of 5 mm², compared with 2.5 10⁻³ mm² for a SPAD. The TCSPC response is clean, without the bumps and the diffusion tails typical for PMTs and SPADs. Most important, the hybrid detector is intrinsically free of afterpulsing. FLIM results are therefore free of signal-dependent background, and FCS curves are free of the known afterpulsing peak. We demonstrate the performance of the new detector for multiphoton NDD FLIM and for FCS. Copyright © 2010 Wiley-Liss, Inc.

  13. Prospective Comparison of F-18 Choline PET/CT Scan Versus Axial MRI for Detecting Bone Metastasis in Biochemically Relapsed Prostate Cancer Patients

    Directory of Open Access Journals (Sweden)

    Wouter Huysse

    2017-10-01

    Full Text Available We compared fluor-18 choline positron emission tomography/computed tomography (PET/CT and axial skeleton magnetic resonance imaging (MRI prospectively obtained for the detection of bone metastases in non-castrated patients with biochemically recurrent prostate cancer following primary treatment. PET/CT was performed 45 min post-injection of 3–4 MBq/kg F-18 methyl choline. MRI included T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were initially blinded from other results and all scans underwent independent double reading. The best valuable comparator (BVC defined the metastatic status. On the basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a patient level, the sensitivity and specificity of MRI and PET were not significantly different. On a lesion level, the sensitivity of MRI was significantly better compared to PET, and the specificity did not differ significantly. In conclusion, axial MRI is an interesting screening tool for the detection of bone metastases because of its low probability of false negative results. However, F-18 choline PET is a valuable addition as it can overrule false positive MRI results and detect non-axial metastases.

  14. Prospective Comparison of F-18 Choline PET/CT Scan Versus Axial MRI for Detecting Bone Metastasis in Biochemically Relapsed Prostate Cancer Patients.

    Science.gov (United States)

    Huysse, Wouter; Lecouvet, Frédéric; Castellucci, Paolo; Ost, Piet; Lambrecht, Valerie; Artigas, Carlos; Denis, Marie-Laurence; Man, Kathia De; Delrue, Louke; Jans, Lennart; Bruycker, Aurélie De; Vos, Filip De; Meerleer, Gert De; Decaestecker, Karel; Fonteyne, Valerie; Lambert, Bieke

    2017-10-17

    We compared fluor-18 choline positron emission tomography/computed tomography (PET/CT) and axial skeleton magnetic resonance imaging (MRI) prospectively obtained for the detection of bone metastases in non-castrated patients with biochemically recurrent prostate cancer following primary treatment. PET/CT was performed 45 min post-injection of 3-4 MBq/kg F-18 methyl choline. MRI included T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were initially blinded from other results and all scans underwent independent double reading. The best valuable comparator (BVC) defined the metastatic status. On the basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a patient level, the sensitivity and specificity of MRI and PET were not significantly different. On a lesion level, the sensitivity of MRI was significantly better compared to PET, and the specificity did not differ significantly. In conclusion, axial MRI is an interesting screening tool for the detection of bone metastases because of its low probability of false negative results. However, F-18 choline PET is a valuable addition as it can overrule false positive MRI results and detect non-axial metastases.

  15. A comparative study on the diagnostic utility of ultrasonography with conventional radiography and computed tomography scan in detection of zygomatic arch and mandibular fractures

    Directory of Open Access Journals (Sweden)

    Koijam Sashikumar Singh

    2014-01-01

    Full Text Available Objectives: The objective of the following study is to evaluate the usefulness of ultrasonography (USG in comparison with conventional radiography and computed tomography (CT scan in the diagnosis of zygomatic arch and mandibular fractures. Materials and Methods: A total of 40 patients with suspected fracture of the zygomatic arch and/or mandibular fractures were included in the study. Two groups (one for zygomatic arch fractures and the other for mandibular fractures of 20 patients each were designed for the study. Ultrasonographic examinations were performed using small linear probe (LA435, Siemens Acuson Antares with 10 MHz frequency. Data from CT and conventional radiography were compared with that of USG. Results: Sensitivity and specificity of USG in assessing zygomatic arch fractures were 100% and 100%, respectively; and that of mandibular fractures were 94.74% and 100%, respectively. Overall sensitivity, specificity, positive predictive value, and negative predictive value of USG against CT in diagnosing zygomatic arch and mandibular fractures were found out to be 97.4%, 100%, 100%, and 66.7%, respectively. Conclusion: USG is a very reliable tool in detection of fractures involving zygomatic arch and mandible. It can be used for screening of suspected fractures of zygomatic arch and mandible to avoid unnecessary radiation exposure from conventional radiography and CT scans.

  16. A comparative study on the diagnostic utility of ultrasonography with conventional radiography and computed tomography scan in detection of zygomatic arch and mandibular fractures.

    Science.gov (United States)

    Singh, Koijam Sashikumar; Jayachandran, S

    2014-04-01

    The objective of the following study is to evaluate the usefulness of ultrasonography (USG) in comparison with conventional radiography and computed tomography (CT) scan in the diagnosis of zygomatic arch and mandibular fractures. A total of 40 patients with suspected fracture of the zygomatic arch and/or mandibular fractures were included in the study. Two groups (one for zygomatic arch fractures and the other for mandibular fractures) of 20 patients each were designed for the study. Ultrasonographic examinations were performed using small linear probe (LA435, Siemens Acuson Antares) with 10 MHz frequency. Data from CT and conventional radiography were compared with that of USG. Sensitivity and specificity of USG in assessing zygomatic arch fractures were 100% and 100%, respectively; and that of mandibular fractures were 94.74% and 100%, respectively. Overall sensitivity, specificity, positive predictive value, and negative predictive value of USG against CT in diagnosing zygomatic arch and mandibular fractures were found out to be 97.4%, 100%, 100%, and 66.7%, respectively. USG is a very reliable tool in detection of fractures involving zygomatic arch and mandible. It can be used for screening of suspected fractures of zygomatic arch and mandible to avoid unnecessary radiation exposure from conventional radiography and CT scans.

  17. Gold-FISH: a new approach for the in situ detection of single microbial cells combining fluorescence and scanning electron microscopy.

    Science.gov (United States)

    Schmidt, Hannes; Eickhorst, Thilo; Mussmann, Marc

    2012-12-01

    A novel fluorescence in situ hybridisation (FISH) method is presented that allows the combination of epifluorescence and scanning electron microscopy (SEM) to identify single microbial cells. First, the rRNA of whole cells is hybridised with horseradish peroxidase-labelled oligonucleotide probes and this is followed by catalysed reporter deposition (CARD) of biotinylated tyramides. This facilitates an amplification of binding sites for streptavidin conjugates covalently labelled with both fluorophores and nanogold particles. The deposition of Alexa Fluor 488 fluoro-nanogold-streptavidin conjugates was confirmed via epifluorescence microscopy and cells could be quantified in a similar way to standard CARD-FISH approaches. To detect cells by SEM, an autometallographic enhancement of the nanogold particles was essential, and allowed the in situ localisation of the target organisms at resolutions beyond light microscopy. Energy dispersive X-ray spectroscopy (EDS) was used to verify the effects of CARD and autometallography on gold deposition in target cells. The gold-FISH protocol was developed and optimised using pure cultures and environmental samples, such as rice roots and marine sediments. The combination of epifluorescence and scanning electron microscopy provides a promising tool for investigating microorganisms at levels of high resolution. Correlative characterisation of physicochemical properties by EDS will allow for the analysis of microbe-surface interactions. Copyright © 2012 Elsevier GmbH. All rights reserved.

  18. Mutation analysis of KRAS prior to targeted therapy in colorectal cancer: development and evaluation of quality by a European external quality assessment scheme

    NARCIS (Netherlands)

    Dequeker, E.; Ligtenberg, M.J.L.; Borght, S. van der; Krieken, J.H. van

    2011-01-01

    In Europe, the use of anti-EGFR monoclonal antibodies is restricted to Kirsten RAS (KRAS) wild-type colorectal tumors. Information on the KRAS status of the patients tumor is thus key for clinical practice; however, there is little guidance or definition on which KRAS mutations to assess and how to

  19. KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients

    NARCIS (Netherlands)

    Knijn, N.; Mekenkamp, L. J. M.; Klomp, M.; Vink-Börger, M. E.; Tol, J.; Teerenstra, S.; Meijer, J. W. R.; Tebar, M.; Riemersma, S.; van Krieken, J. H. J. M.; Punt, C. J. A.; Nagtegaal, I. D.

    2011-01-01

    KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data

  20. The cornerstone K-RAS mutation in pancreatic adenocarcinoma: From cell signaling network, target genes, biological processes to therapeutic targeting.

    Science.gov (United States)

    Jonckheere, Nicolas; Vasseur, Romain; Van Seuningen, Isabelle

    2017-03-01

    RAS belongs to the super family of small G proteins and plays crucial roles in signal transduction from membrane receptors in the cell. Mutations of K-RAS oncogene lead to an accumulation of GTP-bound proteins that maintains an active conformation. In the pancreatic ductal adenocarcinoma (PDAC), one of the most deadly cancers in occidental countries, mutations of the K-RAS oncogene are nearly systematic (>90%). Moreover, K-RAS mutation is the earliest genetic alteration occurring during pancreatic carcinogenetic sequence. In this review, we discuss the central role of K-RAS mutations and their tremendous diversity of biological properties by the interconnected regulation of signaling pathways (MAPKs, NF-κB, PI3K, Ral…). In pancreatic ductal adenocarcinoma, transcriptome analysis and preclinical animal models showed that K-RAS mutation alters biological behavior of PDAC cells (promoting proliferation, migration and invasion, evading growth suppressors, regulating mucin pattern, and miRNA expression). K-RAS also impacts tumor microenvironment and PDAC metabolism reprogramming. Finally we discuss therapeutic targeting strategies of K-RAS that have been developed without significant clinical success so far. As K-RAS is considered as the undruggable target, targeting its multiple effectors and target genes should be considered as potential alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas

    DEFF Research Database (Denmark)

    Schultz, Nicolai Aagaard; Roslind, Anne; Christensen, Ib J

    2012-01-01

    The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied.......The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied....

  2. An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer

    DEFF Research Database (Denmark)

    Vallejo, Adrian; Perurena, Naiara; Guruceaga, Elisabet

    2017-01-01

    KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identifica...

  3. Local detection efficiency of a NbN superconducting single photon detector explored by a scattering scanning near-field optical microscope.

    Science.gov (United States)

    Wang, Qiang; Renema, Jelmer J; Engel, Andreas; van Exter, Martin P; de Dood, Michiel J A

    2015-09-21

    We propose an experiment to directly probe the local response of a superconducting single photon detector using a sharp metal tip in a scattering scanning near-field optical microscope. The optical absorption is obtained by simulating the tip-detector system, where the tip-detector is illuminated from the side, with the tip functioning as an optical antenna. The local detection efficiency is calculated by considering the recently introduced position-dependent threshold current in the detector. The calculated response for a 150 nm wide detector shows a peak close to the edge that can be spatially resolved with an estimated resolution of ∼ 20 nm, using a tip with parameters that are experimentally accessible.

  4. Detection of dentinal cracks after root-end resection: an ex vivo study comparing microscopy and endoscopy with scanning electron microscopy.

    Science.gov (United States)

    von Arx, Thomas; Kunz, Renato; Schneider, Adrienne Christina; Bürgin, Walter; Lussi, Adrian

    2010-09-01

    Dentinal cracks are occasionally observed at the cut root face after root-end resection in apical surgery. The objective of this ex vivo study was to evaluate and compare the efficiency of visual aids to identify root-end dentinal cracks. Twenty-six extracted human molars were decoronated, and the root canals were instrumented and filled. The apical 3 mm of the roots were resected, and the cut root faces were assessed with microscopy at x16 and x24 magnification and with endoscopy at x8 and x64 magnification (four visual aids). Roots were then duplicated for inspection with scanning electron microscopy. The presence, type, and location of cracks were registered by a blinded observer, with the scanning electron microcopy serving as the reference. The percentages of correct identification of dentinal cracks were then statistically compared among the four test configurations. Endoscopy x64 showed the highest sensitivity for crack identification, irrespective of the applied methodology (ie, per root and per crack). However, higher scores of false-positive cracks (lower specificity) were found with endoscopy x64 than with the other tested visual aids. The correct detection and location of complete canal cracks (55.3%, 52.6%, 68.4%, and 78.9%) were higher than the detection of incomplete canal cracks (42.2%, 42.2%, 52.0%, and 64.7%) using the four tested visual aids (microscopy at x16 and x24 magnification and endoscopy at x8 and x64 magnification, respectively). Only one of five intradentin cracks was identified with endoscopy x64. Overall, endoscopy x64 proved the most accurate visual aid for the identification of dentinal cracks after root-end resection in extracted human teeth; however, it also provided the most false identifications. Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. A handheld MEMS-based line-scanned dual-axis confocal microscope for early cancer detection and surgical guidance (Conference Presentation)

    Science.gov (United States)

    Chen, Ye; Yin, Chengbo; Wei, Linpeng; Glaser, Adam K.; Abeytunge, Sanjee; Peterson, Gary; Mandella, Michael J.; Sanai, Nader; Rajadhyaksha, Milind; Liu, Jonathan T.

    2017-02-01

    Considerable efforts have been recently undertaken to develop miniature optical-sectioning microscopes for in vivo microendoscopy and point-of-care pathology. These devices enable in vivo interrogation of disease as a real-time and noninvasive alternative to gold-standard histopathology, and therefore could have a transformative impact for the early detection of cancer as well as for guiding tumor-resection procedures. Regardless of the specific modality, various trade-offs in size, speed, field of view, resolution, contrast, and sensitivity are necessary to optimize a device for a particular application. Here, a miniature MEMS-based line-scanned dual-axis confocal (LS-DAC) microscope, with a 12-mm diameter distal tip, has been developed for point-of-care pathology. The dual-axis architecture has demonstrated superior rejection of out-of-focus and multiply scattered photons compared to a conventional single-axis confocal configuration. The use of line scanning enables fast frame rates (≥15 frames/sec), which mitigates motion artifacts of a handheld device during clinical use. We have developed a method to actively align the illumination and collection beams in this miniature LS-DAC microscope through the use of a pair of rotatable alignment mirrors. Incorporation of a custom objective lens, with a small form factor for in vivo application, enables the device to achieve an axial and lateral resolution of 2.0 and 1.1 microns, respectively. Validation measurements with reflective targets, as well as in vivo and ex vivo images of tissues, demonstrate that this high-speed LS-DAC microscope can achieve high-contrast imaging of fluorescently labeled tissues with sufficient sensitivity for applications such as oral cancer detection and guiding brain-tumor resections.

  6. Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer.

    Science.gov (United States)

    Foltran, Luisa; De Maglio, Giovanna; Pella, Nicoletta; Ermacora, Paola; Aprile, Giuseppe; Masiero, Elena; Giovannoni, Mariella; Iaiza, Emiliana; Cardellino, Giovanni Gerardo; Lutrino, Stefania Eufemia; Mazzer, Micol; Giangreco, Manuela; Pisa, Federica Edith; Pizzolitto, Stefano; Fasola, Gianpiero

    2015-01-01

    To explore the prognostic value of extended mutational profiling for metastatic colorectal cancer (mCRC). We retrospectively reviewed survival results of 194 mCRC patients that were assigned to four molecular subgroups: BRAF mutated; KRAS mutated codons 12-13 only; any of KRAS codons 61-146, PIK3CA or NRAS mutations and all wild-type. Point mutations were investigated by pyrosequencing. BRAF (5.2%) and KRAS 12-13 (31.9%) mutations were associated with poorer survival (HR 2.8 and 1.76, respectively). Presenting with right-sided colon cancer, not resected primary tumor, WBC >10 × 10(9)/l, receiving less chemotherapy or no bevacizumab were all associated with inferior outcome. The all-wild-type subgroup (39.2%) reported the longest survival. Extended mutational profile combined with clinical factors may impact on survival in mCRC.

  7. The regulatory G4 motif of the Kirsten ras (KRAS) gene is sensitive to guanine oxidation

    DEFF Research Database (Denmark)

    Cogoi, Susanna; Ferino, Annalisa; Miglietta, Giulia

    2018-01-01

    KRAS is one of the most mutated genes in human cancer. It is controlled by a G4 motif located upstream of the transcription start site. In this paper, we demonstrate that 8-oxoguanine (8-oxoG), being more abundant in G4 than in non-G4 regions, is a new player in the regulation of this oncogene. We...... designed oligonucleotides mimicking the KRAS G4-motif and found that 8-oxoG impacts folding and stability of the G-quadruplex. Dimethylsulphate-footprinting showed that the G-run carrying 8-oxoG is excluded from the G-tetrads and replaced by a redundant G-run in the KRAS G4-motif. Chromatin...

  8. Bevacizumab with chemotherapy in patients with KRAS wild-type metastatic colorectal cancer: Czech registry data.

    Science.gov (United States)

    Kubáčková, Kateřina; Bortlíček, Zbyněk; Pikus, Tomáš; Linke, Zdeněk; Pokorná, Petra; Vyzula, Rostislav; Prausová, Jana

    2015-01-01

    This retrospective analysis investigated the effectiveness of combination therapy with bevacizumab and chemotherapy in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer. Patients with KRAS wild-type metastatic colorectal cancer in the CORECT registry who initiated treatment with bevacizumab between 2008 and 2012 were enrolled. Overall survival and progression-free survival were the main effectiveness end points. A total of 981 patients were enrolled. Median progression-free survival was 11.3 months (95% CI: 10.7-11.8) and median overall survival was 28.4 months (95% CI: 26.2-30.6). The most common adverse events were thromboembolic disease (4%) and hypertension (3.5%). This retrospective analysis shows the effectiveness of bevacizumab with chemotherapy in patients with KRAS wild-type metastatic colorectal cancer.

  9. Computational analysis of KRAS mutations: implications for different effects on the KRAS p.G12D and p.G13D mutations.

    Directory of Open Access Journals (Sweden)

    Chih-Chieh Chen

    Full Text Available BACKGROUND: The issue of whether patients diagnosed with metastatic colorectal cancer who harbor KRAS codon 13 mutations could benefit from the addition of anti-epidermal growth factor receptor therapy remains under debate. The aim of the current study was to perform computational analysis to investigate the structural implications of the underlying mutations caused by c.38G>A (p.G13D on protein conformation. METHODS: Molecular dynamics (MD simulations were performed to understand the plausible structural and dynamical implications caused by c.35G>A (p.G12D and c.38G>A (p.G13D. The potential of mean force (PMF simulations were carried out to determine the free energy profiles of the binding processes of GTP interacting with wild-type (WT KRAS and its mutants (MT. RESULTS: Using MD simulations, we observed that the root mean square deviation (RMSD increased as a function of time for the MT c.35G>A (p.G12D and MT c.38G>A (p.G13D when compared with the WT. We also observed that the GTP-binding pocket in the c.35G>A (p.G12D mutant is more open than that of the WT and the c.38G>A (p.G13D proteins. Intriguingly, the analysis of atomic fluctuations and free energy profiles revealed that the mutation of c.35G>A (p.G12D may induce additional fluctuations in the sensitive sites (P-loop, switch I and II regions. Such fluctuations may promote instability in these protein regions and hamper GTP binding. CONCLUSIONS: Taken together with the results obtained from MD and PMF simulations, the present findings implicate fluctuations at the sensitive sites (P-loop, switch I and II regions. Our findings revealed that KRAS mutations in codon 13 have similar behavior as KRAS WT. To gain a better insight into why patients with metastatic colorectal cancer (mCRC and the KRAS c.38G>A (p.G13D mutation appear to benefit from anti-EGFR therapy, the role of the KRAS c.38G>A (p.G13D mutation in mCRC needs to be further investigated.

  10. An inducible krasV12 transgenic zebrafish model for liver tumorigenesis and chemical drug screening

    Directory of Open Access Journals (Sweden)

    Anh Tuan Nguyen

    2012-01-01

    Because Ras signaling is frequently activated by major hepatocellular carcinoma etiological factors, a transgenic zebrafish constitutively expressing the krasV12 oncogene in the liver was previously generated by our laboratory. Although this model depicted and uncovered the conservation between zebrafish and human liver tumorigenesis, the low tumor incidence and early mortality limit its use for further studies of tumor progression and inhibition. Here, we employed a mifepristone-inducible transgenic system to achieve inducible krasV12 expression in the liver. The system consisted of two transgenic lines: the liver-driver line had a liver-specific fabp10 promoter to produce the LexPR chimeric transactivator, and the Ras-effector line contained a LexA-binding site to control EGFP-krasV12 expression. In double-transgenic zebrafish (driver-effector embryos and adults, we demonstrated mifepristone-inducible EGFP-krasV12 expression in the liver. Robust and homogeneous liver tumors developed in 100% of double-transgenic fish after 1 month of induction and the tumors progressed from hyperplasia by 1 week post-treatment (wpt to carcinoma by 4 wpt. Strikingly, liver tumorigenesis was found to be ‘addicted’ to Ras signaling for tumor maintenance, because mifepristone withdrawal led to tumor regression via cell death in transgenic fish. We further demonstrated the potential use of the transparent EGFP-krasV12 larvae in inhibitor treatments to suppress Ras-driven liver tumorigenesis by targeting its downstream effectors, including the Raf-MEK-ERK and PI3K-AKT-mTOR pathways. Collectively, this mifepristone-inducible and reversible krasV12 transgenic system offers a novel model for understanding hepatocarcinogenesis and a high-throughput screening platform for anti-cancer drugs.

  11. KRAS biomarker testing disparities in colorectal cancer patients in New Mexico

    Directory of Open Access Journals (Sweden)

    Alissa Greenbaum

    2017-11-01

    Full Text Available Introduction: American Society of Clinical Oncology (ASCO guidelines recommend that all patients with metastatic colorectal cancer (mCRC receive KRAS testing to guide anti-EGFR monoclonal antibody treatment. The aim of this study was to assess for disparities in KRAS testing and mutational status. Methods: The New Mexico Tumor Registry (NMTR, a population-based cancer registry participating in the National Cancer Institute’s Surveillance, Epidemiology and End Results program, was queried to identify all incident cases of CRC diagnosed among New Mexico residents from 2010 to 2013. Results: Six hundred thirty-seven patients were diagnosed with mCRC from 2010–2013. As expected, KRAS testing in Stage 4 patients presented the highest frequency (38.4%, though testing in stage 3 (8.5%, stage 2 (3.4% and stage 1 (1.2% was also observed. In those with metastatic disease, younger patients (≤ 64 years were more likely to have had testing than patients 65 years and older (p < 0.0001. Patients residing in urban areas received KRAS testing more often than patients living in rural areas (p = 0.019. No significant racial/ethnic disparities were observed (p = 0.66. No significant differences were seen by year of testing. Conclusion: Age and geographic disparities exist in the rates of KRAS testing, while sex, race/ethnicity and the year tested were not significantly associated with testing. Further study is required to assess the reasons for these disparities and continued suboptimal adherence to current ASCO KRAS testing guidelines. Keywords: Oncology, Health sciences, Clinical genetics

  12. Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients.

    Science.gov (United States)

    Vincenzi, Bruno; Cremolini, Chiara; Sartore-Bianchi, Andrea; Russo, Antonio; Mannavola, Francesco; Perrone, Giuseppe; Pantano, Francesco; Loupakis, Fotios; Rossini, Daniele; Ongaro, Elena; Bonazzina, Erica; Dell'Aquila, Emanuela; Imperatori, Marco; Zoccoli, Alice; Bronte, Giuseppe; De Maglio, Giovanna; Fontanini, Gabriella; Natoli, Clara; Falcone, Alfredo; Santini, Daniele; Onetti-Muda, Andrea; Siena, Salvatore; Tonini, Giuseppe; Aprile, Giuseppe

    2015-10-13

    Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/tumor sample, are available. We aimed to evaluate the prognostic value of K-Rasmutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.

  13. MRI Scans

    Science.gov (United States)

    Magnetic resonance imaging (MRI) uses a large magnet and radio waves to look at organs and structures inside your body. Health care professionals use MRI scans to diagnose a variety of conditions, from ...

  14. Bone Scan

    Science.gov (United States)

    ... posts Join Mayo Clinic Connect Bone scan About Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  15. Activating K-Ras mutations outwith ‘hotspot' codons in sporadic colorectal tumours – implications for personalised cancer medicine

    Science.gov (United States)

    Smith, G; Bounds, R; Wolf, H; Steele, R J C; Carey, F A; Wolf, C R

    2010-01-01

    Background: Response to EGFR-targeted therapies in colorectal cancer patients has been convincingly associated with Kirsten-Ras (K-Ras) mutation status. Current mandatory mutation testing for patient selection is limited to the K-Ras ‘hotspot' codons 12 and 13. Methods: Colorectal tumours (n=106) were screened for additional K-Ras mutations, phenotypes compared in transformation and Ras GTPase activating assays and gene and pathway changes induced by individual K-Ras mutants identified by microarray analysis. Taqman-based gene copy number and FISH analyses were used to investigate K-Ras gene amplification. Results: Four additional K-Ras mutations (Leu19Phe (1 out of 106 tumours), Lys117Asn (1 out of 106), Ala146Thr (7 out of 106) and Arg164Gln (1 out of 106)) were identified. Lys117Asn and Ala146Thr had phenotypes similar to the hotspot mutations, whereas Leu19Phe had an attenuated phenotype and the Arg164Gln mutation was phenotypically equivalent to wt K-Ras. We additionally identified a new K-Ras gene amplification event, present in approximately 2% of tumours. Conclusions: The identification of mutations outwith previously described hotspot codons increases the K-Ras mutation burden in colorectal tumours by one-third. Future mutation screening to facilitate optimal patient selection for treatment with EGFR-targeted therapies should therefore be extended to codon 146, and in addition should consider the unique molecular signatures associated with individual K-Ras mutations. PMID:20147967

  16. Role of Kras status in patients with metastatic colorectal cancer receiving first-line chemotherapy plus bevacizumab: a TTD group cooperative study.

    Directory of Open Access Journals (Sweden)

    Eduardo Díaz-Rubio

    Full Text Available In the MACRO study, patients with metastatic colorectal cancer (mCRC were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS, overall survival (OS and response rates.KRAS data (tumour KRAS status and type of mutation were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1% in the MACRO study. Wild-type (WT KRAS tumours were found in 219 patients (56% and mutant (MT KRAS in 175 patients (44%. Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77. The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96. Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5% with WT KRAS tumours and 76 patients (43.4% with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64.This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

  17. p53, erbB-2 and K-ras gene alterations are rare in spontaneous and plutonium-239-induced canine lung neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Tierney, L.A.; Hahn, F.F.; Lechner, J.F. [Inhalation Toxicology Research Inst., Albuquerque, NM (United States)

    1996-02-01

    Inhalation of high-linear energy transfer radiation in the form of radon progeny is a suspected cause of human lung cancer. To gain insight into the types of genetic derangements caused by this type of radiation, lung tumors from beagle dogs exposed to {sup 239}PuO{sub 2} and those arising in animals with no known carcinogen exposure were examined for evidence of aberrations in genes known to be altered in lung tumors. Altered expression of the p53 tumor suppressor gene and proto-oncogene erbB-2 proteins (p185{sup erbB2}) was evaluated by immunohistochemical analysis of 117 tumors representing different histological types in exposed (n = 80) and unexposed (n = 37) animals. Twenty-eight tumors were analyzed for K-ras proto-oncogene mutations by polymerase chain reaction amplification and direct sequencing. Fourteen percent (16/116) of all lung neoplasms showed elevated nuclear accumulation of p53 protein. Regardless of exposure history, adenosquamous and squamous cell cancers comprised 94% of all tumors with p53 abnormalities. Eighteen percent (21/117) of all tumors had evidence of erbB-2 protein overexpression. K-ras mutations were not detected in codons 12, 13 or 61 of tumors from unexposed (n = 9) or plutonium-exposed dogs (n = 19). These data indicate that p53 and K-ras gene abnormalities as a result of missense mutation are infrequent events in spontaneous and {sup 239}PuO{sub 2}-induced lung neoplasia in this colony of beagle dogs. Alternative mechanisms of gene alteration may be involved in canine pulmonary carcinogenesis. 45 refs., 3 figs., 2 tabs.

  18. Prognostic Effect of BRAF and KRAS Mutations in Patients With Stage III Colon Cancer Treated With Leucovorin, Fluorouracil, and Oxaliplatin With or Without Cetuximab: A Post Hoc Analysis of the PETACC-8 Trial.

    Science.gov (United States)

    Taieb, Julien; Zaanan, Aziz; Le Malicot, Karine; Julié, Catherine; Blons, Hélène; Mineur, Laurent; Bennouna, Jaafar; Tabernero, Josep; Mini, Enrico; Folprecht, Gunnar; Van Laethem, Jean Luc; Lepage, Come; Emile, Jean-François; Laurent-Puig, Pierre

    2016-01-14

    The prognostic value of BRAF and KRAS mutations in patients who have undergone resection for colon cancer and have been treated with combination leucovorin, fluorouracil, and oxaliplatin (FOLFOX)-based adjuvant chemotherapy is controversial, possibly owing to a lack of stratification on mismatch repair status. To examine the prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with adjuvant FOLFOX with or without cetuximab. This study included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated between December 2005 and November 2009 in the PETACC-8 phase III randomized trial.Mismatch repair, BRAF V600E, and KRAS exon 2 mutational status were determined on prospectively collected tumor blocks from 2559 patients enrolled in the PETACC-8 trial. The data were analyzed in April 2015. Patients were randomly assigned to receive 6 months of FOLFOX4 or FOLFOX4 plus cetuximab after surgical resection for stage III colon cancer. Associations between these biomarkers and disease-free survival (DFS) and overall survival (OS) were analyzed with Cox proportional hazards models. Multivariate models were adjusted for covariates (age, sex, tumor grade, T/N stage, tumor location, Eastern Cooperative Oncology Group performance status). Among the 2559 patients enrolled in the PETACC-8 trial (42.9% female; median [range] age, 60.0 [19.0-75.0] years), microsatellite instability (MSI) phenotype, KRAS, and BRAF V600E mutations were detected in, respectively, 9.9% (177 of 1791), 33.1% (588 of 1776), and 9.0% (148 of 1643) of cases. In multivariate analysis, MSI (hazard ratio [HR] for DFS: 1.10 [95% CI, 0.73-1.64], P = .67; HR for OS: 1.02 [95% CI, 0.61-1.69], P = .94) and BRAF V600E mutation (HR for DFS: 1.22 [95% CI, 0.81-1.85], P = .34; HR for OS: 1.13 [95% CI, 0.64-2.00], P = .66) were not prognostic, whereas KRAS mutation was significantly associated with shorter DFS (HR, 1.55 [95% CI

  19. Detection of bone metastases in breast cancer patients in the PET/CT era: Do we still need the bone scan?

    Science.gov (United States)

    Caglar, M; Kupik, O; Karabulut, E; Høilund-Carlsen, P F

    2016-01-01

    To examine the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of bone metastasis in breast cancer patients and assess whether whole body bone scan (BS) with (99m)Tc-methylene diphosphonate provides any additional information. Study group comprised 150 patients, mean age 52 years (range 27-85) with breast cancer, suspected of having bone metastases. All patients had undergone both FDG-PET/CT and BS with or without single photon emission tomography/computed tomography (SPECT/CT) within a period of 6 weeks. The final diagnosis of bone metastasis was established by histopathological findings, additional imaging, or clinical follow-up longer than 10 months. Cancer antigen 15-3 (CA15-3) and carcinoembryogenic antigen (CEA) were measured in all patients. Histologically 83%, 7% and 10% had infiltrating ductal, lobular and mixed carcinoma respectively. Confirmed bone metastases were present in 86 patients (57.3%) and absent in 64 (42.7%). Mean CA15-3 and CEA values in patients with bone metastases were 74.6ng/mL and 60.4U/mL respectively, compared to 21.3ng/mL and 3.2U/mL without metastases (p<0.001). The sensitivity of FDG-PET/CT for the detection of bone metastases was 97.6% compared to 89.5% with SPECT/CT. In 57 patients, FDG-PET/CT correctly identified additional pulmonary, hepatic, nodal and other soft tissue metastases, not detected by BS. Our findings suggest that FDG-PET/CT is superior to BS with or without SPECT/CT. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  20. Genomic scans detect signatures of selection along a salinity gradient in populations of the intertidal seaweed Fucus serratus on a 12 km scale.

    Science.gov (United States)

    Coyer, J A; Hoarau, G; Pearson, G; Mota, C; Jüterbock, A; Alpermann, T; John, U; Olsen, J L

    2011-03-01

    Detecting natural selection in wild populations is a central challenge in evolutionary biology and genomic scans are an important means of detecting allele frequencies that deviate from neutral expectations among marker loci. We used nine anonymous and 15 EST-linked microsatellites, 362 AFLP loci, and several neutrality tests, to identify outlier loci when comparing four populations of the seaweed Fucus serratus spaced along a 12km intertidal shore with a steep salinity gradient. Under criteria of at least two significant tests in at least two population pairs, three EST-derived and three anonymous loci revealed putative signatures of selection. Anonymous locus FsB113 was a consistent outlier when comparing least saline to fully marine sites. Locus F37 was an outlier when comparing the least saline to more saline areas, and was annotated as a polyol transporter/putative mannitol transporter - an important sugar-alcohol associated with osmoregulation by brown algae. The remaining loci could not be annotated using six different data bases. Exclusion of microsatellite outlier loci did not change either the degree or direction of differentiation among populations. In one outlier test, the number of AFLP outlier loci increased as the salinity differences between population pairs increased (up to 14); only four outliers were detected with the second test and only one was consistent with both tests. Consistency may be improved with a much more rigorous approach to replication and/or may be dependent upon the class of marker used. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary

    Science.gov (United States)

    Nagahashi, Masayuki; Ajioka, Yoichi; Lang, Istvan; Szentirmay, Zoltan; Kasler, Miklos; Nakadaira, Hiroto; Yokoyama, Naoyuki; Watanabe, Gen; Nishikura, Ken; Wakai, Toshifumi; Shirai, Yoshio; Hatakeyama, Katsuyoshi; Yamamoto, Masaharu

    2008-01-01

    AIM: To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS: We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250). RESULTS: Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047). CONCLUSION: It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis. PMID:18176964

  2. Evaluation of K-ras and p53 expression in pancreatic adenocarcinoma using the cancer genome atlas.

    Directory of Open Access Journals (Sweden)

    Liming Lu

    Full Text Available Genetic alterations in K-ras and p53 are thought to be critical in pancreatic cancer development and progression. However, K-ras and p53 expression in pancreatic adenocarcinoma have not been systematically examined in The Cancer Genome Atlas (TCGA Data Portal. Information regarding K-ras and p53 alterations, mRNA expression data, and protein/protein phosphorylation abundance was retrieved from The Cancer Genome Atlas (TCGA databases, and analyses were performed by the cBioPortal for Cancer Genomics. The mutual exclusivity analysis showed that events in K-ras and p53 were likely to co-occur in pancreatic adenocarcinoma (Log odds ratio = 1.599, P = 0.006. The graphical summary of the mutations showed that there were hotspots for protein activation. In the network analysis, no solid association between K-ras and p53 was observed in pancreatic adenocarcinoma. In the survival analysis, neither K-ras nor p53 were associated with both survival events. As in the data mining study in the TCGA databases, our study provides a new perspective to understand the genetic features of K-ras and p53 in pancreatic adenocarcinoma.

  3. KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target.

    Science.gov (United States)

    Román, Marta; Baraibar, Iosune; López, Inés; Nadal, Ernest; Rolfo, Christian; Vicent, Silvestre; Gil-Bazo, Ignacio

    2018-02-19

    Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them represents a potential therapeutic target. Although KRAS mutations are the most frequently oncogene aberrations in lung adenocarcinoma patients, effective therapies targeting KRAS have yet to be developed. Moreover, the role of KRAS oncogene in NSCLC remains unclear and its predictive and prognostic impact remains controversial. The study of the underlying biology of KRAS in NSCLC patients could help to determine potential candidates to evaluate novel targeted agents and combinations that may allow a tailored treatment for these patients. The aim of this review is to update the current knowledge about KRAS-mutated lung adenocarcinoma, including a historical overview, the biology of the molecular pathways involved, the clinical relevance of KRAS mutations as a prognostic and predictive marker and the potential therapeutic approaches for a personalized treatment of KRAS-mutated NSCLC patients.

  4. Focal Adhesion Kinase Regulates the DNA Damage Response and Its Inhibition Radiosensitizes Mutant KRAS Lung Cancer.

    Science.gov (United States)

    Tang, Ke-Jing; Constanzo, Jerfiz D; Venkateswaran, Niranjan; Melegari, Margherita; Ilcheva, Mariya; Morales, Julio C; Skoulidis, Ferdinandos; Heymach, John V; Boothman, David A; Scaglioni, Pier Paolo

    2016-12-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide due to the limited availability of effective therapeutic options. For instance, there are no effective strategies for NSCLCs that harbor mutant KRAS, the most commonly mutated oncogene in NSCLC. Thus, our purpose was to make progress toward the generation of a novel therapeutic strategy for NSCLC. We characterized the effects of suppressing focal adhesion kinase (FAK) by RNA interference (RNAi), CRISPR/CAS9 gene editing or pharmacologic approaches in NSCLC cells and in tumor xenografts. In addition, we tested the effects of suppressing FAK in association with ionizing radiation (IR), a standard-of-care treatment modality. FAK is a critical requirement of mutant KRAS NSCLC cells. With functional experiments, we also found that, in mutant KRAS NSCLC cells, FAK inhibition resulted in persistent DNA damage and susceptibility to exposure to IR. Accordingly, administration of IR to FAK-null tumor xenografts causes a profound antitumor effect in vivo CONCLUSIONS: FAK is a novel regulator of DNA damage repair in mutant KRAS NSCLC and its pharmacologic inhibition leads to radiosensitizing effects that could be beneficial in cancer therapy. Our results provide a framework for the rationale clinical testing of FAK inhibitors in NSCLC patients. Clin Cancer Res; 22(23); 5851-63. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Animal products and K-ras codon 12 and 13 mutations in colon carcinomas

    NARCIS (Netherlands)

    Kampman, E.; Voskuil, D.W.; Kraats, van A.A.; Balder, H.F.; Muijen, van G.N.P.; Goldbohm, R.S.; Veer, van 't P.

    2000-01-01

    K-ras gene mutations (codons 12 and 13) were determined by PCR-based mutant allele-specific amplification (MASA) in tumour tissue of 185 colon cancer patients: 36␑arboured mutations, of which 82 ere located in codon 12. High intakes of animal protein, calcium and poultry were differently associated

  6. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

    DEFF Research Database (Denmark)

    Hollestelle, Antoinette; van der Baan, Frederieke H; Berchuck, Andrew

    2015-01-01

    OBJECTIVE: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing...

  7. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

    DEFF Research Database (Denmark)

    Hollestelle, Antoinette; van der Baan, Frederieke H; Berchuck, Andrew

    2016-01-01

    OBJECTIVE: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing...

  8. K-ras oncogene mutations in sporadic colorectal cancer in The Netherlands Cohort Study

    NARCIS (Netherlands)

    Brink, M.; Goeij, A.F.P.M. de; Weijenberg, M.P.; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Pachen, M.M.M.; Smits, K.M.; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den

    2003-01-01

    Activation of K-ras oncogene has been implicated in colorectal carcinogenesis, being mutated in 30-60% of the adenocarcinomas. In this study, 737 incident colorectal cancer (CRC) patients, originating from 120 852 men and women (55-69 years at baseline) participating in the Netherlands Cohort Study

  9. Fat and K-ras mutations in sporadic colorectal cancer in The Netherlands Cohort Study

    NARCIS (Netherlands)

    Brink, M.; Weijenberg, M.P.; Goeij, A.F.P.M. de; Schouten, L.J.; Koedijk, F.D.H.; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den

    2004-01-01

    Associations between dietary intake of various fats and specific K-ras mutations in colorectal cancer (CRC) were investigated within the framework of The Netherlands Cohort Study on diet and cancer (NLCS). After 7.3 years of follow-up and with exclusion of the first 2.3 years, 448 colon and 160

  10. Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development.

    NARCIS (Netherlands)

    Thunnissen, F.B.J.M.; Prinsen, C.; Hol, B.; Drift, M.A. van der; Vesin, A.; Brambilla, C.; Montuenga, L.; Field, J.K.

    2012-01-01

    BACKGROUND: In a European multicenter prospective study patients with lung cancer were interviewed for smoking history and biological samples centrally collected. The aim of this study was to compare KRAS mutation analysis with smoking status at the time of diagnosis. METHODS: A nested case-study

  11. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

    NARCIS (Netherlands)

    A. Hollestelle (Antoinette); F.H. Van Der Baan (Frederieke H.); A. Berchuck (Andrew); S.E. Johnatty (Sharon); K.K.H. Aben (Katja); B.A. Agnarsson (Bjarni); K. Aittomäki (Kristiina); E. Alducci (Elisa); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); N.N. Antonenkova (Natalia); A.C. Antoniou (Antonis C.); C. Apicella (Carmel); V. Arndt (Volker); N. Arnold (Norbert); B.K. Arun (Banu); B. Arver (Brita Wasteson); A. Ashworth (Alan); L. Baglietto (Laura); R. Balleine (Rosemary); E.V. Bandera (Elisa); D. Barrowdale (Daniel); Y.T. Bean (Yukie T.); L. Beckmann (Lars); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berger (Andreas); R. Berger (Raanan); B. Beuselinck (B.); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); A. Bojesen (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet); B. Bonnani (Bernardo); J.S. Brand (Judith S.); H. Brauch (Hiltrud); H. Brenner (Hermann); L.A. Brinton (Louise); A. Brooks-Wilson (Angela); F. Bruinsma (Fiona); J. Brunet (Joan); T. Brüning (Thomas); A. Budzilowska (Agnieszka); C.H. Bunker (Clareann H.); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra S.); M.A. Caligo (Maria); I. Campbell (Ian); J. Carter (Jonathan); J. Chang-Claude (Jenny); S.J. Chanock (Stephen J.); K.B.M. Claes (Kathleen B.M.); J.M. Collee (Margriet); L.S. Cook (Linda S.); F.J. Couch (Fergus); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); J.M. Cunningham (Julie); C. Cybulski (Cezary); K. Czene (Kamila); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); M. de La Hoya (Miguel); A. DeFazio (Anna); J. Dennis (Joe); P. Devilee (Peter); E. Dicks (Ed); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); I.D.S. Silva (Isabel Dos Santos); A. Du Bois (Andreas); M. Dumont (Martine); A.M. Dunning (Alison); M. Duran (Mercedes); D.F. Easton (Douglas F.); D. Eccles (Diana); R. Edwards (Robert); H. Ehrencrona (Hans); B. Ejlertsen (Bent); A.B. Ekici (Arif); S.D. Ellis (Steve); C. Engel (Christoph); M. Eriksson (Mikael); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); A. Fontaine (Annette); S. Fortuzzi (S.); F. Fostira (Florentia); B.L. Fridley (Brooke); M.O.W. Friebel (Mark ); E. Friedman (Eitan); G. Friel (Grace); D. Frost (Debra); J. Garber (Judy); M. García-Closas (Montserrat); S.A. Gayther (Simon); A. Gentry-Maharaj (Aleksandra); A-M. Gerdes (Anne-Marie); G.G. Giles (Graham); R. Glasspool (Rosalind); G. Glendon (Gord); A.K. Godwin (Andrew K.); M.T. Goodman (Marc T.); M. Gore (Martin); M.H. Greene (Mark H.); M. Grip (Mervi); J. Gronwald (Jacek); D. Gschwantler-Kaulich (Daphne); P. Guénel (Pascal); S.R. Guzman (Starr R.); L. Haeberle (Lothar); C.A. Haiman (Christopher A.); P. Hall (Per); S.L. Halverson (Sandra L.); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. Harter (Philipp); J.M. Hartikainen (J.); S. Healey (Sue); R. Hein (Rebecca); P.U. Heitz; B.E. Henderson (Brian); J. Herzog (Josef); M.A. T Hildebrandt (Michelle A.); C.K. Høgdall (Claus); E. Høgdall (Estrid); F.B.L. Hogervorst (Frans); J.L. Hopper (John); K. Humphreys (Keith); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny N.); C. Isaacs (Claudine); A. Jakubowska (Anna); R. Janavicius (Ramunas); K. Jaworska (Katarzyna); A. Jensen (Allan); U.B. Jensen; N. Johnson (Nichola); A. Jukkola-Vuorinen (Arja); M. Kabisch (Maria); B.Y. Karlan (Beth Y.); V. Kataja (Vesa); N. Kauff (Noah); L.E. Kelemen (Linda); M. Kerin (Michael); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); J.P. Knol-Bout (Jacoba P.); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); C. Krakstad (Camilla); V. Kristensen (Vessela); K.B. Kuchenbaecker (Karoline); J. Kupryjanczyk (Jolanta); Y. Laitman (Yael); D. Lambrechts (Diether); S. Lambrechts (Sandrina); M.C. Larson (Melissa); A. Lasa (Adriana); P. Laurent-Puig (Pierre); C. Lazaro (Conxi); N. Le (Nhu); L. Le Marchand (Loic); A. Leminen (Arto); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); D. Liang (Dong); A. Lindblom (Annika); N.M. Lindor (Noralane); J. Lissowska (Jolanta); J. Long (Jirong); K.H. Lu (Karen); J. Lubinski (Jan); L. Lundvall (Lene); G. Lurie (Galina); P.L. Mai (Phuong); A. Mannermaa (Arto); S. Margolin (Sara); F. Mariette (F.); F. Marme (Federick); J.W.M. Martens (John); L.F. Massuger (Leon); C. Maugard; S. Mazoyer (Sylvie); L. McGuffog (Lesley); W.P. McGuire; C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); F. Menegaux (Florence); P. Menéndez (Primitiva); J. Menkiszak (Janusz); U. Menon (Usha); A.R. Mensenkamp (Arjen); N. Miller (Nicola); R.L. Milne (Roger); F. Modugno (Francesmary); M. Montagna (Marco); K.B. Moysich (Kirsten B.); H. Mul̈ler (Heiko); A.-M. Mulligan (Anna-Marie); T.A. Muranen (Taru); S.A. Narod (Steven A.); K.L. Nathanson (Katherine); R.B. Ness (Roberta B.); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); P. Neven (Patrick); F. Nielsen (Finn); S.F. Nielsen (Sune); B.G. Nordestgaard (Børge); R. Nussbaum (Robert); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); S.H. Olson (Sara); J.C. Oosterwijk (Jan); I. Orlow (Irene); N. Orr (Nick); S. Orsulic (Sandra); A. Osorio (Ana); L. Ottini (Laura); J. Paul (James); C.L. Pearce (Celeste); I.S. Pedersen (Inge Sokilde); B. Peissel (Bernard); T. Pejovic (Tanja); L.M. Pelttari (Liisa); J. Perkins (Jo); J. Permuth-Wey (Jenny); P. Peterlongo (Paolo); J. Peto (Julian); C. Phelan (Catherine); K.-A. Phillips (Kelly-Anne); M. Piedmonte (Marion); M.C. Pike (Malcolm C.); R. Platte (Radka); J. Plisiecka-Halasa (Joanna); E.M. Poole (Elizabeth); B. Poppe (Bruce); K. Pykäs (Katri); P. Radice (Paolo); S.J. Ramus (Susan); R. Rebbeck (Timothy); M.W.R. Reed (Malcolm W.R.); G. Rennert (Gad); H. Risch (Harvey); M. Robson (Mark); G. Rodriguez (Gustavo); A. Romero (Atocha); M.A. Rossing (Mary Anne); J.H. Rothstein (Joseph H.); A. Rudolph (Anja); I.B. Runnebaum (Ingo); R. Salani (Ritu); H.B. Salvesen (Helga); E.J. Sawyer (Elinor); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); A. Schneeweiss (Andreas); M. Schoemaker (Minouk); A. Schrauder (André); F.R. Schumacher (Fredrick); I. Schwaab (Ira); G. Scuvera (Giulietta); T.A. Sellers (Thomas A.); G. Severi (Gianluca); C.M. Seynaeve (Caroline); M. Shah (Mitul); M. Shrubsole (Martha); N. Siddiqui (Nadeem); W. Sieh (Weiva); J. Simard (Jacques); C.F. Singer (Christian); O. Sinilnikova (Olga); D. Smeets (Dominiek); C. Sohn (Christof); M. Soller (Maria); H. Song (Honglin); P. Soucy (Penny); M.C. Southey (Melissa); C. Stegmaier (Christa); D. Stoppa-Lyonnet (Dominique); L. Sucheston (Lara); A.J. Swerdlow (Anthony ); I.L. Tangen (Ingvild L.); M.-K. Tea; P.J. Teixeira; K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); P.J. Thompson (Pamela J.); L. Tihomirova (Laima); M. Tischkowitz (Marc); A.E. Toland (Amanda); R.A.E.M. Tollenaar (Rob); I. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); H. Tsimiklis (Helen); N. Tung (Nadine); S. Tworoger (Shelley); J.P. Tyrer (Jonathan); C. Vachon (Celine); L.J. van 't Veer (Laura); A.M. van Altena (Anne); C.J. van Asperen (Christi); D. Van Den Berg (David); A.M.W. van den Ouweland (Ans); H.C. van Doorn (Helena); E. Van Nieuwenhuysen (Els); E.J. van Rensburg (Elizabeth); I. Vergote (Ignace); S. Verhoef; R.A. Vierkant (Robert); J. Vijai (Joseph); A.F. Vitonis (Allison); A. von Wachenfeldt (Anna); C.S. Walsh (Christine); Q. Wang (Qing); S. Wang-Gohrke (Shan); B. Wapenschmidt (Barbara); M. Weischer (Maren); J.N. Weitzel (Jeffrey); C. Weltens (Caroline); N. Wentzensen (N.); A.S. Whittemore (Alice S.); L.R. Wilkens (Lynne R.); R. Winqvist (Robert); A.H. Wu (Anna); X. Wu (Xifeng); H.P. Yang (Hannah P.); D. Zaffaroni (Daniela); M.P. Zamora (Pilar); W. Zheng (Wei); A. Ziogas (Argyrios); G. Chenevix-Trench (Georgia); P.D.P. Pharoah (Paul); M.A. Rookus (Matti); M.J. Hooning (Maartje); E.L. Goode (Ellen L.); Breast Cancer Family Register; EMBRACE; GENICA Network; HEBON; SWE-BRCA

    2016-01-01

    textabstractObjective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies,

  12. The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    Nygaard, Anneli Dowler; Garm Spindler, Karen-Lise; Pallisgaard, Niels

    2013-01-01

    BACKGROUND: Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality. New agents targeting the epidermal growth factor system are emerging, but only a subgroup of the patients will benefit from the therapy. Cell free DNA (cfDNA......) in the blood allows for tumour specific analyses, including KRAS-mutations, and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS (pmKRAS) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with newly diagnosed, advanced NSCLC eligible...... for chemotherapy were enrolled in a prospective biomarker trial. A pre-treatment blood sample was drawn and subsequently DNA was extracted and pmKRAS analysed. The patients received carboplatin (AUC5) i.v. day 1 and vinorelbine (30mg/m(2) i.v. day 1 and 60mg/m(2) p.o. day 8) for a maximum of six cycles. Response...

  13. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

    NARCIS (Netherlands)

    Hollestelle, Antoinette; van der Baan, Frederieke H.; Berchuck, Andrew; Johnatty, Sharon E.; Aben, Katja K.; Agnarsson, Bjarni A.; Aittomaki, Kristiina; Alducci, Elisa; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; Apicella, Carmel; Arndt, Volker; Arnold, Norbert; Arun, Banu K.; Arver, Brita; Ashworth, Alan; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V.; Barrowdale, Daniel; Bean, Yukie T.; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Berger, Andreas; Berger, Raanan; Beuselinck, Benoit; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Brooks-Wilson, Angela; Bruinsma, Fiona; Brunet, Joan; Bruning, Thomas; Budzilowska, Agnieszka; Bunker, Clareann H.; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Caligo, Maria A.; Campbell, Ian; Carter, Jonathan; Chang-Claude, Jenny; Chanock, Stephen J.; Claes, Kathleen B. M.; Collee, J. Margriet; Cook, Linda S.; Couch, Fergus J.; Cox, Angela; Cramer, Daniel; Cross, Simon S.; Cunningham, Julie M.; Cybulski, Cezary; Czene, Kamila; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; de la Hoya, Miguel; deFazio, Anna; Dennis, Joseph; Devilee, Peter; Dicks, Ed M.; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dork, Thilo; Dos Santos Silva, Isabel; du Bois, Andreas; Dumont, Martine; Dunning, Alison M.; Duran, Mercedes; Easton, Douglas F.; Eccles, Diana; Edwards, Robert P.; Ehrencrona, Hans; Ejlertsen, Bent; Ekici, Arif B.; Ellis, Steve D.; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Fontaine, Annette; Fortuzzi, Stefano; Fostira, Florentia; Fridley, Brooke L.; Friebel, Tara; Friedman, Eitan; Friel, Grace; Frost, Debra; Garber, Judy; Garcia-Closas, Montserrat; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Gerdes, Anne-Marie; Giles, Graham G.; Glasspool, Rosalind; Glendon, Gord; Godwin, Andrew K.; Goodman, Marc T.; Gore, Martin; Greene, Mark H.; Grip, Mervi; Gronwald, Jacek; Kaulich, Daphne Gschwantler; Guenel, Pascal; Guzman, Starr R.; Haeberle, Lothar; Haiman, Christopher A.; Hall, Per; Halverson, Sandra L.; Hamann, Ute; Hansen, Thomas V. O.; Harter, Philipp; Hartikainen, Jaana M.; Healey, Sue; Hein, Alexander; Heitz, Florian; Henderson, Brian E.; Herzog, Josef; Hildebrandt, Michelle A. T.; Bogdan, Claus K.; Hogdall, Estrid; Hogervorst, Frans B. L.; Hopper, John L.; Humphreys, Keith; Huzarski, Tomasz; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; Janavicius, Ramunas; Jaworska, Katarzyna; Jensen, Allan; Jensen, Uffe Birk; Johnson, Nichola; Jukkola-Vuorinen, Arja; Kabisch, Maria; Karlan, Beth Y.; Kataja, Vesa; Kauff, Noah; Kelemen, Linda E.; Kerin, Michael J.; Kiemeney, Lambertus A.; Kjaer, Susanne K.; Knight, Julia A.; Knol-Bout, Jacoba P.; Konstantopoulou, Irene; Kosma, Veli-Matti; Krakstad, Camilla; Kristensen, Vessela; Kuchenbaecker, Karoline B.; Kupryjanczyk, Jolanta; Laitman, Yael; Lambrechts, Diether; Lambrechts, Sandrina; Larson, Melissa C.; Lasa, Adriana; Laurent-Puig, Pierre; Lazaro, Conxi; Le, Nhu D.; Le Marchand, Loic; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Liang, Dong; Lindblom, Annika; Lindor, Noralane; Lissowska, Jolanta; Long, Jirong; Lu, Karen H.; Lubinski, Jan; Lundvall, Lene; Lurie, Galina; Mai, Phuong L.; Mannermaa, Arto; Margolin, Sara; Mariette, Frederique; Marme, Frederik; Martens, John W. M.; Massuger, Leon F. A. G.; Maugard, Christine; Mazoyer, Sylvie; McGuffog, Lesley; McGuire, Valerie; McLean, Catriona; McNeish, Lain; Meindi, Alfons; Menegaux, Florence; Menendez, Primitiva; Menkiszak, Janusz; Menon, Usha; Mensenkamp, Arjen R.; Miller, Nicola; Milne, Roger L.; Modugno, Francesmary; Montagna, Marco; Moysich, Kirsten B.; Mueller, Heiko; Mulligan, Anna Marie; Muranen, Taru A.; Narod, Steven A.; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Finn C.; Nielsen, Sune F.; Nordestgaard, Berge G.; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olson, Sara H.; Oosterwijk, Jan C.; Orlow, Irene; Orr, Nick; Orsulic, Sandra; Osorio, Ana; Ottini, Laura; Paul, James; Pearce, Celeste L.; Pedersen, Inge Sokilde; Peissel, Bernard; Pejovic, Tanja; Pelttari, Liisa M.; Perkins, Jo; Permuth-Wey, Jenny; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M.; Phillips, Kelly-Anne; Piedmonte, Marion; Pike, Malcolm C.; Platte, Radka; Plisiecka-Halasa, Joanna; Poole, Elizabeth M.; Poppe, Bruce; Pylkas, Katri; Radice, Paolo; Ramus, Susan J.; Rebbeck, Timothy R.; Reed, Malcolm W. R.; Rennert, Gad; Risch, Harvey A.; Robson, Mark; Rodriguez, Gustavo C.; Romero, Atocha; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo; Salani, Ritu; Salvesen, Helga B.; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schrauder, Michael G.; Schumacher, Fredrick; Schwaab, Ira; Scuvera, Giulietta; Sellers, Thomas A.; Severi, Gianluca; Seynaeve, Caroline M.; Shah, Mitul; Shrubsole, Martha; Siddiqui, Nadeem; Sieh, Weiva; Simard, Jacques; Singer, Christian F.; Sinilnikova, Olga M.; Smeets, Dominiek; Sohn, Christof; Soller, Maria; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stegmaier, Christa; Stoppa-Lyonnet, Dominique; Sucheston, Lara; Swerdlow, Anthony; Tangen, Ingvild L.; Tea, Muy-Kheng; Teixeira, Manuel R.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Thompson, Pamela J.; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda Ewart; Tollenaar, Rob A. E. M.; Tomlinson, Ian; Torres, Diana; Truong, Therese; Tsimiklis, Helen; Tung, Nadine; Tworoger, Shelley S.; Tyrer, Jonathan P.; Vachon, Celine M.; Van 't Veer, Laura J.; van Altena, Anne M.; Van Asperen, C. J.; van den Berg, David; van den Ouweland, Ans M. W.; van Doom, Helena C.; Van Nieuwenhuysen, Els; van Rensburg, Elizabeth J.; Vergote, Ignace; Verhoef, Senno; Vierkant, Robert A.; Vijai, Joseph; Vitonis, Allison F.; von Wachenfeldt, Anna; Walsh, Christine; Wang, Qin; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weischer, Maren; Weitzel, Jeffrey N.; Weltens, Caroline; Wentzensen, Nicolas; Whittemore, Alice S.; Wilkens, Lynne R.; Winqvist, Robert; Wu, Anna H.; Wu, Xifeng; Yang, Hannah P.; Zaffaroni, Daniela; Zamora, M. Pilar; Zheng, Wei; Ziogas, Argyrios; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Rookus, Matti A.; Hooning, Maartje J.; Goode, Ellen L.

    Objective. Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing

  14. Clinical relevance of the K-ras oncogene in colorectal cancer: Experience in a Mexican population

    Directory of Open Access Journals (Sweden)

    F. Cabrera-Mendoza

    2014-07-01

    Conclusions: No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature. Further studies that include both a larger number of patients and those receiving monoclonal treatment, need to be conducted. There were only 5 patients in the present study that received cetuximab, resulting in a misleading analysis.

  15. Scanning table

    CERN Multimedia

    1960-01-01

    Before the invention of wire chambers, particles tracks were analysed on scanning tables like this one. Today, the process is electronic and much faster. Bubble chamber film - currently available - (links can be found below) was used for this analysis of the particle tracks.

  16. Scan Statistics

    CERN Document Server

    Glaz, Joseph

    2009-01-01

    Suitable for graduate students and researchers in applied probability and statistics, as well as for scientists in biology, computer science, pharmaceutical science and medicine, this title brings together a collection of chapters illustrating the depth and diversity of theory, methods and applications in the area of scan statistics.

  17. Scanning transmission electron microscope

    OpenAIRE

    Kruit, P.

    2006-01-01

    The invention relates to a scanning transmission electron microscope comprising an electron source, an electron accelerator and deflection means for directing electrons emitted by the electron source at an object to be examined, and in addition a detector for detecting electrons coming from the object and, connected to the detector, a device for processing the detected electrons so as to form an object image, wherein a beam splitter is provided for dividing the electron beam from the electron...

  18. Scanning transmission electron microscope

    NARCIS (Netherlands)

    Kruit, P.

    2006-01-01

    The invention relates to a scanning transmission electron microscope comprising an electron source, an electron accelerator and deflection means for directing electrons emitted by the electron source at an object to be examined, and in addition a detector for detecting electrons coming from the